September 2020
What is the ideal time for hip sonography screening?
Mahmut Nedim Aytekin 1, Temel Oğuz 1, Enes Uluyardimci 1, İbrahim Bozkurt 1, Recep Öztürk 2
1 Department of Orthopedics and Traumatology, Ankara Yildirim Beyazit University, Ataturk Training and Research Hospital, 2 Department of Orthopedics and Traumatology, Dr Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Ankara, Turkey
DOI:10.4328/ACAM.20048 Received: 24-07-2019 Accepted:18-08-2019 Published Online: 01-09-2019 Printed: 2020-09-01 Ann Clin Anal Med 2020;11(5):488-491
Corresponding Author: Recep Öztürk, Dr Abdurrahman Yurtslan Ankara Oncology Training And Research Hospital, Department of Orthopedics and Traumatology, Mehmet Akif Ersoy Mh., 13. Cadde No: 56, Yenimahalle, 06200, Ankara, Turkey. E-mail : ozturk_recep@windowslive.com Phone: +903123360909 Fax: 0 312 334 03 52 Tel : +905054634794 Corresponding Author ORCID ID: https://orcid.org/ 0000-0002-6753-9321
Aim: The necessity of hip sonography scan is accepted by all authors. However, there is no clear information about when the scan is required. In this study, we tried to find out the most appropriate time for screening and reported our results of hip sonography performed in our clinic.
Material and Methods: Records of 351 infants were retrospectively investigated, and spontaneous correction in developmentally retarded hips was evaluated by Graf’s method. Ages of infants were between 3-29 days; the average age was 11 days.
Results: Three hundred and eighty hips were evaluated as type 1 (%54). Babies who were evaluated at three and four weeks of age, the ones that assessed as types 2c, d, 3 and 4 got initial treatment. Fourteen hips of 11 babies received treatment. All of the type 2a+ (71 hips) and all but two of type 2a- (82, %97.6) had become type 1 without treatment. Among 11 hips that were type 3 at week one, 3 type 3 hips of two babies that came back for control, returned to normal without treatment. Even the hips considered type 2c in this age group can return to normal without treatment.
Discussion: According to our dataset, because hips that were evaluated as undeveloped at the first screening returned to normal at an average of 7 weeks, the ideal time for screening is 7th week of life.
Keywords: Hip; Ultrasound; DDH; Graf’s Method; Time
Introduction
Developmental dysplasia of the hip (DDH) is an important dis- ease which causes many comorbidities especially osteoarthritis [1-5]. Although there is no exact statistical data, developmen- tal dysplasia of the hip (DDH) is seen at a frequency between 0.5% and 1.5% in Turkey [6]. On the other hand, studies using hip ultrasonography reported the frequency of this condition as 0.86%-17% in our country [7,8]. When not diagnosed and treat- ed early, DDH is known to cause serious morbidity and therefore additional treatment costs. An important portion of the total hip replacements in our country occur against the background of DDH.
The necessity of hip sonography scan is accepted by all authors. However, there is no clear information about when the scan is required. In this study, we tried to find out the ideal time for hip sonography screening.
Material and Methods
Among the infants screened in our clinic, 702 hips of 351 in- fants that received the scan at 0-1 months of age were exam- ined.
Babies screened in our clinic are followed up in the way de- scribed below. First, information is given to parents about de- velopmental dysplasia of the hip and about the procedure to be followed. Risk factors related to baby and the family were questioned. The physical examination has been performed after sonography so that babies did not cry. Hip sonography has been performed and alpha and beta angles were measured according to the Graf method. Data of babies that received hip sonog- raphy have been noted into the registration form and parents were informed about the results.
When the records were examined retrospectively it was seen that all of the babies who received screening at one or two weeks of age, except for type 1 babies, were called for control. Again, according to our clinical practice, among the babies that were found undeveloped no treatment was given to the ones at their first 2 weeks of age because of emergent compliance problems, instead, we waited them to be at least 3 weeks of age. Babies who were evaluated at three and four weeks of age, the ones that assessed as type 2c, typed, type 3 and type 4 received initial treatment while type 2a+ and 2a- ones were de- cided to be monitored and called for control. The Pavlik harness was preferred in the treatment. The Pavlik harness was placed by us in front of families, and signs were placed at strap points for convenience. To understand the treatment compliance and make sure that the families understood the method, patients were called for follow-up after 1 week. Infants who started re- ceiving treatment were called for follow-up every 2 weeks and the treatment continued until type 1 hip was obtained. Ex- cept for 2 babies, no other treatment than Pavlik harness was needed; in those 2 babies, closed reduction under general anes- thesia was performed and pelvipedal hip spica cast was used. Cast treatments were renewed after 6 weeks and at the end of the 3rd month, they were removed and abduction orthosis was given. The treatment was terminated after three months. Statistical comparisons were made in 95% confidence interval, the Student’s t-test was used for parametric data, and the Chi- square test was used in non-parametric data. Windows 2003 / SSPS 12.0 program was used for statistical analysis.
Results
Among 702 hips of 351 infants that were included in the study, 380 hips were evaluated as type 1 according to Graf’s sono- graphic classification, 119 hips were evaluated as type 2a+, 138 hips were 2a-, 49 hips were type 2c, 2 hips were type d, 11 hips were type 3a and 3 hips were type 4. The distribution of ages of those hips is shown in Table 1.
The follow-up of 128 hips could not be performed because the infants did not come for control. Of all the babies that came for control, 71 infants with 2a+ type detected on the first ul- trasound, turned into type 1 without treatment (%100). Eighty- four type 2a- hips that were followed up turned into normal without treatment (%97). Two babies were treated with Pavlik harness and got their first sonography at 4 weeks of age. Thirty-three of 45 hips that received first sonography at the age of 1 or 2 weeks and evaluated as type 2c came for control and 29 of them returned to normal without treatment (%87). Four babies that were screened at the age of 3 weeks and eval- uated as type 2c received treatment, and among 3 babies that came back for the follow-up, 2 were treated with Pavlik harness while 1 of them was treated after receiving a closed reduction in the operating room after Pavlik harness.
Two babies were considered as type d at the first two weeks one of them did not come back for control. The other one that was followed up was found to be type d when he came back at the 6th week, and was treated with Pavlik harness. Of the 11 hips with type 3 at week one, 8 did not come back for control, 3 hips of two babies with type 3 that came back for control, be- came normal without treatment. One of two babies identified as type 4 at the first week did not come for control, while the other one was evaluated as type 3a at the 5th week and treated with closed reduction following Pavlik harness. One baby was identified as type 4 at four weeks of age and the treatment was given, but that baby could not be followed up. In this way, the treatment was given to 14 hips of 11 babies and among these we completed treatment of12 hips of 9 babies. Only two babies needed closed reduction and pelvipedal spica cast. Hips that recovered without treatment are shown in Table 2.
Among 142 babies that were evaluated as type 2a-, 2c, d, 3 and 4, 61 were male and 81 of them were female (%43 – %57). Fourteen babies had positive either first- or second-degree family history (%10). Thigh pili asymmetry was found in 49 ba- bies (%35), 26 babies (%19) had limited abduction, 4 babies were born with breech presentation.
Eight of the babies who received treatment were female and 3 of them were male (%72-%28). Three of them had a family his- tory (28%), 5 had pili asymmetry (45%), 3 had limited abduction (%28), 1 had breech presentation history.
When we look at our dataset with the weighted average, hips that were evaluated as displaced at the first screening returned to normal at an average of 7 weeks, and when the whole data are handled, the average time for screening was found to be 4 weeks. This result is not a test result, it is a detection.
Discussion
Although it is not clearly defined when to do hip sonography in DDH screening, it is stated that it would be appropriate to screen at 4-6 weeks [9]. Bialik et al. stated that only 10% of hip pathologies that were detected at the first and third day of life persisted at the end of 6 weeks [10]. In this study, we found out that in all age groups, type 2a+ hips returned to normal. Again, we saw that all type 2a- hips that were detected by sonogra- phy performed in the first 3 weeks of life, returned to normal. According to the results of the fourth-week sonography, 2 of 7 babies that were identified as type 2a- needed treatment. If we look at the results obtained in the babies with hips identified as type 2a- or worse in the first two weeks, we will see that when these patients came back for control at the fifth and sixth weeks, only 5% of them had persistent pathology. According to our statistical study, it took an average of 5,5 weeks (39 days) for these hips to become type 1. According to the results, in the third and fourth-week, pathology was persistent at a rate of 36%. In the light of these findings, even if any pathology is found at sonography screening at the first two weeks, we be- lieve that treatment is unnecessary.
Okur et al. found limited abduction in 26% of the babies that had pathology in sonography, while 17% of them had pili sym- metry [11]. Tonnis et al. reported that limited abduction was the most frequently seen clinical finding in babies that had pa- thology in their ultrasound scans [8]. In our study, when type 2a- and worse hips were considered as “pathological”, the most frequent clinical finding was pili asymmetry (%35). Limited ab- duction was the second most frequent finding (19%). However, 21% of the babies, who were evaluated as type 1 in ultrasound, also had piliasymmetry. However, we would like to state that these findings were viewed by more than one hand, and are not standardized enough.
In hip sonography screening, family history, breech presenta- tion, and foot problems have been reported as the most com- mon risk factors [12,13]. Oguz et al. in their series with 1099 cases, put emphasis on the first baby in DDH risk factors [14]. Omeroglu et al. reported the incidence of DDH in babies with and without risk factors for DDH as 28.1%-8.1% respectively [15].
As it is well known, there are many risk factors for this condition [16]. In our study, family history ranks first (10%). This was fol- lowed by the breech presentation. On the other hand, Atalar et al. pointed out that maternal height and infant body mass index are also possible risk factors for developmental dysplasia of the hip in female infants [17].
Omeroglu et al. reported female/male ratio as 16/9 in babies with sonographic pathology [15]. In our study, among the babies that were evaluated as type 2a- and worse in the first inspec- tion, 43% were male while 57% were female. However, in the second inspection, among the group with persistent pathology, female/male ratio was found to be 8/3 and we concluded that compared to the first case, female/male ratio increased dra- matically.
In a study published recently, Gokharman et al. has investigated the same question as our study using a different method and they found 8th week as the ideal time for screening which is a similar to the result of our study [18].
In total, 128 hips, 18% of all hips did not come for control. Of these, 23 were hip type 2c and worse, which corresponds to a higher number than the number of hips we treated. When we performed ultrasonography and found pathological results, in the first month especially in the first two weeks, although we informed families in detail, and told them that this situation will most probably recover, and they must come back for control, we experienced significant losses. We later contacted these fami- lies by telephone and learned that most of them admitted to another center.
Eventually, we identified hip dysplasia that does not require treatment, with ultrasound performed in the first two months. Graf et al. reported that surgical treatment rate was 0% in babies with DDH who were diagnosed and received treatment [19]. However, we do not think that all of them have to receive initial treatment. There is no doubt that we should start treat- ment for type 2c and worse hips when we see them at the third of fourth weeks. In the first and second week, we recommend follow-up without treatment. We believe that in type 2a hips, treatment plan should be determined at follow-up in the sixth week.
According to our dataset, because hips that were evaluated as undeveloped at the first screening returned to normal at an av- erage of 7 weeks, the ideal time for screening is 7th week of life. However, new studies with much more wider series may be required.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical stan- dards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
1. Ermiş MN, Dilaveroğlu B, Erçeltik O, Tuhanioğlu U, Karakaş ES, Durakbaşa MO. Intermediate-term results after uncemented total hip arthroplasty for the treatment of developmental dysplasia of the hip. Eklem Hastalik Cerrahisi. 2010; 21:15-22.
2. Atik OŞ, Daldal İ. Salter innominate osteotomy for the treatment of devel- opmental dysplasia of the hip: 37 years of follow-up. Eklem Hastalik Cerrahisi. 2015; 26:168-70.
3. Baki ME, Timurkaynak A, Aydın H, Baki C. Metal-on-metal dysplasia cup total hip arthroplasty for hip osteoarthritis secondary to developmental dysplasia of the hip. Eklem Hastalik Cerrahisi. 2014; 25:154-7.
4. Altintaş F, Gökçe A, Güven M, Inan M. Analyzing acetabular deficiency by com- puted tomography in osteoarthritis after Crowe type 2 developmental dysplasia of the hip. Eklem Hastalik Cerrahisi. 2009; 20:127-30.
5. Atalar H, Gunay C, Aytekin MN. Abnormal Development of the Femoral Head Epiphysis in an Infant with no Developmental Dysplasia of the Hip Apparent on Ultrasonography. J Orthop Case Rep. 2014; 4:46-8.
6. Bursalı A, editors Gelişimsel Kalça Displazisi Ve Koruyucu Hekimlik. Gelişimsel Kalça Displazisi. Istanbul: TOTBİD Yayınları; 2007. p.8-15.
7. Kutlu A, Memik R, Mutlu M, Kutlu R, Arslan A. Congenital dislocation of the hip and its relation to swaddling used in Turkey. J Pediatr Orthop. 1992; 12: 598-602.
8. Doğruel H, Atalar H, Yavuz OY, Uras I, Günay C, Sayli U. Türkiye’de Gelişimsel Kalça Displazisi Sıklığının ve Tarama Programlarının Değerlendirilmesi. J Med Sci. 2008;28(3):357-60.
9. Wientroub S, Grill F. Ultrasonography in developmental dysplasia of the hip. J Bone Joint Surg [Am]. 2000; 82:1004-18.
10. Bialik V, Bialik GM, Blazer S, Sujov P, Wiener F, Berant M. Developmental dysplasia of the hip: A new approach to incidence. Pediatrics. 1999; 103:93-9. 11. Okur A, Nakşılar F, Karsan O, Alparslan B. Doğuştan kalça çıkığı tanısı ve taramasında ultrasonografik muayenenin değeri. Acta Orthop Traumatol Turc. 1996; 30: 107-12.
12. Tonnis D, Storch K, Ulbrich H. Results of newborn screening for CDH with and without sonography and correlation of risk factors. J Pediatr Orthop. 1990;10:145-52.
13. Paton RW, Hinduja K, Thomas CD. The significance of at-risk factors in ultra- sound surveillance of developmental dysplasia of the hip. A ten-year prospective study. J Bone Joint Surg [Br]. 2005;87:1264-6.
14. Oğuz T, Ege A, Güngör Ş, Toppare MF, Erdemtok N. Ultrasonographic Evalua- tion of 1099 Babies by Graf Method. Joint Dis Rel Surg. 1996; 7(2):64-66.
15. Ömeroğlu H, Koparal S, Biçimoğlu A, Karademir A. Gelişimsel kalça displa- zisinde risk faktörleri ve klinik muayene bulguları ile ultrasonografik bulgular arasındaki ilişki. Acta Orthop Traumatol Turc. 1999; 33: 30-34.
16. Öztürk R, Gençoğlu M, Ateş Ö, Aytekin M, Toktaş O. Pediatri Polikliniğinden Ortopedi Bölümüne Danışılan 0-3 Yaş Arası Ardışık 100 Hastanın Analizi. Zeynep Kamil Tıp Bülteni. 2019; 50 (2): 39-43. DOI: 10.16948/zktipb.429353
17. Atalar H, Gunay C, Yavuz OY, Camurdan AD, Uras I, Eren A. Maternal Height and Infant Body Mass Index Are Possible Risk Factors for Developmental Dyspla- sia of the Hip in Female Infants. Acta Med Okayama. 2015; 69:349-54.
18. Gokharman FD, Aydin S, Fatihoglu E, Ergun E, Kosar PN. Optimizing the Time for Developmental Dysplasia of the Hip Screening: Earlieror Later? Ultrasound Q. 2019;35(2):130-35. DOI: 10.1097/RUQ.0000000000000348.
19. Graf R, Tschauner C, Klapsch W. Progress in prevention of late developmental dislocation of the hip by sonographic newborn hip “screening”: Results of a com- parative follow-up study. J Pediatr Orthop B. 1993;2:115-21.
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The effect of working time in cold conditions on pain and fibromyalgia syndrome symptoms
Yasin Devran Altuntaş 1, Tamer Çankaya 1, Ramazan Kurul 1, Muhammet Fatih Uysal 1, Elif Duygu 1, Gökhan Mehmet Karatay 1, Fatma Asena Karatay 1, Barış Alkan 2
1 Department of Physiotherapy and Rehabilitation, Faculty of Health Science, Bolu Abant İzzet Baysal University, 2 Bolu Izzet Baysal State Hospital, Bolu, Turkey
DOI: 10.4328/ACAM.20054 Received: 2019-08-27 Accepted: 2019-12-13 Published Online: 2020-01-22 Printed: 2020-09-01 Ann Clin Anal Med 2020;11(5):406-410
Corresponding Author: Yasin Devran Altundaş, Department of Physical Therapy and Rehabilitation, Faculty of Health Sciences, Bolu Abant İzzet Baysal University: 14280 Bolu, Turkey. E-mail: ydaltuntas@gmail.com F.: +903742534663 GSM: +903742541000/4123 Corresponding Author ORCID ID: https://orcid.org/0000-0002-1863-9385
Aim: This study aimed to investigate the effect of working time on cold and fibromialgia syndrome symptoms.
Material and Methods: The study included 568 individuals with a mean age of 36.9 years. Visual analog scale (VAS), The Revised Fibromyalgia Impact Questionnaire (FIQR) and 2016 Revisions to the 2010/2011 fibromyalgia diagnostic criteria were used for evaluation. The groups were formed as 2 years or less, 3-5 years, 6-9 years and 10 years or more. For daily working hours, two groups created as less than 8 hours and 8 hours or more.
Results: It was found that the score for VAS pain felt when working was higher compared to pain felt when resting (p=0.046). FIQR scores increased significantly in the cold work year (p=0.006) but there was no significant change in resting or working pain as working years increase (p> 0.05). FIQR total score, resting and working pain VAS values were found to increase for the group work more than 8 hours daily (p <0.05).
Discussion: As a conclusion, the results of this study showed that increasing working years and daily working hours caused an increase in the severity of FM related symptoms. Especially those who have been working for 10 years or more and/or more than 8 hours in cold were feeling greater pain and their fibromyalgia related symptoms were worse.
Keywords: Fibromyalgia; Musculoskeletal Pain
Introduction
Occupational exposure to cold is a risk factor that can lead to a variety of health problems, cold-related diseases, and symp- toms and also increases workload [1, 2]. The food processing industries must comply with strict standards regarding the temperature of the storage facilities. This may contradict the health conditions of workers. Cardiovascular, lung, peripheral circulation, skin, and musculoskeletal symptoms, complaints and diseases are common problems in these industries [3-5]. Besides, exposure to cold can lead to cooling injuries such as lo- cal cold bites, and hypothermia [6-8]. Cold exposure may cause various chronic diseases or may lead to worsening of existing diseases [4]. Epidemiological studies have shown that cold can be a risk factor for the exacerbation of disorders in various body areas [9-12].
Many tasks in the food processing industries are performed at low temperatures below 15oC. Fresh food is processed at tem- peratures ranging from -10oC to 6oC and frozen food is usually stored at -25oC. The cold conditions in the indoor environment are more predictable than the open-air environment, and gen- erally, the temperature is constant throughout the year without any change depending on time. Moreover, contact with cold surfaces or cold materials is a risk for workers [13-15].
FM is a rheumatic disease because it causes pain in the joints and connective tissue. It has been reported that people with FM are often affected by other rheumatic diseases (e.g. rheu- matoid arthritis, systemic lupus erythematosus, and ankylosing spondylitis) [16,17]. To date, the cause of FM has remained un- known. There is general evidence that traumatic events, obe- sity, and genetic predisposition will increase the likelihood of FM diagnosis in a person [18]. Lapossy et al. [19] reported that cold-induced vasospasm was greater in FM patients (38%) than in patients with low back pain (20%) and healthy controls (8%), indicating that the effect of cold on individuals under different conditions could change.
Protecting the health of working individuals, revealing the occu- pational risks and preventing these health problems are gaining importance both socially and economically. This study aimed to investigate the effects of working time in cold on pain and fibromyalgia syndrome symptoms.
Material and Methods
This study was approved by the Clinical Research Ethics Committee at Abant Izzet Baysal University (No. 121 dated 26/05/2017, Decision No: 2017/37). The study was carried out according to the Declaration of Helsinki. All procedures were performed after written informed consent was obtained from all participants.
Design
This is a descriptive study with subgroup analysis. The groups were formed less than 8 hours, 8 hours or more for daily work- ing hours. For working years individuals grouped as ≤2 years, 3-5 years, 6-9 years and ≥10 years.
Population
This study included individuals who were involved in cutting, shredding, packing, bagging and transportation operations at a poultry factory at an ambient temperature of 9°C and lower.
The assessments were done at the factory where the individu- als worked. Inclusion criteria were as follows: working in a cold environment at least 9 degrees below the factory, not to have cooperative and mental problems, to be between the ages of 18-60 and to be a volunteer. The exclusion criteria were as fol- lows: to have undergone surgery due to an orthopedic disorder, a history of trauma in the musculoskeletal system that still af- fects the person, and receiving physical therapy treatment. Variables
The demographic information form, 2016 Revisions to the 2010/2011 Fibromyalgia Criteria, The Revised Fibromyalgia Effect Questionnaire (FIQR) were applied to the individuals in- cluded in the study. Demographic information form was used to determine the characteristics of the participants in terms of gender, age, the years of current work, working hours per week, how many hours a day in the cold environment, height, body weight, dominant extremity, and presence of chronic disease. The level of pain felt during resting and working was ques- tioned with VAS.
Measures
Demographic Variables
A questionnaire was used to collect information about gender, date of birth, daily working hours in cold, working days in a week, body weight and height, dominant extremity, presence of chronic disease, use of painkillers, the level of pain felt while resting and working.
Fibromyalgia diagnosis
The 2016 revision of ACR 2010-2011 fibromyalgia diagnostic criteria consists of 2 stages. In the first section, the widespread pain index (WPI), the regions where the individual feels pain during the last week are identified from the 12 regions indi- cated in the questionnaire. Chin, shoulder girdles, upper arms, forearms, hips, thighs, legs, neck, back, waist, chest, and abdo- men are inquired. Each box marked is worth 1 point. The final score is between 0-19 for WPI. In the second section, symp- tom severity scale (SSS), fatigue, waking unrefreshed, cogni- tive symptoms, headache, abdominal pain or cramps, depres- sion are questioned. The final score is between 0-12 for SSS. If symptoms have been generally present for at least 3 months and WPI≥7 and SSS≥5, or WPI 4-6 and SSS≥9, meets the crite- ria for FM diagnosis [20].
Fibromyalgia Symptoms
The Revised Fibromyalgia Impact Questionnaire consists of 3 stages. The first stage inquires about daily activities. The sec- ond stage inquires about symptoms of FM and its effects. The third stage inquires about the level of sensitivity of the partici- pant to pain, energy, sleep pattern, depression, memory prob- lems, anxiety and fear, pain-pain sensitivity, mental balance problems and high sounds and bright lights are questioned. There are 11 boxes to choose from for each question. Leftmost boxes represent 0 and rightmost boxes represent 11 as sever- ity. High scores indicate severe symptoms [21].
Pain severity
The VAS had a 10 cm horizontal line defining the minimum and maximum ends of the pain felt. Zero (0) ‘’no pain’’ and ten (10) ‘’irresistible pain’’ terms used as explanation at minimum and maximum ends, respectively.
Data Analysis
Descriptive statistical methods used for demographic informa- tion. The chi-square test was used to determine the normal distribution of gender, dominant extremity and smoking status. The Wilcoxon test was used to compare the pain levels felt dur- ing resting and working. Comparison of VAS resting, VAS work- ing and FIQR scores were performed by the Kruskal- Wallis Test. The Kruskal-Wallis Post hoc Dunn test was used to show the difference between working years groups. The Mann-Whitney U test was used in the analysis of daily working hours, VAS resting, VAS working and FIQR scores. The statistical signifi- cance level was taken as p <0.05 in the analysis of the data. SPSS 22 program was used for analysis. Groups were formed as ≤2 years, 3-5 years, 6-9 years, ≥10 years. To determine the number of individuals required during the planning phase of the study, a study conducted with healthy workers was selected as an example [22]. The minimum number of individuals required was calculated to be 80% using the G * Power program and found to be 368.
Results
Five hundred sixty-eight individuals were enrolled in this study. Individuals’ ages ranged between 18-65 years and the mean age was 36,9 years. Individuals’ weight ranged between 42- 130 kgs and the mean weight was 71,4 kgs. Individuals’ height ranged between 140-199 cms and the mean height was 165,3 cms. Individuals’ BMI ranged between 16,7-41,9 kg/m2 and the mean BMI was 26,1 kg/m2.
Three hundred nineteen of the individuals were female (56.1%)
and 249 were male (43.9%). The dominant side of the individu- als was in 512 (90.3%) right and 56 (9.7%) in the left. Gender and dominant extremities of the individuals according to study year groups are presented below (Table 1).
According to the results of the ACR criteria, the mean pain in- dex scores were found to be 3.42 ± 3.50 and the mean score of symptom severity was 6.73 ± 2.18. 92 individuals meet the cri- teria for diagnosis. Sixty-two of these individuals were female and 30 were male. Thirty-five, 20, 22, and 25 individuals meet the criteria for working year groups; 2 years or less, 3-5 years, 6-9 years and 10 years or more, respectively. There was no sta- tistical difference between the working year groups in terms of diagnosis of fibromyalgia.
Pain felt during working, the pain felt during resting and the FIQR scores were examined for working year groups. Only FIQR scores were found to be significantly increased as the working years increase (p = 0.006). When the post hoc evaluations of the analysis of FIQR scores of the individuals according to the years of study were examined, statistically difference was ob- served in FM symptom scores of the employees with more than a decade of study, less than two years and two to five years (p = 0.005, p = 0,01 respectively) (Table 2).
Three hundred ninety-three (69.1%) individuals worked more than 8 hours daily and 174 (30.9%) individuals worked in less than 8 hours in a cold environment. It was observed that VAS scores for resting and working pain and FIQR scores were sig- nificantly higher for the group worked more than 8 hours in a cold environment. (Table 3).
When VAS scores for resting (3,07) and working (3,3) pain levels were compared, the pain levels felt in working were significant- ly higher (p <0.046).
Discussion
The results of this study showed that in cold conditions the workers felt pain while working and relaxing. It was found that the pain felt while working was higher. It was revealed that the pain felt during the rest and working in individuals working more than 8 hours a day was higher. Increased work years and more than 8 hours of daily study have been shown to increase the severity of FM symptoms.
It was shown in this study that increasing working years and daily working hours caused an increase in the severity of FM symptoms. This may be responsible for the negative effects of cold on pain and muscle function, cumulative fatigue caused by repetitive movements and microtrauma, and/or diseases such as FM, which can lead to changes in the perception of pain. Stevens et al. [23] examined the response of FM patients to cold pressor test by electroencephalography (EEG). According to the results of their study, the individuals with FM were less likely to feel the pain sooner than the control group, even if the EEG measurement for the pain was the same, and it was earlier that they defined the pain as intolerable. This indicates that FM patients treat painful warnings abnormally. Giannoccaro et al. [24], in their study of small fiber neuropathy in individu- als with FM, in 30% of diagnosed individuals have determined the density of decreased epidermal nerve fiber. Abnormalities of adrenergic and cholinergic nerve fibers of these individuals were also observed. This suggests that FM is a condition that may have an impact on sensory and autonomic symptoms [24].
Nørregaard et al. [25] found a decrease in voluntary muscle strength of the elbow flexors and extensors by 20-30% in FM patients. We think that FM can affect the quality of life nega- tively in individuals working in a cold environment and increase the sensibility of non-FM pain, especially since the effects of FM on the musculoskeletal and nervous system can be related to cold. McDonald et al. [26]. reported that arthritis, back, and FM pain were mostly clinically significant, and were associated with significantly lower levels of health-related quality of life. They stated that the presence of pain was associated with higher levels of work efficiency loss.
In this study, it has been concluded that the complaints about FM have reached peak value in cold environment employees in a period of 10 years and more, although no association with FM diagnosis was detected. This raises the question of whether se- vere FM symptoms are caused by other diseases. Musculoskele- tal problems and carpal tunnel syndrome are the usual suspects that may cause similar symptoms with FM. Fatigue, weakness, or not being able to perform normal tasks or difficulties can be associated with these diseases. Waylonis et al. [27] reported that FM activities were reported to aggravate FM symptoms; computer use or writing (37%), prolonged sitting (37%), pro- longed standing and walking (27%), stress (21%), heavy lifting (19%) and repeated movement and load-carrying (18%) were reported. These activities aggravated the symptoms of the in- dividuals participating in this study; long periods of standing, heavy lifting, repetitive movements and transporting goods. Lapossy et al. [20] reported that cold-induced vasospasm was more common in FM patients (38%) than in healthy controls (8%); this suggests that the cold effect may cause negative effects in the musculoskeletal system of individuals with FM. Exacerbation of FM symptoms due to increased working years and daily working hours is a factor that can reduce work ef- ficiency. It is concluded that this factor is a problem that can lead to a loss of workforce in the occupations that increase the risk of FM.
It was found that the pain felt while working was higher than at rest. Individuals who worked for 8 hours and over had sig- nificantly higher levels of pain felt in working and at rest. It has been shown that the prevalence of pain increases as the working hours spent on repetitive strenuous physical activities increase [28]. Exposure to occupational cold has been identified as a risk factor that can lead to various health outcomes, in- cluding increased workload and symptoms such as cold-related diseases and pain [1,3,4].
Conclusion
As a result of this study, some risks of working in a cold environ- ment have been revealed. Especially those who have been work- ing for 10 years or more and more than 8 hours in cold were found to be under greater risk. To reduce this risk, it may be advisable to reduce daily or weekly working hours or scheduling more breaks. The use of protective clothing can be encouraged to reduce the effect of cold. To reduce long-term physical activ- ity and continuous work in the same posture, doing different works with rotation may reduce the symptoms. The use and regular maintenance of auxiliary equipment to reduce the work- load may benefit employee health. The use of robotic systems and automation can reduce the number of employees at risk.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical stan- dards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be consid- ered potential conflict of interest regarding the manuscript or its submission.
References
1. Påsche A. Occupational health in the fish processing industry-An activity to improve the work environment by preventing cold exposures. Barents newsletter. 2001;4:12-14.
2. Jeebhay M, Robins T, Lopata A. World at work: fish processing workers. Int J Occup Environ Med. 2004; 61:471-4.
3. Chen F, Li T, Huang H, Holmér I. A field study of cold effects among cold store workers in China. Arctic. 1991;50:99-103.
4. Griefahn B, Mehnert P, Bröde P, Forsthoff A. Working in moderate cold: a pos- sible risk to health. J Occup Healt. 1997;39:36-44.
5. Campbell DS. Health hazards in the meatpacking industry. Occup Med. 1999;14:351-72.
6. Georgitis J. Extensor tenosynovitis of the hand from cold exposure. J Maine Med Assoc. 1978; 69:129-31.
7. Granberg PO. Freezing cold injury. Arctic. 1991;50:76-79.
8. Hassi J, Rytkönen M, Kotaniemi J, Rintamäki H. Impacts of cold climate on human heat balance, performance and health in circumpolar areas. Int J Circum- polar Health. 2005;64:459-67.
9. Niedhammer I, Landre MF, Leclerc A, Bourgeois F, Franchi P, Chastang JF. Shoulder disorders related to work organization and other occupational factors among supermarket cashiers. Int J Occup Environ Health. 1998; 4:168-78.
10. Inaba R, Mirbod SM, Kurokawa J, Inoue M, Iwate H. Subjective symptoms among female workers and winter working conditions in a consumer cooperative. J Occup Health. 2005;47:454-65.
11. Bang BE, Aasmoe L, Aardal L, Andorsen, Bjørnbakk AK, Egeness C. Feeling cold at work increases the risk of symptoms from muscles, skin, and airways in seafood industry workers. Am J Ind Med. 2005;47:65-71.
12. Dovrat E, Katz-Leurer M. Cold exposure and low back pain in store workers in Israel. Am J Ind Med. 2007;50:626-31.
13. Holmér I, Hassi J, Mäkinen T, Påsche A, Risikko T, Toivonen L. Cold work manual. Sweden: Arbetslivsinstitutet; 2002.p.37-41.
14. Chen F, Nilsson H, Holmér I. Finger cooling by contact with cold aluminium surfaces – effects of pressure, mass and whole body thermal balance. Eur J Appl Physiol. 1994;69:55-60.
15. Havenith G, Heus R, Daanen HA. The hand in the cold, performance and risk. Arch Med Res. 1995;54:37-47.
16. Dougados M, Logeart I, Szumski A, Coindreau J, Jones H. Evaluation of wheth- er extremely high enthesitis or Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores suggest fibromyalgia and confound the anti-TNF response in early non-radiographic axial spondyloarthritis. Clin Exp Rheumatol. 2017;35:50- 53.
17. Wallace DJ, Gavin IM, Karpenko O, Barkhordar F, Gillis BS. Cytokine and chemokine profiles in fibromyalgia, rheumatoid arthritis and systemic lupus erythematosus: a potentially useful tool in differential diagnosis. Rheumatol Int. 2015;35:991-6.
18. Wolfe F, Ross K, Anderson J, Russell IJ, Hebert L. The prevalence and char- acteristics of fibromyalgia in the general population. Arthritis Rheumatol. 1995;38:19-28.
19. Lapossy E, Gasser P, Hrycaj P, Dubler B, Samborski W, Muller W. Cold-induced vasospasm in patients with fibromyalgia and chronic low back pain in compari- son to healthy subjects. J Clin Rheumatol. 1994;13:442-5.
20. Wolfe F, Clauw DJ, Fitzcharles MA, Goldenberg DL, Katz RS, Mease P. The American College of Rheumatology preliminary diagnostic criteria for fibromy- algia and measurement of symptom severity. Arthritis Care Re. 2010;62:600-10.
21. Ediz L, Hiz O, Toprak M, Tekeoglu I, Ercan S. The validity and reliability of the Turkish version of the Revised Fibromyalgia Impact Questionnaire. J Clin Rheu- matol. 2011;30:339-46.
22. Eaves S, Gyi DE, Gibb AG. Building healthy construction workers: Their views on health, wellbeing and better workplace design. Appl Ergon. 2016;54:10-18.
23. Stevens A, Batra A, Kötter I, Bartels M, Schwarz J. Both pain and EEG re- sponse to cold pressor stimulation occurs faster in fibromyalgia patients than in control subjects. Psychiatry. 2000;97:237-47.
24. Giannoccaro MP, Donadio V, Incensi A, Avoni P, Liguori R. Small nerve fiber involvement in patients referred for fibromyalgia. Muscle Nerve. 2014;49:757-9.
25. Nørregaard J, Bülow P, Lykkegaard J, Mehlsen J, Danneskiold-Samsøoe B. Muscle strength, working capacity and effort in patients with fibromyalgia. Scand J Rehabil Med. 1997;29:97-102.
26. McDonald M, Dibonaventura MD, Ullman S. Musculoskeletal pain in the work- force: the effects of back, arthritis, and fibromyalgia pain on quality of life and work productivity. Int J Occup Environ Med. 2011;53:765-70.
27. Waylonis GW, Ronan PG, Gordon C. A profile of fibromyalgia in occupational environments. Am J Phys Med Rehabil. 1994;73:112-15.
28. Guo HR. Working hours spent on repeated activities and prevalence of back pain. Occup Environ Med. 2002;59:680-8.
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Yasin Devran Altuntaş, Tamer Çankaya, Ramazan Kurul, Muhammet Fatih Uy- sal, Elif Duygu, Gökhan Mehmet Karatay, Fatma Asena Karatay, Barış Alkan. The effect of working time in cold conditions on pain and fibromyalgia syndrome symptoms. Ann Clin Anal Med 2020;11(5):406-410
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The V position versus sitting position in craniotomy cases
Ayşe Mızrak Arslan, Elzem Sen, Merve Esra Kara, Berna Kaya Uğur
Department of Anesthesiology and Reanimation, University of Gaziantep, School of Medicine, Gaziantep, Turkey
DOI: 10.4328/ACAM.20069 Received: 2019-10-30 Accepted: 2020-01-08 Published Online: 2020-01-20 Printed: 2020-09-01 Ann Clin Anal Med 2020;11(5):385-389
Corresponding Author: Berna Kaya Uğur, Department of Anesthesiology and Reanimation, University of Gaziantep, School of Medicine, Sahinbey, Gaziantep, Turkey. E-mail: metegurolugur@hotmail.com GSM: +905325727651 Corresponding Author ORCID ID: https://orcid.org/0000-0003-0044-363X
Aim: In this study, the researchers aimed to investigate satisfaction of anesthetists with the alternative V position compared to the sitting position in neuro- anesthesia, as well as the number of VAE and complications and hemodynamics changes, and compare these results to clinical impact and side effect rates obtained in other studies in the literature still using the sitting position.
Material and Methods: The data of a total of 78 patients aged between 20-70 years, classified as ASA I, II or III who underwent a craniotomy operation for tumor (74 patients) or neurovascular lesion (4 patients) in the V position in the research- ers’ clinic between January 2011 and December 2015 were examined retrospectively and assessed in a case series plan.
Results: During the study, records of 78 patients who have had a craniotomy operation in the alternative V position were analyzed (n=78). Forty-one (52.5%) and 37 (47.5%) of the patients were male and female, respectively. Venous air embolisms or pulmonary embolisms were not observed in any patient. The satisfaction of the practicing anesthetist was 100% median min-max: 1.0 (1.0-1.0).
Discussion: In this study, the V position, which was used as an alternative to the sitting position, provided the advan- tages of the sitting position through elaborate anesthesia applications and surgical planning and additionally removed the risk of complications such as VAE, post-operative quadriplegia, tension pneumocephalus, subdural hematoma, and peripheral nerve injuries. Conclusion: The use of V position proposed by this research as an alternative in neurosurgery cases requiring the sitting and prone positions, provided the necessary advantages to neurosurgeons, improved the patient’s venous drainage, offered better vision of the surgical site and enables less bleeding in the patient, did not develop any VAE, decreased the need for cerebellar retraction in posterior fossa cases and minimized or inhibited pre-operative mortality through low intracranial pressure.
Keywords: Neurosurgery; Alternative V Position; Neuroanesthesia; VAE
Introduction
The use of the sitting position in neuroanesthesia in craniotomy operations is still a matter of debate. The head- up sitting position of patients offers certain advantages to neurosurgeons; however, it constitutes various difficulties for anesthetists. It shortens the duration of surgery and decreases the loss of blood as it facilitates access to the lesion, enables cerebral venous drainage and reduces intracranial pressure. However, it is known that the sitting position leads to severe complications such as hypotension, venous air embolism (VAE), pneumocephalus and peripheral neuropathy [1]. The incidence of VAE has been reported to range from 7% to 76% in the sitting position [2] and as 21% in the semi-sitting position [3]. There is no evidence that one position is superior to another, and suitable surgical results can be obtained with each position. The V position, which is an alternative to the sitting position, is a position developed with the aim of providing convenience to surgeons in the researchers’ clinic and of preventing complications that might be fatal (VAE, hypotension, pneumocephalus, peripheral neuropathy). In this study, the researchers aimed to investigate the satisfaction of anesthetists with the alternative V position compared to the sitting position in neuroanesthesia, as well as the number of VAE and complications and hemodynamics changes, and compare these results to clinical impact and side effect rates obtained in other studies in the literature still using the sitting position.
Material and Methods
The data of a total of 78 patients aged between 20-70 years, classified as ASA (American Society of Anesthesiologists) I, II or III and had a craniotomy operation for tumor (74 patients) or neurovascular lesion (4 patients) in the V position in the researchers’ clinic between January 2011 and December 2015 were examined retrospectively, and assessed in a case series plan. Patients who had heart failure, liver-kidney failure, anemia and thrombocytopenia, and who did not want to be enrolled were excluded from the study.
The alternative V position is defined as a position in which an angle of 45 degrees is created between the vertical line of the ground where the patient sits and the thorax is leaned, and an angle of 45 degrees is created between the surface where upper legs are leaned upon and the vertical line of the ground. In other words, the angle between thorax and upper legs is a total of 90 degrees; however, the angle between the thorax and the operating table and between the upper legs and the operating table is 45° and 45°, respectively. In this position, the angle between knees and shoulders/neck is still 80°- 90°.
As for the demographic details of the patients, gender (n, %), age (years) and body mass indices (BMI, kg/m2) were determined and recorded. Gender was coded 0 for women and 1 for men. After the general anesthesia, information and the position technique were explained and written informed consent was obtained from the patients, the patients were monitored via ECG, non-invasive blood pressure measurement and pulse oximetry. A 20G peripheral venous catheter (I.V. FLON®, La-med Healthcare Pvt. Ltd., Haryana, India) was placed on the dorsal surface of the left hand. Saline solution (0.9%; 200 ml) was given to the patients every hour. Patients inhaled 100% O2for general anesthesia and 3-4mg/kg sodium thiopental (Pental Sodium®, 0.5 g Vial, İbrahim Etem Ulugay Ilaç Sanayi Türk A.Ş., Turkey), 2 mcg/kg fentanyl citrate (Talinat®, 0.5 mg/10 ml, Vem İlaç, Turkey) and 0.5 mg/kg rocuronium bromide (Curon®, 50 mg/ ml, Mustafa Nevzat İlaç Sanayi A.Ş., Turkey) were administered intravenously (iv) as muscle relaxants. Ventilation with a mask was applied for three minutes, and female and male patients were intubated with 7.5 mm endotracheal tube and 8.5 mm spiral endotracheal tube (GALENA®, Hamburg, Germany), respectively. The endotracheal cuff was inflated with the lowest pressure to inhibit air leak during ventilation. A tube test was performed after confirming via the bilateral auscultation of thorax that the tube was in the trachea, and both lungs were ventilated evenly. Maintenance of the patients’ anesthesia was ensured with 2% sevoflurane (Sevorane liquid® 100%, 250 ml, solution, Abbvie Tıbbi İlaçlar San. Tic. Ltd. Şti, Italy), 50% O2 50% air and 0.05 mcg/kg/min remifentanil (Rentanil®, 5 mg vial, Vem İlaç, Turkey). Afterwards, the left radial artery catheterization was performed using a 22G cannula (I.V. FLON®, La-med Healthcare Pvt. Ltd., Haryana, India). Invasive arterial blood pressure was monitored via the left radial artery using a disposable pressure transducer kit (OKUMAN®, SCW Medicath LTD, Guangdong, China). Zero point of invasive arterial blood pressure kit was determined at the level of the mastoid process. A 7F Arrow 3-lumen catheter (Arrow International Inc, Reading, PA) was used for central venous catheterization. Zero point of central venous pressure (CVP) transducer was kept at heart level (the point at which left 4-5 intercostal space intersects with anterior axillary line). CVP values were first measured and recorded in patient placed in the supine position. Later, the values were measured and recorded again in the patient placed in V position. The difference of CVP due to the change of position was recorded. All invasive catheterization procedures were performed by the same experienced anesthetist while another anesthetist recorded the assessments and measurements. Fentanyl (0.5 mcg/kg) was administered intravenously to the patients before the fixation of head, and a distance of 4-5 cm was kept to prevent excessive flexion between the chin and sternum and potential venous return of the brain. Elastic bandages were used around the legs of the patients to prevent venous lake. All potential points of pressure were supported using pads. At the end of the surgery, the patients were returned to supine position and extubated by reversing the neuromuscular block with 0.06 mg/kg of neostigmine (Plantigmin® , 0.5 mg/ml of Polifarma, Turkey) and 0.02 mg/kg of atropine (Atropine Sulfate®, 1/2 mg 1 ml, Galen, Turkey). All patients were extubated and transferred to the intensive care unit.
Pre-operative, intraoperative, and post-operative body temperatures, total crystalloid and colloid amount administered to the patient, blood gas values measured at intervals of thirty minutes and any complications were recorded.
The central venous pressure (CVP), mean arterial blood pressure (MAP) and heart rate (HR) were recorded before and after the V position. The parameters required for the monitorization of air embolism (ETCO2, PaO2, HR, MAP) were monitored intraoperatively. The VAE was defined as a decrease in end- tidal PCO2 value at or above 0.7 kPa (5.25 mmHg).
Also, the satisfaction of the anesthetists, as well as the number (n) and frequency (%) of venous air embolism and other complications were investigated. Satisfaction of the anesthetists was coded as 1 for “satisfied”, and 0 for “not satisfied”.
Statistics
Statistical analysis was done using STATA 11.2 (Statacorp, Texas, USA). The data were represented as mean value [with standard deviation (SD)], median value [with range] or as a number [with percentage]. The Chi-square analysis was performed to compare categorical variables. Non-parametric numerical data were analyzed using the Mann-Whitney U test. P- value <0.05 was considered statistically significant.
Results
During the study, records of 78 patients who had a craniotomy operation in the alternative V position were analyzed (n=78). Forty-one (52.5%) and 37 (47.5%) of the patients were male and female, respectively. The mean age was 47.3±14 years. The mean Body Mass Index (BMI) of the patients was 22.8±3.6 kg/m2 (Table 1).
Venous air embolisms or pulmonary embolisms were not observed in any patient. The satisfaction of the practicing anesthetist was 100% median min-max: 1.0 (1.0-1.0) (Table 2). The CVP, MAP, and HR values were compared in mean±SD value before and after the V position. It was found that the CVP value was 6 cmH2O before positioning and 3 cmH2O after positioning. While the mean of MAP values was 93 mmHg before positioning, it decreased to 83 mmHg after positioning. HR was recorded as 83 beats per minute before positioning and as 80 beats per minute after positioning (Table 3, Figure 1).
Discussion
There is still debate as to the optimum position of patients for lesions in the posterior fossa, occipital or occipitoparietal localizations during neurosurgical interventions. Although the use of the sitting position for neurosurgery is gradually decreasing, some centers still commonly use this position. It was seen that cranial nerve function was preserved better and less blood loss occurred with the sitting position in neurosurgery [4]. Enabling an optimal surgical application, the sitting position restored cerebral venous drainage while decreasing the risk of cranial nerve damage and tissue retraction [5]. However, complications such as bradycardia, pneumocephalus, subdural hematoma and quadriplegia, and primarily venous air embolism were reported in surgeries with the sitting position [4,5]. VAE might occur when large open veins are exposed to the atmosphere and surgical site in such veins is above the horizontal level of heart. When the surgical site is above the heart level, intravenous pressure might be sub-atmospheric and air intake through these open veins might occur during surgery. Generally, this risk is best described in neurosurgery procedures in the sitting position where there is a height difference between the surgical site and heart, and venous sinuses cannot be compressed [6]. In a published review, Fathi et al. reported the incidence of VAE as 39% during posterior fossa surgeries in the sitting position [7]. The main issue in the sitting position is VAE, and various methods, such as clinical observation, monitorization (arterial tension, pulse, end-expiratory carbon dioxide), TEE (transesophageal echocardiography) and precordial Doppler are used to detect it [8]. Accordingly, there are different results regarding the incidence of VAE. In their study conducted on pigs, Schafer et al. found the rate of VAE as 52.8% with TEE and 46.8% with precordial Doppler [9]. In a study by Dilmen et al., they reported the incidence of VAE in adults who had neurosurgery in the sitting position as 20.4% [10]. Some other studies advocated that EtCO2 monitoring was sufficient alone for monitorization in the sitting position [11]. A decrease of 3 to 5 mmHg in EtCO2 was used for the diagnosis of VAE [4,12]. In this current study, the EtCO2 decrease and clinical evaluations (hypotension, bradycardia) were used for the diagnosis of VAE. Pre-existing hypovolemia is, though slightly, associated with VAE [11]. With regards to intraoperative fluid management, colloids were thought to be superior to crystalloids in increasing intravascular volume in patients who had pre-existing hypovolemia [13]. Fluid filling with hydroxyethyl starch (HES) boluses resulted in positive responses in cardiac and stroke volume index during the sitting position. It was thought that a smaller volume of HES than crystalloids and a less positive fluid balance were important in craniotomy patients with decreased brain compliance [14]. In this current study, the researchers met the patient’s need for intravenous maintenance fluid with NS for 50% and HES for 50%. Hemodynamic changes in patients who underwent neurosurgical operation under general anesthesia might occur both in the sitting position and prone position [15]. Harrison et al. reported the incidence of intraoperative hemodynamic instability as 24.1% in posterior fossa surgeries in the sitting position [11]. Gupta et al. found the rate of hemodynamic instability as 12.3% and reported that the rates were diverse, as definitive criteria of hemodynamic instability were different [15]. Dilmen et al. reported that 37.6% of adult patients undergoing neurosurgical operation developed hypotension when the supine position was switched to the sitting position [10]. These hemodynamic changes are essentially associated with a reduced preload. Upright position causes a shift from the intrathoracic space to the extrathoracic space. This decreases cardiac output and mean arterial pressure [16].
In this current study, the researchers observed that physiological hemodynamic responses altered at the moment the V position was applied in patients who were under general anesthesia. CVP values were found as 6.4±3.3 on average in the supine position, 3.9±2.5 after V positioning and 5.0±2.1 after colloid fluid infusion in the V position.
We believe that this decrease, which is much less than the decrease amounts in the literature, may have mitigated or even prevented the possibility of venous air embolism.
In this current study, a 45-degree elevation of lower limbs in the position, which resembles the letter V, enables the abdomen to be under a slight pressure between the thorax and upper limbs. This compression is also reflected in the V. Cava Inferior in the abdominal region and increases CVP in the patient [17]. CVP, increasing with this mechanism, makes the incidence of air embolism lower than expected. Compared to the sitting position, the V position also prevents CVP to decrease more by shortening the distance between heart and operating table as well as decreasing the possibility of air embolism [18].
The sitting position enables optimum access to posterior fossa lesions, improves venous and cerebrospinal fluid drainage, reduces intracranial pressure, decreases airway pressure, improves access to endotracheal tube and enables observation of face for cranial nerve stimulations during the neurosurgery [1].1 In this current study, the V position, which was used as an alternative to the sitting position, provided the advantages of the sitting position to neurosurgeons through elaborate anesthesia applications and surgical planning, and additionally removed the risk of complications which could lead to destructive results such as VAE, post-operative quadriplegia, tension pneumocephalus, subdural hematoma and peripheral nerve injuries [19,20] .
Stabilization of hemodynamics in the prone position is one of the most troublesome positions as the preservation of intravenous lines and the tracheal tube is difficult. Access to patients’ airway is not easy. Pressure sores, vascular compression, brachial plexus injuries, air embolism, blindness and quadriplegia are among other reported complications [5]. Jadik et al. defined the semi-sitting position as the flexion of hip up to maximum 90 degrees, positioning legs and feet above the head, reclining upper body as much as possible and forward flexion of the head [1]. Feigl et al. reported that, although air bubbles were detected in 55.7% of patients on TEE in this position, they could not aspirate air with central venous catheter and did not experience a clinically significant VAE. However, they emphasized that the potential risk of VAE remained in the semi-sitting position and complications should be observed [21].
VAE might occur in all positions when there is an open vein and a venous pressure gradient occurs between heart and operation site. In this current study, the patients’ legs up with a 45-degree angle in the V position increased central venous pressure by increasing the return of volume which has the potential to form a lake in legs (like a colloid effect) to the heart [39]. It is thought that the development of VAE can be inhibited through the increase of central venous pressure [23].
Consequently, the use of V position proposed by this research as an alternative in neurosurgery cases requiring the sitting and prone positions, provided the necessary advantages to neurosurgeons, improved the patient’s venous drainage, offered better vision of the surgical site and enables less bleeding in the patient, did not develop any VAE, decreased the need for cerebellar retraction in posterior fossa cases and minimized or inhibited pre-operative mortality through low intracranial pressure. Therefore, the researchers believe that the alternative V position would provide great benefits in neurosurgeries that are to be performed with the sitting position.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
1. Jadik S, Wissing H, Friedrich K, Beck J, Seifert V, Raabe A. A standardized protocol for the prevention of clinically relevant venous air embolism during neurosurgical interventions in the semisitting position. Neurosurgery. 2009; 64(3): 533-8.
2. Leslie K, Hui R, Kaye AH. Venous air embolism and the sitting position: a case series. J Clin Neurosci. 2006; 13(4): 419-22.
3. Saladino A, Lamperti M, Mangraviti A, Legnani FG, Prada FU, Casali C, et al. The semisitting position: analysis of the risks and surgical outcomes in a contemprorary series of 425 adult patients undergoing cranial surgery. J Neurosurg. 2017; 127(4): 867-76.
4. Rath GP, Bithal PK, Chaturvedi, Dash HH. Complications related to positioning in posterior fossa craniectomy. J Clin Neurosci. 2007; 14: 520-5. DOI: 10.1016/j. jocn.2006.02.010
5. Rozet I, Vavilala MS. Risks and benefits of patient positioning during neurosurgical care. Anesthesiol Clin. 2007; 25(3): 631-x.
6. Kapruch CJ, Abcejo AS, Pasternak JJ. The relationship between end-expired carbon dioxide tension and severity of venous air embolism during sitting neurosurgical procedures- A contemporary analysis. J Clin Anesth. 2018; 51: 49- 54.
7. Fathi AR, Eshtehardi P, Meier B. Patent foramen ovale and neurosurgery in sitting position: a systematic review. Br J Anaesth. 2009; 102(5): 588-96.
8. Brull SJ, Prielipp RC. Vascular air embolism: A silent hazard to patient safety. J Crit Care. 2017; 42: 255-63.
9. Schafer ST, Lindemann J, Brendt P, Kaiser G, Peters J. Intracardiac transvenous echocardiography is superior to both precordial doppler and transesophageal echocardiography techniques for detecting venous air embolism and catheter- guided air aspiration. Anesth Analg. 2008;106(1):45-54.
10. Dilmen OK, Akcil EF, Tureci E, Tunali Y, Bahar M, Tanriverdi T, et al. Neurosurgery in the sitting position: retrospective analysis of 692 adult and pediatric cases. Turk Neurosurg. 2011; 21(4): 634-40.
11. Harrison EA, Mackersie A, Ewan MC, Facer E. The sitting position in neurosurgery in children: A review of 16 years’experience. Br J Anaesth. 2002; 88: 12-7.
12. Girard F, Ruel M, McKenty S, Boudreault D, Chouinard P, Todorov A, et al. Incidences of venous air embolism and patent foramen ovale among patients undergoing selective peripheral denervation in the sitting position. Neurosurgery. 2003; 53: 316-20.
13. Verheij J, van Lingen A, Beishuizen A, Christiaans HM, de Jong JR, Girbes AR, et al. Cardiac response is greater for colloid than saline fluid loading after cardiac or vascular surgery. Intensive Care Med. 2006; 32: 1030-8.
14. Lindroos AC, Nilya T, Silvasti-Lundell M, Randell T, Hernesniemi J, Niemi TT. Stroke volume-directed administration of hydroxyethyl starch or Ringer’s acetate in sitting position during craniotomy. Acta Anaesthesiol Scand. 2013; 57(6): 729- 36.
15. Gupta P, Rath GP, Prabhakar H, Bithal PK. Complications related to sitting position during pediatric neurosurgery: An institutional experience and review of literature. Neurol India. 2018; 66(1): 217-22.
16. Buhre W, Weyland A, Buhre K, Buhre K, Kazmaier S, Mursch K, et al. Effects of the sitting position on the distribution of blood volume in patients undergoing neurosurgical procedures. Br J Anaesth. 2000; 84: 354-7.
17. Dabrowski W. Changes in intraabdominal pressure and central venous and brain venous blood pressure in patients during extracorporeal circulation. Med Sci Monit. 2007; 13(12): 548-54.
18. Wyoski MG, Covey A, Pollak J, Rosenblatt M, Aruny J, Denbow N. Evaluation of various maneuvers for prevention of air embolism during central venous catheter placement. J Vasc Int Radiol. 2001; 12(6):764-6.
19. Himes BT, Mallory GW, Abcejo AS, Pasternak J, Atkinson JLD, et al. Contemporary analysis of the intraoperative and perioperative complications of neurosurgical procedures performed in the sitting position. J Neurosurg. 2017; 127(1): 182-8.
20. Gale T, Leslie K. Anesthesia for neurosurgery in the sitting position. J Clin Neurosci. 2004; 11(7): 693-6.
21. Feigl GC, Decker K, Wurms M, Krischek B, Ritz R, Unerti K, et al. Neurosurgical procedures in the semisitting position: evaluation of the risk of paradoxical venous air embolism in patients with a patent foramen ovale. World Neurosurg. 2014; 81(1): 159-64.
22. Fredholm M, Jörgensen K, Houltz E, Ricksten E. Load-dependence of myocardial deformation variables-a clinical strain -echocardiographic study. Acta Anaesthesiol Scand. 2017; 61(9): 1155-65.
23. McCarthy CJ, Behravesh S, Naidu SG, Oklu R. Air Embolism: Practical Tips for Prevention and Treatment. J Clin Med. 2016; 5(11): 93.
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Ayşe Mızrak Arslan, Elzem Sen, Merve Esra Kara, Berna Kaya Uğur. The V position versus sitting position in craniotomy cases. Ann Clin Anal Med 2020;11(5):385- 389
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Magnesium sulfate and acute migraine: A randomized clinical trial
Hassan Motamed, Javad Mozafari, Samaneh Porozan, Mojtaba Sasani
Emergency Medicine Department, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
DOI: 10.4328/ACAM.20072 Received: 2019-11-07 Accepted: 2020-01-05 Published Online: 2020-01-08 Printed: 2020-09-01 Ann Clin Anal Med 2020;11(5):369-373
Corresponding Author: Javad Mozafari, Emergency Medicine Department, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. E-mail: mozafari.taha@yahoo.com T: +98-612439152 Corresponding Author ORCID ID: https://orcid.org/0000-0002-8903-7138
Aim: In the current study we have aimed to evaluate the magnesium sulfate, as an adjuvant treatment, in managing acute migraine. Further knowledge of the migraine pathology elucidates the role of magnesium in the treatment of the disease.
Materials and Methods: Patients with migraine referred to Ahvaz Golestan Hospital emergency department were included in this randomized clinical trial. Patients’ characteristics including gender, age, and weight were extracted from the files. Patients were randomly divided into two equal groups using block randomization method. Group A received 2 g intravenous infusion (I.V) of Magnesium sulfate along with 10 mg metoclopramide. And group B received 10 mg metoclopramide and placebo. The pain level was measured by NRS at baseline, 15, 30, and 45 minutes after intervention.
Results: Eighty patients were randomly assigned into two groups, forty (50%) were male. Most patients were between 30 and 40 years old. The baseline characteristics have not shown significant differences between the groups. The mean pain level at admission was not significantly different (9.94 and 10, respectively). Although pain reduction was significant in both groups, there was a significant difference between the two groups. The pain reduction slope in group A was significantly more severe.
Discussion: The findings of this study showed that the use of magnesium sulfate along with metoclopramide increased the effect of metoclopramide in manag- ing acute migraine. However, our findings could not support the independent effect of magnesium sulfate on the reduction of migraine headaches.
Keywords: Acute Migraine; Headaches; Metoclopramide; Magnesium Sulfate; Clinical Trial; Emergency Department
Introduction
Migraine is one of the main causes of primary and secondary headaches that affects about 70-80% of the world’s population [1]. Migraine is the second most leading cause of headache, after tension headache. It is a neurobiological disorder caused by increased irritability of the central nervous system (CNS) and associated with periodic unilateral and pulsating headaches [2]. The prevalence of migraines has been reported by the Interna- tional Headache Society (IHS) as 13% in Asia (3% in men and 10% in women). The scattering epidemiological reports of Iran have shown its prevalence from 6.1 to 15.5%, which is higher than in other Asian countries [3].
The most common symptoms are nausea, vomiting, photopho- bia, and phonophobia [4]. Although the main cause of migraine is unknown, several genetic and environmental predisposing factors have been reported [5]. Methylenetetrahydrofolate Re- ductase (MTHFR) gene mutations and increased homocysteine levels, abnormal levels of vitamin D, production of inflamma- tory substances around the nerves and cerebrospinal fluid, in- creased serotonin production from the platelets, increased vas- cular sensitivity to nitric oxide, and reduced levels of metabolic enzymes are the most known causes of migraine [6,7]. Choosing the optimal treatment for a patient depends on many factors, the most important of which is the severity of the pain. Migraine patients are normally managed with one of the three main drug groups including non-steroidal anti-inflammatory drugs (NSAID), -5HT1 agonists, and dopamine antagonists [8]. NSAIDs cause some potential side effects such as indigestion, gastrointestinal irritation. Because of the different side effects and inefficiency of these drugs, it is essential to discover new medication.
Recent studies have also shown that magnesium deficiency can play a major role in the pathophysiology of migraine [9]. The ex- act mechanism of magnesium effect is not fully understood, it affects the Na-K-ATPase pump and also sodium-potassium and calcium channels. It also reduces the release of acetylcholine at the site of the musculoskeletal system, thereby increasing vascular tone. The serotonin functions were also controlled by magnesium, thereby this intracellular cation affects many phys- iological processes [10]. There are about 24 grams of magne- sium in the body which majorly located in bone and soft tissues, and less than 1% present in the circulation [11]. Evidence sug- gests that the level of magnesium in migraine patient’s serum, blood cells, and cerebrospinal fluid is significantly lower than healthy people. On the other hand, trial studies have shown contradictory findings on the effect of magnesium infusion in alleviating migraine symptoms [12,13]. In the current study, we aimed to evaluate the magnesium sulfate, as an adjuvant treat- ment, in managing acute migraine.
Material and Methods
Study Design
This randomized clinical trial included patients with migraine that have referred to Ahvaz Golestan Hospital emergency de- partment between October 2017 and November 2018. In this study, we aimed to compare the therapeutic effects of meto- clopramide and magnesium sulfate along with metoclopramide in patients with acute migraine. Migraine diagnosis was carried
out according to the International Crisis Association (CID) head- ache criteria. The study has been approved by Ahvaz Jundisha- pur University of Medical Sciences ethical committee (R.AJUMS. REC.1396.1142). The informed consent was signed by patients willing to participate in the study. The study was registered in Iran randomized clinical trial registry (IRCT).
Patients aged over 18 years with pain scores more than 4 (Measured by the Numerical Rating Scale (NRS)) and those who were willing to participate in the study were eligible candidates. The exclusion criteria were any history of drug adverse reac- tions such as gastrointestinal complications, pregnancy, lacta- tion, renal failure, migraine headache for the first time, allergy to magnesium or metoclopramide, use of the medications for three consecutive days before the study.
Therapeutic intervention
Patients’ characteristics including gender, age, and weight were extracted from the files. Before the beginning of the study, the patients were informed about the medical treatment procedure and side effects. All patients were observed by the emergency physician during the treatment. The subjects, a nurse who ad- ministrates the drug and also a physician who measures the pain level were not informed about the intervention type.
At the beginning of the study, the patients specified the level of the pain using NRS on a range of zero to ten which indicates no pain and the worst, respectively. Patients were randomly di- vided into two equal groups using block randomization method. Patients in group A received 2 g intravenous infusion (I.V) mag- nesium sulfate along with 10 mg metoclopramide. Patients in group B received 10 mg metoclopramide and placebo. The pain level was measured at baseline, 15, 30 and 45 minutes after the medication administration. Patients whose NRS score re- mained more than 4 or patients in whom the severity of head- ache did not decrease by 50% received half dose of medication after 15 and 30 min in both groups.
Statistical analysis
According to the Cete et al. study [14], with 95% confidence interval (95% CI) and accuracy of 5%, the minimum required sample size was calculated to be 80 persons (40 persons per group). All data were analyzed by descriptive statistics includ- ing mean, standard deviation (SD) and frequency. Independent t-test and the Mann-Whitney test were used to compare the mean based on the normality of the data. Multiple mean com- parisons were done using the Tukey test. A Linear regression test was carried out to compare the slopes. All analyses were performed using SPSS version 22 software. A p- value less than 0.05 was considered significant.
Results
Eighty-eight patients were enrolled in the study, 8 of them were excluded due to pregnancy, renal failure, and allergy to meto- clopramide and 80 patients were randomly assigned into two groups (Figure 1). Forty (50%) were male and 40 were female. Most patients were between 30 and 40 years old. The baseline characteristics have not shown significant differences between the groups (Table 1).
The medication side effects were not reported for any of the patients in both groups. In each of the groups A and B, three patients could not tolerate pain severity and received 5 mg morphine as the rescue analgesic. They were excluded from the study after 30 minutes.
The mean pain level at admission in Group A and Group B were 9.94 and 10, respectively, which differences were not statisti- cally significant. In both groups, pain level decreased signifi- cantly 15 minutes after intervention. However, the intensity of pain reduction was more severe in group A (Figure 2, Figure 3). Linear regression tests were used to compare pain reduction slope in both groups. Although pain reduction was significant in both groups, there was a significant difference between the two groups. The pain reduction slope in group A, was signifi- cantly more severe (Table 2) (Figure 4).
Discussion
Migraine headache is a common complication in patients re- ferred to the emergency department and accounts from 1 to 2% of all referrals. For a long time, the standard treatment for migraine attacks in the emergency department was opioid analgesics. Recently, several treatments including metoclo- pramide, chlorpromazine, prochlorperazine, Sumatriptan, and Dihydroergotamine have been proposed for the treatment of migraines in the ED. Metoclopramide has become more ac- cepted as a safe and effective treatment. At first, it has been used for nausea managing that is associated with migraine. Further studies showed that its dopamine antagonist quality may make it as an important treatment for acute migraine to relieve pain and nausea [15]. Metoclopramide at a dose of 10 to 20 mg could be effective in managing migraine headaches [2,16,17]. On the other hand, with further knowledge of the migraine pathology, the role of magnesium in the treatment of this disease has been increased. The mechanism of magnesium therapy for migraine is through its effect on serotonin function, as an important factor in developing migraine headaches. Mag- nesium can also help improve migraine symptoms by affecting the vascular tone (another important factor in developing a mi- graine headache). In a study by Massoud et al., the magnesium level in patients with migraine headache was evaluated. They have shown that the mean serum level of magnesium at the onset of headache was significantly decreased (P = 0.001) [18]. Moreover, several other studies declared the underlying role of magnesium in migraine pathophysiology. Even though migraine patients mostly referred to the emergency department, there is still no general agreement on the management of acute mi- graines [19]. In the present study, we have investigated the ef- fect of magnesium sulfate as an adjunct to metoclopramide in migraine treatment.
The findings of this study showed that the use of magnesium sulfate significantly increases the metoclopramide effects on relieving migraine headache. Our results have shown that the pain reduction slope in the patients treated by metoclopramide along with magnesium sulfate was significantly more severe than those treated by metoclopramide alone. Magnesium sul- fate also was used by Maleki et al. as an adjunctive drug in acute renal colic treatment, results of their double-blind clinical trial showed that magnesium sulfate did not have an effect on renal colic pain reduce [20]. In a study by Shahrami et al., the therapeutic effect of magnesium sulfate versus dexametha- sone/metoclopramide in the treatment of acute migraine was investigated and showing that magnesium sulfate reduced the severity of pain more effective than dexamethasone/metoclo- pramide [21]. The effects of magnesium on migraine pain re- duction have also been shown in previous studies. In another RCT study, the effects of 1g of I.V magnesium versus I.V dihy- droergotamine were compared and the results indicated that the effects of both medications are similar [22]. In another in- tervention study, it was shown that the administration of 600 mg of magnesium for 12 weeks significantly decreased the frequency and duration of migraine attacks, the severity of the headache and the use of anti-migraine drugs [23]. However, in these studies, the beneficial effect of magnesium sulfate on the management of acute migraine attacks has not been discussed. Contrary to our findings, Cete Y et al. failed to find any pri- ority of magnesium sulfate therapeutic effect on alleviating migraine headache when compared with metoclopramide [14]. The contrary could be explained by the differences in treatment types. Although in our study magnesium sulfate was prescribed in combination with metoclopramide, Cete Y et al. administrat- ed the drugs separately and in two groups. In another study by Corbo et al., similar to the current study, patients referred to the emergency department were treated with magnesium sulfate/ metoclopramide or metoclopramide/normal saline for migraine headache. Contrary to our findings, they have concluded that the magnesium sulfate inhibited the metoclopramide effects; the percentage of patients with 50% VAS reduction was signifi- cantly lower in magnesium sulfate/metoclopramide recipients [24]. The statistical analysis approach in the study by Corbo et al. was very different from ours, which could be one of the most important causes of the contrary. In addition, in the Corbo’s study, more than 95% of the patients were female, that caused selection error, while in our study we selected an equal number of male and female to eliminate the interventional effects of gender variable.
Conclusion
The findings of this study showed that the use of magnesium sulfate along with metoclopramide increased the effect of metoclopramide in managing acute migraine. However, our findings could not support the independent effect of magne- sium sulfate on the reduction of migraine headaches. We have not evaluated the drugs related to adverse events and it was the major limitation of the study.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
This study was conducted in accordance with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards for research involving human subjects and has been approved by Ahvaz Jundishapor University of Medi- cal Sciences ethical committee (R.AJUMS.REC.1396.1142). The informed consent was signed by patients willing to include in the study. The study was registered in Iran randomized clinical trial registry (IRCT).
Funding: Ahvaz Jundishapur University of Medical Sciences (research code: U-97002).
Conflict of interest
None of the authors received any type of financial support that could be consid- ered potential conflict of interest regarding the manuscript or its submission.
References
1. Lea R, Colson N, Quinlan S, Macmillan J, Griffiths L. The effects of vitamin supplementation and MTHFR (C677T) genotype on homocysteine-lowering and migraine disability. Pharmacogenet Genomics. 2009;19(6):422-8.
2. Cahill CM, Cook C, Pickens S. Migraine and Reward System- Or is It Aversive? Curr Pain Headache Rep. 2014;18(5):410.
3. Zarei S, Bigizadeh S, Pourahmadi M, Ghobadifar MA. Chronic pain and its determinants: a population-based study in Southern Iran. Korean J Pain. 2012;25(4):245.
4. Unalp A, Dirik E, Kurul S. Prevalence and clinical findings of migraine and ten- sion type headache in adolescents. Pediatr Int. 2007;49(6):943-9.
5. Sadeghi O, Askari G, Maghsoudi Z, Nasiri M, Khorvash F. Migraine and risk of stroke: Review of current evidence. Jundishapur Journal of Chronic Disease Care. 2014;3(3).
6. Mottaghi T, Khorvash F, Askari G, Iraj B, Ghiasvand R. Vitamin D and Migraine: Review of Current Evidence. Journal of Isfahan medical school. 2013;31(223): 32- 40.
7. Sadeghi O, Maghsoudi Z, Nasiri M, Khorvash F, Askari G. The association be- tween anthropometric measurements and homocysteine levels. Iranian Journal of Nutrition Sciences & Food Technology. 2014;9(3):45-52.
8. Bartleson J, Cutrer FM. Migraine update. Minn Med. 2010; 93(5) 36-41.
9. Talebi M, Savadi-Oskouei D, Farhoudi M, Mohammadzade S, Ghaemmaghami- hezaveh S, Hasani A, et al. Relation between serum magnesium level and mi- graine attacks. Neurosciences (Riyadh). 2011;16(4):320-3.
10. Serefko A, Szopa A, Wlaź P, Nowak G, Radziwoń-Zaleska M, Skalski M, et al. Magnesium in depression. Pharmacol Rep. 2013;65(3):547-54.
11. Volpe SL. Magnesium in disease prevention and overall health. Adv Nutri. 2013;4(3):378S-83S.
12. Lodi R, Montagna P, Soriani S, Iotti S, Arnaldi C, Cortelli P, et al. Deficit of brain and skeletal muscle bioenergetics and low brain magnesium in juvenile mi- graine: an in vivo 31 P magnetic resonance spectroscopy interictal study. Pediatr Res. 1997;42(6):866.
13. Köseoglu E, Talaslıoglu A, Gönül AS, Kula M. The effects of magnesium pro- phylaxis in migraine without aura. Magnes Res. 2008;21(2):101-8.
14. Cete Y, Dora B, Ertan C, Ozdemir C, Oktay C. A randomized prospective pla- cebo-controlled study of intravenous magnesium sulphate vs. metoclopramide in the management of acute migraine attacks in the Emergency Department. Cephalalgia. 2005;25(3):199-204.
15. Colman I, Brown MD, Innes GD, Grafstein E, Roberts TE, Rowe BH. Parenteral metoclopramide for acute migraine: meta-analysis of randomised controlled tri- als. BMJ. 2004;329(7479):1369-73.
16. Stovner LJ, Andree C. Prevalence of headache in Europe: a review for the Eurolight project. J Headache Pain. 2010;11(4):289.
17. Yoon M, Katsarava Z, Obermann M, Fritsche G, Oezyurt M, Kaesewinkel K, et al. Prevalence of primary headaches in Germany: results of the German Headache Consortium Study. J Headache Pain. 2012;13(3):215.
18. Masoud SA, Vali GR. Magnesium changes in migraine and non-migraine at- tacks. KAUMS Journal (FEYZ). 2003;7(3):81-6.
19. Najjar M, Hall T, Estupinan B. Metoclopramide for acute migraine treat- ment in the emergency department: an effective alternative to opioids. Cureus. 2017;9(4). DOI: 10.7759/cureus.1181.
20. Verki MM, Porozan S, Motamed H, Fahimi MA, Aryan A. Comparison the anal- gesic effect of magnesium sulphate and ketorolac in the treatment of renal colic patients: double-blind clinical trial study. Am J Emerg Med. 2019;37(6):1033-6.
21. Shahrami A, Assarzadegan F, Hatamabadi HR, Asgarzadeh M, Sarehbandi B, Asgarzadeh S. Comparison of therapeutic effects of magnesium sulfate vs. dexa- methasone/metoclopramide on alleviating acute migraine headache. J Emerg Med. 2015;48(1):69-76.
22. Rahimdel A, Eslami MH, Zeinali A. A Randomized controlled study of mag- nesium sulfate versus dihydroergotamine in the management of acute migraine attacks. Pakistan Journal of Neurological Sciences (PJNS). 2007;2(2):92-5.
23. Peikert A, Wilimzig C, Köhne-Volland R. Prophylaxis of migraine with oral magnesium: results from a prospective, multi-center, placebo-controlled and double-blind randomized study. Cephalalgia. 1996;16(4):257-63.
24. Corbo J, Esses D, Bijur PE, Iannaccone R, Gallagher EJ. Randomized clinical tri- al of intravenous magnesium sulfate as an adjunctive medication for emergency department treatment of migraine headache. Ann Emerg Med. 2001;38(6):621-7.
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Hassan Motamed, Javad Mozafari, Samaneh Porozan, Mojtaba Sasani. Magne- sium Sulfate and Acute Migraine: A Randomized Clinical Trial. Ann Clin Anal Med 2020;11(5):369-373
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An Investigation of the Effect of Antioxidant on Biochemical Parameters in ELF-EMF Exposure
Mehmet Cihan Yavaş 1, Mehmet Zülküf Akdağ 2, Mustafa Salih Çelik 3, Özkan Görgülü 4
1 Department of Biophysics, Faculty of Medicine, Kırşehir Ahi Evran University, Kırşehir, 2 Department of Biophysics, Faculty of Medicine, Dicle University, Diyarbakır, 3 Department of Nursing, School of Health, Batman University, Batman, 4 Department of Biostatistics, Faculty of Medicine, Kırşehir Ahi Evran University, Kırşehir, Turkey
DOI: 10.4328/ACAM.20076 Received: 2019-11-20 Accepted: 2019-12-10 Published Online: 2019-12-30 Printed: 2020-09-01 Ann Clin Anal Med 2020;11(5):365-368
Corresponding Author: Mehmet Cihan Yavaş, Department of Biophysics, Faculty of Medicine, Kırşehir Ahi Evran University, 40100, Kırşehir, Turkey. E-mail: mcihanyavas@ahievran.edu.tr P: +90 386 280 2504 Corresponding Author ORCID ID: https://orcid.org/0000-0002-2923-050X
Aim: The purpose of our study was to investigate the effect of electromagnetic fields originating from high voltage lines and antioxidant on serum biochemical values of Wistar albino male rats.
Material and Methods: A total of 48 rats were included in the study and 3 groups were formed in two different time periods (26/52 days) as follows: Group 1- High voltage (HV), Group 2- HV+Ganoderma lucidum (GL), Group 3- Control. The magnetic field and the electric field were measured. Ganoderma was administered at a dosage of 20 mg/kg/day as a gavage.
Results: In the implementation that took 26 days, no significant difference was found between groups in terms of AST, ALT, Ca, amylase, glucose ve creatine values (P>0.05), and a significant difference was found between groups in terms of urea variable (P<0.01). In the implementation that took 52 days, no statistically significant difference was found between groups in terms of AST, ALT, Ca, amylase, glucose, creatine and urea values (P>0.05).
Discussion: It is seen that extremely low – frequency electromagnetic fields generated by high voltage lines may cause changes in serum biochemistry values and the use of some antioxidant (ganoderma) products may be beneficial.
Keywords: Biochemical Values; High Voltage; Electromagnetic Field; Ganoderma, Rat
Introduction
With the development of technology, electromagnetic field exposures increase. The extremely low frequency electric and magnetic field exposures caused by the electrical energy used from 50 Hz power frequency cause concern in the society. Based on limited epidemiological evidence, in 2002 the Inter- national Agency for Research on Cancer (IARC) classified ELF- MF as a possible carcinogen for humans [1]. It is emphasized that working on long term high voltage lines will have negative consequences on human health [2]. However, for many years, researchers have not been able to fully establish a validated correlation of the impact of electromagnetic radiation on hu- man health. The debate on this issue is still ongoing [3]. In re- cent years, the use of electricity in industry and households has been increasing. The need for electricity leads to an increase in high-voltage lines. High voltage systems are located in the 50/60 Hz frequency band. It is emphasized that the formation of ionic dipoles cause changes in membrane potential and can affect biochemical processes in cells, as electric fields can pen- etrate into the body [4, 5]. The electromagnetic fields that we encounter in our daily lives have a frequency of 3-300 Hz. They are particularly described as extremely low frequency electro- magnetic fields (ELF-EMFs). Studies on the impact of these areas on public health and employee health are insufficient. ELF-EMF domains have effects on metabolic and biochemical processes [6]. In case of continuous exposure to or induction of electric fields, various biological processes can be initiated. It is emphasized that changes in exposure may lead to changes in renal and liver functions [7].
Ganoderma is used in the treatment and prevention of various diseases, especially in eastern countries. Ganoderma is used to prevent oxygen radicals and oxidative damages. It has a protec- tive effect against DNA damage caused by UV radiation and has a good radioprotective effect [8]. Ganoderma, commonly used in traditional Chinese medicine to promote health and lon- gevity, has been widely accepted as herbal supplements. The medical properties of GL can be attributed to antioxidant and anti-inflammatory activities [9]. Ganoderma lucidum may be useful in the treatment of chronic liver damage and in strength- ening the body’s antioxidant capacity [10].
It is now impossible to avoid electromagnetic field exposures. These areas are risk and concern. We have created a high volt- age line model in the laboratory environment. In this study, we aimed to investigate the effects of a very low-frequency electromagnetic field and antioxidant (Ganoderma lucidum) on some biochemical values.
Material and Methods
Animals and experimental protocol
A total of 48 Wistar albino male rats were included in this study. Rats were divided into 3 groups in two different time periods (26 days and 52 days) as follows: Group 1- High voltage group (HV), Group 2- High voltage+Ganoderma (GL), Group 3- Con- trol. Experimental groups were exposed to daily 8 hours during 26 and 52 days. The animals were maintained in an appropri- ate medium (12 hours light/dark, the temperature of 23±1 oC, and 45-55% humidity). Ganoderma (Gano Excel, Industries Sdn. Bhd., Kedah, Malaysia) extracts were prepared with distilled wa-
ter according to appropriate standards. Ganoderma was given at a dosage of 20 mg/kg/day as a gavage. Two separate trans- formers were used to generate the electromagnetic field (for the first transformer, the input was 220 volts, and the output was 10 kilovolts (10kV). For the second transformer, the input was 10 kilovolts, and the output was 220 volts and 5,000 volts amps). Electromagnetic field measurements were performed using Spectran NF5035 (Aaronia, Germany) model device. Elec- tromagnetic field measurements were made in plexiglass cages where rats were encaged during the experiment. Daily mea- sured areas were averaged. The readings were taken in volt per meter (V/m) for the electric field and microTesla (μT) for the magnetic field. Field measurements were 80.3 V/m for electric field and 2.48 microTesla for the magnetic field. Figure 1 shows the experimental setup. This study protocol was initiated after the approval of the Kirsehir Ahi Evran University Animal Eth- ics Local Ethics Committee decision (AEUHADYEK, 30/10/2019, 20-2) and the study continued according to the standards set out in the Helsinki Declaration.
Blood collection and analysis of biochemistry parameters
At the end of the work, the rats were anesthetized with intra- muscular injection (1ml for one rat (0.1 cc xylazine + 0.9 cc ketamine)). Then, the blood of the rats from the intracardiac route was drawn. Blood samples from the control and experi- mental groups of animals were collected (BD Vacutainer 5.0 ml, UK). Serum was separated directly by centrifugation (NF 1200 R Nuve, Turkey) at 5000 rpm for 5 minutes and was kept at -20oC until the analysis. An automated analyzer method was applied for the analysis of the data (Abbott Architect® c16000). Statistical analysis
The normality hypothesis was tested by the Kolmogorov- Smirnov and the Shapiro-Wilk tests. The Levene test was used to test the assumption of homogeneity of variances. For the comparison of the groups in the study, ANOVA was used. Com- parison of the groups which revealed significant difference was analyzed through DUNCAN multiple comparison test. Descrip- tive statistics of variables are given as Mean ± Standard devia- tion. In all statistical analyses, cases with a p-value less than 0.05 were interpreted as statistically significant. Statistical analysis of the study was performed using Statistical Package for Social Sciences version 21.0 software for Windows (IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp., USA).
Results
Three different groups (HV, HV+Ganoderma and Control) were tested during two different processes (26 and 52 days) in the study. Statistics of the groups during 26 days of implementa- tion and the results of the analysis are displayed in Table 1. According to the results revealed in Table 1, the difference between the groups was not found significantly related to the AST, ALT, Ca, amylase, glucose and creatine values (P>0.05). The difference between the groups relating to the urea variable is found statistically significant (P<0.01). The value of urea in the control group was lower than Group 1 and Group 2. Statistics of 52 days of implementation of the groups are dis- played in Table 2. According to the results in Table 2, no signifi- cant difference was found between groups in terms of AST, ALT, Ca, amylase, urea, glucose and creatine values. (P>0.05). Statistics of 52 days of implementation of the groups are dis- played in Table 2. According to the results in Table 2, no signifi- cant difference was found between groups in terms of AST, ALT, Ca, amylase, urea, glucose and creatine values. (P>0.05).
Discussion
Peighambarzadeh and Tavana in their study, included partici- pants who worked in high voltage electric line for at least ten years. The serum of the blood drawn in the study was analyzed. They found a statistically significant change in AST and urea values in control and experimental group comparisons, but a statistically insignificant change in ALT, glucose, creatine and Ca parameters [2]. Researchers investigated the effect of elec- tromagnetic radiation resulting from cell phones with 500-900
MHz frequency on 60 swiss albino mice during two different time periods of 20 and 40 days. They found a decrease in se- rum creatine and glucose levels and an increase in serum AST and ALT levels in long-term exposures [3]. Coşkun et al. empha- sized that the 50 Hz electric fields reduced some of the serum biochemistry (plasma total cholesterol and triglyceride rates) characteristics. It is stated that the mechanism of action of electric fields is not fully understood yet [11]. The researchers found that 50 Hz magnetic fields had no significant effect on growth or most of the biochemical parameters of blood, except for creatine and cholesterol. However, changes in creatinine and cholesterol have been found to be relatively small [6]. DNA damage was investigated by exposure to electromagnetic field on workers working in the power line in Iran. As a result of the study, a significant increase (p<0.05) was found in the workers’ tail moment and DNA tail percentage in experimental and con- trol groups comparisons [12]. Lai et al. found that exposure to 100μT- 50 Hz ELF EMF for 20 hours per day for 3 months would not affect blood hematogram and blood biochemistry (including lipid profile, blood glucose, liver function and renal function of rats) in the experimental and control groups [13].
In our study, it is found out that there is an increase in the high voltage group of AST, ALT, amylase and urea values in compari- son with the parameters of 26 and 52 days of implementation with the control group and a decrease in glucose group. It is found that Ca values of 26 days of high voltage group increased compared to the control group, and no significant change was revealed during 52 days of exposure. This study also revealed that no significant difference was found in creatin values of 26 days of high voltage group; and an increase was found in 52 days of implementation according to the control group. In the literature, similar to our study, it is revealed that AST and ALT values are consistent with an increase in the experimental group. Likewise, the results of amylase, urea, Ca, glucose and creatine are similar to the results as in the literature. However, some studies have indicated that there is no change in electro- magnetic field exposures.
There are many studies on the protective effect of ganoderma. Ganoderma triterpenoids reduced oxidative stress and inflam- mation in liver injuries, and because of its rich biological activ- ity, it was emphasized that it may play a role in minimizing the effects of electromagnetic induced exposures and damages in various tissues [10, 14, 15, 16]. In this study, when high voltage (HV) group and HV+GL group are compared, AST and ALT values in HV+GL groups were found lower in 26 and 52 days of imple- mentation. No significant difference was found in Ca and urea groups. As the implememntation process increases, it is seen that values in the parameters of amylase, glucose and creatin in HV+GL group increased. In this study, according to results of 26 and 52 days of HV groups, a decreasea in AST, ALT, urea and amylase and glucose values may indicate a protective effect of ganoderma.
Although the biophysical and biochemical mechanisms of the biological effects of EMF at low-density levels are not fully known, significant progress has been made in recent years, and there is a great deal of data indicating that these mechanisms can overlap the effects of ELF and RF [17]. Many studies have shown that transduction of weak electrical signals in the ELF range involves interactions with the cell membrane, resulting in cytoplasmic biochemical responses involving changes in cellular functionality and proliferative states [18]. Although the electri- cal and magnetic field values measured in our study are below the limit values of the International Commission on Non-Ioniz- ing Radiation Protection, it is seen that they can cause some changes in biochemical parameters that is investigated in this study.
Conclusion
In our study, it was found that extremely low-frequency electro- magnetic fields caused some increases and partially decreases in serum biochemistry parameters of rats. It is thought that Ganoderma may have shown a possible protective effect. How- ever, in the literature, it is seen that the mechanism of effect on biochemistry parameters is not fully known and further re- searches on effects of ELF-EMF are needed.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical stan- dards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be consid- ered potential conflict of interest regarding the manuscript or its submission.
References
1. Y Fei, L Su, H Lou, C Zhao, Y Wang, G Chen. The effects of 50 Hz magnetic field-exposed cell culture medium on cellular functions in FL cells. J Radiat Res. 2019; 60(4): 424-31.
2. Sert C, Yazgan P. Bone quality, biochemical and blood markers in high power electrical workers. J Int Dent Med Res. 2017; 10 (3): 1042-47.
3. Peighambarzadeh SZ, Tavana M. Effects of electromagnetic field radiation on biochemical parameters in swiss albino mice. Banats J Biotechnol. 2017; 8(16): 48-53.
4. Forgacs Z, Thuroczy G, Paksy K, Szabo DL. Effect of sinusoidal 50 Hz magnetic field on the testosterone production of mouse primary Leydig cell culture. Bioelec- tromagnetics. 1998; 19:429-31.
5. Sadeghi H, Zare S, Hayatgeibi H, Alivandi S, Ebadi AG. Biological effect of power frequency magnetic fields on serum biochemical parameters in Guinea pigs. Pak J Biol Sci. 2006; 6: 1083-87.
6. Luo X, Ma L, Gao P, Zhang Y. Effects of subchronic extremely low-frequency electromagnetic field exposure on biochemical parameters in rats. Toxicol Ind Health. 2017; 33(4): 365–72.
7. Kulkarni GA, Gandhare WZ. Effect of extremely low frequency electric field on liver, kidney, and lipids of Wistar rats. Int J Med Sci Public Health. 2015; 4(12): 1755-60.
8. Kim KC, Kim IG. Ganoderma lucidum extract protects DNA from strand break- age caused by hydroxyl radical and UV irradiation. Int J Mol Med. 1999; 4(3): 273-80.
9. Hsu PL, Lin YC, Ni H, Mo FE. Ganoderma triterpenoids exert antiatherogenic effects in mice by alleviating disturbed flow-induced oxidative stress and inflam- mation. Oxid Med Cell Longev. 2018; 3491703. DOI: 10.1155/2018/3491703.
10. Li T, Yu Haroran, Song Y, Zhang R, Ge Ming. Protective effects of Ganoderma triterpenoids on cadmium-induced oxidative stress and inflammatory injury in chicken livers. J Trace Elem Med Biol. 2019; 52: 118-25.
11. Coskun O, Çömlekçi S. Effect of ELF electric field on some on biochemistry characters in the rat serum. Toxicol Ind Health. 2010; 27(4): 329–33.
12. Zendehdel R, Yu II J, Hajipour-Verdo B, Panjali Z. DNA effects of low level occupational exposure to extremely low frequency electromagnetic fields (50/60 Hz). Toxicol Ind Health. 2019; 35(6): 424-30.
13. Lai J, Zhang Y, Zhang J, Liu X, Ruan, Chaugai S, et al. Effects of 100-μT extremely low frequency electromagnetic fields exposure on hematograms and blood chemistry in rats. J Radiat Res. 2015; 57(1): 16-24.
14. Doğan MS, Yavaş MC, Yavuz Y, Erdoğan S, Yener İ, Şimşek İ, et al. Effect of electromagnetic fields and antioxidants on trace element content in rat teeth. Drug Des Devel Ther. 2017; 11: 1393-98.
15. Tanık A, Yavaş MC. The protective effect of melatonin and ganoderma lu- cidum aganist the negative effect of extremely low-frequency electromagnetic fields (EMF) on alveolar bone of rats. Anal Quant Cytol. 2019; 41(2): 55-66.
16. Doğan MS, Yavaş MC, Günay A, Yavuz İ, Deveci E, Akkuş Z, et al. The protec- tive effect of melatonin and ganoderma lucidum against the negative effects of extremely low frequency electricity and magnetic fields on pulp structure in rat teeth. Biotechnol Biotechnol Equip. 2017; 31(5): 979-88.
17. Belyaev I, Dean A, Eger H, Hubmann G, Jandrisovits R, Kern M, et al. EURO- PAEM EMF Guideline 2016 for the prevention, diagnosis and treatment of EMF- related health problems and illnesses. Rev Environ Health. 2016; 31(3): 363-97.
18. ICNIRP Guidelines. For limiting exposure to time-varying electric, magnetic and electromagnetic fields (up to 300 GHz). Health Phys. 1998; 74(4): 494-522.
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Mehmet Cihan Yavaş, Mehmet Zülküf Akdağ, Mustafa Salih Çelik, Özkan Görgülü. An Investigation of the Effect of Antioxidant on Biochemical Parameters in ELF- EMF Exposure. Ann Clin Anal Med 2020;11(5):365-368
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Sepsis-Related Mortality with SOFA and qSOFA in Emergency Department Patients
Bedriye Müge Sönmez 1, Aysel Kocagül Çelikbaş 2
1 Department of Emergency Medicine, Bilkent City Hospital, Ankara, 2 Department of Infectious Disease, Hitit Univercity Medical Faculty, Çorum, Turkey
DOI: 10.4328/ACAM.20079 Received: 2019-11-23 Accepted: 2019-12-23 Published Online: 2019-12-28 Printed: 2020-09-01 Ann Clin Anal Med 2020;11(5):359-364
Corresponding Author: Bedriye Müge Sönmez, Ankara Yıldırım Beyazıt Education and Research Hospital Ziraat Mah. Şehit Ömer Halisdemir Cad. No: 20 Dışkapı/Ankara. E-mail: mugesonmez06@yahoo.com GSM: +90 5055823208 Corresponding Author ORCID ID: https://orcid.org/0000-0003-3970-8922
Aim: Prediction of sepsis-related mortality in the emergency department (ED) is important. In this study, we aimed to assess the predictive power of the newly defined scoring systems in sepsis-related mortality and reduce it in the ED.
Materials and Methods: A prospective cohort study was conducted on a sample of patients who presented to the ED with sepsis. Patients aged <18 years and those with shock from non-septic causes were excluded. Age, vital signs, laboratory findings on admission, culture time, time of empiric antibiotic therapy, results of scoring systems, duration of ED stay and hospitalization, focus of infection and clinical outcome were recorded.
Results: A total of 48 patients were enrolled in the study. SOFA scores were higher in patients who died (p = 0.001, 95% CI, 0.639–0.902). The best cut-off point for diagnostic performance was a SOFA score of 4.5. At this point, sensitivity was 82.61%, specificity was 56.0%, positive predictive value was 63.3% and negative predictive value was 77.8%.
Discussion: qSOFA and SIRS cannot provide adequate prognostic information in the ED, whereas, SOFA reliably predicted mortality. Our results indicate that vital signs are more flexible and efficient data sources. Although it is presently not precisely understood how RDW is associated with clinical outcomes but patients with increased RDW levels should be more aggressively treated and admission RDW could also be used for prognostic purposes, particularly in busy EDs. Also, lactate levels were correlated with SOFA and qSOFA scores and that the former could predict mortality (p= 0.012) is consistent with previous stud- ies of infection
Conclusion: In conclusion, qSOFA had poor performance for the prediction of sepsis-related mortality in the ED. SOFA had the best performance.
Keywords: Sepsis; SOFA; qSOFA; Emergency Department; Mortality
Introduction
Sepsis refers to organ dysfunction threatening the host’s life that results from an impaired host response elicited by the cul- prit infection and remains a major concern in ED as a result of determining the mortality in one-hour-therapeutic manage- ment, so the emergency physicians play a major role [1, 2]. De- lay in adequate treatment, subsequently impacts mortality and cost in sepsis [3].
According to Sepsis 3, SOFA is mainly a clinical diagnostic cri- terion; qSOFA is a screening tool to predict sepsis-related out- comes [3-5]. Recently many studies have tried to figure out the diagnostic and prognostic value of these newly defined scoring tools [6–10]. No consensus has been reached, because some studies are based on the ED septic patients and others on pa- tients seen outside. Because emergency physicians are the first to encounter patients with sepsis, tests and tools that can be used for bedside diagnostic and prognostic purposes are desir- able.
We conducted a study to assess the predictive power of the newly defined scoring systems SOFA and qSOFA compared with traditional SIRS criteria for sepsis-related mortality in the ED patients.
Material and Methods
This single-center, prospective cohort study was assessed be- tween November 1, 2017 and March 31, 2018 in the ED of an academic tertiary care hospital. The study was approved by the local ethics committee. Consent for participation in the study was obtained from the patients or from the relatives of pa- tients who could not give consent because of unconsciousness, mental retardation, psychiatric illness, or Alzheimer’s or other dementia.
Data were obtained from hospital electronic records and pa- tient follow-up forms. The subjects were examined by ED physi- cians for assessment and fulfillment of the clinical criteria for severe sepsis or septic shock according to the guidelines of the Surviving Sepsis Campaign and were subsequently admitted to the hospital between the dates indicated (n = 187). Patients who were diagnosed with sepsis and hospitalized or discharged from the ED were included in the study. The extracted data included the presence of SIRS criteria, the qSOFA and SOFA scores and the time required to meet the criteria. We excluded patients younger than 18 years, patients referred from outside facilities and patients with shock from non-septic causes, such as cardiogenic shock, left heart failure, right heart failure, ar- rhythmia, acute coronary syndrome, pulmonary embolism, ten- sion pneumothorax, cardiac tamponade, hypovolemic shock, vasodilatory (distributive) shock, neurogenic (spinal) shock, ad- renal shock and anaphylaxis.
A study form was used that included age, vital signs (blood pressure, heart rate, body temperature, oxygen saturation and shock index) and laboratory findings (complete blood count, biochemistry and blood gas measurements) on admission and culture time, time of empiric antibiotic therapy, results of scor- ing systems (SOFA, qSOFA, and SIRS), duration of ED stay and hospitalization, focus of infection and in-hospital mortality. Chart reviews were completed by trained emergency physi- cian researchers (following predetermined guidelines defining abstraction criteria) to determine the presence and timing of the various components of the SIRS, qSOFA, and SOFA criteria. The qSOFA criteria were altered mental status, respiratory rate (RR)>22/min and systolic blood pressure (SBP)>100 mmHg. The SIRS criteria were heart rate (HR)>90 bpm, white blood cell (WBC) count >12,000/dL or<4000/dL, RR>20/min, temper- ature >38.5°C or <36°C, and a five-degree SOFA score consist- ing of respiratory (PaO2/FiO2[mmHg]), coagulation (platelets [*103mm3]), hepatic (bilirubin [mg/dL]), cardiovascular (hypo- tension, defined as mean arterial pressure ≤65 mmHg and need for vasopressor support), central nervous system (Glasgow Coma Scale) and renal (creatinine [mg/dL]) functions.
The sample size required to achieve our objectives was primar- ily determined by the accuracy (width of the confidence interval around the point estimate of sensitivity) of SOFA for the pri- mary outcome. Before the study, we estimated that the mean SOFA score would be approximately 4±2 in the surviving group and 6 in the deceased group. Based on these values, the re- quired sample size was 16 for each group, with a type1 error of 0.05 and a power of 80%. The mean SOFA score was 4.56±2.66 in the surviving group and 8.61±4.43 in the deceased group. According to these scores, the minimum sample size was 7 for each group, with a type1 error of 0.05 and a power of 80%.The patient flow is shown in Figure 1.
Statistical analysis was performed with SPSS version 23.0 soft- ware (SPSS Inc., Chicago,IL, USA). For the variables, a normal distribution was determined using the one-sample Kolmogorov- Smirnov test; continuous variables that were not normally dis- tributed were expressed as medians (min–max), and categori- cal variables were expressed as numbers and percentages. The Mann-Whitney U test was used to compare continuous variables between two groups. The significance of differences between categorical variables was calculated using the Chi- Square test. Correlations between two continuous variables were calculated by the Spearman’s rank correlation coefficient (rho). Coefficients between 0 and 0.3 indicated weak correla- tion, coefficients between 0.3 and 0.7 indicated moderate cor- relation and coefficients between 0.7 and 1 indicated strong correlation. Comparison of prognostic performances of SOFA and qSOFA with SIRS and the influence of the continuous SOFA score on mortality was performed by receiver operating charac- teristic (ROC) analyses; the best cut-off point was determined as the point at which the sum of sensitivity and specificity was the greatest. P-values <0.05 were considered to indicate statis- tical significance.
Results
A total of 48 patients presenting to our ED with sepsis were eligible for this study. The mean age was 69.25±15.38 years (minimum, 22; maximum, 94). The most common site of infec- tion was the pulmonary system (n=20, 41.7%), and the least common site was the central nervous system (n=1, 2.1%). qSO- FA was ≥2 in 25 patients (52.1%), SOFA was ≥2 in 45 patients (93.7%) and SIRS was ≥ in 38 patients (79.1%).
Tables 1 and 2 show the predictive values of variables affect- ing mortality. Initial red cell distribution width (RDW), aspar- tate aminotransferase (AST), lactate and base deficit (BD) were greater in patients who died (p = 0.001, 0.014, 0.012 and 0.003, respectively), whereas bicarbonate (HCO3) and fever were low- er (p=0.003 and 0.002, respectively) (Table 1). Among patients who died, SOFA scores were greater (p=0.001) and hospital stay was shorter (0.016) (Table 2).
Correlations of variables with the scoring systems are shown in Table 3. SBP, fever, glomerular filtration rate (GFR) and BD had moderate negative correlations with SOFA score, while the Glasgow Coma Scale (GCS), mean platelet volume (MPV), blood urea nitrogen (BUN), creatinine and lactate had moderate posi- tive correlations with SOFA score. Age and GCS had moderate positive correlations and MPV and lactate had weak positive correlations with qSOFA. HR, RR, fever and platelet count had moderate positive correlations and SO2 had a moderate nega- tive correlation with SIRS.
Overall, in-hospital mortality was 47.9% (n= 23). The ROC curve of the SOFA score for predicting mortality is shown in Figure 2 (AUC=0.770; p=0.001; 95% CI, 0.639–0.902). Based on diag- nostic performance, the best cut-off point was a SOFA score of 4.5. However, we cannot use a SOFA score of 4.5 as a cut-off because it is not an integer. We calculated the mortality rates above and below a SOFA score of 4. At this point, the mortality rate was 62.5%, the sensitivity was 82.61%, the specificity was 56.0%, the positive predictive value was 63.3% and the nega- tive predictive value was77.8% (Figure 2).
According to our results, qSOFA and SIRS cannot provide ad- equate diagnostic and prognostic information in the ED (Table 2). In contrast, SOFA reliably predicted mortality (Figure 2).
Discussion
Recent studies comparing sepsis scores have produced differ- ent results [11–14]. According to our results, while maintaining the value of SOFA in predicting mortality, qSOFA scores could not identify patients with the most severe forms of infection early in the course in the ED. The latter result is inconsistent with previous studies on the use of qSOFA to predict patients with increased risk of prolonged stay in the intensive care unit or death [11, 15].
Although several scoring systems exist to assess the prognosis in critically ill patients, they are difficult to apply in patients pre- senting to acute care because of time constraints. Vital signs can provide important prognostic information in patients with acute illness [16]. We found that haemoglobin, fever, and GCS correlated well with SOFA and qSOFA (r = 0.349, 0.412, and 0.692 respectively), indicating that vital signs are more flexible and efficient data sources.
The sepsis-induced inflammatory milieu and organ damage ul- timately resulting in death have been poorly described. The liver is the laboratory of the human body, which is capable of per- forming more than 200 functions, including detoxification, stor- age, energy production, nutrient conversion, hormonal balance and coagulation, all of which render the liver a critical organ in sepsis [17]. The liver plays prominent roles in the septic pro- cess, such as removing bacteria, mediating the inflammatory response and regulating coagulation, which may play a role in the pathogenesis of renal failure, acute lung injury, acute respi- ratory distress syndrome, coagulopathy and hepatic encepha- lopathy. The liver is vulnerable to injury from pathogens, toxins, and inflammatory compounds, which may lead to hepatocellular dysfunction, hepatic injury, and ultimately hepatic failure [18]. Septic injuries to the liver can be broadly classified as hypoxic hepatitis or the jaundice type. The latter is the more common type and is the main component of SOFA, which should be as- sessed as a part of the overall clinical presentation [19]. Rise in hepatic transferase is not sufficient when the use of SOFA is contemplated in the ED, as shown in our study.
It is presently not precisely understood how RDW is patho- physiologically formed and associated with clinical outcomes. However, it is known that RDW is elevated by inflammatory processes that interfere with iron metabolism, augment eryth- rocyte apoptosis, decrease erythropoietin production and sup- press bone marrow [20, 21]. We found a significantly higher RDW level in patients who died (p=0.001), suggesting that pa- tients with increased RDW levels should be more aggressively treated and admission RDW could also be used for prognostic purposes, particularly in busy EDs.
Although the role of MPV in sepsis is not fully understood, it has been reported to remain at normal levels in localized bacterial infections, but to be significantly elevated in half of patients with sepsis [22]. We found that MPV was positively correlated with SOFA and qSOFA scores (r = 0.313 and 0.93, respectively) and according to previous reports [23] impaired thrombocyte production and function caused by the impact of sepsis on bone marrow may be reflected in MPV as an indirect sign of dysfunc- tion; this parameter can be used in the ED as a quick and reli- able sign of sepsis.
We found that lactate levels were correlated with SOFA and qSOFA scores and that the former could predict mortality (p= 0.012), this result is consistent with previous studies of infec- tion [24]. At present, although the use of three scoring systems cannot be universally recommended, lactate measurements should be combined with them when an infection is suspected. Limitations
The most obvious limitation of this research was that of a small sample size. Although the sample size was small, we adequately addressed the research questions or generalized beyond the context of the study and still, the small population did not ne- gate recognition of importance of SOFA in predicting sepsis- related mortality in ED, but with a larger sample, including a greater number of culturally different participants any real dif- ferences would almost certainly have emerged. Our study pro- duced statistically significant results concerning sepsis scoring systems and encouraged to find results similar to larger and more inclusive studies. Secondly, baseline information on car- diovascular risk factors, comorbidities and concurrent medica- tion, which were important potential confounders in this con- text, was not collected or available to the data extractors, and any potential influence on vital signs was not controlled. Larger, multisite, prospective studies are needed to control for multiple confounders and find clinically important associations. Conclusion
In conclusion, this study highlighted the poor performance of qSOFA and the reliable performance of SOFA for the predic- tion of sepsis-related mortality in the ED. We hope this small study will provoke more investigation into the appropriateness of fully adopting mortality predicting sepsis scores as a screen- ing tool by emergency medicine physicians.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical stan- dards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be consid- ered potential conflict of interest regarding the manuscript or its submission.
References
1. Raith EP, Udy AA, Bailey M, McGloughlin S, MacIsaac C, Bellomo R, et al. Prog- nostic accuracy of the SOFA Score, SIRS Criteria, and qSOFA Score for in-hospital mortality among adults with suspected infection admitted to the intensive care unit. JAMA. 2017;317(3):290–300.
2. Moskowitz A, Patel PV, Grossestreuer AV, Chase M, Shapiro N, Berg K, et al. Quick sequential organ failure assessment and systemic inflammatory response syndrome criteria as predictors of critical care intervention among patients with suspected infection. Crit Care Med. 2017;45:1813–19.
3. de Groot B, Stolwijk F, Warmerdam M, Lucke JA, Singh GK, Abbas M, et al. The most commonly used disease severity scores are inappropriate for risk stratifi- cation of older emergency department sepsis patients: an observational multi- centre study. Scand J Trauma Resusc Emerg Med. 2017;25:91.
4. Zhou X, Wu F. It is SOFA score rather than quick SOFA (qSOFA) score that con- stitutes the clinical criteria of sepsis. Am J Infect Control. 2018;46:1315.
5. Guirgis FW, Puskarich MA, Smotherman C, Sterling SA, Gautam S, Moore FA, et al. Development of a simple sequential organ failure assessment score for risk assessment of emergency department patients with sepsis. J Intensive Care Med. 2017; DOI:10.1177/0885066617741284
6. Maitra S, Som A, Bhattacharjee S. Accuracy of quick Sequential Organ Failure Assessment (qSOFA) score and systemic inflammatory response syndrome (SIRS) criteria for predicting mortality in hospitalized patients with suspected infection: a meta-analysis of observational studies. Clin Microbiol Infect. 2018;24:1123–29.
7. Khwannimit B, Bhurayanontachai R, Vattanavanit V. Comparison of the per- formance of SOFA, qSOFA and SIRS for predicting mortality and organ failure among sepsis patients admitted to the intensive care unit in a middle-income country. J Crit Care. 2018;44:156–60.
8. van der Woude SW, van Doormaal FF, Hutten BA, J Nellen F, Holleman F. Classi- fying sepsis patients in the emergency department using SIRS, qSOFA or MEWS. Neth J Med. 2018;76:158–66.
9. Rudd KE, Seymour CW, Aluisio AR, Augustin ME, Bagenda DS, Beane A, et al. Association of the Quick Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA) score with excess hospital mortality in adults with suspected ınfection in low- and middle-income countries. JAMA. 2018;319:2202–11.
10. Baig MA, Sheikh S, Hussain E, Bakhtawar S, Subhan Khan M, Mujtaba S, et al. Comparison of qSOFA and SOFA score for predicting mortality in severe sepsis and septic shock patients in the emergency department of a low middle income country. Turk J Emerg Med. 2018;18:148–51.
11. Tusgul S, Carron PN, Yersin B, Calandra T, Dami F. Low sensitivity of qSOFA, SIRS criteria and sepsis definition to identify infected patients at risk of compli- cation in the prehospital setting and at the emergency department triage. Scand J Trauma Resusc Emerg Med. 2017;25:108.
12. Kushimoto S, Gando S, Ogura H. The qSOFA requires validation as a promptly applicable clinical criterion. Acute Med Sur. 2017;4:225–6.
13. Asiimwe SB, Abdallah A, Ssekitoleko R. A simple prognostic index based on admission vital signs data among patients with sepsis in a resource-limited set- ting. Crit Care. 2015;19:86.
14. Askim Å, Moser F, Gustad LT, Stene H, Gundersen M, Åsvold BO, et al. Poor performance of quick-SOFA (qSOFA) score in predicting severe sepsis and mor- tality – a prospective study of patients admitted with infection to the emergency department. Scand J Trauma Resusc Emerg Med. 2017;25:56.
15. Haydar S, Spanier M, Weems P, Wood S, Strout T. Comparison of QSOFA score and SIRS criteria as screening mechanisms for emergency department sep- sis. Am J Emerg Med. 2017;35:1730–33.
16. Kim KS, Suh GJ, Kim K, Kwon WY, Shin J, Jo YH, et al. Quick Sepsis-related Or- gan Failure Assessment score is not sensitive enough to predict 28-day mortality in emergency department patients with sepsis: a retrospective review. Clin Exp Emerg Med. 2019;6:77–83.
17. Canabal JM, Kramer DJ. Management of sepsis in patients with liver failure. Curr Opin Crit Care. 2008;14:189–97.
18. Yan J, Li S, Li S. The role of the liver in sepsis. Int Rev Immunol. 2014;33:498– 510.
19. Wang D, Yin Y, Yao Y. Advances in sepsis-associated liver dysfunction. Burns Trauma. 2014;2:97–105.
20. Wang AY, Ma HP, Kao WF, Tsai SH, Chang CK. Red blood cell distribution width is associated with mortality in elderly patients with sepsis. Am J Emerg Med. 2018;36:949–53.
21. Ju XF, Wang F, Wang L, Wu X, Jiang TT, You DL, et al. Dynamic change of red cell distribution width levels in prediction of hospital mortality in Chinese elderly patients with septic shock. Chin Med J (Engl). 2017;130:1189–95.
22. Van der Lelie J, Von dem Borne AK. Increased mean platelet volume in septi- caemia. J Clin Pathol. 1983;36:693–6.
23. Becchi C, Al Malyan M, Fabbri LP, Marsili M, Boddi V, Boncinelli S. Mean platelet volume trend in sepsis: Is it a useful parameter? Minerva Anestesiol. 2006;72:749–56.
24. Shetty A, MacDonald SP, Williams JM, van Bockxmeer J, de Groot B, Esteve Cuevas LM, et al. Lactate ≥2 mmol/L plus qSOFA improves utility over qSOFA alone in emergency department patients presenting with suspected sepsis. Emerg Med Australas. 2017;29:626-34.
Download attachments: 10.4328ACAM.20079
Bedriye Müge Sönmez, Aysel Kocagül Çelikbaş. Sepsis-Related Mortality with SOFA and qSOFA in Emergency Department Patients. Ann Clin Anal Med 2020;11(5):359-364
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Determination of cancer antigen-125 level and its association with preeclampsia among Sudanese women
Amal Alaagib Karrar 1, Amna O. M. Elzein 2, Husham O. Elzein 3
1 Faculty of Medical laboratory Sciences, Al zaiem Al Azhari University, Khartoum, Sudan, 2 Department of clinical chemistry, faculty of Medical laboratory Sciences, Al zaiem Al Azhari University-Sudan, 3 Department of medical laboratory, faculty of applied medical sciences, Northern Border University, Arar, Saudi Arabia
DOI: 10.4328/ACAM.20081 Received: 2019-12-02 Accepted: 2020-01-21 Published Online: 2020-01-23 Printed: 2020-09-01 Ann Clin Anal Med 2020;11(5):416-419
Corresponding Author: Husham O.Elzein, Department of medical laboratory, faculty of applied medical sciences, Northern Border University, Arar, Saudi Arabia. E-mail: hushamelzein@hotmail.com T: 00966504924396 Corresponding Author ORCID ID: https://orcid.org/0000-0001-8517-0348
Aim: Cancer antigen 125 (CA-125) is suggested to correlate with preeclampsia. This study aimed to determine the association between CA-125 and pre- eclampsia in Sudan.
Material and Methods: The study included 40 normotensive women (Control group), and 40 women with preeclampsia, further subdivided into a mild group (n = 23), and severe group (n = 17). Venous blood was taken from all the participants, and determination of CA-125 level was carried out using the sandwich Enzyme-Linked Immunosorbent Assay (ELISA) technique according to the manufacturer’s instructions. Data were analyzed using statistical package for social sciences (SPSS-version11.5). Data were expressed in tables and figures as mean ± S.D. The T-test, One-way ANOVA were used to compare between the groups (cases and control). The Pearson’s correlation coefficient was used to assess the correlation between different variables.
Results: The current study showed a significant difference in the mean values of CA-125 in case (52.400±2.550) and control group (27.800±6.026 U/ml; p < 0.0001). Women with mild and severe preeclampsia had significantly higher levels of CA-125 (50.869±1.816, and 54.470±1.841 U/ml, respectively, p < 0.0001), than in control group. CA-125 levels in mild and severe cases were positively correlated with blood pressure (r = 0.7275, p < 0.0001), and proteinuria (r = 0.3740, p = 0.0174).
Discussion: This study suggests that CA-125 is an essential biochemical marker that should be used to detect the underlying inflammatory process of pre- eclampsia. Increased cancer antigen-125 level is associated with the severity of preeclampsia. The study confirmed that preeclampsia is positively correlated with blood pressure and proteinuria.
Keywords: Cancer Antigen-125; Preeclampsia; Sudan; ELISA
Introduction
Preeclampsia is a global pregnancy complication, it affects roughly 3% of pregnant women worldwide and responsible for the increased risk of maternal and fetal morbidity and mortality, universally [1- 4]. Preeclampsia has been subdivided into mild (blood pressure ≥140/90 and proteinuria ≥0.3 g/day), and severe (blood pressure ≥160/110 mm Hg and proteinuria is ≥ 5 g/day) after 20 weeks of gestation [5, 6]. The etiology of preeclampsia remains one of the medical obscurities [7, 8], however the indications demonstrated that inherited thrombophilic disorders during pregnancy, placental insufficiency with associated abnormalities such as inflammatory placental decidual vasculopathy, and abnormal trophoblastic invasion of the endometrium may play a role in its pathophysiology [9,10]. Cancer antigen 125 (CA-125) is a high molecular weight glycoprotein (110 to more than 2000kD), first identified in the 1980s by Bast et al. [11]. The normal range of serum CA125 level is less than 35 U/mL [12, 13]. Mainly CA125 is derived from the decidua and amniotic fluid; then it passes to the blood circulation in case of decidual cells damage through chorionic villus invasion in early gestation and during the separation of the placenta [14, 15]. Therefore continuous decidual destruction and separation of trophoblasts from the decidua are suggested to play a key role in the elevation of CA125 levels in women with preeclampsia [16]. Many previous studies have proposed that there is a positive correlation between serum CA125 concentration and preeclampsia [17-20]. So the main objective of this study is to determine the concentration of CA125 level in normotensive and preeclamptic Sudanese women, and then explore its association with the severity of preeclampsia.
Material and Methods
Ethical issue:
This study was approved by the research ethics board at the faculty of medical laboratory science, Alzaiem Alazhari University, Khartoum, Sudan. All enrolled participants signed the informed consent; data were collected on their medical history, socio-demographic and obstetrics characteristics using a structured questionnaire.
Study design:
This is a case-control study conducted at Omdurman maternity hospital and Soba university hospital, Khartoum state, Sudan, from March 2017 to June 2017. The subjects were enrolled in this study during and after 20 weeks of gestation and had similar socioeconomic backgrounds. The study groups included 40 healthy and normotensive pregnant women known as (Control group), and 40 women with preeclampsia (Case group), which further were subdivided into mild preeclampsia group (n = 23) when their blood pressure was >140/90 mmHg and a proteinuria >300 mg/day, and severe preeclampsia group (n = 17) if systolic blood pressure increased to at least 160 mmHg, diastolic blood pressure increased to at least 110 mmHg, and proteinuria >5 g/day [21].
Women with a history of ovarian cancer, endometrial cancer, breast cancer or benign conditions such as chronic hypertension, endometriosis, liver cirrhosis, renal disease, and, cardiovascular disease, were excluded from the study.
To obtain an appropriate serum sample, 3 ml fasting venous 417 | Annals of Clinical and Analytical Medicine blood was taken under all septic conditions from each group (case and control) of the study, in plain blood containers, and the sample was allowed to clot, then centrifuged at (3000 rpm) for 5 minutes. Serum samples were stored at (-20 °C) until the assay time of CA-125 using the Sandwich Enzyme- Linked Immunosorbent Assay (ELISA) technique according to the manufacturer’s instructions (Fortress Diagnostics Ltd, Unit 2C Antrim Technology Park, Antrim, BT411QS, UK).
Statistical analysis
Datawereenteredandanalyzedusingstatisticalpackagefor social sciences (SPSS-version16) on a programmed computer. Datawereexpressedasmean±S.D,andtheresultswereshown in tables. The t-test was used to compare between the two groups (cases and controls). While One-way ANOVA was used to compare the parametric variables of three groups (control, mild preeclampsia, and severe preeclampsia and Tukrey post- test were used for further multiple comparisons between the three groups. The Pearson’s correlation coefficient (Pearson’s r) was used to assess the correlation between different variables. A p-value of <0.05 was considered significant.
Results
As can be seen in Table 1 which compares the mean differences of the demographic and clinical characteristics between case and control group, the current study did not reveal any differences in the mean values for the participant’s age and gestational age between women with preeclampsia and control group. Our data generally showed a significant difference in the mean values of CA-125 level in case and control group as showed in Figure 1A. Women with severe preeclampsia had significantly higher levels of CA-125 in comparison with the levels of CA-125 in the control group Figure 1B. It was also found that serum level of CA-125 in women with mild preeclampsia revealed significant results in comparison with the control group as illustrated in Figure 1B. There was a positive correlation between CA-125 level and proteinuria, and also there was a positive correlation between CA-125 level and blood pressure in preeclampsia as shown in Figure 2A and Figure 2B, respectively.
Discussion
The current study indicates that there are no significant alterations in the maternal age, parity and gestational age, therefore confirming the demographic equivalence in the two groups (Case and control) of this study. There are a lot of studies around the relation of CA-125 with preeclampsia in the literature, but with contradictory results. In the current study, our data showed that there was a significant increase in the mean concentration of serum CA-125 level in mild and severe cases of preeclampsia when compared with control group (p < 0.0001), this finding may to some extent assume that the failure
in trophoblastic invasion and the induction of an inflammatory process within placenta may trigger the expression of CA-125. This result matching many previous studies suggested that CA- 125 is inspiring biochemical markers and can reveal the severity of the inflammatory process in preeclampsia [4, 23]. This study showed that the serum CA-125 level was significantly higher in the severe case group of preeclampsia when compared with the control group (p < 0.0001), and this finding agrees with the finding of Karaman et al’s. study [19].On the other hand, this study revealed a significant difference in CA-125 levels between mild preeclampsia and control group (p-value < 0.0001) which agrees with Cebesoy et al.’s study [20] that measured the serum CA-125 levels of women with severe preeclampsia, mild preeclampsia and found statistically significant high results compared to the control group (p < 0.001). In contrast, some previous studies did not find any significant differences in CA- 125 levels between severe and mild cases of preeclampsia group and control group as in Schröcksnadel et al. [24] study which considered as the first study to compare CA-125 levels of 50 normal pregnant women with 50 hypertensive pregnant women, but no significant findings were noted. The current study also verified the positive correlation between CA-125 level in mild and severe cases of preeclampsia with blood pressure (r = 0.7275, p < 0.0001), and proteinuria (r = 0.3740, p = 0.0174). Our study is hospital-based so there were some limitations including the sample size which may not represent the general population level. Further researches are needed to clear up the association of elevated serum CA-125 level in Sudanese women with preeclampsia.
Conclusion
The study concluded that the serum CA-125 level was significantly increased in preeclampsia when compared with the control group; therefore, increased maternal CA-125 levels may be associated with the increase manifestation of preeclampsia.
Acknowledgment
The authors would like to thank all the women who were included in this study, and the medical staff of Omdurman maternity hospital and Soba university hospital for their cooperation.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
1. Hutcheon JA, Lisonkova S, Joseph KS. Epidemiology of pre-eclampsia and the other hypertensive disorders of pregnancy. Best Pract Res Clin Obstet Gynaecol. 2011;25(4):391-403.
2. Abalos E, Cuesta C, Carroli G, Qureshi Z, Widmer M, Vogel JP, et al. WHO Multicountry Survey on Maternal and Newborn Health Research Network. Pre- eclampsia, eclampsia and adverse maternal and perinatal outcomes: a secondary analysis of the World H ealth O rganization Multicountry S urvey on M aternal and N ewborn Health. BJOG. 2014;121(Suppl. 1):14-24.
3. English FA, Kenny LC, McCarthy FP. Risk factors and effective management of preeclampsia. Integr Blood Press Control. 2015;8:7-12.
4. Liberis A, Stanulov G, Ali EC, Hassan A, Pagalos A, Kontomanolis EN. Pre- eclampsia and the vascular endothelial growth factor: a new aspect. Clin Exp Obstet Gynecol. 2016;43(1):9-13.
5. Abalos E, Cuesta C, Grosso AL, Chou D, Say L. Global and regional estimates of preeclampsia and eclampsia: a systematic review. Eur J Obstet Gynecol Reprod Biol. 2013;170(1):1-7.
6. Lo JO, Mission JF, Caughey AB. Hypertensive disease of pregnancy and maternal mortality. Curr Opin Obstet Gynecol. 2013;25(2):124-32.
7. Gagnon A, Wilson RD, Audibert F, Allen VM, Blight C, Brock JA, et al. Obstetrical complications associated with abnormal maternal serum markers analytes. J Obstet Gynaecol Can. 2008;30(10):918-32.
8. Huppertz B. The critical role of abnormal trophoblast development in the etiology of preeclampsia. Curr Pharm Biotechnol. 2018;19(10):771-80.
9. Ahmed NA, Adam I, Elzaki SE, Awooda HA, Hamdan HZ. Factor-V Leiden G1691A and prothrombin G20210A polymorphisms in Sudanese women with preeclampsia, a case-control study. BMC medical genetics. 2019;20(1):2.
10. Hladunewich M, Karumanchi SA, Lafayette R. Pathophysiology of the clinical manifestations of preeclampsia. Clin J Am Soc Nephrol. 2007;2(3):543-9.
11. Bast RC, Feeney M, Lazarus HE, Nadler LM, Colvin RB, Knapp RC. Reactivity of a
monoclonal antibody with human ovarian carcinoma. J Clin Invest. 1981;68(5):1331-7.
12. Draghici S, Chatterjee M, Tainsky MA. Epitomics: serum screening for the early detection of cancer on microarrays using complex panels of tumor antigens. Expert Rev Mol Diagn. 2005;5(5):735-43.
13. Zhang Z, Bast RC, Yu Y, Li J, Sokoll LJ, Rai AJ, et al. Three biomarkers identified from serum proteomic analysis for the detection of early stage ovarian cancer. Cancer Res. 2004;64(16):5882-90.
14. Ayaty S, Vahid Roudsari F, Tavassoly F. CA-125 in normal pregnancy and threatened abortion. Int J Reprod Biomed (Yazd). 2007;5(2):57-60.
15. Weiland F, Fritz K, Oehler MK, Hoffmann P. Methods for identification of CA125 from ovarian cancer ascites by high resolution mass spectrometry. Int J Mol Sci. 2012;13(8):9942-58.
16. Tyler C, Kapur A, Felder M, Belisle JA, Trautman C, Gubbels JA, et al. The Mucin MUC 16 (CA 125) Binds to NK Cells and Monocytes from Peripheral Blood of Women with Healthy Pregnancy and Preeclampsia. Am J Reprod Immunol. 2012;68(1):28-37.
17. Ibrahem W, Al-Assaly RK, Al-Haddad NS. CA-125, plasma fibrinogen and C-reactive protein in correlation with severity of preeclampsia. J Fac Med Baghdad. 2017;59(1):31-5.
18. Santulli P, Streuli I, Melonio I, Marcellin L, M’Baye M, Bititi A, et al.Increased serum cancer antigen-125 is a marker for severity of deep endometriosis. J Minim Invasive Gynecol. 2015;22(2):275-84.
19. Karaman E, Karaman Y, Alkış İ, Han A, Yıldırım G, Ark HC. Maternal serum CA-125 level is elevated in severe preeclampsia. Pregnancy Hypertens: An International Journal of Women’s Cardiovascular Health. 2014;4(1):29-33.
20. Cebesoy FB, Balat O, Dikensoy E, Kalayci H, Ibar Y. CA-125 and CRP are elevated in preeclampsia. Hypertens Pregnancy. 2009;28(2):201-11.
21. American College of Obstetricians and Gynecologists. Report of the national high blood pressure education program working group on high blood pressure in pregnancy. Am J Obstet Gynecol. 2000; 183(1):S1-22.
22. Ozat M, Kanat-Pektas M, Yenicesu O, Gungor T, Danisman N, Mollamahmutoglu L. Serum concentrations of CA-125 in normal and preeclamptic pregnancies. Arch Gynecol Obstet. 2011;284(3):607-12.
23. Cebesoy FB, Balat O, Dikensoy E, Kalayci H, Ibar Y. CA-125 and CRP are elevated in preeclampsia. Hypertens Pregnancy. 2009;28(2):201-11.
24. Schröcksnadel H, Daxenbichler G, Artner E, Steckel-Berger G, Dapunt O. Tumor markers in hypertensive disorders of pregnancy. Gynecol Obstet Invest. 1993;35(4):204-8.
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Amal Alaagib Karrar, Amna O.M.Elzein, Husham O.Elzein. Determination of cancer antigen-125 level and its association with preeclampsia among Sudanese women. Ann Clin Anal Med 2020;11(5):416-419
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Investigation of lifestyle behaviors of women with and without stress urinary incontinence
Gizem Galioğlu Çiftçioğlu 1, Ayşe Nur Tunalı 2, Müberra Tanrıverdi 3
1 Enstitute of Health Sciences, Haliç University, İstanbul, Turkey, 2 Department of Physiotherapy and Rehabilitation, Faculty of Health Sciences, Eastern Mediterranean University, Famagusta, North Cyprus, 3 Department of Physiotherapy and Rehabilitation, Faculty of Health Sciences, Bezmialem Vakıf University, İstanbul, Turkey
DOI: 10.4328/ACAM.20086 Received: 2019-12-06 Accepted: 2020-01-15 Published Online: 2020-01-20 Printed: 2020-09-01 Ann Clin Anal Med 2020;11(5):395-401
Corresponding Author: Müberra Tanrıverdi, Department of Physiotherapy and Rehabilitation, Faculty of Health Sciences, Bezmialem Vakıf University, İstanbul, Turkey. E-mail: mtanriverdi@bezmialem.edu.tr GSM: +90 533 604 61 88 Corresponding Author ORCID ID: https://orcid.org/0000-0002-7770-9718
Aim: The aim of this study was to compare the lifestyle behaviors of women with and without stress urinary incontinence (SUI), and to investigate the effects of lifestyle behaviors on SUI.
Material and Methods: The study included 30 women who were diagnosed with SUI, 25-50 years old, who agreed to participate in the study voluntarily and 30 healthy women who met our study criteria with a total of 60 women. The data were evaluated using a questionnaire including demographic information and urinary incontinence risk factors of the women prepared by the researcher, and healthy lifestyle behaviors by Healthy Lifestyle Behavior Scale-II (HLBS-II), SUI by International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF).
Results: When the HLBS-II scores of the groups were examined, it was observed that the scores of the group with SUI were lower and a statistically significant difference was found between the groups (p<0.005). There was a negative statistically significant relationship between the total score HLBS-II and total score ICIQ-SF (p=0.026).
Discussion: As a result, healthy lifestyle behaviors are associated with SUI, and will affect the lifestyle positively.
Keywords: Behavior; Female; Healthy Lifestyle; Urinary Incontinence
Introduction
Urinary incontinence (UI) is defined by the International Continence Society (ICS) in 2002 as ‘’complaint of involuntary incontinence of any kind, regardless of quantity’’ in standardization report on terminology [1]. According to the literature, although urinary incontinence is a common problem especially after middle age, it is a chronic condition experienced by women of all ages and negatively affects the quality of life. While urge or mixed type incontinence is seen more frequently with older age, stress type incontinence is seen more frequently in young women [2]. It is reported that more than 200 million individuals worldwide have incontinence problems and the majority of them are women and the most common type is stress incontinence [3]. Presence of stress incontinence most seen in women aged 25-49 years, and the incidence of urge and mixed urinary incontinence increases with age [4].
Among the risk factors of urinary incontinence in women, behavioral risk factors are associated with individuals’ lifestyle choices and are thought to be less common in individuals who have adopted a healthier lifestyle. Healthy lifestyle behaviors emphasize the awareness of an individual health. Regular exercise, proper sleep, regular and balanced nutrition, and good communication in social relations are examples of healthy lifestyle behaviors [5].
There are many studies in the literature on healthy lifestyle behaviors. The individuals selected in the studies were mostly university students and healthcare professionals from different fields. The number of studies conducted on women with biological, psychological, social aspects and characteristics different from men remained inadequate. Studies have shown that individuals’ health status is associated with lifestyle behaviors. However, it has not been investigated that healthy lifestyle behaviors are effective in preventing the occurrence of chronic diseases. Healthy lifestyle behaviors contribute to the prevention of many chronic diseases such as urinary incontinence and/or the prognosis of these diseases in a positive way [6]. Our study aims to determine the lifestyle changes in women with stress urinary incontinence to compare them with healthy women and to raise awareness about these differences.
Material and Methods
Design
Our study was completed in accordance with the Helsinki Declaration Rules and approved by our university’s Non- Interventional Ethics Committee on 28/02/2019 and numbered 46. Informed consent form was obtained from the women who volunteered to participate in the study. Our study is a questionnaire survey that includes a healthy control group. Participants
The study was conducted face to face with a total of 60 participants. Thirty women diagnosed with stress urinary incontinence in the gynecology department of the hospital between 25-50 years of age who agreed to participate in the study voluntarily and 30 healthy women who match the inclusion criteria were included in the study.
Inclusion criteria were as follows: 25-50 years of age; voluntarily agree to participate in the study; diagnosis of stress urinary
incontinence made by the physician.
Exclusion criteria were as follows: the presence of urinary incontinence due to neurological disease in addition to stress urinary incontinence; having undergone gynecological surgery; insufficient cooperation.
Evaluation Criteria included researcher questionnaire including demographic information and urinary incontinence risk factors prepared by the researcher, 3 questionnaires including Healthy Lifestyle Behavior Scale II (HLBS-II) to evaluate healthy lifestyle behaviors, International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) to assess stress urinary incontinence which were filled in a face-to-face interview under the supervision of the researcher.
Researcher Questionnaire is a form prepared by the researcher and prepared by considering the subjects we intend to evaluate in the participants. Demographic information, educational and occupational information, marital status and obstetric history, assessment of existing health problems, physical activity and sports status, smoking and fluid consumption habits were recorded.
Healthy Lifestyle Behavior Scale II (HLBS-II): Healthy Lifestyle Behaviors Scale measures how much an individual adopts healthy lifestyle behaviors. The validity and reliability study of HLBS-II was performed by Bahar et al. [7]. The subtitles of the scale are Health Responsibility, Physical Activity, Nutrition, Spiritual Development, Interpersonal Relations and Stress Management. Each subheading can be used as a stand-alone assessment method. Individuals answer the scale questions on healthy lifestyle behaviors by marking one of the rating statements that they think is appropriate for them. The rating was made as a 4-point likert. The answers are given 1 for the “never” response, 2 for the “sometimes” response, 3 for the “frequent” response, and 4 for the “regular” response. The lowest total score was 52 and the highest total score was 208. As the total score increases, it is accepted that individuals have healthier lifestyle behaviors.
International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF Turkish Version) is an assessment scale developed and approved by ICS for the purpose of creating a questionnaire that will demonstrate in detail all aspects of urinary incontinence and its impact on quality of life for use in research. Validity and reliability of the Turkish version was studied by Çetinel et al [8]. This questionnaire is used to determine the presence, severity, frequency and type of incontinence and to understand the situations in which it occurs. It may also indicate the extent to which urinary incontinence affects an individual’s quality of life. It consists of 6 questions. The first 2 questions include date of birth and gender. ICIQ Total Score is the total score of the 3rd, 4th and 5th questions, scored between 0 and 21. The higher the score, the more the impact indicates. The sixth question includes questions to determine in which cases urinary incontinence occurs.
Statistical analysis
In the data analysis of the study, Package Statistical Package for Social Sciences (SPSS) Version 22.0 (SPSS inc. Chicago Province USA) statistical program was used. “One sample Kolmogorov-Smirnov” test was used to determine whether the distribution of the data groups was normal in order to select the appropriate advanced statistical analyzes in the data analysis of the study. The baseline demographic characteristics and questionnaire measurements of both groups were compared with “Independent Samples t-Test“ and “Student t-Test”. The comparison of categorical data was performed with the Chi- Square test. Parametric variables were expressed as mean ± standard deviation (mean ± SD) and descriptive variables were expressed as percentages. In all analyzes, p <0.05 (bidirectional) values were considered statistically significant.
Results
The results of the researcher questionnaire evaluation according to the groups and the comparison between the groups is shown in Table 1, HLBS-II scores and the comparison of the groups in Table 2, ICIQ-SF questionnaire total score and subcategories, and total score and subscales. The relationship results were shown in Table 3.
There was no statistically significant relationship between ICIQ- SF3 incontinance incidence frequency and height (p = 0.893), weight (p = 0.264), and BMI (p = 0.189) in the study group (p> 0.005). There was a statistically significant relationship between age (p = 0.001) and ICIQ-SF3 incontinance incidence frequency (p <0.005). There was no statistically significant relationship between ICIQ-SF4 urinary incontinence score and age (p = 0.862), height (p = 0.595), weight (p = 0.887), BMI (p = 0.975) of the study group (p> 0.005). There was no statistically significant relationship between ICIQ-SF5 urinary incontinence effect on daily life score and age (p = 0.300), height (p = 0.176), weight (p = 0.489) and BMI (p = 0.913) in the study group (p > 0.913). There was no statistically significant relationship between ICIQ-SF total score and height (p = 0.311), weight (p = 0.266), and BMI (p = 0.521) in the study group (p > 0.005). There was a statistically significant relationship between age (p = 0.022) and ICIQ-SF total score (p < 0.005). There was no statistically significant relationship between ICIQ-SF6 urinary incontinence score and height (p = 0.645), weight (p = 0.112) and BMI (p = 0.084) in the study group (p> 0.005). There was a statistically significant relationship between age (p = 0.002) and ICIQ-SF6 urinary incontinence score (p < 0.005). In our study, ICIQ-SF questionnaire score was 0 in the control group and was not included in the comparison. There was a statistically significant relationship between ICIQ-SF3 incontinence frequency score and educational status (p = 0.027), occupation (p = 0.037), and sitting time during work (p = 0.037) in the study group (p < 0.005). There was no statistically significant relationship between income statuses (p = 0.258). There was no statistically significant relationship between ICIQ-SF4 urinary incontinence quantity score and education status (p = 0.648), occupation (p = 0.127), sitting time during work (p = 0.182), income status (p = 0.096) in the study group (p > 0.005). There was a statistically significant relationship between ICIQ-SF5 urinary incontinence and effect on daily living score of study group (p = 0.816), occupation (p = 0.568), sitting time during work (p = 0.550) and income (p = 0.477). There was no statistically significant relationship between ICIQ-SF total score and educational status (p = 0.310), occupation (p = 0.516), sitting time during work (p = 0.549), income status (p = 0.855) of the study group. There was no statistically significant relationship between ICIQ-SF6 urinary incontinence score and education status (p = 0.066), occupation (p = 0.817), sitting time during work (p = 0.481), income status (p = 0.989) in the study group (p > 0.005). There was no statistically significant relationship between ICIQ-SF3 incontinance frequency and marital status (p = 0.584) and cesarean delivery (p = 0.611) in the study group. There was a statistically significant relationship between the number of births (p = 0.001), delivery type (p = 0.001), normal birth (p = 0.001) and menopause (p = 0.004). There was no statistically significant relationship between ICIQ-SF4 incontinence quantity and marital status (p = 0.438), number of births (p = 0.067), normal birth (p = 0.485), and menopause (p = 0.745). There was a statistically significant relationship between type of delivery (p = 0.043) and cesarean section (p = 0.022). Marital status (p = 0.729), number of deliveries (p = 0.162), delivery type (p = 0.960), normal delivery (p = 0.065), cesarean section (p = 0.485) and the effect of ICIQ-SF5 urinary incontinence on daily life of the study group subjects, menopause (p = 0.242). There was no statistically significant relationship between ICIQ-SF total score and marital status (p = 0.875), delivery type (p = 0.105), cesarean delivery (p = 0.983) in the study group. There was a statistically significant relationship between the number of births (p = 0.005), normal birth (p = 0.003) and menopause (p = 0.038). The relationship between ICIQ-SF6 urinary incontinence and marital status (p = 0.394), delivery type (p = 0.332), normal delivery (p = 0.054), cesarean section (p = 0.540) and menopause (p = 0.086) between the study group cases no statistically significant relationship was found (p> 0.005). There was a statistically significant relationship between the number of births (p = 0.028). There were no statistically significant differences between ICIQ-SF3, ICIQ-SF4, ICIQ-SF5, ICIQ-SF Total, ICIQ-SF6 scores and regular sports, duration of sports, presence of chronic disease, presence of constipation and frequent urinary tract infection (p > 0.05). There was no statistically significant relationship between ICIQ-SF3, ICIQ- SF4, ICIQ-SF5, ICIQ-SF Total, ICIQ-SF6 and cigarette use, water consumption, tea consumption, coffee consumption, acidic / carbonated beverage consumption (p > 0.05). When ICIQ-SF3 frequency of incontinence was evaluated in the study group, 26.7 % once or less than once a week, 43.3 % 2-3 times a week, 16.7 % once a day, 13.3 % urinary incontinence several times a day (p = 0.001). When the ICIQ-SF4 urinary incontinence quantity was examined, 96.7 % of the study group patients had a small amount and 3.3 % of them had moderate incontinence (p = 0.001). ICIQ-SF6 incontinence was examined, it was found that 43.3 % of the study group cases had coughing and / or sneezing, 10 % were on the move and / or doing sports, and 46.7% had incontinence in both cases ( p = 0.001). There was a statistically significant relationship between ICIQ-SF total score and ICIQ-SF3 urinary incontinence and the effect of ICIQ- SF5 urinary incontinence on daily life (p = 0.001).
Discussion
The aim of this study was to investigate the healthy lifestyle behaviors of women with and without stress urinary incontinence and to compare the relationship of these behaviors with incontinence and to raise awareness about the possibility that lifestyle behaviors may cause urinary incontinence problem.
It was found that women with more healthy lifestyle behaviors have less stress urinary incontinence.
Fat tissue accumulated in the body due to excess weight and obesity regularly causes intra-abdominal pressure, causing stress-type urinary incontinence. BMI increases in proportion to weight. Studies have reported that the incidence of urinary incontinence is more common in overweight and obese individuals with high BMI, and that stress is the most common cause of urinary incontinence [9-11]. In our study, the mean BMI values found to be 26.38 kg/m2 in the study group, 21.34 kg/ m2 in the control group. There was a statistically significant difference between the groups in BMI. Our study is consistent with the studies in which the above mentioned BMI increase leads to urinary incontinence and shows parallelism to the literature.
There are different findings in the relationship between education level and urinary incontinence in the literature. Along with studies indicating that there is no relationship between education level and urinary incontinence [10, 12] there are also studies indicating that the incidence of urinary incontinence is higher in women with low educational level [13-15]. In our study, there was no significant relationship between education level and SUI. The reason for this is the scores of the study and control group were close to each other.
There are differences in the relationship between income status and urinary incontinence. In response to studies indicating that income status is not associated with urinary incontinence [16] in our study, occupational and income status were found to be statistically related to urinary incontinence. As a reason of difference thought that the participants of control group have higher occupation level and income status. There are differences in the relationship between marital status and urinary incontinence. Fritel et al. In their study, no significant relationship was found between marital status and urinary incontinence [12]. In our study, no significant difference was found between the groups.
Studies show that women who gave birth multiple times have a higher rate of stress urinary incontinence than women who have not given birth. It is reported that the prevalence of urinary incontinence increases with each additional delivery after the first delivery [2, 18]. In our study, the relationship between the number of births and stress urinary incontinence was found to be significant and consistent with the literature. It is stated that there is a close relationship between the delivery type and urinary incontinence. It is determined that normal birth causes urinary incontinence more compared to c-section birth. Caesarean delivery has a protective effect in stress incontinence [3, 17, 19]. Rortveit et al. reported that the rate of delivery was higher in those with normal delivery type compared to those with cesarean section [20]. In our study, no significant relationship was found between marital status and menopause and urinary incontinence. Studies with a close relationship between urinary incontinence and menopause have been found in the literature [20]. Our study is not compatible with the literature. Since the sample group was selected from the premenopausal period, it was thought that the small number of menopausal participants had an effect on this.
In literature, systemic diseases such as congestive heart failure, diabetes mellitus, diabetes insipitus, and chronic obstructive pulmonary disease-causing chronic cough cause urinary incontinence [12, 14, 21]. In the study group of our study, diabetes mellitus was found in 1 participant. In our study, no significant relationship was found between the presence of chronic disease and regular drug use and stress urinary incontinence. The reason for this is thought to be due to the presence of chronic diseases in a small number of participants and the absence of drugs in the risk group causing urinary incontinence.
Recurrent bladder infections are risk factors for urinary incontinence. The increased incidence of urinary incontinence in women with frequent urinary tract infections most often associated with stress and urge type incontinence [11, 17]. It has been reported that the prevalence of urinary incontinence is high in women with frequent urinary tract inflammation [14, 20, 22]. Gunhilde et al. in their study, found that women with urinary tract infection had a higher rate of stress urinary incontinence [9]. In our study, the relationship between frequent urinary tract infection and stress urinary incontinence was found to be statistically significant and consistent with the studies.
The presence of constipation leads to increased intra-abdominal pressure by straining during defecation. If this condition is experienced for a long time, it causes tension in the pelvic nerves. Constipation causes stress and urge type incontinence mostly [15]. Constipation has been reported to increase urinary incontinence [22, 23]. In our study, the relationship between the presence of constipation and stress urinary incontinence was found to be statistically significant, and the result was parallel to the literature.
Stress urinary incontinence was found to be lower in women with higher levels of physical activity, but it was found that women with stress urinary incontinence did not prefer some physical activities and decreased physical activities [24, 25]. Nygaard et al. in their study, has found that physical activity such as jumping increased the incidence of stress urinary incontinence [26]. In our study, the relationship between regular exercises and sport duration and stress urinary incontinence was found to be statistically significant; 66.72 % of the control group did regular sports and weekly sports duration was 4.26 hours; It was determined that 23.3 % of the study group did regular sports and weekly sports duration was 0.60 hours. It was found that the control group had more regular sports and the duration of sports was longer. In our study, the participants were asked about the type of sport and control group participants preferred pilates, yoga, jogging and zumba sports, and the study group preferred regular walking. The reason for this is thought to be that individuals with stress urinary incontinence do not prefer coercive activities.
Smoking disrupts estrogen levels and leads to a decrease in collagen synthesis. Smoking causes all types of urinary incontinence. Smoking leads to chronic cough and increases intra-abdominal pressure and stress causes urinary incontinence [24]. In our study, the relationship between smoking and stress urinary incontinence was insignificant. The reason for this is thought to be related to the fact that smoking and smoking rates were parallel in the study and control groups.
In the literature, it has been found that consuming caffeine-containing beverages such as coffee is a bladder irritant and may cause involuntary detrusor contractions, leading to urinary incontinence. Inadequate fluid intake increases urine density, irritating the bladder and urethra, resulting in more frequent incontinence and constipation. It is emphasized that at least 1.5 liters of water should be consumed daily in order to prevent urinary incontinence [27]. Gleason et al. [28] found the relationship between caffeine consumption and urinary incontinence, Hannestad et al. [24] found a significant relationship between urinary incontinence and tea consumption, although Hirayama et al. did not find a significant relationship between caffeine consumption and urinary incontinence in their study [29]. In our study, no significant relationship was found between coffee and tea consumption and stress urinary incontinence. The reason for this is thought to be the similarity of the consumption amounts of the study and control groups and the type of coffee consumed is not known. Detailed research on this subject is recommended. Ge et al. reported that reducing daily water consumption leads to urinary incontinence [15]. Hu et al. and O’Neil et al. in their studies, found that high consumption of high-sugar drinks containing carbonated beverages by increasing weight gain has affected many chronic diseases such as stress urinary incontinence [5, 6]. In our study, the relationship between water consumption and acid/carbonated beverage consumption and stress urinary incontinence was found to be significant. It is seen that 83.4 % of the study group consumed 1.5 lt and below water and this is thought to be the reason of general habits.
If we look at the studies carried out using HLBS-II in our country, these studies were conducted in different groups such as women, teachers, teaching staff, assistants, nurses, health workers, university students, housewives, pregnant women, elderly people and were not examined in cases with urinary incontinence. In our study, two groups with and without stress urinary incontinence were investigated and no other study investigating HLBS-II in patients with urinary incontinence was found. In our study, it was found that the total score of the HLBS-II was low in the study group as 108.77 ± 10.94, and the control group had a moderate score of 148.43 ± 15.19. In most of the studies conducted on women in our country, the total score of HLBS-II was found to be low and moderate as in our study, and our study is parallel to literature. In our study, the lowest score in the study group was 11.80 ± 3.05, and this was thought to be related to the fact that women had low habit of exercising and did not prefer to exercise for individual and cultural reasons.
When ICIQ-SF3 incontinence frequency is examined, in a study of women aged 18 and over; 45.9 % of women reported that they leak urine less than two times a week, 17.4 % 2-3 times a week, 9.9 % once a day, 13.2 % several times a day [11]. In our study, when the frequency of ICIQ-SF3 urinary incontinence in the study group was examined, 26.7 % was 1 week or less, 43.3 % was 2-3 times a week, 16.7 % was once a day, 13.3 % few have been found to leak a few times per day. When ICIQ-SF4 incontinence quantity is examined, 96.7 % of the study group is incontinent and our results are consistent with the literature. Looking at the effect of ICIQ-SF5 incontinence on daily life, the mean score of the study group was found to be 4.5, and as stated in the literature, quality of life was poorly affected. In our study, when the effects of stress urinary incontinence on quality of life were examined, the overall effect of women’s quality of life was found to be low and moderate. Looking at ICIQ-SF6 incontinence cases, 43.3 % of the study group was found to have coughing and/or sneezing, 10 % while on the move and / or doing sports, and 46.7 % of them were leaking in both cases an it is consistent with stress urinary incontinence findings. Conclusion
Choosing healthy lifestyle behaviors positively affects stress urinary incontinence. Stress urinary incontinence is affected by age, BMI, occupation, income status, number of births, mode of delivery, duration of marriage, presence of constipation, frequency of urinary tract infection, regular exercise, duration of sports, water consumption and acid / carbonated beverage parameters. In women with stress urinary incontinence, the quality of life of women with high health responsibility scores was less affected.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
1. Abrams P, Cardozo L, Fall M, Griffiths D, Rosier P, Ulmsten U, et al. The standardisation of terminology of lower urinary tract function: report from the Standardisation Sub-committee of the International Continence Society. Neurourology and Urodynamics: Official Journal of the International Continence Society 2002; 21(2), 167-78. DOI:10.1002/nau.10052
2. Luber KM. The definition, prevalence, and risk factors for stress urinary incontinence. Rev Urol. 2004; 6(Suppl. 3): S3.
3. Norton P, Brubaker L. Urinary incontinence in women. The Lancet. 2006; 367(9504): 57-67. DOI:10.1016/S0140-6736(06)67925-7
4. Hannestad YS, Rortveit G, Sandvik H, Hunskaar S. A community-based epidemiological survey of female urinary incontinence: The Norwegian EPİNCONT Study. J Clin Epidemiol. 2000; 53(11): 1150-57. DOI:10.1016/S0895- 4356(00)00232-8
5. Hu FB, Liu Y, Willett WC. Preventing chronic diseases by promoting healthy diet and lifestyle: public policy implications for China. Obes Rev. 2011; 12(7): 552-9. DOI:10.1111/j.1467-789X.2011.00863.x
6. O’Neil CE, Deshmukh-Taskar P, Mendoza JA, Nicklas TA, Liu Y, Relyea G, et al. Dietary, Lifestyle and Health Correlates of Overweight and Obesity in Adults 19 to 39 Years of Age: The Bogalusa Heart Study. Am J Lifestyle Med. 2012; 6(4): 347-58. DOI:10.1177/1559827611404923
7. Bahar Z, Beşer A, Gördes N, Ersin F, Kıssal A. Sağlıklı yaşam biçimi davranışları ölçeği II’nin geçerlik ve güvenirlik çalışması (The validity and reliability study of healthy lifestyle behaviors scale II). Cumhuriyet Üniversitesi Hemşirelik Yüksekokulu Dergisi/ Journal of Republic University School of Nursing. 2008; 12(1): 1-13.
8. Çetinel B, Özkan B, Can G. ICIQ-SF Türkçe versiyonu validasyon (geçerlilik) çalışması (ICIQ-SF Turkish version validation study). Türk Üroloji Dergisi/ Turkish Journal of Urology. 2004; 30(3): 332-8.
9. Gunhilde GM, Chin M, Glantz C, Guzick D. Prevalence of urinary incontinence and associated risk factors in a cohort of nuns. Obstet Gynecol. 2002; 100(2): 226-9.DOI:10.1016/S0029-7844(02)02076-8
10. Sampselle CM, Harlow SD, Skurnick J, Brubaker L, Bondarenko I. Urinary incontinence predictors and life impact in ethnically diverse perimenopausal women. Obstet Gynecol. 2002; 100(6): 1230-38. DOI:10.1016/S0029- 7844(02)02241-X
11. Kocak I, Okyay P, Dundar M, Erol H, Beser E. Female urinary incontinence in the west of turkey: prevalence, risk factors and impact on quality of life. Eur Urol. 2005; 48(4): 634-41. DOI:10.1016/j.eururo.2005.04.017
12. Fritel X, Ringa V, Varnoux N, Fauconnier A, Piault S, Bréart G. Mode of delivery and severe stress incontinence. A cross-sectional study among 2625 perimenopausal women. BJOG: An International Journal of Obstetrics & Gynaecology. 2005; 112(12): 1646-51. DOI:10.1111/j.1471-0528.2005.00763.x
13. Özerdoğan N, Beji NK, Yalçın O. Urinary Incontinence: Its Prevalence, Risk Factors and Effects on the Quality of Life of Women Living in a Region of Turkey. Gynecol Obstet Invest. 2004; 58(3):145-50. DOI:10.1159/000079422
14. Liu B, Wang L, Huang SS, Wu Q, Wu DL. Prevalence and risk factors of urinary incontinence among Chinese women in Shanghai. Int J Clin Exp Med. 2014; 7(3): 686.
15. Ge J, Yang P, Zhang Y, Li X, Wang Q, Lu Y. Prevalence and risk factors of urinary incontinence in Chinese women: a population-based study. Asia Pac J Public Health. 2015 27(2): NP1118-31. DOI:10.1177/1010539511429370
16. Jahanlu D, Qureshi SA, Hunskaar S. The Hordaland Women’s Cohort: a prospective cohort study of incontinence, other urinary tract symptoms and related health issues in middle-aged women. BMC Public Health. 2008; 8(1): 296. DOI:10.1186/1471-2458-8-296
17. Parazzini F, Colli E, Origgi G, Surace M, Bianchi M, Benzi G, et al. Risk factors for urinary incontinence in women. Eur Urol. 2000; 37(6): 637-43. DOI:10.1159/000020231
18. Stothers L, Friedman B. Risk factors for the development of stress urinary incontinence in women. Curr Urol Rep. 2011; 12(5): 363-9. DOI:10.1007/s11934- 011-0215-z
19. Farrell SA, Allen VM, Baskett TF. Parturition and urinary incontinence in primiparas. Obstet Gynecol. 2001; 97(3): 350-6. DOI:10.1016/S0029- 7844(00)01164-9
20. Rortveit G, Daltveit AK, Hannestad YS, Hunskaar S. Norwegian EPINCONT Study. Urinary incontinence after vaginal delivery or cesarean section. N Engl J Med. 2003; 348(10): 900-7. DOI:10.1056/NEJMoa021788
21. Danfort KN, Townsend MK, Lifford K, Curhan GC, Resnick NM, Grodstein F. Risk factor for urinary incontinence among middle-aged women. Am J Obstet Gynecol. 2006; 194(2): 339-45. DOI:10.1016/j.ajog.2005.07.051
22. Bodhare TN, Valsangkar S, Bele SD. An epidemiological study of urinary incontinence and its impact on quality of life among women aged 35 years and above in a rural area. IJ U: IJU: Journal of the Urological Society of India. 2010; 26(3): 353. DOI:10.4103/0970-1591.70566
23. Lian WQ, Li FJ, Huang HX, Zheng YQ, Chen LH. Constipation and risk of urinary incontinence in women: a meta-analysis. Internat Urogynecol J. 2019; 30(10):1629–34. DOI:10.1007/s00192-019-03941-w
24. Hannestad YS, Rortveit G, Daltveit AK, Hunskaar S. Are smoking and other lifestyle factors associated with female urinary incontinence? The Norwegian EPİNCONT Study. BJOG: An International Journal of Obstetric and Gynaecology. 2003; 110(3): 247-54. DOI:10.1046/j.1471-0528.2003.02327.x
25. Carvalhais A, Da Roza T, Vilela S, Jorge RN, Bø K. Association between physical activity level and pelvic floor muscle variables in women. Int J Sports Med. 2018; 39(13): 995-1000. DOI:10.1055/a-0596-7531
26. Nygaard IE, Shaw JM, Bardsley T, Egger MJ. Lifetime physical activity and female stress urinary incontinence. Am J Obstet Gynecol. 2015; 213(1): 40.e1-40. e10. DOI:10.1016/j.ajog.2015.01.044
27. Stach-Lempinen B, Hakala AL, Laippala P, Lehtinen K, Metsanoja R, Kujansu, E. Severe depression determines quality of life in urinary incontinent women. Neurourol Urodyn. 2003; 22(6): 563-8. DOI:10.1002/nau.10137
28. Gleason JL, Richter HE, Redden DT, Goode PS, Burgio KL, Markland AD. Caffeine and urinary incontinence in US women. Int Urogynecol J. 2013; 24(2): 295-302. DOI:10.1007/s00192-012-1829-5
29. Hirayama F, Lee AH. Is caffeine intake associated with urinary incontinence in Japanese adults? J Prev Med Public Health. 2012; 45(3): 204. DOI:10.3961/ jpmph.2012.45.3.204
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Gizem Galioğlu Çiftçioğlu, Ayşe Nur Tunalı, Müberra Tanrıverdi. Investigation of lifestyle behaviors of women with and without stress urinary incontinence. Ann Clin Anal Med 2020;11(5):395-401
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Relationship between mannose-binding lectin and febrile neutropenia in acute leukemia patients
Selcuk Akan 1, Sule Mine Bakanay 2, Yusuf Bilen 3, MD Baran Balcan 4, Fuat Erdem 3
1 Internal Medicine Department, Ankara Cıty Hospital, Ankara, 2 Hematology Department, Ankara Yıldırım Beyazıt University Medical School, Ankara Cıty Hospital Ankara, 3 Adıyaman University, Adıyaman Training and Research Hospital, Hematology, Adıyaman, 4 Department of Chest Diseases, Baskent University Istanbul Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.20088 Received: 2019-12-11 Accepted: 2020-01-12 Published Online: 2020-01-20 Printed: 2020-09-01 Ann Clin Anal Med 2020;11(5):402-405
Corresponding Author: Selcuk Akan, Internal Medicine Department, Ankara City Hospital, Bilkent, Ankara, Turkey. E-mail: dr_selcukakan@hotmail.com GSM :+90 5464745678 Corresponding Author ORCID ID: https://orcid.org/0000-0002-5053-6896
Aim: Mannose-binding lectin (MBL) is an important component of the natural immune system. Its low levels have been linked to increased frequency of oppor- tunistic infections. This study aimed to determine the association of serum MBL levels and duration of febrile neutropenia (FN) after cytotoxic chemotherapy in patients with acute leukemia.
Material and Methods: Seventy patients aged 15-75 years with acute leukemia (40 AML (Acute myeloid leukemia), 30 ALL (Acute lymphoblastic leukemia)), and 30 age-matched healthy subjects were included in this study. Blood MBL levels were measured using ELISA Kit before chemotherapy (MBL1) and at FN (MBL2).
Results: The MBL1 levels of the patient group (Median 466 ng/ml; interquartile range (iqr): 4507) were higher than that of the control group (Median 485 ng/ml; iqr: 1872), but this difference was statistically insignificant (p=0.92). During FN, MBL levels of 49 (70%) patients increased and 21 (30%) patients remained at the same level. The MBL2 levels (Median 772 ng/ml; iqr: 5870) of the patients were significantly higher than the MBL1 levels (p< 0.001). Patients with very low (<100 ng/ml) MBL2 levels had significantly longer FN duration than patients with normal (>1000 ng/ml) MBL2 levels (p=0.016).
Discussion: Our results suggest that duration of FN is longer when MBL level is low especially less than 100 ng/ml. These patients seem to have the highest risk for infection-related morbidity and mortality and deserve interest for trials of MBL replacement.
Keywords: MBL; Acute Leukemia; Febrile Neutropenia
Introduction
At the present time, it has been possible to obtain complete remission of the underlying disease in many patients with hematological malignancies and even prolong their survival times with appropriate treatment approaches. However, the aggressive and invasive treatment modalities applied to these patients cause defects in their immune systems and result in opportunistic infections. Approximately 85% of the leukemia patients who undergo aggressive cytotoxic chemotherapy have opportunistic infections with or without fever [1,2].
Various studies have described new factors increasing the risk of infections in patients with malignancies. Mannose-binding lectin (MBL), which is an important component of the natural immune system, is bound to the carbohydrate structures on cell walls of bacteria, fungi or viruses and activates the complement system. Mannose- binding lectin acts like an opsonin and enhances phagocytosis [3,4,5].
Mannose-binding lectin level in the human bloodstream is mainly genetically determined and ranges from 0.1 ng/ml to 10.000 ng/ml [6]. However, the MBL level may increase up to 1.5-3 folds after an infection or trauma because it is an acute- phase reactant [7]. It has been stated that MBL synthesis is insufficient in one-third of the normal population and low serum levels may result in a predisposition to recurrent infections [8]. For these reasons, there has been an increased interest in the role of MBL replacement in some patients with sepsis, septic shock or for the immunosuppressed patients due to treatment [9,10].
High levels of MBL may be important for protection of the patients from sepsis and septic shock. On the other hand, its lower levels have been reported to lengthen the duration of FN after chemotherapy and serious opportunistic infections [8,9]. However, it has also been claimed in other reports that MBL levels do not affect the duration of FN and the developing of pneumonia or sepsis in patients undergoing chemotherapy [9,11-14].
Conflicting results were obtained in clinical studies regarding the effects of MBL levels and/or low MBL producing polymorphisms on the infections occurring during the neutropenic period in cancer patients undergoing chemotherapy. Thus, the present study was planned to determine the association of serum MBL levels and the duration of FN after cytotoxic chemotherapy in patients with acute leukemia.
Material and Methods
Seventy patients aged 15-75 years who admitted to a single hematology center from August 2017 to August 2018 and diagnosed with acute leukemia were included in the study. The patients who had metabolic disease or solid organ tumor were excluded. Blood samples of 5 ml were obtained from each patient before chemotherapy (MBL1) and during the first 2 hours at the first FN episode after chemotherapy (MBL2), and stored at -800C. Mannose-binding lectin levels of all patients were measured using ELISA kit (E1480Hu) (USCN Life Science Inc. Wuhan, P.R. China). Febrile neutropenia was defined as fever ≥ 38.30C on a single measurement or fever between 38.0-38.2 0C lasting at least for an hour in a patient who has an absolute neutrophil count < 500/mm3 or between 500-1000/ mm3 and expected to fall below 500/mm3 in the following 24- 48 hours. All patients received the standard FN protocol of the institution, starting with piperacillin/tazobactam and expanding the coverage according to the IDSA (Infectious Diseases Society of America) guidelines [15]. Multinational Association for Supportive Care in Cancer (MASCC) scoring system was used to categorize the patients as low or high risk according to clinical parameters [16]. The duration of FN was calculated from the day the patient had the first FN episode until the feverless recovery of neutrophils ≥1500/mm3 for two consecutive days. In order to compare the MBL levels of the patients with healthy subjects, 30 age-matched healthy subjects without known systemic disease were used as control. Informed consent was obtained from each subject included in this study. Ethic approval was obtained from the local ethical committee of the University.
Statistics
All statistical evaluations were performed using the SPSS software package (SPSS for Windows XP, version 20, SPSS Incorporated, Chicago, IL, USA). Since the distribution of samples was not normal in groups, non-parametric tests were used to compare the MBL levels of control group and patients group (Mann-Whitney U test) and also within the patient group (MBL1 versus MBL2) (Wilcoxon signed ranks test). Multiple comparisons between the subgroups of MBL2 (Very low, low, normal) and duration of FN were done by using LSD test. A p-value less than 0.05 was accepted as statistically significant.
Results
In the study group, 40 patients (57.1%) had acute myeloid leukemia (AML), and 30 patients (42.9%) had acute lymphocytic leukemia (ALL). The numbers of the male and female patients were 47 (67.1 %) and 23 (32.9%) in the study group and 19 (63.3%) and 11 (36.7%) in the control group, respectively. After chemotherapy, FN developed in all patients. The patients and the control subjects were divided into three groups according to their MBL levels as follows: less than 100 ng/ml (very low), between 100-999 ng/ml (low), and more than 1000 ng/ml (normal). The mean MBL level of the patients before chemotherapy (MBL1) was 2032 ng/ml (95% CI 1441-2623 ng/ ml). The percentages of patients with very low, low, and normal MBL1 levels were 23%, 36%, and 41%, respectively.
The mean MBL value in the control group was 1553 ng/ml (95% CI 766-2340 ng/ml). In the control group, MBL levels were very low, low, and normal in 20%, 40%, and 40% of the patients, respectively. The MBL1 levels of the patient group (Median 466 ng/ml; interquartile range: 4507) were higher than that of the control group (Median 485 ng/ml; interquartile range: 1872), but this difference was statistically insignificant (p=0.92). During the FN period, MBL levels of 49 (70%) patients increased and 21 (30%) patients remained at the same level. The MBL2 levels (Median 772 ng/ml; interquartile range: 5870) of the patients were significantly higher than the MBL1 levels (p< 0.001). The increase in the MBL level remained in the same subgroup in 63 patients. Only 7 patients were upgraded to a higher subgroup. MBL2 subgroups were compared with each other with respect to age, CRP levels, ferritin levels, and the MASCC Scores and no statistically significant difference was found between the groups (Table 1).
The duration of FN ranged from 6 to 40 days, and the mean duration was 11.6 ± 5.9 days. As shown in the Figure 1, the FN duration lengthened as the MBL2 level decreased and the difference was very close to significance (p=0.052). Patient groups with different MBL2 levels were compared with each other with regard to the duration of FN (Table 2). Patients with very low (<100 ng/ml) MBL2 levels had significantly longer FN duration than patients with normal (>1000 ng/ml) MBL2 levels (p=0.016).
Discussion
The association of the MBL levels or different MBL genotypes with the duration of FN in patients receiving chemotherapy has been a challenge for many investigators for more than a decade [11,12,17,18]. However, controversial results have been reported. First of all, there is a great interindividual difference in MBL levels which has resulted in difficulty in finding a cut- off level for MBL deficiency. Clinical trials have indicated that at least 200 ng/ml MBL level is required for reconstituting in vitro functional activity. On the other hand, studies have also indicated that leukemia patients may require higher levels [19,20]. According to the results of the present study, the mean level of MBL was 2032 (95% CI 1441-2622) ng/ml and 2232 (95% CI 1634-2829) ng/ml before chemotherapy and at FN, respectively. However, other studies have demonstrated higher MBL levels in similar patient groups [11-14]. For example, Vekemans et al. assessed MBL concentration as a risk factor for infection in 255 patients with hematological malignancy receiving chemotherapy. The authors defined the levels below 500 ng/ml as MBL deficiency and demonstrated that 62 patients (24%) had MBL deficiency [9]. Schlapbach et al. analyzed 94 neutropenic pediatric cancer patients and found that very low MBL levels were associated with more frequent FN episodes, mainly due to severe bacterial infections. These investigators used the cut-off value for the MBL level similar to ours [17].
In the present study, mean MBL1 levels of the study group were higher than the control group, but this was not statistically significant. This signifies that having the diagnosis of leukemia does not necessarily increase the MBL levels in a patient. MBL is an acute phase reactant and the levels may increase up to three fold after an insult. However, the MBL levels are generally genetically determined and the influence of genotype seems to have much higher effect on the MBL level of each individual. Thus, the difference between the patient and the control groups might have also resulted from diversity in the patient group. Klostergaard et al. investigated the distribution of polymorphism in MBL gene in cancer patients and the polymorphism in this gene (MBL2) was associated with low, medium, and high MBL levels in 53%, 32%, and 15% patients, respectively. They could not demonstrate any statistically significant relationship between MBL2 polymorphism and sepsis developing after chemotherapy [12]. Dahl et al. conducted a large study and genotyped an ethnically homogenous Caucasian population for three MBL alleles (B,C, and D) known to be associated with MBL deficiency as opposed to the normal A allele, and could not find any evidence for significant differences in infectious disease or mortality in MBL-deficient individuals versus controls [18]. In the present study, we have found that the duration of FN was statistically significantly longer in patients whose MBL levels were less than 100 ng/ml than those of the patients whose MBL levels were more than 1000 ng/ml (p=0.016). The relationship between MBL levels and the frequency and duration of FN has been investigated in various studies. Neth et al. demonstrated in children with ALL that the duration of FN was longer in patients having polymorphic MBL alleles and in patients whose MBL levels were less than 1000ng/ml [20]. On the contrary, other studies could not demonstrate any association between the MBL levels and the duration, frequency, and severity of FN. In one of these studies, MBL, L-ficolin, and H-ficolin were measured in 128 patients with hematological malignancies treated with chemotherapy alone or combined with bone marrow transplantation. MBL, L-ficolin, and H-ficolin, independently or in combination, did not have a major influence on susceptibility to infection in these patients rendered neutropenic by chemotherapy [11]. A study by Lausen et al. could not demonstrate an increased frequency of infection after induction chemotherapy in children with genotypes encoding low serum levels of MBL [20]. Bergmann et al. investigated the clinical significance of low serum concentrations of MBL in 80 consecutive, newly diagnosed, and unselected adult AML patients undergoing remission induction chemotherapy. They showed that low levels of MBL did not affect overall survival or morbidity in terms of incidence or duration of fever, or occurrence of septicemia or pneumonia [14]. Vekemans et al. also could not demonstrate that MBL deficiency predisposed adults with hematological cancer to more-frequent or more-prolonged febrile episodes during myelosuppressive chemotherapy. However, they found that MBL-deficient patients had a greater number of severe infections and experience their first severe infection earlier, compared with non-deficient patients [9]. According to a prospective study on 110 pediatric oncology patients, the MBL deficient neutropenic children did not have more severe infections than children with normal MBL levels [13]. Conclusion
Our results suggest that the duration of FN is longer when MBL level is low, especially less than 100 ng/ml. Different results from various studies might have originated from the differences in patient groups, different chemotherapy regimens, the use of antibiotics and granulocyte-colony stimulating factor and also MBL measurements. New studies are required to better understand how MBL levels affect the duration or severity of FN. If the clear association can be established, MBL replacement for the patients who are known to be MBL deficient may be a promising approach in cancer patients undergoing cytotoxic chemotherapy.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical
standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
1. Azap A. Microorganisms in different immunocompromised patients. In Akova M, Akan H, editors. Febril Nötropeni. 1st ed. Ankara: Bilimsel Tıp Publisher. 2010. p.75-89.
2. Wade JC. Treatment of fungal and other opportunistic infections in immunocompromised patients. Leukemia. 1997;11 (Suppl. 4):S38-9.
3. Nakagawa T, Ma BY, Uemura K, Oka S, Kawasaki N, Kawasaki T. Role of mannan-binding protein, mbp, in innate immunity. Anticancer Res. 2003; 23(6a): 4467-71.
4. Eisen DP, Minchinton RM. Impact of mannose-binding lectin on susceptibility to infectious diseases. Clin Infect Dis. 2003; 37: 1496-505.
5. Alan R, Ezekowitz B. Mannose-binding lectin in prediction of susceptibility to infection. Lancet. 2001; 358: 598-9.
6. Kilpatrick DC, Liston WA, Midgley PC. Mannan binding protein in human umbilical cord blood. Nat Immun. 1997; 15(5): 234-40.
7. Thiel S, Holmskov U, Hviid L, Laursen SB, Jensenius JC. The concentration of the C-type lectin, mannan-binding protein, in human plasma increases during an acute phase response. Clin Exp Immunol. 1992; 90(1): 31-35.
8. Neth O, Hann I, Turner MW, Klein NJ. Deficiency of mannose-binding lectin and burden of infections in children with malignancy: A prospective study. Lancet. 2001; 358: 614-18.
9. Vekemans M, Robinson J, Georgala A, Heymans C, Muanza F, Paesmans M, et al. Low mannose-binding lectin concentration is associated with severe infection in patients with hematological cancer who are undergoing chemotherapy. Clin Infect Dis. 2007; 44(12): 1593-601.
10. Kawasaki T, Etoh R, Yamashina I. Isolation and characterization of mannan binding protein from rabbit liver. Biochem Biophys Res Commun. 1978; 81(3): 1018-24.
11. Kilpatrick DC, McLintock LA, Allan EK, Copland M, Fujita T, Jordanides NE, et al. No strong relationship between mannan binding lectin or plasma ficolins and chemotherapy related infections. Clin Exp Immunol. 2003; 134: 279–84.
12. Klostergaard A, Steffensen R, Møller JK, Peterslund N, Juhl-Christensen C, Mølle I. Sepsis in acute myeloid leukaemia patients receiving high-dose chemotherapy: No impact of chitotriosidase and mannose-binding lectin polymorphism. Eur J Haematol. 2010; 85(1): 58–64.
13. Frakking FN, van de Wetering MD, Brouwer N, Dolman KM, Geissler J, Lemkes B, et al. The role of mannose-binding lectin (MBL) in pediatric oncology patients with FN. Eur J Cancer. 2006; 42(7): 909-16.
14. Bergmann OJ, Christiansen M, Laursen I, Bang P, Hansen NE, Ellegaard J, et al. Low levels of mannose binding lectin do not affect occurrence of severe infections or duration of fever in acute myeloid leukaemia during remission induction therapy. Eur J Haematol. 2003; 70: 91–97.
15. Hughes WT, Armstrong D, Bodey GP, Bow EJ, Brown AE, Calandra T, et al. 2002 guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Clin Infect Dis. 2002; 34(6):730–51.
16. Klastersky J, Paesmans M, Rubenstein EB, Boyer M, Elting L, Feld R, et al. The multinational association for supportive care in cancer risk index: A multinational scoring system for identifying low-risk febrile neutropenic cancer patients. J Clin Oncol. 2000; 18(16): 3038-51.
17. Schlapbach LJ, Aebi C, Otth M, Luethy AR, Leibundgut K, Hirt A, et al. Serum levels of mannose binding lectin and the risk of fever in neutropenia pediatric cancer patients. Pediatr Blood Cancer. 2007; 49(1): 11-16.
18. Dahl M, Tybjaerg-Hansen A, Schnohr P, Nordestgaard BG. A population-based study of morbidity and mortality in mannose-binding lectin deficiency. J Exp Med. 2004; 199(10): 1391–99.
19. Peterslund NA, Koch C, Jensenius JC, Thiel S. Association between deficiency of mannose-binding lectin and severe infections after chemotherapy. Lancet. 2001;358(9282):637-8.
20. Lausen B, Schmiegelow K, Andreassen B, Madsen HO, Garred P. Infections during induction therapy of childhood acute lymphoblastic leukemia – no association to mannose-binding lectin deficiency. Eur J Haematol. 2006;76(6):481-7.
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Approach to angry patients and anger expression styles of emergency medical services professionals
İshak Şan 1, Birgül Özkan 2, Günseli Uzunhasanoğlu 2
1 Department of Emergency Medicine, University of Health Sciences, Ankara, 2 Department of Psychiatric Nursing, Yıldırım Beyazıt University, Ankara, Turkey
DOI: 10.4328/ACAM.20089 Received: 2019-12-11 Accepted: 2020-01-13 Published Online: 2020-01-22 Printed: 2020-09-01 Ann Clin Anal Med 2020;11(5):411-415
Corresponding Author: İshak Şan, Department of Emergency Medicine, University of Health Sciences, Ankara Acil Sağlık Hizmetleri Başkanlığı (EMS Administration of Ankara Province) Mehmet Akif Ersoy Mah. Bağdat cad. No:62 Yenimahalle/Ankara – Turkey. E-mail: ishaksan02@gmail.com T: +90 312 5924716 / +90 312 5924734 Corresponding Author ORCID ID: https://orcid.org/0000-0002-9658-9010
Aim: The aim of this study is to determine the anger and anger expression styles of the emergency medical services (EMS) professionals, to determine whether they see themselves as adequate when working with angry patients or patient relatives, and contribute to the field.
Material and Methods: The sample of the study consisted of 564 people working in Ankara EMS. Demographic Questionnaires and Anger and Anger Expres- sion Style Scales (AAES) were used in the study. All data were analyzed using SPSS for Windows version 21.
Results: For the participants, the mean Anger score was 19.8 (± 5.5), the mean Anger-out score was 16.8 (± 5.6), the mean Anger-in score was 17.3 (± 4.3), and the mean Anger Control score was 22.8 (± 5.8). Those who felt inadequate to approach an angry patient were found to have higher continuous anger and anger-in scores, while their anger control scores were lower.
Discussion: In this study, the rate of encountering with angry patients of employees was found to be 96.6%. According to the findings of this study, employees having high levels of anger and less anger control levels are experiencing inability to interfere with angry individuals. Employees can ignore their anger by considering patients and their relatives as angry.
Conclusions: According to the findings, EMS workers need training on anger management and effective communication.
Keywords: Emergency Medicine; Anger; Health Professionals
Introduction
The health Professionals in EMS are facing with several different cases. In the majority of the cases, there are individuals who are frightened, anxious, intense stressed and cannot cope with the situation which they have experienced [1-3].When these individuals are insufficient to cope with the crisis and stress situation they faced, they can exhibit anxiety, anger expression and aggressive behaviors. EMS personnel may experience an inability to manage individuals and their families who have experienced physical and mental trauma under intense stresses [1-3] . Although it is known that individuals react differently to the stress they experience, the main outcomes of this chaos environment can often be anxiety, anger, feel guilt or indecision. These feelings also can be expressed by both service receivers and service providers [4]. EMS professionals may experience inadequate anger control and anger expression while serving individuals suffering pain and fear [5-7].
Anger is a basic feeling that people are experiencing [8] Anger can also be defined as a negative emotional state accompanied by thoughts of physiological arousal and hostility towards a person or object, often seen as the cause of a negative event [9]. Spielberger (1983) [10] considers continuous anger as a concept that reflects how frequently anger situation was usually experienced by the individual, “anger-in” as the tendency to suppress thoughts and emotions that bring out anger; “anger- out” as the tendency tends to show aggressive behavior towards individuals or objects in the environment; “anger control” as the ability to reflect the control of anger expression .
The feeling of anger that cannot be expressed by appropriate means may often result in verbal or physical violence. In many studies, it has been revealed that emergency healthcare workers are frequently exposed to violence by the patients and their relatives [11,12]. Health workers facing violent behaviors were stated mostly having anger expression feelings. Consequently, as a result of this stressful environment, the stress of anger feeds the violence and the sense of anger again [11,12] Failure to identify and respond appropriately to angry patients may become the source of many problems, particularly violence to health professionals. The number of studies on the expression styles and approaches to “anger”, “anger-in”, “anger-out” and “anger control” is limited and it is seen that these studies are mostly directed to the personnel working in emergency clinics, and there is no study for the employees working in EMSs. This study was conducted in order to contribute to the literature in this field due to insufficient number of studies
The aim of this study was to determine the anger and anger expression styles of the health professionals in Ankara 112 EMS, to determine whether they are competent to work with angry patients or their relatives.
Material and Methods
The population of this study was composed of health centers serving in Ankara 112 EMS stations. The sample was not determined in the study and it was aimed to reach the whole population. The total number of personnel working under the presidency of emergency healthcare services is 2361. Healthcare personnel number is 1757 (113 Doctors, 99 Nurses, Midwife, Health Officer, 1131 EMT (Emergency Medicine Technician), 414 Paramedic), and 604 of them are other employees (Secretary, Housekeeper, driver, etc.).
The study was conducted between June 2014 and September 2014 with 564 people who agreed to participate in the study from 1536 employees actively working in the university. Nine hundred seventy-two employees were excluded from the study due to different reasons such as not accepting to participate in the study and 221 employee’s absence due to leaves and reports.
In the study, the Socio-Demographic Questionnaire developed by the researchers as a result of the literature review and “Anger/Anger Expression Style Scale (AAES)” forms were used. Socio-Demographic Questionnaire
Socio-Demographic data form consists of 7 questions about gender, age, marital status, educational status, professional status, duration of professional experience and duration of their work in 112, the questions for determining the situations that employees faced as a necessity of their jobs were including; whether or not he/she individually faced with a patient showing aggressive behavior; whether he/she feels adequate when serving the individual with aggressive behavior.
Anger/Anger Expression Style Scale (AAES): It was developed by Spielberger [10] in 1983 and its validity and reliability were performed by Özer [13]. The scale consists of 4 sub-scales and 34 items including anger-in, anger-out, anger control, and continuous anger. While the first 10 items of the scale measure the level of continuous anger, 24 items determine individuals’ anger styles (anger-in, anger-out and anger-control sub- dimensions). High scores on continuous anger subscale indicate high levels of anger, high scores on anger control subscale indicate individual can control the anger, high scores on the anger-out subscale indicate that anger is easily expressed, and high scores on anger-in subscale show that the anger was suppressed [14]. For this study, Cronbach’s alpha coefficients were found to be 0.79 for ‘continuous anger’ dimension, 0.78 for ‘anger-out expression’ dimension, 0.62 for ‘anger-in expression dimension and 0.84 for ‘anger control’ dimension
Ethical aspect of the study
Ethical Board Permission for the study was obtained from the ethics committee of Yıldırım Beyazıt University in Ankara and in writing from the relevant institution whose name was specified in the ethics committee form (18/09/2018-41). Written informed consent was obtained from individuals who wanted to participate in the study.
Statistical analysis of the research
In the statistical evaluations, socio-demographic characteristics of the patients were given as number, percentage distribution, mean, standard deviation values. The relationships between socio-demographic data, categorized open-ended questions and AAES scores were evaluated by SPSS 21 Statistical Package Program. Since the continuous variables used in the study did not show normal distribution according to the Shapiro-Wilk normality test, the post-hoc analysis of the significant variables using the Kruskal-Wallis and the Mann-Whitney U test was evaluated with the Bonferroni test in the evaluation of AAES scores with socio-demographic variables. The power analysis of the study was done with G power 3.1.9.2 Statistical Program and (n: 564), group 4, α: 0.05, effect size F: 0.15 power (1-β): 0.86 was found.
Results
Frequency distributions of socio-demographic characteristics are shown in Table 1. In our study group, 65.1% of participants were female. The mean age was 32±6,5 and 57,9 % were between 26 to 35 years of age. Those who have a bachelor’s degree accounted for 69,7 of all participants, 76,6 % of them were married. While the experience of the participants in the EMS field is mean 7.8±4,7 years, it is 10,4±5,9 years for all health services (Table 1).
Comparison of scale scores of socio-demographic characteristics is given in Table 2. Table 2 shows that there was a significant difference between Professional Status and anger-in score (p <0.05). In post-hoc analyzes of the data, anger-in scores of Doctors, were statistically significant compared to other occupational groups. When we look at the working years in the unit, there was a significant difference between years and anger control score (p <0.05). In post-hoc analysis of the data, it was concluded that the anger control scores were significantly lower for people working in the unit for 20 years or more.
When the scores and answers given to the question of ‘How do you find yourself to approach the patient who cannot control his anger?’ were compared, there was a significant difference between the anger, anger-in, and anger control scores (p <0.05). In advanced analyzes, it was found that those who felt incapable to approach the angry patient had higher scores in continuous anger and anger-in scores but lower anger control scores.
Socio-demographic characteristics of the respondents to the question ‘How do you find yourself to approach the patient who cannot control his anger?’ are shown in Table 3.
Discussion
EMS professionals often serve individuals who experience anger. In this study, the rate of encountering with angry patients of employees was found to be 96.6%. Given that aggressive behavior is a trigger of violence, it is important for employees to have the knowledge and skills to approach angry patient and to be able to recognize their anger status and professionally keep it under control. Employees can ignore their anger by considering patients and their relatives as angry [15].
In the study, when the total anger scores of the participants were evaluated, total score of Continuous Anger was found as 19.8 ± 5.5; Anger-In scores were found as 17.3 ± 4.3; Anger-Out scores were found as 16.8 ± 5.6; Anger Control scores were found as 22.8 ± 5.8.
In a study conducted by Kaya et al. [16] on nurses, while the mean score was 20.41 ± 4.36 for continuous anger, it was 16.22 ± 3.46 for anger-in, 15.25 ± 3.04 for anger-out 22.89 ± 4.23 for controlled anger.
In our study, a comparison of the anger level and anger expression style scores of the EMS employees with the other health workers showed similarities.
The majority of the participants in our study were female workers (65%, n= 367). In terms of gender, there was no significant difference between anger level and anger expression styles. In the literature, it was found that the continuous anger scores of the males were statistically significantly higher in some
sources [17] and that the female anger-out scores were higher than the males [18] and there was no difference between the anger scores in terms of gender for the other studies[ 14,15,19] Studies investigating the relationship between gender and anger do not provide clear information in this context. According to the findings, it is recommended to do more in-depth studies in this subject.
No significant relationship was found between age, education level, marital status, occupational age variables and AAES sub- dimensions.
In Kaya et al. [16], study it was found that the controlled anger scores were decreased when the age increased. Kayalı et al. [20] in their study, found that married and unmarried people were showing more anger control than divorced people. The results showed that the anger-out and continuous anger scores of university graduates were higher than those of high school graduates [17]. Similarly, no differences were found between these variables and the anger scores in some studies [14]. When compared the professional status, there was a statistically significant difference between these categories and AAES scores of anger-in scores. The post-hoc tests showed that the anger-in scores of the Doctors were significantly higher than other employees. In both domestic and foreign literature, there was not enough information about the continuous anger and anger expression styles of Doctors. However, in a study, it was found that emergency physicians occasionally showed verbal violent behavior, and this behavior was shown as a result of inappropriate behaviors and aggressive behaviors of the patients and their relatives [21]. Violence against physicians was frequently heard in recent years. Therefore, new studies on the continuous anger and anger expression styles of physicians may contribute to the literature.
When the answers given to the open-ended questions created by the researchers were examined, it was found that those who felt inadequate to approach the angry patient had higher scores in anger and anger, and anger control scores were lower. When the literature was examined, no information was found in this direction. In this case, it can be said that employees who cannot express their anger in appropriate ways have inability and difficulty to approach an angry patient.
EMS professionals are serving in a very stressful environment. Employees may not be aware of their own feelings of anger and anger control levels when they were under stress working environment for a long period. Mutual anger can often result in violence. According to the findings of this study, employees having high levels of anger and less anger control levels are experiencing inability to interfere with angry individuals. Therefore, employees need training programs on anger management, expression of anger in an appropriate way, and skills development related to the angry patient approach.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
1. Bernaldo-De-Quirós M, Piccini AT, Gómez MM, Cerdeira JC. Psychological consequences of aggression in pre-hospital emergency care: Cross sectional survey. Int J Nurs Stud. 2015;52(1):260-70. DOI:10.1016/j.ijnurstu.2014.05.011
2. LeBlanc VR, Regehr C, Tavares W, Scott AK, Macdonald R, King K. The Impact of Stress on Paramedic Performance During Simulated Critical Events. Prehosp Disaster Med. 2012;27(4):369-74. DOI:10.1017/S1049023X12001021
3. Reuter-Oppermann M, van den Berg PL, Vile JL. Logistics for Emergency Medical Service systems. Health Systems. 2017;6(3):187-208. DOI:10.1057/ s41306-017-0023-x
4. Wloszczak-Szubzda A, Jarosz MJ, Goniewicz M. Professional communication competences of paramedics – practical and educational perspectives. Ann Agric Environ Med. 2013;20(2):366-72.
5. Bounds R. Factors affecting perceived stress in pre-hospital emergency medical services. Calif J Health Promot. 2006;4(2):113-31.
6. Garnham P. Understanding and dealing with anger, aggression and violence. Nursing Standard. 2001;16(6):37-42. DOI:10.7748/ns2001.10.16.6.37.c3102
7. Rybojad B, Aftyka A, Baran M, Rzońca P. Risk Factors for Posttraumatic Stress Disorder in Polish Paramedics: A Pilot Study. Int J Emerg Med. 2016;50(2):270-6. DOI:10.1016/j.jemermed.2015.06.030
8. Carmassi C, Gesi C, Corsi M, Cremone IM, Bertelloni CA, Massimetti E, et al. Exploring PTSD in emergency operators of a major University Hospital in Italy: a preliminary report on the role of gender, age, and education. Ann Gen Psychiatry. 2018;17(1):17. DOI:10.1186/s12991-018-0184-4
9. Lubke GH, Ouwens KG, de Moor MHM, Trull, TJ, Boomsma DI. Population heterogeneity of trait anger and differential associations of trait anger facets with borderline personality features, neuroticism, depression, Attention Deficit Hyperactivity Disorder (ADHD), and alcohol problems. Psychiatry Res. 2015;230(2):553-60. DOI:10.1016/j.psychres.2015.10.003
10. Spielberger CD, Jacobs G, Russell S, Crane, R. S. Assessment of anger: The state-trait anger scale. In J. N. Butcher & C. D. Spielberger, editors, Advances in personality assessment. Hillsdale, NJ: Lawrence Erlbaum; 1983. p. 159-87.
11. Bigham BL, Jensen JL, Tavares W, Drennan IR, Saleem H, Dainty KN, et al. Paramedic Self-reported Exposure to Violence in the Emergency Medical Services (EMS) Workplace: A Mixed-methods Cross-sectional Survey. Prehosp Emerg Care. 2014;18(4):489-94. DOI:10.3109/10903127.2014.912703
12. Özdemir A, Karasu F, Hakan A. Gaziantep 112 acil sağlık hizmetleri çalışanlarının maruz kaldıkları şiddetin değerlendirilmesi (Assessment of violence experienced by Gaziantep 112 emergency health care workers). Hastane Öncesi Dergisi/ Prehospital Journal. 2018;3(1):31-42.
13. Ozer A. Surekli Ofke ve Ofke Ifade Tarzi Olcekleri On Calismasi (Continuous anger and anger expression style scales: preliminary study). Turkish Journal of Psychology. 1994;9(31):26-35.
14. Duran S, Karadaş A, Kadder E. Hemşirelik öğrencilerinin tolerans düzeyleri ile öfke kontrolleri arasındaki ilişkinin incelenmesi (Investigation of the relationship between tolerance levels and anger controls of nursing students). SDU Journal of Health Sciences. 2016;7(3):39-44.
15. Arik C, Anat R, Arie E. Encountering anger in the emergency department: identification, evaluations and responses of staff members to anger displays. Emerg Med Int. 2012;2012. DOI:10.1155/2012/603215.
16. Kaya N, Solmaz Ş. Bir üniversite hastanesinin kulak burun boğaz kliniğinde çalışan hemşirelerin öfke ve öfke ifadesi (Anger and anger expression of nurses working in a university hospital ear nose and throat clinic). Turkiye Klinikleri J Nurs Sci. 2009;1(2):56-64.
17. Keskin G, Gümüş AB, Engin E. Bir Grup Sağlık Çalışanında Öfke ve Mizaç Özellikleri: İlişkisel Bir İnceleme (Anger and Temperament Characteristics in a Group of Health Workers: A Relational Review). Dusunen Adam. 2011;24(3). DOI:10.5350/DAJPN2011240305
18. Ham E-M, You M-J. Role of Irrational Beliefs and Anger Rumination on Nurses’ Anger Expression Styles. Workplace Health Saf. 2018;66(5):223-32. DOI:10.1177/2165079917737090
19. Bostancı N, Çoban Ş, Tekin Z, Özen A. Üniversite öğrencilerinin cinsiyete göre öfke ifade etme biçimleri (Ways of anger expressions of university students by gender). Kriz Dergisi/ Crisis Journal. 2006;14(3):9-18.
20. Kayalı S, Durmuş MK, Aren A. Acil Tıp Kliniğinde Çalışan Sağlık Personelinin Sosyo-Demografik Özelliklerinin Öfke Tarzları ve Saldırganlık Düzeyleri Üzerine Etkisi (The Effect of Socio-Demographic Characteristics of Health Personnel Working in Emergency Medicine Clinic on Anger Styles and Aggression Levels) . Istanbul Medical Journal. 2018;19(1):18-21. DOI:10.5152/imj.2018.25902
21. Darian AA, Masoumi K, Forouzan A. A Survey of Violence against Patients and Staff Working in the Emergency Department in Ahvaz, Iran. Trends Med Res. 2015;10(1):19-25. DOI:10.3923/tmr.2015.19.25
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İshak Şan, Birgül Özkan, Günseli Uzunhasanoğlu. Approach to angry patients and anger expression styles of emergency medical services professionals. Ann Clin Anal Med 2020;11(5):411-415
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Serum levels of apolipoprotein E in colorectal cancer patients and its relationship with the diagnosis of the disease
Marwah A. Al-Sahafi 1, Ayat B. Al-Ghafari 1, 2, 3, 4, Huda A. Al Doghaither 1, Ulfat M. Omar 1, Atlal M. Abusanad 5, Shadi S. Khayyat 5, Ekramy M. Elmorsy 6, Hanaa M. Tashkandi 7
1 Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia, 2 Experimental Biochemistry Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia, 3 Cancer Metabolism and Epigenetics Unit, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia, 4 Cancer and Mutagenesis Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia, 5 Department of Medicine, Faculty of Medicine, King Abdulaziz, University, Jeddah, Saudi Arabia, 6 Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Mansoura University, Mansoura, Egypt, 7 General Surgery department, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
DOI: 10.4328/ACAM.20092 Received: 2019-12-14 Accepted: 2020-01-07 Published Online: 2020-01-20 Printed: 2020-09-01 Ann Clin Anal Med 2020;11(5):379-384
Corresponding Author: Ayat Badr Al-Ghafari, Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia, P.O. Box (8795), Jeddah (23817), Saudi Arabia. E-mail: abalghafari@kau.edu.sa GSM: +966504686549 Corresponding Author ORCID ID: https://orcid.org/ 0000-0001-9156-4263
Aim: The reprogramming of energy metabolism is one of the emerging hallmarks of cancer. Lipid metabolism plays a critical role in the pathogenesis of many diseases including cancer. Colorectal cancer (CRC) is one of the most aggressive tumors and death-related cancers worldwide. Apolipoprotein E (ApoE) is widely involved in the metabolism of many lipids including cholesterol and chylomicron. Therefore, this study aims to determine the serum ApoE levels in CRC patients and to assess its relationship with the diagnosis and prognosis of CRC.
Material and Methods: Blood samples were collected from 46 normal controls and 62 CRC patients to determine the lipid profile and serum ApoE levels. The demographic characteristics of all the participants were recorded. The expression of ApoE levels in the blood of CRC patients was determined by real-time polymerase chain reaction and compared with the adjusted lipid profile controls.
Results: CRC patients had lower ApoE levels in their serum than the controls (mean of ApoE in the CRC patients was 7.346±0.71 vs. 14.86±1.03 in the controls, p < 0.0001). However, this reduced level was not correlated with the progression of CRC. Moreover, the expression of mRNA for ApoE showed a non-significant difference between the groups.
Discussion: The current data revealed for the first time that ApoE levels were highly significantly reduced among the CRC patients, but it might not be appropriate to be used as a prognostic marker for CRC progression.
Keywords: Colorectal Cancer; ApoE Expression; Lipid Metabolism
Introduction
Colorectal cancer (CRC) is one of the most common cancers worldwide. One to two million new cases are diagnosed every year [1]. Overall, CRC ranks third in terms of incidence and second in terms of mortality [2]. CRC is considered the third and the second most common type of cancer occurring in men and women, respectively, worldwide [2]. It is one of the main health problems in Saudi Arabia and ranks first in men and third in women as the most commonly occurring cancer [3]. The middle age for occurrence is 60 years for men and 55 years for women [4]. Although a remarkable improvement has been made in the cancer treatment field, the mortality rate of some cancer types, such as CRC, remains high especially in patients with high-grade tumors. One of the most studied reasons for the increased mortality rate for CRC is drug resistance. This resistance is not only caused by disorders in genetic and epigenetic factors but also by energy metabolism reprogramming in cancer [5]. Recently, advanced cancer research has shown that energy metabolism, especially lipid metabolism, is markedly increased during carcinogenesis [6,7]. Disorders of lipid metabolism have been found to promote cancer development, invasion, and metastasis, indicating that the targeting of lipid metabolism could be a new way to prevent and treat cancer [8]. Apolipoprotein E (ApoE) plays a major role in lipid metabolism, especially in cholesterol metabolism, as it controls the cellular uptake of lipoprotein particles by binding to low- density lipoprotein (LDL) and chylomicron receptors [9]. It has many other functions that may be important for neoplastic growth, such as cell reproduction, immune regulation, and angiogenesis [10,11]. ApoE overexpression has been reported in different carcinomas and adenocarcinomas, and it has been related to different aspects of tumorigenesis such as invasion, metastasis, and carcinogenesis of gastric tumor [12], progression of endometrium cancer [13], increase in lung cancer cells proliferation, migration, and resistance to chemotherapy [14], and moderation of the colon homeostasis, thus making it a risk factor for colon carcinogenesis [15]. Although many studies have shown that ApoE may influence CRC development through inflammation and other pathways such as lipid metabolism reprogramming and insulin regulation [16-18], studies on its functional expression and prognostic significance for CRC, especially in Saudi Arabia, have not been conducted yet. Studies performed on CRC patients in Saudi Arabia showed that most patients developed this type of cancer because of their poor lifestyle choices and limited physical activity. Therefore, this case-control study was performed to determine the expression of ApoE in the blood of CRC patients and to compare it with that in healthy subjects with a normal body mass index (BMI) and lipid profile to elucidate the role of ApoE in the lipid metabolism of CRC patients with different clinical stages and thus its contribution to CRC carcinogenesis. To the best of our knowledge, this study is the first to determine the novel relationship between ApoE levels and CRC tumorigenesis in Saudi Arabia.
Material and Methods
The extraction of RNA from whole blood was conducted using the QIAamp RNA blood mini kit (catalog no. 52304, Qiagen,
Germany). The cDNA samples were prepared using a high- capacity cDNA reverse transcription kit (catalog no. 4368814, Thermo Fisher Scientific, Lithuania). The 2X PowerUPTM SYBR® Green master mix (catalog no. A25741, Thermo Fisher Scientific, USA) was used in the quantitative polymerase chain reaction (qPCR) workflows. The human apolipoprotein E (Apo-E) ELISA kit (catalog no. SG-00319, SinoGeneClon Biotech Co., Ltd., China) was used for measuring serum levels of ApoE.
Subjects and Samples
This case-control study was approved by the research committee of the Unit of Biomedical Ethics at the Faculty of Medicine, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia (reference number 379-17). The study was conducted on 108 male and female volunteers (n=62 CRC patients and n=46 controls) who were interested in participating after signing a research consent form and agreeing to give two blood samples. The blood samples were collected in a lavender top vacutainer containing an EDTA anticoagulant for the RNA extraction and in a red top vacutainer for the serum collection for the biochemical analysis. Samples were collected from September 2017 to August 2018 from the day care unit at King Abdulaziz University Hospital for the CRC patients and from blood banks in King Fahad General Hospital in Jeddah for the healthy controls. The practical work was performed at the Central Lab and Cancer and Mutagenesis Unit at the King Fahd Medical Research Center at King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia.
Demographic Characteristics
Body weight was measured to the nearest 0.1 kg with a balance scale, and height was measured to the nearest centimeter. BMI was estimated by dividing the body weight (in kilograms) by the square of height (in meters). Waist circumference was measured to the nearest centimeter at the level of the umbilicus with the subject standing and breathing normally. Hip circumference was measured to the nearest centimeter at the level of the iliac crest. The waist-to-hip ratio (WHR) was calculated manually by dividing the waist circumference by the hip circumference.
Determination of the Lipid Profile
The serum levels of triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low- density lipoprotein cholesterol (LDL-C), and cholesterol in mg/dl were calculated automatically by the colorimetric test on the ADVIA Centaur using a chemiluminescent reaction at the biochemistry lab in King Abdulaziz University Hospital.
Determination of the Serum ApoE Levels
The quantitative measurement of the human ApoE level (ng/ml) in serum was performed using a sandwich ELISA commercial kit. Each sample measurement was performed in duplicate for a more accurate result. The reagents of the kit were prepared just before running the experiment based on the manufacturer’s instructions. The absorbance of the standard and samples was measured at 450 nm within 15 min after adding the stop solution, and the absorbance of the blank was subtracted from the readings for each standard and sample. A standard
curve was drawn on a linear-log graph paper with the optical densities on the y-axis and the ApoE concentration in (ng/ml) on the x-axis. The concentrations of the samples were calculated by interpolating the regression curve formula (Y=0.0061X + 0.0637) and then by multiplying the samples by the serum dilution factor. The measuring range was 1–60 ng/ml, and the minimum detectable concentration was 0.1 ng/ml.
Extraction of the RNA Samples and the qPCR Primer Design
Following the manufacturer’s instructions for the QIAGEN- QIAmp RNA blood mini kit, the RNA samples were extracted from the whole blood EDTA samples. The final RNA concentration was determined by reading the 260 nm wavelength absorbance with the DeNovix DS-11 spectrophotometer. Any RNA samples that had an A260 measurement of greater than 0.15 and a reading percentage of A260/A280 ratio in the range of 1.9–2.1 were excluded from the experiments.
The qPCR primers for the human ApoE and the housekeeping gene glyceraldehyde 3-phosphate dehydrogenase (GAPDH) were designed using the University of California Santa Cruz Genomic Institute (USCS) genome browser. Using the primer 3 website, the primers were designed after confirming all the requirements needed for the qPCR primers. To validate the design, the sequences of the primers were confirmed again in in silico PCR using the USCS browser. For the human ApoE, the forward primer was (5’- CTCAGCTCCCAGGTCACC-3’), and the reverse primer was (5’-GGGTCAGTTGTTCCTCCAGT-3’). For the GAPDH, the forward primer was (5’-CACATCGCTCAGACACCATG-3’), and the reverse primer was (5’-ACCAGAGTTAAAAGCAGCCC-3’)
RT buffer, 0.8 μL of 100 mM 25X dNTP mix, 2.0 μL of 10X RT random primers, 1.0 μL of Multi ScribeTM reverse transcriptase, 1.0 μL of RNase inhibitor, and 3.2 μL of nuclease-free water were added into the RNA samples in the same tube. The cDNA synthesis was completed using the following four-step thermocycler reaction: step 1) incubation for 10 min at 25 °C, step 2) incubation for 120 min at 37 °C, step 3) incubation for 5 min at 85 °C, and step 4) maintaining of samples for ∞ at 4 °C. All of the synthesized cDNA samples were kept at –20 °C until use for the qPCR experiments.
Real-time qPCR
The SYBR® Green master mix was used to perform the qPCR experiments to measure the expression level of ApoE. To prepare a 20 μL/well reaction, the following mixture was prepared and added to each assigned well: 10 μL of PowerUPTM SYBRTM Green master mix (2X), 1 μL of each forward and reverse primers, 8 μL of nuclease- free water, and 1 μL of template cDNA. The experiment was performed in duplicate for each sample. The optical plate was sealed using an adhesive cover. Depending on the primer melting temperature (Tm) of less than 60 °C, the thermal cycler condition settings were applied for the two genes as shown in the protocol of the SYBR Green’s kit as follows: step 1) Uracil-DNA glycosylase (UDG) activation for 2 min at 50 °C), step 2) Dual-LockTM DNA polymerase for 2 min at 95 °C), step 3) Denaturation at 40 cycles for 15 s at 95 °C), step 4) Annealing at 40 cycles for 15 s at 55 °C–60 °C depending on the primer Tm), and step 5) Extension at 40 cycles for 1 min at 72 °C).
Synthesis of the Complementary DNA (cDNA)
The cDNA samples were synthesized from highly purified RNA samples using the instructions for the random primer scheme mentioned in the high-capacity cDNA reverse transcription kit. The reagents of the kit were combined to form a 20 μL reverse transcription master mix as follows: 10 μL of the 300 ng RNA samples was added into an Eppendorf tube after a normalization step with nuclease-free water. Then, 2 μL of 10X
Statistical Analysis
The laboratory data were recorded on an investigative report form. Statistical analysis of the data was performed using GraphPad Prism version 5. The descriptive data were presented as the mean ± standard error of the mean (SEM). For the other statistics, the Mann-Whitney U was used to compare between two groups and the Kruskal-Wallis (H) test was employed to compare among more than two groups. The Spearman’s rank-order correlation was used to examine the relation between two variables in the same group. Furthermore, the expression levels of mRNA were determined with the REST2009 software after comparing them with the expression levels of GAPDH (housekeeping gene). A p- value less than 0.05 (level of significance) was considered statistically significant.
Results
Determination of the Demographic Characteristics and Lipid Profiles of the Study Subjects
This study included CRC patients (n=62) who were grouped by their gender into males (n=47, 75.8%) and females (n=15, 24.2%). The controls (n=46) were grouped into males (n=28, 60.9%) and females (n=18, 39.1%). The comparison between the CRC patients and the controls was conducted using the Mann-Whitney test (Table 1). To analyze the relationship of the ApoE level with the physical and biochemical parameters (lipid profile), the Spearman’s rank-order correlation (r) was used. The results showed no significant correlation between the ApoE level and any of the physical and biochemical parameters in the patient group. In the control group, a significant correlation was observed between the ApoE level and the LDL level (p=0.03). This result was independent of the other variables obtained from the partial correlation (Table 2).
Determination of the Serum ApoE Level and its Correlation with CRC Progression
Analysis of the data from the ELISA assay showed a highly significant difference ApoE level in the serum (p < 0.0001). The mean of the ApoE level was 7.346±0.71 in the serum of the CRC patients compared with 14.86±1.03 of the controls (Figure 1). In this study, most of the CRC patients were clinically classified as high-grade CRC patients: stage I (n=7), stage II (n=7), stage III (n=17), and stage IV (n=31). The comparison of the mean values of the serum ApoE levels in each clinical stage by the Kruskal- Wallis analysis with the Dunn’s multiple comparison post-test (Table 3) showed no significant association between the serum ApoE levels and the clinical progression of CRC (Figure 1).
Expression of ApoE mRNA in the CRC Patients
The analysis of the qPCR data in this study showed that the expression of ApoE mRNA in the CRC blood samples was not significantly different in comparison with the control samples (p=0.23). The mean of the mRNA expression level of ApoE was 34.45±0.32 in the CRC patients and 33.77±0.39 in the controls.
Discussion
CRC is considered the third and the second most commonly occurring cancer in men and women worldwide, respectively [2]. In Saudi Arabia, CRC has been considered the first and third most commonly occurring cancer in men and women since 2002. The median age for occurrence is 60 years in men and 55 years in women [4]. CRC begins in the large intestine (colon) or rectum. In classic adenoma-carcinoma sequence, it begins as benign polyp (adenoma) and over a period of time with the accumulation of additional mutations, some of these colonic adenomas give rise to colorectal adenocarcinomas. The signs and symptoms of CRC include change in bowel habits, for example, diarrhea or constipation, blood in stool, abdominal pain, incomplete bowel emptying, weakness and fatigue, and weight loss. Some of the factors increasing the risk of CRC include older age, family history of CRC or polyps, chronic colon inflammation, obesity, smoking, alcohol abuse, and physical inactivity. The treatment for CRC depends on the stage of cancer, but there are three main treatment options that are widely used in CRC based on the clinical diagnosis: surgery, chemotherapy, and radiation therapy [19].
Lipid metabolism is strongly associated with cancer tumorigenesis. Reprogramming the energy metabolism is known to be one of the emerging factors of cancer. Knowledge about the correlation between the ApoE expression and CRC tumorigenesis in patients in Saudi Arabia is limited. Studies performed on CRC patients in Saudi Arabia showed that most of the patients developed this type of cancer because of their poor lifestyle choices and limited physical activity. Therefore, this case-control study determined the profile of different lipids and the ApoE expression in the blood of CRC patients and compared them with those of healthy subjects with a normal lipid profile to elucidate the correlation between ApoE and lipid metabolism in CRC patients at different clinical stages and therefore its contribution to CRC progression. To the best of our knowledge, the current study is the first to determine the relationship between ApoE and CRC tumorigenesis in Saudi CRC patients.
ApoE is a 299-amino-acid glycoprotein [20]. The ApoE gene is located on chromosome 19 and expressed in three isoforms or alleles: Ɛ2, Ɛ3, and Ɛ4; the most common isoform is Ɛ3 [20]. ApoE is not only produced in the liver but also in the brain, kidney, adrenal glands, and macrophages [21]. ApoE has a molecular weight of 34 kDa and a variable plasma concentration based on the assessment and calibration methods that were used to identify ApoE blood level, ethnic group and gender [22]. ApoE is an essential component in the blood plasma because it is responsible for the transportation of cholesterol and its metabolites [21]. Therefore, it reduces the plasma cholesterol level and controls lipid metabolism [20,23]. It also plays a major role in altering the metabolism of cholesterol and bile acids, which are required by carcinogenic cells for their growth and metastasis [23]. In the current study, ApoE was found to be significantly reduced in the serum of CRC patients in comparison with the controls. This finding may help in the diagnosis of CRC. However, the correlation test showed that ApoE was not correlated with any of the physical, biochemical, and clinical stages of CRC patients. These data indicate that the serum level of ApoE may not be helpful in the clinical prognosis of CRC patients.
Less is known about the correlation between ApoE serum or plasma level and carcinogenesis as most published articles on different tumors examined only the effect of the mutations and the single nucleotide polymorphisms in the ApoE gene on the lipid profile levels. The few studies that examined the effect of serum or plasma ApoE level were performed either on healthy subjects or in other diseases and disorders rather than cancer. A study performed on 815 healthy Chinese subjects to determine the effect of ApoE polymorphisms and serum ApoE level on the lipid profile found that the ApoE level was influenced by ApoE polymorphism in a gene-dependent manner and had different effects on the serum lipid parameters with increasing age and BMI [24]. In a meta-analysis on 1,498 Alzheimer’s disease (AD) patients, the level of blood ApoE was reduced in AD patients but not in the healthy controls, and this reduction is a potential risk factor for AD [25]. A case-control study performed on 47 breast cancer patients and 165 controls revealed that the participants with genotypes that include either ε2 or ε3 had lower triglyceride, cholesterol, and LDL-C levels and higher HDL-C levels than those with homozygous ε3 and heterozygous ε3 and ε4. Moreover, the serum levels of the lipids in the blood of breast cancer patients were found to be higher than those of the controls. Therefore, ApoE polymorphisms play a major role in the development of breast cancer especially when it is combined with high triglyceride levels [26]. Shinomiya et al. [27] found that altered lipid metabolism may be differentially associated with tumorigenesis in the proximal and distal colorectal cancers. Interestingly, a recent cohort research on 105,949 individuals to determine whether the plasma ApoE level and ApoE polymorphisms are associated with all-cause and cause-specific mortality found that the elevated plasma levels of ApoE were associated with the increased risk of cardiovascular and cancer mortality in the ApoE-adjusted group and Ɛ3 Ɛ3 carriers only, and that the reduced plasma levels of
ApoE were associated with the increased dementia-associated mortality in the same adjusted group and carriers [28].
In conclusion, to the best of our knowledge, this study is the first to examine the serum level of ApoE in CRC patients as a diagnostic marker. The serum level tended to be significantly lower in the CRC patients than in the healthy controls. However, this decrease was not correlated with the lipid profile or with the progression of cancer. Further studies are required to confirm this association in a larger population by performing cohort or meta-analysis studies and to reveal the mechanisms behind this association by examining the signaling pathways related to lipid metabolism.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
1. Mármol I, Sánchez-de-Diego C, Pradilla Dieste A, Cerrada E, Rodriguez Yoldi M. Colorectal carcinoma: a general overview and future perspectives in colorectal cancer. Int J Mol Sci. 2017;18(1):pii:E197. DOI: 10.3390/ijms18010197.
2. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424. DOI: 10.3322/ caac.21492.
3. Mosli MH, Al-Ahwal MS. Colorectal cancer in the Kingdom of Saudi Arabia: need for screening. Asian Pac J Cancer Prev. 2012;13(8):3809-13. DOI: 10.7314/ apjcp.2012.13.8.3809.
4. Alsanea N, Abduljabbar AS, Alhomoud S, Ashari LH, Hibbert D, Bazarbashi S. Colorectal cancer in Saudi Arabia: incidence, survival, demographics and implications for national policies. Ann Saudi Med. 2015;35(3):196-202. DOI: 10.5144/0256-4947.2015.196.
5. Zaal EA, Berkers, CR. The influence of metabolism on drug response in cancer. Front Oncol. 2018;8:500. DOI: 10.3389/fonc.2018.00500.
6. Cairns RA, Harris IS, Mak TW. Regulation of cancer cell metabolism. Nat Rev Cancer. 2011;11:85-95. DOI: 10.1038/nrc2981.
7. Lunt SY, Fendt S-M. Metabolism-A cornerstone of cancer initiation, progression, immune evasion and treatment response. Curr Opin Syst Biol. 2017;8:67-72. DOI: 10.1016/j.coisb.2017.12.006.
8. Long J, Zhang CJ, Zhu N, Du K, Yin YF, Tan X, et al. Lipid metabolism and carcinogenesis, cancer development. Am J Cancer Res. 2018;8(5):778-91.
9. Gliemann J. Receptors of the low density lipoprotein (LDL) receptor family in man. Multiple functions of the large family members via interaction with complex ligands. Biol Chem. 1998;379(8-9):951-64.
10. Vogel T, Guo NH, Guy R, Drezlich N, Krutzsch HC, Blake DA, et al. Apolipoprotein E: a potent inhibitor of endothelial and tumor cell proliferation. J Cell Biochem. 1994;54(3):299-308. DOI:10.1002/jcb.240540306.
11. Zhao Z, Zou S, Guan X, Wang M, Jiang Z, Liu Z, et al. Apolipoprotein E overexpression is associated with tumor progression and poor survival in colorectal cancer. Front Genet. 2018;9:650. DOI: 10.3389/fgene.2018.00650.
12. Oue N, Hamai Y, Mitani Y, Matsumura S, Oshimo Y, Aung PP, et al. Gene expression profile of gastric carcinoma: identification of genes and tags potentially involved in invasion, metastasis, and carcinogenesis by serial analysis of gene expression. Cancer Res. 2004;64:2397-405. DOI:10.1158/0008-5472. can-03-3514.
13. Huvila J, Brandt A, Rojas CR, Pasanen S, Talve L, HirsimÄKi P, et al. Gene expression profiling of endometrial adenocarcinomas reveals increased apolipoprotein E expression in poorly differentiated tumors. Int J Gynecol Cancer. 2009;19(7):1226-31. DOI: 10.1111/IGC.0b013e3181b33be0.
14. Su WP, Chen YT, Lai WW, Lin CC, Yan JJ, Su WC. Apolipoprotein E expression promotes lung adenocarcinoma proliferation and migration and as a potential survival marker in lung cancer. Lung Cancer. 2011;71(1): 28-33. DOI:10.1016/j. lungcan.2010.04.009.
15. El-Bahrawy AH, Tarhuni A, Kim H, Subramaniam V, Benslimane I, Abd Elmajeed ZY, et al. ApoE deficiency promotes colon inflammation and enhances the inflammatory potential of oxidized-LDL and TNF-α in primary colon epithelial cells. Biosci Rep. 2016;36:e00388. DOI: 10.1042/BSR20160195.
16. Slattery ML, Sweeney C, Murtaugh M, Ma KN, Potter JD, Levin TR, et al. Associations between apoE genotype and colon and rectal cancer. Carcinogenesis. 2005;26(8):1422-29. DOI:10.1093/carcin/bgi088.
17. Mrkonjic M, Chappell E, Pethe VV, Manno M, Daftary D, Greenwood CM, et al. Association of apolipoprotein E polymorphisms and dietary factors in colorectal cancer. Br J Cancer. 2009;100:1966-1974. DOI: 10.1038/sj.bjc.6605097.
18. Kato I, Land S, Majumdar AP, Barnholtz-Sloan J, Severson RK. Functional polymorphisms to modulate luminal lipid exposure and risk of colorectal cancer. Cancer Epidemiol. 2010;34(3):291-7. DOI: 10.1016/j.canep.2010.02.010.
19. Keum N, Giovannucci E. Global burden of colorectal cancer: emerging trends, risk factors and prevention strategies. Nat Rev Gastroenterol Hepatol. 2019;16:713–32. DOI: 10.1038/s41575-019-0189-8.
20. Phillips MC. Apolipoprotein E isoforms and lipoprotein metabolism. IUBMB life. 2014;66(9):616-23. DOI: 10.1002/iub.1314.
21. Chen YC, Pohl G, Wang TL, Morin PG, Risberg B, Kristensen GB, et al. Apolipoprotein E is required for cell proliferation and survival in ovarian cancer. Cancer Res. 2005;65(1):331-7.
22. Kaneva AM, Bojko ER, Potolitsyna NN, Odland J. Plasma levels of apolipoprotein-E in residents of the European North of Russia. Lipids Health Dis. 2013;12:43. DOI: 10.1186/1476-511X-12-43.
23. Tian Y, Wang J, Ye Y, Sun L, Fan Y, Wang L, et al. Apolipoprotein E polymorphism and colorectal neoplasm: results from a meta-analysis. PLoS One. 2014;9(7):e102477. DOI: 10.1371/journal.pone.0102477.
24. Han S, Xu Y, Gao M, Wang Y, Wang J, Liu Y, et al. Serum apolipoprotein E concentration and polymorphism influence serum lipid levels in Chinese Shandong Han population. Medicine (Baltimore). 2016;95(50):e5639. DOI: 10.1097/ MD.0000000000005639.
25. Wang C, Yu J-T, Wang H-F, Jiang T, Tan C-C, Meng X-F, et al. Meta-analysis of peripheral blood apolipoprotein E levels in Alzheimer’s disease. PLoS One. 2014;9(2):e89041. DOI: 10.1371/journal.pone.0089041.
26. Cibeira GH, Giacomazzi J, Aguiar E, Schneider S, Ettrich B, De Souza CI, et al. Apolipoprotein E genetic polymorphism, serum lipoprotein levels and breast cancer risk: a case-control study. Mol Clin Oncol. 2014;2(6):1009-15. DOI:10.3892/ mco.2014.369.
27. Shinomiya S, Sasaki J, Kiyohara C, Tsuji E, Inoue H, Marugame T, et al. Apolipoprotein E genotype, serum lipids, and colorectal adenomas in Japanese men. Cancer Lett. 2001;164(1):33-40. DOI:10.1016/s0304-3835(00)00724-2.
28. Rasmussen KL, Tybjaerg-Hansen A, Nordestgaard BG, Frikke-Schmidt R. Plasma levels of apolipoprotein E, APOE genotype, and all-cause and cause- specific mortality in 105 949 individuals from a white general population cohort. Euro Heart J. 2019;40(33):2813-24. DOI: 10.1093/eurheartj/ehz402.
Download attachments: 10.4328ACAM.20092
Marwah A. Al-Sahafi, Ayat B. Al-Ghafari, Huda A. Al Doghaither, Ulfat M. Omar, Atlal M. Abusanad, Shadi S. Khayyat, Ekramy M. Elmorsy, Hanaa M. Tashkandi. .Serum levels of apolipoprotein E in colorectal cancer patients and its relationship with the diagnosis of the disease. Ann Clin Anal Med 2020;11(5):379-384
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The effect of fenugreek seed extract in the protection against gentamicin nephrotoxicity: a biochemical and histological study
Huda Mohammed Alkreathy, Ahmed Shaker Ali
Department of Pharmacology, Faculty of Medicine, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia
DOI: 10.4328/ACAM.20096 Received: 2019-12-28 Accepted: 2020-01-20 Published Online: 2020-01-31 Printed: 2020-09-01 Ann Clin Anal Med 2020;11(5):429-437
Corresponding Author: Huda Mohammed Alkreathy, Department of Pharmacology, Faculty of Medicine, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia. E-mail: halkreathy@kau.edu.sa P: +966-0505712119 Corresponding Author ORCID ID: https://orcid.org/0000-0002-7824-8802
Aim: Gentamicin (GM) is an effective antibiotic against many Gram-negative bacterial infections, but it has a narrow therapeutic range. The application of gen- tamicin causes nephrotoxicity due to its accumulation in renal cortex and the oxidative stress it causes. The present study was aimed to carry out comparative biochemical and histopathological studies on the efficacy of niphedipine, fenugreek (FG) seeds against gentamicin-induced nephrotoxicity in rats.
Material and Methods: Nephrotoxicity was induced in rats by administering gentamicin IP for 9 days at a dose of 125 mg/kg. The nephroprotective effect of the orally administered water extract of fenugreek seeds (FG) at a dose of 200 mg/kg or niphedipine (NF) at a dose of 20 mg/kg individually or in combina- tion were studied. In order to determine the nephroprotective role of the compounds, serum biochemical parameters analyses and histology studies on kidney were performed.
Results: Reduction in weight of body, liver, right kidney and heart in rats treated with gentamicin was rescued with the help of fenugreek seed extract and nifedipine. Fenugreek and nifedipine treatment also reduces uric acid levels in the gentamicin treated group as compared to the group treated with gentamicin alone; no such change was observed in serum creatinine levels. Histological studies demonstrated the protective role of fenugreek and nifedipine against the extensive damage caused by the gentamicin treatment.
Discussion: In conclusion, this study showed potential or mild protection of fenugreek seed extract and nifedipine on gentamicin-induced nephrotoxicity in rats.
Keywords: Nephrotoxicity; Gentamicin; Fenugreek Seeds; Nifedipine
Introduction
Gentamicin, an aminoglycoside antibiotic, is widely used to treat a variety of infections caused by Gram-negative (e.g. – ocular, pulmonary, and intestinal infections) or Gram-positive bacteria (e.g.-endocarditis) [1]. Treatment with gentamicin also results in unwanted toxic effects, nonetheless, it is still used as an effective therapeutic alternative against the bacteria that are resistant to other antibiotics. Widespread use of gentamicin can be primarily attributed to its chemical stability, fast bactericidal property, synergy with beta-lactam antibiotics, low resistance, and low cost of treatment [2]. However, the usefulness of this drug is limited due to its nephrotoxic and ototoxic effects [3]. Therefore, measurements of serum levels and dose regimen adjustment are important to avert toxicity. The incidences of gentamicin nephrotoxicity have progressively increased since the time of its introduction despite accurate control and follow-up of the patients [4, 5]. According to a study, up to 30% of the patients who are treated with aminoglycosides for more than seven days, show signs of nephrotoxicity [6]. It has been reported that gentamicin nephrotoxicity is a consequence of the reduction in total antioxidant capacity of renal tissue and plasma coupled with increased synthesis of lipid peroxidation products [7].
Fenugreek seed extract (dose-400 mg/kg) was found to possess antioxidant activity and conferred protection against anticancer drug hepatotoxicity [8]. Furthermore, its antioxidant property protected testicles against doxorubicin-induced toxicity [9]. It has also been reported that fenugreek seed extract protects against pesticide-induced nephrotoxicity [10].
Previous studies have demonstrated that treatment of rats with nifedipine (10, 20 mg/kg) significantly reduces renal dysfunction, total nitric oxide levels in tissue and urine, renal oxidative stress, and also prevents alterations in renal morphology, all of which were caused by cyclosporine A exposure [11]. Nifedipine administered to rats at a dose of 15 mg/kg/day has been shown to confer protection against gentamicin nephrotoxicity [12]. Since oxidative stress plays an important role in gentamicin nephrotoxicity, antioxidant compounds such as fenugreek seed extract can help in significantly reduce the ill effects. Fenugreek seed extract also showed renoprotective ability against diabetic nephropathy.
This study was aimed to test the synergistic effects of fenugreek seed extract and nifedipine to alleviate gentamicin induced nephrotoxicity in male Wistar rats. The effectiveness of fenugreek seed extracts alone and a combination of fenugreek seed extract with nifedipine were assessed for the protection against gentamicin nephrotoxicity using both biochemical and histological studies.
Material and Methods
The study was approved by the Research ethics committee, Faculty of Medicine, King Abdulaziz University (KAU), Jeddah, Saudi Arabia.
Plant Material
Fenugreek seeds were purchased from the local market, cleaned of extraneous matter and were finally soaked in boiling distilled water (DW) (20 g/100ml) for 1h. The supernatant was used as an aqueous extract. The extract was prepared daily.
Chemicals
All chemicals were obtained from Sigma Chemical Co, USA. Gentamicin and nifedipine were purchased from Sigma Aldrich (St. Louis, MO, USA).
Study design
Healthy adult male albino Wistar rats (n= 30) weighing between 200- 250 g and aged 2-3 months, were used throughout this study. Standard conditions were maintained for the animals, allowing free access to rodent diet and water ad libitum. Animals were weighed before and after the experiment. Hygienic conditions were maintained for the animals who were individually housed in metabolic cages under 12 h light and dark cycles.
The rats were randomly divided into five groups (n=6) as follows: Group 1: Served as a control. Kept on a normal diet and water on ad libitum .
Group 2: Injected intraperitoneally with gentamicin 125mg/ kg for 9 days and served as animal model of gentamicin nephrotoxicity.
Group 3: Treated with nifedipine 20 mg/kg orally, in addition to gentamicin.
Group 4: Received water extract of fenugreek seed orally at a dose of 200 mg/kg twice daily for 9 days starting from the day of gentamicin injection.
Group 5: Animals were injected with gentamicin and received a combination therapy of nifedipine 20 mg/kg orally and fenugreek seed water extract for 9 days. All the groups were provided with food and water ad libitum.
After 9 days, rats from all the groups were anesthetized using diethyl ether.
Post the treatment period, animals were made to fast overnight. On a subsequent day, blood samples were collected from orbital sinus and stored in plain tubes. Serum was separated from the blood centrifuging the samples at 3500 rpm for 10 min. Serum was then divided into several aliquots and stored at -80°C until further analysis. Sera were further used to assay total antioxidant status, kidney functions tests (creatinine, urea, uric acid, and blood urea nitrogen (BUN) and albumin, using commercially available kits (Flex® reagent cartridge, Newark, USA).
Histological study:
First, animals were anesthetized and then were sacrificed by cervical dislocation. Kidneys were dissected out quickly, weighed, and finally fixed in 10% neutral buffered formalin. Right kidney was then processed for histological evaluations. Sections of 7.0 μm were cut from the tissues. Some sections were stained with Periodic Acid Schiff (PAS), and the rest with Hematoxylin and Eosin. For electron microscopy, small pieces of kidney including cortex and medulla were fixed in 3% glutaraldehyde in phosphate buffer (pH 7.4).
The scoring of glomerular histopathological changes and mesangial lesions was done by semi-quantitatively measuring the glomerular mesangial expansion (increase in the mesangial matrix). A four-point scale (normal; mild segmental mesangial expansion up to 50%; 2- mild diffuse expansion; 3- more than moderate diffuse expansion) was used to score mesangial expansion [9].
Preparation and staining of the sections were done according
to a previously described protocol [13]. Stained sections were examined under Olympus EX51 light microscope. Images of the sections were taken using the digital camera attached to the microscope and the computer with pro-image analyzer software.
Statistical Analysis
Statistical analyses were performed using SPSS software version 20. Data are presented as mean ± standard derivation (SD). Analyses between parameters were performed using the one-way ANOVA test for unrelated data. P-value of less than 0.05 was considered significant.
Results
During the initial experiments, body weights of the rats in different groups were measured. The body weights in Fenugreek and Gentamicin + Nifedipine groups were significantly higher than the control and Gentamicin treated groups (P =0.0001 for all); meanwhile, the body weight observed in the Gentamicin + Fenugreek + Nifedipine group was significantly lower than the control group (P =0.016) (Table 1). During further investigations, liver weight in the fenugreek treated group was found to be significantly higher (P =0.001) as compared with the control whereas, liver weight observed in the Gentamicin group was found to be significantly lower than all other groups (Table 1). Right kidney weight in Gentamicin + Nifedipine group was significantly higher than the control and gentamicin treated groups (P =0.01 and P =0.022) (Table 1). Left kidney weight was found to be significantly higher in control group than the Gentamicin, Fenugreek, Gentamicin + Fenugreek, Gentamicin + Nifedipine and Gentamicin + Fenugreek + Nifedipine groups (P =0.007, P =0.007, P =0.014, P =0.0001 and P =0.008, respectively); meanwhile, left kidney weight of Gentamicin + Nifedipine group was significantly higher than the gentamicin treated group (P =0.010) (Table 1). Next, heart weight in different groups was measured and it was found that heart weight in Fenugreek and Gentamicin + Nifedipine groups was significantly higher than the gentamicin treated group (P =0.002 and P =0.048, respectively) (Table 1). Further, left testis weight in different groups was measured, and it was observed that testis weight in the Gentamicin + Fenugreek + Nifedipine group was significantly lower than the control group (P =0.021) (Table 1).
Further, the percentage of liver weight in the Gentamicin + Fenugreek + Nifedipine group was found to be significantly higherthanthegentamicintreatedgroup(P=0.020)(Table2). Similarly, the percentage of right kidney weight in the Fenugreek group was significantly lower than gentamicin treated group (P =0.011) (Table 2). In control and Fenugreek groups, the percentage of left kidney weight was significantly lower than the gentamicin treated group (P =0.008 and P =0.002) (Table 2). Further, in different groups, comparison of kidney and liver function tests and lipid profile was done. Serum creatinine level in Gentamicin + Fenugreek and Gentamicin + Nifedipine groups was significantly higher than control (P =0.014 and P =0.045), meanwhile serum creatinine level in control and Fenugreek groups was significantly lower than the gentamicin treated group (P =0.02 and P =0.021) (Table 3). Upon analysis of the uric acid levels, Gentamicin + Fenugreek, Gentamicin + Nifedipine and Gentamicin + Fenugreek + Nifedipine groups showed significantly lower uric acid level as compared to the gentamicin treated groups (P =0.005, P =0.009 and P =0.019, respectively) (Table 3). Serum cholesterol level in the Gentamicin + Fenugreek and Gentamicin + Nifedipine groups was significantly higher than the control (P =0.006 and P =0.0001); meanwhile, serum cholesterol level in the Gentamicin + Nifedipine group was found to be significantly higher than the cholesterol levels observed in gentamicin treated group (P =0.005) (Table 3). Triglyceride serum level in Gentamicin and Gentamicin + Fenugreek groups was significantly higher than control group (P =0.005 and P =0.0001), on the other hand, triglyceride serum level in Gentamicin + Fenugreek group was significantly higher than gentamicin treated group (P =0.025) (Table 3). Low-density lipoprotein cholesterol in Gentamicin + Nifedipine group was significantly higher than control and Gentamicin treated groups (P =0.0001 for both) (Table 3). Similarly, high-density lipoprotein cholesterol level in the Gentamicin + Nifedipine group was significantly higher than control and Gentamicin treated groups (P =0.0001 and P =0.009) (Table 3).
Histology of control rat kidney
The histological structure of the kidney in the control group was similar to that reported in previous studies. The cortex contains renal corpuscles with its two components. Bowman capsule lined by simple squamous epithelium, glomerular capillary tuft is present with normal cellular density, renal tubules showing intact epithelium, and normal lumina, free of any cell debris or casts (Figure 2). Similar results were observed in the proximal tubule sections, under electron microscope, where normal epithelial cells were observed with euchromatic rounded nucleus, intact brush border and normal population of mitochondria (Figure 5).
Histology of kidney in gentamicin administrated group
In this group, features of induced nephrotoxicity were observed. Marked damage of renal tubules was present in the form of atrophy or damage of lining epithelium, dilatation of their lumina, and the presence of cell debris and casts (Figure 1). Atrophy and lobulation of glomerular tufts were observed, and infiltration of interstitial inflammatory cells was evident in some samples (Figure 1). Electron microscopic assessment showed accumulation of lipids within basal parts of the epithelial cells, deformed mitochondria with vesiculated cristae and smaller nucleus (Figure 5).
Histology of kidney in gentamicin + fenugreek seeds administrated group
In this group, variation was observed in response to fenugreek protection. Moderate to higher protection was observed where the number of affected glomeruli and damaged tubules decreased, but in other samples, no improvement or even exaggerated damage was observed (Figure 2). The electron microscopic evaluation showed potential protection where proximal tubule cells showed normal nucleus, brush border clumped, few mitochondria and cells containing irregular dense body, most probably degenerated organelles near lysosomes (Figure 5). The rest of cytoplasm was depleted from cell organelles (Figure 5).
Histology of kidney in gentamicin + nifedipine drug administrated group
In this group, it was observed that nifedipine provides protection against gentamicin-induced histological features of nephrotoxicity, especially changes in glomerular tufts (Figures 2, 3). Electron microscopic evaluation revealed proximal epithelial cells having normal brush border with mitochondrial population and a well-defined nucleus (Figure 5).
Histology of kidney in gentamicin +fenugreek seeds + nifedipine drug administrated group
Mild or no protection was offered by combination of fenugreek seeds and nifedipine where kidney parenchyma showed damaging effect of renal tubules and glomeruli (Figures 2, 4). Electron microscopic evaluations showed intact cells with normal nuclei and healthy brush border. The cells contained lipid droplets and few deformed mitochondria (Figure 5).
Discussion
Gentamicin nephrotoxicity limits its usage against Gram- negative bacteria. It is also used as a tool to induce acute nephrotoxicity in experimental animals. In most investigations, oxidative stress plays a central role in induction of nephrotoxicity by gentamicin. Antioxidants have been found to be protective agents against gentamicin nephrotoxicity [14-17]. Fenugreek seeds are potential antioxidants due to their phytochemical constituents like polyphenolic flavonoids, steroid saponins/
steroidal sapogenins, polysaccharides mostly galactomannans and 4-hydroxy isoleucine [18]. On the other hand, nifedipine is another potential nephroprotective agent as it significantly attenuates the changes in tissue and urine total nitric oxide levels, and renal oxidative stress thereby prevents morphological changes in kidney [11, 19, 20].
In the present study, we investigated the effect of fenugreek seed extract and nifedipine during gentamicin-induced acute renal failure in rats. We observed a two-fold increase in blood creatinine level, which indicates distinct renal structural damage. An increase in urea and creatinine serum levels was observed due to gentamicin toxicity, as these parameters essentially depend on the glomerular filtration, which in turn is impacted by gentamicin treatment. Nifedipine and fenugreek treatment showed marked alleviation in the gentamicin-induced changes in serum creatinine and uric acid levels. As reported in previous studies, gentamicin-induced weight loss results from renal tubular injury and increased catabolism resulting in acidosis, impaired dehydration, and anorexia [14, 21, 22]. But, in the present study weight loss caused by gentamicin was ablated to a great extent by fenugreek seed extract treatment (Table 1) In the present work, we observed severe and extensive histological alterations in the renal tissue caused by gentamicin mediated oxidative damage to macromolecules and cellular organelles, which is in concurrence with previous studies [7, 14, 23-25].
The histopathology results demonstrated the cellular anti- inflammatory property of fenugreek seed extract as its treatment to the group showed ablated inflammatory events, most likely due to polyphenols, especially flavonoids, and/or 4-hydroxy isoleucine present in fenugreek seed extract. Balakumar et al. reported that gentamicin-induced acute renal failure occurs due to necrosis, mainly in proximal convoluted tubules, which is characterized by cellular desquamation, parenchymal degeneration and tubular obstruction causing marked nephrotoxicity [21]. The tubular necrosis and degeneration observed in the present work conform to the findings of earlier investigations [24, 26].
Chade et al. reported that increased susceptibility to end- stage renal disease, development, and progression of atherosclerotic process and fibrosis in the stenotic kidney is caused by hypercholesterolemia [27]. Our results showed that the treatment with gentamicin + nifedipine significantly elevated serum TC, LDL, and HDL levels when compared to both the control group and gentamicin treated group. Rashid et al. observed that gentamicin treated rats showed increased serum cholesterol and also caused prominent damage in the kidney tissue [28]. In our study, treatment with gentamicin + fenugreek combination showed a significant increase in triglyceride levels, which in itself is an important risk factor because it influences lipid deposition and clotting mechanism [29]. Hypercholesterolemia, as observed in the Gentamicin + Nifedipine group as compared to the Gentamicin + Fenugreek + Nifedipine group, may be attributed to the presence of polyphenols, especially flavonoids, and/or 4-hydroxy isoleucine in fenugreek seed extract [30-34].
The nephroprotective potential of nifedipine and fenugreek seed extract can be a result of the increase in the activities of antioxidant enzymes in the proximal tubule that in turn reduces the production of gentamicin-induced reactive oxygen species, thereby also halts progress of apoptosis [30, 31, 35]. Conclusion: Administration of fenugreek seed water extract was found to provide potential or mild protection against gentamicin-induced nephrotoxicity in rats. The results of the study have demonstrated the protective role of fenugreek and nifedipine against the extensive damage caused by the gentamicin treatment.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: This study was funded by the Deanship of Scientific Research (DSR) at King Abdulaziz University, Jeddah (grant no. 156/247/1433). The authors acknowledge, with gratitude, the DSR for technical and financial support.
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
1. Chen LF, Kaye D. Current use for old antibacterial agents: polymyxins, rifamycins, and aminoglycosides. Infect Dis Clin North Am. 2009;23(4):1053-75.
2. Edson RS, Terrell CL. The aminoglycosides. Mayo Clin Proc. 1999;74:519-28.
3. Moore RD, Lietman PS, Smith CR. Clinical response to aminoglycoside therapy: importance of the ratio of peak concentration to minimal inhibitory concentration. J Infect Dis. 1987;155(1):93-9.
4. Bertino JS Jr, Booker LA, Franck PA, Jenkins PL, Franck KR, Nafziger AN. Incidence of and significant risk factors for aminoglycoside-associated nephrotoxicity in patients dosed by using individualized pharmacokinetic monitoring. J Infect Dis. 1993;167(1):173-9.
5. Laurent G, Kishore BK, Tulkens PM. Aminoglycoside-induced renal phospholipidosis and nephrotoxicity. Biochem Pharmacol. 1990;40(11):2383-92.
6. Mathew TH. Drug-induced renal disease. Med J Aust. 1992;156(10):724-8.
7. Aksoy N, Dogan Y, Iriadam M, Bitiren M, Uzer E, Ozgonul A, et al. Protective and therapeutic effects of licorice in rats with acute tubular necrosis. J Ren Nutr. 2012;22:336-43.
8. Sakr SA, Abo-El-Yazid SM. Effect of fenugreek seed extract on adriamycin-induced hepatotoxicity and oxidative stress in albino rats. Toxicol Ind Health. 2012;28(10):876-85.
9.SakrSA,El-ShenawySM,Al-ShabkaAM.Aqueousfenugreekseedextractame- liorates adriamycin-induced cytotoxicity and testicular alterations in albino rats. Reprod Sci. 2012;19(1):70-80.
10. Sushma N, Devasena T. Aqueous extract of Trigonella foenum graecum (fenu- greek) prevents cypermethrin-induced hepatotoxicity and nephrotoxicity. Hum Exp Toxicol. 2010;29(4):311-9.
11. Chander V, Chopra K. Nifedipine attenuates changes in nitric oxide levels, renal oxidative stress, and nephrotoxicity induced by cyclosporine. Ren Fail. 2005;27(4):441-50.
12. Li J, Li QX, Xie XF, Ao Y, Tie CR, Song RJ. Differential roles of dihydropyri- dine calcium antagonist nifedipine, nitrendipine and amlodipine on gentamicin- induced renal tubular toxicity in rats. Eur J Pharmacol. 2009;620(1-3):97-104.
13. Carleton HM, Drury RAB, Wallington EA. Carleton’s histological technique. 5th ed. New York : Oxford University Press; 1980.
14. Chaware VJ, Chaudhary BP, Vaishnav MK, Biyani KR. Protective effect of the aqueous extract of Momordica charantia leaves on gentamicin induced nephro- toxicity in rats. Int J Pharm Tech Res. 2011;3:553-55.
15. Eslami SH, Ebrahimzadeh MA, Moghaddam AH, Nabavi SF, Jafari N, Nabavi SM. Renoprotective effect of Eryngium caucasicum in Gentamicin-induced neph- rotoxic mice. Arch Biol Sci. 2011;63:157-60.
16. Kore KJ, Shete RV, Kale BN, Borade AS. Protective Role Of Hydroalcoholic Extract Of Ficus Carica In Gentamicin Induced Nephrotoxicity In Rats. Int J of Pharm Life Sci. 2011;2: 978-82.
17. Soliman KM, Abdul-Hamid M, Othman AI. Effect of carnosine on gentamicin- induced nephrotoxicity. Med Sci Monit. 2007;13:BR73-83.
18. Wani SA, Kumar P. Fenugreek. A review on its nutraceutical properties and utilization in various food products. Journal of the Saudi Society of Agricultural Sciences. 2018;17:351-8.
19. Berkels R, Egink G, Marsen TA, Bartels H, Roesen R, Klaus W. Nifedipine in- creases endothelial nitric oxide bioavailability by antioxidative mechanisms. Hy- pertension. 2001;37(2):240-5.
20. Kamal S. Nephroprotection of lacidipine against gentamycin-induced nephro- toxicity in albino rats. J Exp Pharmacol. 2010;2:59-63.
21. Balakumar P, Rohilla A, Thangathirupathi A. Gentamicin-induced nephrotox- icity: Do we have a promising therapeutic approach to blunt it? Pharmacol Res. 2010;62(3):179-86.
22. Sodimbaku V, Pujari L, Mullangi R, Marri S. Carrot (Daucus carota L.): Nephro- protective against gentamicin-induced nephrotoxicity in rats. Indian J Pharmacol. 2016;48:122-7.
23. Abdel-Naim AB, Abdel-Wahab MH, Attia FF. Protective effects of vitamin e and probucol against gentamicin-induced nephrotoxicity in rats. Pharmacol Res. 1999;40(2):183-7.
24. Dehghani F, Namavar MR, Noorafshan A, Karbalay-Doust S, Esmaeilpour T. Evaluation Of The Kidney Extract On Gentamicin-Induced Nephrotoxicity In Rat. Kidney Res. 2011;1:24-32.
25. Karahan I, Atessahin A, Yilmaz S, Ceribasi AO, Sakin F. Protective effect of lycopene on gentamicin-induced oxidative stress and nephrotoxicity in rats. Toxi- cology. 2005;215(3):198-204.
26. Ali BH, Al Za’abi M, Blunden G, Nemmar A. Experimental gentamicin nephro- toxicity and agents that modify it: a mini-review of recent research. Basic Clin Pharmacol Toxicol. 2011;109(4):225-32.
27. Chade AR, Rodriguez-Porcel M, Grande JP, Zhu X, Sica V, Napoli C, et al. Mech- anisms of renal structural alterations in combined hypercholesterolemia and re- nal artery stenosis. Arterioscler Thromb Vasc Biol. 2003;23(7):1295-301.
28. Rashid F, Kaleem M, Sheema, Bano B. Comparative effect of olive oil and fish oil supplementation in combating gentamicin induced nephrotoxicity in rats. Indian J Clin Biochem. 2005;20(1):109-14.
29. Harnafi H, Aziz M, Amrani S. Sweet basil (Ocimum basilicum L.) improves lipid metabolism in hypercholesterolemic rats. E Spen Eur E J Clin Nutr Metab. 2009;4:e181-6.
30. Belguith-Hadriche O, Bouaziz M, Jamoussi K, El Feki A, Sayadi S, Makni-Ayedi F. Lipid-lowering and antioxidant effects of an ethyl acetate extract of fenugreek seeds in high-cholesterol-fed rats. J Agric Food Chem. 2010;58(4):2116-22.
31. Dixit P, Ghaskadbi S, Mohan H, Devasagayam TP. Antioxidant properties of germinated fenugreek seeds. Phytother Res. 2005;19(11):977-83.
32. Jette L, Harvey L, Eugeni K, Levens N. 4-Hydroxyisoleucine: a plant-derived treatment for metabolic syndrome. Curr Opin Investig Drugs. 2009;10:353-8.
33. Kaviarasan S, Naik GH, Gangabhagirathi R, Anuradha CV, Priyadarsini KI. In vitro studies on antiradical and antioxidant activities of fenugreek (Trigonella foenum graecum) seeds. Food Chemistry. 2007;103:31-37.
34. Narender T, Puri A, Shweta, Khaliq T, Saxena R, Bhatia G, et al. 4-hydroxyiso- leucine an unusual amino acid as antidyslipidemic and antihyperglycemic agent. Bioorg Med Chem Lett. 2006;16(2):293-6.
35. Hilmi SR, Dewan ZF, Kabir AKMN, Islam MM. Comparison of Effect of Si- lymarin and Ethanol Extract of Trigonella foenum-graecum on Gentamicin In- duced Nephrotoxicity in Rats. Journal of Current and Advance Medical Research. 2019;6(1):23-27.
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Role of hematological parameters in the selection of acute appendicitis treatment
Mehmet Cagri Goktekın 1, Mustafa Yılmaz 1, Ahmet Bozdag 2
1 Department of Emergency Medicine, 2 Department of General Surgery, Firat University, School of Medicine, Elazig, TURKEY
DOI: 10.4328/ACAM.20097 Received: 2019-12-24 Accepted: 2020-01-14 Published Online: 2020-01-23 Printed: 2020-09-01 Ann Clin Anal Med 2020;11(5):420-424
Corresponding Author: Mehmet Cagri Goktekın, Firat University School of Medicine, Department of Emergency Medicine, 23200, Elazig/Turkey. E-mail: dr23mcg@gmail.com P: +90 424 2370000/ 1231 Corresponding Author ORCID ID: https://orcid.org/0000-0001-7911-8965
Aim: The aim of this study was to compare hematological parameters of patients hospitalized and undertaken operative and non-operative antibiotherapy due to acute appendicitis (AA) in the emergency unit, and to investigate its effect on decision-making for the treatment.
Material and Methods: Files of the patients hospitalized in the emergency unit due to AA within two years were obtained from electronic records and were retrospectively evaluated. Patients were grouped according to their treatments as non-operative antibiotherapy and surgical treatment. Hematological param- eters of the groups on admission to the emergency unit were compared.
Results: Among the 94 patients hospitalized in the emergency unit due to AA and undertaken surgical treatment, 40.4% (n=38) were females and 59.6% (n=56) were males. Among the 108 patients undertaken medical treatment, 38.9% (n=42) were female and 61.2% (n=66) were male. The mean age was 33.4±14.8 which was similar between groups. Among the hematological parameters compared between antibiotherapy (AT) and surgical treatment (ST) groups, white blood cell (WBC) count (p<0.001), neutrophil count (p<0.01), monocyte count (p=0.010) and neutrophil/lymphocyte ratio (p=0.005) were found to be signifi- cantly increased in the surgery group. According to ROC analysis, sensitivity, specificity, positive predictive value ( PPV) and negative predictive (NPV) values for WBC count at a cut-off level of >13,3 were 58,51, 65,74, 59,78, and 64,55, respectively.
Discussion: WBC, neutrophil and monocyte count, and neutrophil/lymphocyte ratio parameters significantly differed between patients receiving surgical or medical therapy.
Conclusion: Hematological parameters may be helpful for the clinician in the selection of the treatment in combination in acute appendicitis, however, they are insufficient alone.
Keywords: Acute Appendicitis; WBC; Neutrophil Count; Monocyte; Neutrophil/Lymphocyte Ratio
Introduction
Appendicitis, which is one of the common causes of acute abdominal pain in emergency units, is a clinically urgent situation. Although several factors such as infections have a role in the development of appendicitis, the most important cause is the obstruction of appendiceal lumen. Abdominal pain typically begins in the periumbilical area and subsequently localizes in the lower right quadrant, which is the major symptom, and may be accompanied by loss of appetite, nausea, and vomiting [1]. The most specific findings in physical examination are rebound tenderness, pain on percussion, rigidity and guarding. Tenderness of the lower right quadrant is observed in 96% of the patients, but is a non-specific finding. Methods such as ultrasonography, computed abdominal tomography, laparoscopy and scoring systems are used for the diagnosis of AA [2,3]. Computed tomography has 100% specificity and 97% sensitivity, ultrasonography has 90% specificity and 76% sensitivity [4]. Although appendectomy is preferred as the standard treatment approach in order to avoid complications of acute appendicitis, Coldrey has reported a case series defining non-surgical approach to acute appendicitis, with recovery in most of the cases without surgery [5,6]. Parallel to the advances in imaging technologies, perforations in cases with AA could be determined easily, and non-operative antibiotherapy (AT) is preferred in cases with especially non-perforated acute appendicitis [7,9]. Although non-surgical, antibiotics mediated medical therapy has been preferred in cases at risk for uncomplicated surgery such as those with advanced age, cardiological or respiratory diseases, or obese patients, there is no standardization for the selection of antibiotherapy. In most of the studies, selection of surgical therapy or antibiotherapy has been made upon randomization, and comparisons such as complications or duration of hospital stay have been made [7, 10, 11]. Studies on hematological parameters in patients with acute appendicitis are generally related to the diagnosis of appendicitis. However, studies on the selection between surgical treatment or antibiotherapy, or hematological parameters on admission to the emergency unit are insufficient [12].
In our study, we aimed to compare the hematological parameters of patients treated surgically and non-surgically using antibiotherapy, who were hospitalized in the emergency unit due to acute appendicitis, and to determine the effect of these parameters on the decision of the treatment.
Material and Methods
The study was started upon approval of the local ethical committee of the university. Patients hospitalized due to AA within the recent 24 months, subsequent to clinical, examinational and imaging methods, were included in the study. Demographic characteristics, imaging technique reports and treatment methods of the patients obtained from the electronic records were recorded into the prepared standard data forms. Patients were grouped according to their treatments as AT and ST. The diagnosis of non-complicated AA in the AT group was confirmed using abdominal tomography and abdominal ultrasonography combination. Antibiotherapy was started as 1 g IV ceftriaxone twice daily and 500 mg metronidazole IV three times daily for 2 days, and was followed by oral ampicillin/ sulbactam (750 mg twice daily) and oral metronidazole (500 mg three times daily) for 10 days. Ciprofloxacin was used for the patients with penicillin allergy. Ciprofloxacin was used for patients with penicillin allergy.
Patients with a history of cardiac failure, peripheral vascular disease, acute or chronic infection, hematological disease, cancer or hepatic disease, those using anticoagulants, nonsteroidal anti-inflammatory drugs or oral contraceptives, those who were not histopathologically confirmed to have appendicitis following surgery, and those who were diagnosed to have a disease other than appendicitis following hospitalization were excluded. The study included patients over 18 years of age.
Hematological parameters including WBC count (range 3.8–8.6 103/ micL), hemoglobin (HGB) level (range: 11.1-17.1 g/dL), hematocrit (HCT) level (range: 33-57%), mean corpuscular volume (MCV) (range: 76-100 fL), red cell distribution width (RDW) (range: 12-15%), red blood cell (RBC) (range: 4.1-6.0 106/micL), platelet (PLT) (range: 140-360 103/micL), mean platelet volume (MPV) (range: 7-9 fL), neutrophile count (range: 2.1-6.1 103/micL), lymphocyte count (range: 1.3-3.5 106/micL) and neutrophil/lymphocyte ratio (NLR) were measured using Advia 2120i (Siemens, Germany) automated analyzer. Statistical Analysis
Data obtained in the study were analyzed using SPSS 21.0 (IBM Corporation, Armonk, NY, USA) and MedCalc (Version 10.1.6.0) program packages. The Kolmogorov-Smirnov normality test and distribution of continuous variables were performed. Comparison of normally distributed continuous variables between two groups was analyzed via the Student t-test. Numeric variables were expressed as mean ± standard deviation, and qualitative data were expressed as percentages. Outcomes of ROC Curve analysis were expressed as specificity % and sensitivity % [Area under the ROC curve (AUC), p, 95% Confidence Interval (CI)]. A p-value <0.05 was accepted as statistically significant.
Results
Among the 94 patients hospitalized in the emergency unit due to AA and undertaken ST, 40.4% (n=38) were females (F) and 59.6% (n=56) were males (M). Among the 108 patients undertaken medical treatment, 38.9% (n=42) were females and 61.2% (n=66) were males. M/F ratio was 1.52, the mean age was 33.4±14.8 (range: 18-94). The mean age was similar between groups (Table 1).
Among the hematological parameters compared between AT and ST groups, WBC count (p<0.001), neutrophil count (p<0.01), monocyte count (p=0.010) and neutrophil/lymphocyte ratio (p=0.005) were found to be significantly increased in the surgery group. No significant difference was observed between groups with regard to the remaining parameters (Table 1). According to ROC analysis, sensitivity, specificity, PPV and NPV values for WBC count at a cut-off level of >13,3 were 58,51, 65,74, 59,78, and 64,55, respectively. ROC analysis outcomes of other hematological parameters are presented in Table 2.
Discussion
Acute appendicitis is an emergency surgical situation that may have complications such as perforation, abscess or peritonitis. However, surgical complications such as intestinal infection, intraabdominal abescess or ileus increase attention to non- surgical alternative treatments [13].
Hematological parameters are generally measured for the diagnosis of AA, and the results are found to be variable. The first hematological parameter is WBC count. Many studies have reported that increased WBC count was generally an early indicator of the inflammation in the appendix, increased leukoocyte count was observed in most of the patient as well [14, 15]. In various studies, WBC sensitivity has been recorded as 85.8%, 97.8%, 67%, and 76%; specificity as 31.9%, 55.6%, 80%, and 56%; and PPV as 89.2% in AA diagnosis. Xharra et al. [16] in a prospective, double-blind study, specificity and sensitivity of WBC count for the diagnosis of AA were found to be 85.1% and 68%, respectively; the positive predictive value was found to be 94%. WBC count was found to be normal in 8 patients with histopathologically confirmed AA, and as increased in the remaining. WBC count was reported to be increased in cases with AA in the presence of complications. In the study of Kaya et al. [17], WBC count was found to be significantly increased in cases with perforated appendicitis than those with phlegmonous appendicitis. A total of 126 patients were included in the study of Yardeni et al. [12], among those, 38 were operated within 6 hours and 88 were operated within 24 hours; no difference was found between the WBC count measure at the emergency unit. Likewise, in the prospective study of Malik AA et al. [11] including 80 patients 40 of whom were undertaken surgical treatment and the remaining were undertaken medical therapy, treatment method was performed in a randomized manner and it was observed that WBC count showed a rapid decrease in the antibiotherapy group. In the study of Hansson et al. on 369 patients with AA, medical and surgical treatments were compared, where treatment method was performed in a randomized manner as well. Patients undertaken surgery demonstrated a higher level of WBC, higher body temperature and peritonitis risk compared to patients undertaken antibiotherapy [8]. Kırkıl et al. [18] have reported that WBC count had no effect in predicting recurrence in patients undertaken non-operative antibiotherapy. In our study, we observed that WBC count on admission to the emergency unit was significantly higher in the surgical treatment group. However, sensitivity, specificity, PPV, and NPV values were found to be 60%. We believe that WBC count, which is an increased marker in patients with AA, may be effective for the decision of the treatment between surgery and antibiotherapy, and that WBC count alone may not be a sufficiently effective parameter. Neutrophil count or neutrophil percentage which are known to increase in inflammatory situations, have been shown to increase in AA as well [19, 20]. Albayrak et al. [21] have reported that neutrophil percentage was significantly increased in patients with AA compared to the healthy control group and the sensitivity, specificity, PPV and NPV values were 68.6%, 86.4%, 84.7% and 71.5, respectively. Bilici et al. [22] have reported significantly increased neutrophil percentage in pediatric patients with a specificity and sensitivity level of 90% and 93%, respectively. Lin et al. [23] have reported that the duration of symptoms, peritoneal signs and increased CRP were predictors of a rupture in patients with acute appendicitis, but leukocyte count did not differ between patients with or without rupture. In our study, neutrophil count on admission to the emergency unit was found to be significantly increased in the surgery group with a sensitivity and specificity of 52.13% and 75.93%, respectively.
Left shift of neutrophilia and hemogram in acute appendicitis is generally associated with lymphopenia and was reported to be presented by monocytosis, which is a characteristical finding of acute infections [14, 24]. In our study, no difference was observed between patients undertaken surgical treatment or antibiotherapy with regard to lymphocyte count, however, monocyte count was found to be higher in the surgery group. A monocyte count >0,64 had a sensitivity and specificity of 84% and 38.8%, respectively.
Neutrophil-to-lymphocyte ratio and mean platelet volume (MPV) are hematological parameters that have been shown to have a relationship with inflammatory conditions. Many studies have reported increased neutrophil count and decreased lymphocyte count in acute appendicitis, and related increase in neutrophil/ lymphocyte ratio (NLR) was found to have a high sensitivity for the diagnosis of the disease. In the study of Markar et al. investigating 1117 patients undertaken appendectomy, NLR was reported to have significantly higher diagnostic sensitivity compared to leukocyte count and CRP.
Another hematological parameter investigated for the diagnosis of AA is RDW, which has demonstrated different results. Narcı et al. [29] have retrospectively evaluated the data of 590 patients operated due to AA for 3 years and compared the outcomes of these patients to those of healthy controls (n=121). They have detected significantly lower RDW in patients with AA, and the sensitivity and specificity levels were found to be 47 and 67% respectively, when the cutoff value was accepted as 15.6%. In the study of Tanrıkulu et al., no significant difference was observed between RDW of patients with AA and individuals in the control group. In our study, no difference was observed between RDW values of patients planned to undergo surgical treatment and those planned to receive medical therapy. Albayrak et al. [ 21] have reported significantly reduced MPV in patients with AA compared to healthy controls as well. The best MPV level cutoff point for AA was 7.6 fL, with a sensitivity of 73% and a specificity of 84%. Bilici et al. have reported significantly reduced MPV in pediatric patients with AA as well, with a specificity of 60% and a sensitivity of 87%. In our study, no significant difference was observed between MPV values of the patients planned to undergo surgical treatment and those planned to receive medical therapy.
Treatment decision for patients with AA is made upon factors such as the clinical situation and imaging outcomes of the patient, and response to therapy. Hematological parameters may be used for the diagnosis of AA, and may help the clinician in the selection of the treatment. However, we believe that this alone is not sufficient for decision making compared to hematological parameters, and other factors should carefully be considered as well.
Limitations of the study
This study had the following limitations: it was designed on the blood samples collected in the emergency unit on admission, no standardization was performed for the patients undertaken surgical treatment or antibiotherapy, the design was retrospective, decision of surgery was left completely to the choice of the surgeon, no histopathological discrimination of perforation, abscess or inflammation was performed, the diagnosis was made upon physical examination, patient history, clinical, laboratory and imaging findings for especially patients undertaken antibiotherapy, which are not 100% diagnostic, and no histopathological data were present for precise diagnosis of these patients.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
1. Yeh B. Does this adult patient have appendicitis? Ann Emerg Med. 2008;52(3):301-3.
2. Fike FB, Mortellaro VE, Juang D, Sharp SW, Ostlie DJ, Peter SDS. The impact of postoperative abscess formation in perforated appendicitis. J Surg Res. 2011;170(1):24-6.
3. Noh H, Chang S-J, Han A. The diagnostic values of preoperative laboratory markers in children with complicated appendicitis. J Korean Surg Soc. 2012;83(4):237-41.
4. Poortman P, Hamming J. Prospective trial of computed tomography and ultrasonography for diagnosing appendicitis in the atypical patient. Am J Surg. 2001;182(3):305.
5. Fitz R. Perforating inflammation of the vermiform appendix, with special reference to its early diagnosis and treatment. Am J Med Sci. 1886;92:321–346.
6. Coldrey E. Five years of conservative treatment of acute appendicitis. J Int Coll Surg. 1959;32(3):255-61.
7. Styrud J, Eriksson S, Nilsson I, Ahlberg G, Haapaniemi S, Neovius G, et al. Appendectomy versus antibiotic treatment in acute appendicitis. a prospective multicenter randomized controlled trial. World J Surg. 2006;30(6):1033.
8. Hansson J, Körner U, Khorram-Manesh A, Solberg A, Lundholm K. Randomized clinical trial of antibiotic therapy versus appendicectomy as primary treatment of acute appendicitis in unselected patients. Br J Surg. 2009;96(5):473-81.
9. Turhan AN, Kapan S, Kutukcu E, Yigitbas H, Hatipoglu S, Aygun E. Comparison of operative and non operative management of acute appendicitis. Ulus Travma Acil Cerrahi Derg. 2009;15(5):459-62.
10. Farahnak M, Talaei-Khoei M, Gorouhi F, Jalali A, Gorouhi F. The Alvarado score and antibiotics therapy as a corporate protocol versus conventional clinical management: randomized controlled pilot study of approach to acute appendicitis. Am J Emerg Med. 2007;25(7):850-2.
11. Malik AA, Bari S-u. Retracted Article: Conservative Management of Acute Appendicitis. J Gastrointest Surg. 2009;13(5):966-70.
12. Yardeni D, Hirschl RB, Drongowski RA, Teitelbaum DH, Geiger JD, Coran AG. Delayed versus immediate surgery in acute appendicitis: do we need to operate during the night? J Pediatr Surg. 2004;39(3):464-9.
13. Mason RJ. Surgery for appendicitis: is it necessary? Surg Infect. 2008;9(4):481- 8.
14. Andersson R. Meta-analysis of the clinical and laboratory diagnosis of appendicitis. Br J Surg. 2004;91(1):28-37.
15. Birchley D. Patients with clinical acute appendicitis should have pre-operative full blood count and C-reactive protein assays. Ann R Coll Surg Engl. 2006;88(1): 27-32.
16. Xharra S, Gashi-Luci L, Xharra K, Veselaj F, Bicaj B, Sada F, et al. Correlation of serum C-reactive protein, white blood count and neutrophil percentage with histopathology findings in acute appendicitis. World J Emerg Surg. 2012;7(1):27.
17. Kaya B, Sana B, Eris C, Karabulut K, Bat O, Kutanis R. The diagnostic value of D-dimer, procalcitonin and CRP in acute appendicitis. Int J Med Sci. 2012;9(10):909.
18. Kırkıl C, Yiğit MV, Aygen E. Long-term results of nonoperative treatment for uncomplicated acute appendicitis. Turk J Gastroenterol. 2014;25(4):393-7.
19. Tanrikulu CS, Tanrikulu Y, Sabuncuoglu MZ, Karamercan MA, Akkapulu N, Coskun F. Mean platelet volume and red cell distribution width as a diagnostic marker in acute appendicitis. Iran Red Crescent Med J. 2014;16(5):e10211.
20. Uyanik B, Kavalci C, Arslan ED, Yilmaz F, Aslan O, Dede S, et al. Role of mean platelet volume in diagnosis of childhood acute appendicitis. Emery Medi Int. 2012;2012: 823095-99.
21. Albayrak Y, Albayrak A, Albayrak F, Yildirim R, Aylu B, Uyanik A, et al. Mean platelet volume: a new predictor in confirming acute appendicitis diagnosis. Clini Appl Thromb Hemost. 2011;17(4):362-6.
22. Bilici S, Sekmenli T, Göksu M, Melek M, Avci V. Mean platelet volume in diagnosis of acute appendicitis in children. Afr Health Sci. 2011;11(3): 427-32..
23. Lin CJ, Chen JD, Tiu CM, Chou YH, Chiang JH, Lee CH, et al. Can ruptured appendicitis be detected preoperatively in the ED? Am J Emerg Med. 2005;23(1):60-6.
24. Kamran H, Naveed D, Nazir A, Hameed M, Ahmed M, Khan U. Role of total leukocyte count in diagnosis of acute appendicitis. J Ayub Med Coll Abbottabad. 2008;20(3):70-1.
25. Ekiz O, Balta I, Sen BB, Rifaioglu EN, Ergin C, Balta S, et al. Mean platelet volume in recurrent aphthous stomatitis and Behçet disease. Angiology. 2014;65(2):161-5.
26. Fu SJ, Shen SL, Li SQ, Hua YP, Hu WJ, Liang LJ, et al. Prognostic value of preoperative peripheral neutrophil-to-lymphocyte ratio in patients with HBV- associated hepatocellular carcinoma after radical hepatectomy. Med Oncol. 2013;30(4):721.
27. Goodman DA, Goodman CB, Monk JS. Use of the neutrophil: lymphocyte ratio in the diagnosis of appendicitis. Am Surg. 1995;61(3):257-9.
28. Markar S, Karthikesalingam A, Falzon A, Kan Y. The diagnostic value of neutrophil: lymphocyte ratio in adults with suspected acute appendicitis. Acta Chirurgica Belgica. 2010;110(5):543-7.
29. Narci H, Turk E, Karagulle E, Togan T, Karabulut K. The role of red cell distribution width in the diagnosis of acute appendicitis: a retrospective case- controlled study. World J Emerg Surg. 2013;8(1):46.
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Mehmet Cagri Goktekın, Mustafa Yılmaz, Ahmet Bozdag. Role of hematological parameters in the selection of acute appendicitis treatment. Ann Clin Anal Med 2020;11(5):420-424
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Chronic heavy alcohol consumption and asymptomatic cardiovascular effects: An observational study
Ertan Aydın 1, Murat Akcay 2
1 Clinic of Cardiology, Giresun University, Prof. Dr. A. Ilhan Ozdemir Training and Research Hospital, Giresun, 2 Department of Cardiology, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey
DOI: 10.4328/ACAM.20100 Received: 2020-01-02 Accepted: 2020-06-17 Published Online: 2020-06-21 Printed: 2020-09-01 Ann Clin Anal Med 2020;11(5):492-497
Corresponding Author: Murat Akcay, Department of Cardiology, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey. E-mail: drmuratakcay@hotmail.com GSM: +90 506 779 57 60 Corresponding Author ORCID ID: https://orcid.org/0000-0002-4610-8514
Aim: The association between chronic heavy alcohol consumption and a number of adverse cardiovascular consequences such as hypertension, dyslipidemia, dysrhythmia, coronary artery disease, sudden cardiac death, and particularly dilated cardiomyopathy is becoming increasingly more evident.
In this study, our objective was to determine the preclinical cardiac effects of chronic heavy alcohol consumption in young and middle-aged asymptomatic healthy individuals.
Material and Methods: The study is planned as cross-sectional and observational. A total of 40 men between 25 and 55 years of age with weekly alcohol consumption of ≥ 850 g for a minimum duration of 8 years (chronic heavy alcohol group) and 40 men with no alcohol use (control group) were included. The demographic characteristics, results of echocardiographic and electrocardiographic assessments and epicardial adipose tissue thickness were recorded.
Results: Individuals with alcohol use had significantly higher systolic and diastolic blood pressures, increased left atrial antero-posterior diameter, increased interventricular septum and posterior wall thickness, and higher incidence of stage 1 diastolic dysfunction (p< 0.05). Epicardial adipose tissue thickness was higher in alcohol users group compared to the control group (5.46±1.65 vs 3.20±1.03, p = 0.0001). Also, the incidence of atrial fibrillation and right bundle branch block were increased compared to the control group.
Discussion: Our results have shown that chronic heavy alcohol consumption is associated with diastolic dysfunction, increased epicardial adipose tissue thick- ness, electrocardiographic disturbances, and atrial fibrillation. These findings show that alcohol use leads to a variety of asymptomatic changes in cardiac functions.
Keywords: Chronic alcohol; Cardiovascular effects; Epicardial adipose
Introduction
Alcohol is one of the most widely abused drinks worldwide and influences many organ systems, covering the cardiovascular system [1, 2]. Alcohol consumption in light and moderate doses has a beneficial and protective effect against cardiovascular events; however chronic heavy alcohol intake causes different cardiovascular diseases [3, 4]. In these individuals, the mechanisms of alcohol toxicity and potential cardio-protective effects continue to be investigated due to different outcomes in various studies [5, 6, 7].
Chronic heavy alcohol drinking may lead to cardiovascular, metabolic, and toxic disorders, abnormalities in ventricular diastolic and/or systolic dysfunction, elevated arterial blood pressure, angina pectoris, coronary artery disease, arrhythmia, and even sudden cardiac death, increased risk of stroke, obesity, cancer, liver diseases, etc [6-13]. Therefore, early detection of the sub-clinical cardiac abnormalities is essential to chronic heavy alcohol drinkers which can be detected with electrocardiographic and echocardiographic evaluation and, benefit from early treatment.
In this study, we aimed to detect the pre-clinical cardiac effects of chronic heavy alcohol consumption in asymptomatic young and middle-aged subjects using echocardiographic and electrocardiographic alterations. Also, we examined the association between chronic heavy alcohol consumption and epicardial adipose tissue thickness, which is a marker of visceral fat tissue, is being increasingly investigated, associated with a variety of untoward atherosclerotic cardiac diseases [14].
Material and Methods
Study Design
The present study is cross-sectional and observational.
Study Population
The study included 40 subjects who were followed up at the department of Psychiatry with a diagnosis of alcohol dependence or alcohol use disorder and 40 control subjects from the department of Cardiology matched for demographic and clinical characteristics. Asymptomatic male individuals with no history of systemic or cardiac disease and no substance abuse other than smoking who met the diagnostic criteria for alcohol abuse established by the American Psychiatric Association were included if they had a weekly consumption of ≥ 850 g of alcohol and ≥ 4 days/week, for a minimum duration of 8 years (Group 1). The patients drank alcohol one week before the examination at the earliest and blood alcohol levels were not evaluated. The control group (Group 2) consisted of healthy age-matched men who had never used alcohol. Since all subjects in Group 1 were smokers, control subjects were also chosen among smokers. For the measuring of the amount of ethanol in grams, the mean alcohol percentage in the drinks was recorded. Then, the amount of pure alcohol intake in ml/week was measured according to the alcoholic concentration of each drink. The total duration of alcohol use, the weekly amount of unit consumption and alcohol drinks species such as beer, wine, whiskey, etc were recorded. A 70 cl Raki (a local drink) contains 248 g of ethanol and most subjects reported regular use of Raki. Ethanol content of Raki is 45%. A 70 cl Raki is 700 cm3 and the density of ethyl alcohol is 0.79 g / cm3 [15]. If the mean weekly consumption of ethanol was below 850 g when all beverages were considered, the subject was excluded from the study. Again, a minimum duration of 8 years of alcohol use was a prerequisite for study participation. Those with light alcohol consumption or those without psychiatric abuse were excluded. In both groups, subjects were > 25 and < 55 years of age, had no additional substance abuse problem and no history of hypertension, diabetes, systemic or cardiac disease history. Also, poor echocardiographic image quality and unwillingness for the study were reasons for exclusion from the study. Female subjects were not included in the study due to the extreme rarity of chronic heavy alcohol use among women and also social factors.
Clinical and Laboratory Assessments
A complete physical examination was performed in all subjects. Age, anthropometric assessments of height and weight were recorded, and body mass index (BMI, kg/m2) was calculated by dividing body weight in kilograms by the square of the height in meters. Systolic and diastolic blood pressures and heart rate were calculated after 10 min of rest in a quiet room. Routine biochemistry and lipid parameters could not be assessed, as most of the laboratory results consisted of hepatic and renal function test that were performed in other health clinics on an irregular basis, and were detected at normal limits and as most of the subjects experienced the compliance problems.
The study protocol was confirmed by the local ethics committee. Patients provided written informed consent after oral and written information was given.
Transthoracic Echocardiographic Evaluation
All echocardiographic measurements were performed with a Vivid 7 device (GE Vingmed Ultrasound, Horten, Norway) with a 2.5 MHz probe. The following were measured using parasternal long axis two-dimensional transthoracic echocardiography: left atrium (anterior-posterior) diameter, right ventricle diastolic diameter, the thickness of interventricular septum and posterior wall, and the systolic and diastolic diameters of the left ventricle. Using two-dimensional images, septum and posterior wall movements, valvular morphology, and left atrial and left and right ventricular chambers were evaluated. Apical four and two-chamber views were used to calculate the left ventricular ejection fraction using the modified Simpson’s technique with left ventricular end-systolic and end-diastolic volume measurements.
Using the apical 4-chamber views, transmitral flow rates (E, A, E/A) were assessed and time-analyses (IVRT, DT) were performed. Also, tissue Doppler examination was performed on the mitral annulus, including the mitral septal and lateral annulus tissue (E’, A’, S’). The mean of the three consecutive mitral annulus pulsed wave tissue Doppler measurements was obtained. In apical 4-chamber views, a continuous wave Doppler cursor was placed on the trans-tricuspid flow, and the estimated right atrial pressure value was added to this flow to calculate the pulmonary artery pressure. The right atrial pressure was calculated using the subcostal images based on the diameter of the inferior vena cava and its variability during respiration.
Epicardial Adipose Tissue Measurement
For epicardial adipose tissue measurements, the aortic annulus
was taken as an anatomic reference in the parasternal long and short axes, and the area between pericardial layers with the lowest echo-density perpendicular to the RV free wall was measured two-dimensionally and with the M-mode (Figure 1). The average end-diastolic value measured in three cardiac cycles was recorded.
Electrocardiography (ECG)
Twelve-lead ECGs were obtained after a 10-minute rest, with 10 mm/mV amplitude and 25 mm/s rate with standard lead positions an ECG machine (Nihon Kohden, Tokyo, Japan). ECGs were manually measured by the use of a magnifying lens and subsequently, ECG recordings were examined with respect to rate, rhythm, axes, and time intervals (PR, QRS, QTc) as well as pathological findings.
Statistical Analyses
Data obtained from study participants were entered into the database of SPSS v.15.0 software for Windows (SPSS Inc. Chicago, Illinois, USA). Normal distribution of the data was tested using the Kolmogorov-Smirnov test. For data without normal distribution, the Kruskal- Wallis analysis of variance and the Mann-Whitney U tests were used. The data were presented as number, percentage, and arithmetic mean ± standard deviation. Groups were compared using the Student’s t-test and the Chi-square test, and the correlations between variables were evaluated by means of the Pearson’s correlation analysis. The grade of importance was set at a P- value of less than 0.05.
Results
When comparing alcohol users (Group 1) and non-users (Group 2) a trend toward higher bodyweight and BMI in Group 1 was shown, but there was no statically significant difference (p > 0.05). There were no significant differences in terms of age, height, body weight, and baseline demographic characteristics (p > 0.05). However, alcohol users had significantly higher heart rate and systolic and diastolic blood pressure (p = 0.001; p = 0.005; p = 0.034, respectively) (Table 1).
Individuals in Group 1 had significant increase in the left atrial anterior-posterior diameter, septal and posterior thickness, and systolic pulmonary artery pressure (sPAB) (p = 0.003; p = 0.001; p = 0.016 and p = 0.001 respectively). There were no important variations in terms of left ventricular end- diastolic diameter, end-systolic diameter, and right ventricular diameter between the two groups (p > 0.05). Also, epicardial adipose tissue thickness (EAT) was significantly higher in Group 1 (5.46±1.65 vs 3.20±1.03, p = 0.0001) (Table 1). When comparing the transmitral flow (E, A), time parameters (IVRT, DT), and mitral annulus tissue Doppler parameters (S’, E’, A’), there were no significant differences between two groups (p > 0.05). There was only statically significant higher E/A ratio and grade 1 diastolic dysfunction in Group 1 (p = 0.011; p = 0.034, respectively) (Table 2).
Electrocardiographic analysis showed significant elevation of heart rate in alcohol users (77 bpm/min vs 68 bpm/min p = 0.001). Atrial fibrillation and right bundle branch block were identified in each of the two patients, while there were no such cases in alcohol non-users (Table 3).
Discussion
In this study, asymptomatic cardiac effects were compared between young and middle-aged, asymptomatic chronic heavy alcohol users and age-matched, healthy males with no known medical conditions. Alcohol users were found to have significantly elevated systolic and diastolic blood pressure, heart rate, left atrial dimensions, interventricular septal and posterior wall thickness, systolic pulmonary artery pressure, epicardial fat tissue thickness, and diastolic dysfunction (Grade 1) as compared to alcohol non-users. In electrocardiography, asymptomatic right bundle branch block and atrial fibrillation were detected in two patients each.
Alcohol is among the most widely abused drinks worldwide and affects many organ systems, including the heart and vessels [1]. Currently, disorders involving alcohol use are categorized with DSM-IV criteria, into two groups: alcohol use disorder and alcohol dependence [16]. These disorders are a significant cause of mortality, morbidity, and social problems in many countries. Some epidemiological studies have shown beneficial effect of low alcohol consumption [6-13]. Although low alcohol consumption has some beneficial effects, the number of investigations of side effects of alcohol consumption commonly increase, as in our study [6-13].
Alcoholic cardiomyopathy (CMP) is defined as enlarged cardiac chambers with largely hypertrophy and extracellular matrix (ECM) remodeling [1]. Major mechanisms implicated in the development of alcoholic cardiomyopathy include the direct toxic effect of ethanol and it metabolites (acetaldehyde and acetate) on the myocardium; vitamin (thiamine) and mineral (selenium) deficiencies as well as electrolyte (Mg, P, K) imbalance-deficits seen in heavy alcohol users; additional toxic effect of substances such as lead or cobalt found in alcoholic beverages; and genetic predisposition for ethanol toxicity (e.g. ACE gene) [17, 20]. Chronic and intense toxic effects lead to systolic dysfunction and dilated cardiomyopathy [17, 18, 20]. In the current study, alcohol use was found to be associated with significant diastolic dysfunction, although no subjects had systolic failure. These findings are in corroboration with the observation that diastolic heart failure represents an initial stage in the development of alcoholic CMP [17, 18]. Accordingly, in a study by Fernandez Sola J et al. [18], involving a total of 112 chronic heavy alcohol users, diastolic dysfunction was present in two-thirds of those with systolic HF and in one-third of individuals with an ejection fraction of higher than 50%, and these findings correlated with the amount of alcohol consumed irrespective of age. Similarly, in our study alcohol users had significantly higher incidence of diastolic dysfunction. In an echocardiographic study, involving 34 young (< 45 age) male alcoholic subjects with no cardiovascular symptoms, patients were found to have diastolic abnormality despite normal systolic functions, suggesting that this represents an early sign in the process of alcoholic CMP [19]. In another study by Kycina P et al. [20], a total of 100 individuals with mean daily alcohol consumption of ≥ 120 g and < 120 g alcohol were assessed clinically and echocardiographically during a 4-year follow up period. No significant differences between the two groups were observed with regard to LV ejection fraction, LA diameter, biochemical parameters, DM, and atrial fibrillation. Except for LA dimensions, these findings are consistent with our observations regarding the left ventricular ejection fraction. Therefore, diastolic dysfunction associated with alcohol use carries clinical significance as an initial sign of the CMP process [1, 9, 17, 20]. It should also be borne in mind that other factors may have a predictive role in the development of alcoholic cardiac disease and these include the duration, frequency, and amount of alcohol consumption, the type of alcohol consumed, presence of additional substance abuse (cigarette, marihuana), and family history of cardiomyopathy [3, 4, 12, 13].
Alcohol leads to an elevation of systemic arterial blood pressure, particularly when consumed in moderate or high quantities. Comparisons between age- and gender-matched individuals suggest that those with daily consumption of >2 units of alcohol (20-30 g ethanol) are 1.5 to 2-times more likely to experience hypertension [4, 8]. In the Polish Wobasz study [21] with the participation of 6912 males between 20 and 74 years of age, the cardiovascular risk was classified on the basis of daily alcohol consumption, and a positive correlation between systolic/diastolic blood pressure and alcohol use was found. Polish men with a daily > 30 g of alcohol consumption had a 52% increased risk of developing hypertension [21]. Also, in our study alcohol users had significantly elevated systolic and diastolic blood pressure values than those without alcohol consumption. On average, systolic and diastolic blood pressures were 10.250 mmHg and 4.875 mmHg were higher in alcohol users. However, there were 10 individuals (25%) with systolic and diastolic hypertension in our study; these measurements did not have diagnostic value as they represent values measured in a single visit.
Hypertension, which may occur in patients with chronic alcoholism, is also associated with increased left ventricular filling pressure, ventricular hypertrophy, diastolic dysfunction, and atrial remodeling and dilatation [22]. So, increased left atrial diameter is a risk factor for stroke and death [22]. In our study, alcohol users had higher left atrial diameter than those without alcohol use. Again, alcohol users with diastolic dysfunction and LA enlargement in our study had statistically significantly higher systolic pulmonary arterial pressure, suggesting that this process may be related to a backward effect of increased pressure secondary to left cardiac disease, i.e. diastolic dysfunction.
Alcohol use may be associated with the occurrence of a number of atrial or ventricular rhythm disorders. The most common dysrhythmia is atrial or ventricular premature beats, while other rhythm disturbances such as supraventricular tachycardia, atrial flutter, atrial fibrillation, ventricular tachycardia, and ventricular fibrillation may also occur. The most common chronic rhythm disorder due to ethanol is atrial fibrillation [23]. Although cardiac routine was not routinely monitored in our study, two individuals with heavy alcohol consumption were found to have atrial fibrillation. Also, the study by Thayer JH, et al. [24] from the US found reduced heart rate variability and increased heart rate among 542 male drinkers. Consistent with these reports, alcohol users in our study had a significantly higher heart rate. Epicardial adipose tissue (EAT) is a structure of mesodermal origin that is located on the epicardium [14, 25] and that functions as a cushion against accumulation of toxic levels of fatty acids among the myocardium and local vascular layer and also a marker of increased visceral adiposity [25]. Recent studies have suggested a strong correlation between increased epicardial adipose tissue thickness and obesity, impaired glucose tolerance, metabolic syndrome, hypertension, diabetes, atherosclerosis [14, 25]. In our study, alcohol users had a statistically significant increase in epicardial adipose thickness. When one considers the causative role of alcohol in the above- mentioned conditions, a link between alcohol use and an increase in epicardial adipose thickness may exist. For instance, alcohol consumption may represent an independent precursor or even a prognostic marker for the development of alcoholic heart disease through an increase in epicardial adipose mass. At least, it can be assumed that alcohol may lead to increased epicardial fat mass, i.e. visceral adiposity.
Heavy alcohol use is related to an increased incidence of atherosclerotic coronary heart disease, hence the increased cardiovascular morbidity and mortality [5-7, 11]. This elevated risk is at least partially related to traditional risk factors commonly present in heavy drinkers such as systemic arterial hypertension, increased left ventricular muscle mass, and hypertriglyceridemia [11,12,13]. Furthermore, cigarette smoking is also a frequent habit among heavy drinkers. No further assessments for coronary artery disease were performed in our study.
Study Limitations
A major limitation of our study is the fact that the amount of alcohol consumption was estimated on the basis of self-reports of the participants (i.e. days without alcohol use, variability in the type of alcoholic beverages utilized, different amounts of alcohol consumption on different days, etc.). Another limitation of our study is not including female subjects due to the extreme rarity of chronic heavy alcohol use among women. Again, although our participants consisted of asymptomatic individuals, absence of objective assessments for the functional status and physical exercise capacity represent another limitation. Also, arterial blood pressure measurements were performed in a single visit without continuous blood pressure measurements, inadequate access to previous laboratory test results, operator-dependency of the echocardiographic assessments, and small sample size (light and moderate drinkers could also have been included for a more comprehensive comparison between the groups) should be mentioned in this respect.
Conclusion
As compared to a group of individuals with no use of alcohol and with similar baseline characteristics, from young to middle age and apparently healthy males with chronic heavy alcohol users were found to have a number of asymptomatic abnormalities including impaired diastolic function, increased systolic and diastolic blood pressure, LV hypertrophy, dilatation of LA, increased systolic pulmonary artery pressure, and elevated heart rate. Also, to the best of our knowledge, this study represents the first study to show an increased epicardial adipose thickness in chronic heavy alcohol users.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
1. Ninh VK, El Hajj EC, Mouton AJ, El Hajj MC, Gilpin NW, Gardner JD. Chronic Ethanol Administration Prevents Compensatory Cardiac Hypertrophy in Pressure Overload. Alcohol Clin Exp Res. 2018; 42; 8; 1408-17.
2. Delker E, Brown Q, Hasin DS. Alcohol Consumption in Demographic Subpopulations: An Epidemiologic Overview. Alcohol Res. 2016; 38; 1: 7-15.
3. Wood AM, Kaptoge S, Butterworth AS, Willeit P, Warnakula S, Bolton T, et al. Risk thresholds for alcohol consumption: combined analysis of individual- participant data for 599 912 current drinkers in 83 prospective studies. Lancet. 2018; 391; 10129: 1513-23.
4. Stockwell T, Zhao J, Panwar S, Roemer A, Naimi T, Chikritzhs T. Do “Moderate” Drinkers Have Reduced Mortality Risk? A Systematic Review and Meta-Analysis of Alcohol
Consumption and All-Cause Mortality. J Stud Alcohol Drugs. 2016; 77; 2: 185-98.
5. Pai JK, Mukamal KJ, Rimm EB. Long-term alcohol consumption in relation to all-cause and cardiovascular mortality among survivors of myocardial infarction: the Health Professionals Follow-up Study. Eur Heart J. 2012; 33; 13: 1598-605.
6. Roerecke M, Rehm J. Alcohol consumption, drinking patterns, and ischemic heart disease: a narrative review of meta-analyses and a systematic review and meta-analysis of the impact of heavy drinking occasions on risk for moderate drinkers. BMC Med. 2014; 12: 182.
7. Onat A, Hergenç G, Küçükdurmaz Z, Uğur M, Kaya Z, Can G, et al. Moderate and heavy alcohol consumption among Turks: long-term impact on mortality and cardiometabolic risk. Turk Kardiyol Dern Ars. 2009; 37; 2: 83-90.
8. Abe H, Kawano Y, Kojima S, Ashida T, Kuramochi M, Matsuoka H, et al. Biphasic effects of repeated alcohol intake on 24-hour blood pressure in hypertensive patients. Circulation. 1994; 89: 2626-33.
9. Wang Y, Shan G, Shen J, Zhou Q, Tan B, Liu Y, et al. Assessment of left ventricular function in chronic alcoholics by real-time three-dimensional echocardiography. Medicine (Baltimore). 2017; 96; 5: e6033.
10. Kocabay G, Karabay CY, Kalaycı A, Oduncu V, Akgun T, Guler A, et al. Left Atrial Function by Speckle-Tracking Echocardiography in Chronic Asymptomatic Alcoholic Patients. Cardiovasc Toxicol. 2015; 15; 2; 189–96.
11. Song RJ, Nguyen XT, Quaden R, Ho YL, Justice AC, Gagnon DR, et al. Alcohol Consumption and Risk of Coronary Artery Disease (from the Million Veteran Program). Am J Cardiol. 2018; 121; 10: 1162-8.
12. Leong DP, Smyth A, Teo KK, McKee M, Rangarajan S, Pais P, et al; INTERHEART Investigators. Patterns of alcohol consumption and myocardial infarction risk: observations from 52 countries in the INTERHEART case-control study. Circulation. 2014; 130; 5: 390-8.
13. Ilic M, Grujicic Sipetic S, Ristic B, Ilic I. Myocardial infarction and alcohol consumption: A case-control study. PLoS One. 2018; 13; 6: e0198129.
14. Iacobellis G, Assael F, Ribaudo MC, Zappaterreno A, Alessi G, Di Mario U, et al. Epicardial fat from echocardiography: A new method for visceral adipose tissue prediction. Obes Res. 2003; 11: 2; 304–10.
15. Yilmaztekin M, Cabaroglu T. Confirmatory method for the determination of volatile congeners and methanol in Turkish raki according to European Union Regulation (EEC) No. 2000R2870: single-laboratory validation. J AOAC Int. 2011; 94; 2: 611-7.
16. American Psychiatric Association .Substance-related and addictive disorders in the DSM-5. In: Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5). Arlington, VA: American Psychiatric Publishing American Psychiatric Association. 2013; p. 310-56.
17. Steiner JL, Lang CH. Alcoholic Cardiomyopathy: Disrupted Protein Balance and Impaired Cardiomyocyte Contractility. Alcohol Clin Exp Res. 2017; 41; 8: 1392- 401.
18. Fernández-Solà J, Nicolás JM, Paré JC, Sacanella E, Fatjó F, Cofán M, et al. Diastolic function impairment in alcoholics. Alcohol Clin Exp Res. 2000; 24; 12: 1830-5.
19. Kupari M, Koskinen P, Suokas A, Ventilä M. Left ventricular filling impairment in asymptomatic chronic alcoholics. Am J Cardiol. 1990; 66; 20: 1473-7.
20. Kycina P, Murin J. Alcoholic cardiomyopathy and cardiovascular events – an insight from the Liptov region. Bratisl Lek Listy. 2013; 114; 6: 337-41.
21. Waśkiewicz A, Sygnowska E. Alcohol intake and cardiovascular risk factor profile in men participating in the WOBASZ study. Kardiol Pol. 2013; 71; 4: 359- 65.
22. Tsang TS, Barnes ME, Bailey KR, Leibson CL, Montgomery SC, Takemoto Y, et al. Left atrial volume: important risk marker of incident atrial fibrillation in 1655 older men and women. Mayo Clin Proc. 2001; 76: 467-75.
23. Menz V, Grimm W, Hoffmann J, Maisch B. Alcohol and rhythm disturbance: The holiday heart syndrome. Herz. 1996; 21; 4: 227-31.
24. Thayer JF, Hall M, Sollers JJ 3rd, Fischer JE. Alcohol use, urinary cortisol, and heart rate variability in apparently healthy men: Evidence for impaired inhibitory control of the HPA axis in heavy drinkers. Int J Psychophysiol. 2006; 59; 3: 244-50.
25. Iacobellis G, Bianco AC. Epicardial adipose tissue: emerging physiological, pathophysiological and clinical features. Trends Endocrinol Metab. 2011; 22: 450-7.
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Assessment of anterior cruciate ligament (ACL) arthroscopic reconstruction using gracilis and semitendinosus tendon autograft
Minh-Hoang Nguyen, Quang-Tri Le
Department of Orthopedics, 7A Military Hospital, 466 Nguyen Trai Street, Ward 8, District 5, Ho Chi Minh City, 72706, Vietnam
DOI: 10.4328/ACAM.20101 Received: 2019-12-30 Accepted: 2020-01-09 Published Online: 2020-01-10 Printed: 2020-09-01 Ann Clin Anal Med 2020;11(5):374-378
Corresponding Author: Quang Tri Le, Director of 7A Military Hospital, Head of Department of Orthopedics, 7A Military Hospital, 466 Nguyen Trai Street, Ward 8, District 5, Ho Chi Minh City, 72706, Vietnam. E-mail: lqtri@ntt.edu.vn P: (+084)0839241868 / (+084)0913126229 Corresponding Author ORCID ID: https://orcid.org/0000-0002-2777-0828
Aim: The purpose of this study is to examine the clinical features and MRI of ACL rupture and evaluate the results of ACL arthroscopic reconstruction using gracilis and semitendinosus tendon autograft.
Material and Methods: This prospective study included 85 patients with ACL rupture getting ACL arthroscopic reconstruction using gracilis and semitendino- sus tendon autograft at 7A Military Hospital (Ho Chi Minh City, Viet Nam) from July 2015 to December 2018.
Results: The results showed that ACL ruptures were common in men within working age; the ACL were often complete broken and has combined lesions, most commonly meniscus tears. 12.2 months of surgery, 86.2% of patients achieved very good and good results, 11.3% of patients achieved average results, and 2.5% of patients achieved bad results.
Discussion: Research showed that ACL arthroscopic reconstruction using gracilis and semitendinosus tendon autograft tend to be highly effective in restoring joint motor function.
Keywords: Anterior; Cruciate Ligament; Arthroscopic; Reconstruction Surgery; Gracilis; Semitendinosus; Tendon Autograft
Introduction
An anterior cruciate ligament (ACL) plays an essential role in ensuring the normal motor function of the knee joint. Knee joint injury with ACL rupture makes the knee joint unstable. If not treated promptly, it will cause secondary damages to other components such as the meniscus, synovial membrane, articular cartilage, cartilage meniscus, causing osteoarthritis, and accelerate the knee injury process. Therefore, it is necessary to prescribe ACL reconstructive surgery [1].
The studies aimed at ACL recovery have been conducted by many authors over the years [2, 3]. In 1963, Kenneth Jones introduced an open surgery method using one-third of the patellar tendon threaded in a drilled channel through the lateral femoral condyle to replace the ACL [4, 5]. Recently, ACL reconstruction arthroscopy surgery has become routine in many places, minimizing invasive surgery, helping the joint functions recover sooner and more perfectly.
There are many materials used to reconstruct the ACL. The patellar tendon is a good graft; however, taking this material can cause complications such as weakening of the knee, rupture of the kneecap, prolonged pain in front of the knee [6]. From the above limitations, many surgeons chose gracilis and semitendinosus tendons instead. These grafts are easy to get, have little effect on function and aesthetics [7-11]. Therefore, we conducted this study to investigate the clinical features, specifications of ACL rupture image on Magnetic resonance imaging (MRI), and arthroscopy. At the same time, we assessed the results of ACL reconstruction through arthroscopy using gracilis and semitendinosus tendons.
Material and Methods
Subject, time and place of research
A total of 85 patients with ACL rupture underwent ACL arthroscopic reconstruction using gracilis and semitendinosus tendon autograft at 7A Military Hospital (Hochiminh City, Vietnam) from July 2015 to December 2018.
Selected patients were aged 17-50 years, having ACL ruptures due to trauma and having first time ACL reconstructive surgery. Excluded patients with ACL ruptures combined with other ligaments ruptures that needed surgery or reconstructive at the same time, patients with ACL ruptures with complicated knee joint injuries, patients with severe knee osteoarthritis, and patients with ACL ruptures were aged under 17 or over 50 years old.
Research design
Prospective research
– Sample size: Calculated by the formula: n=X2(1-α/2)p(1-p)/(εp)2
In which: Z1- / 2 = 1.96 (95% confidence coefficient), p = 0.3 (according to previous studies); ε = 0.4. Inferred sample size: n ≥ 41.
– Clinical characteristics: age, gender, cause, time of surgery, clinical symptoms.
– Clinical signs: drawer, Lachman, Pivot shift.
– Image characteristics of the injuries on MRI and arthroscopy.
Methods of surgery
The patient laid on his back, a tourniquet was placed around the thigh, an arthroscopic leg holder was placed to hold the thigh, the surgical leg hanged freely. After endoscopy ports were established to detect and diagnose injuries, combined lesions were managed, ruptured ligaments were cleaned. Preparation of grafts: gracilis and semitendinosus tendons were taken on the same side, two ends of the tendons were braided, tendons were doubled, the diameter and length to select the size of the bit to drill the tibial-femoral tunnel were measured.
Tunnels drilling: Tibial tunnel was drilled following the tibial tunnel locator from below the joint line and medial to the tibial tubercle to the center of ACL insertion. The femoral tunnel was drilled following the femoral tunnel locator, between the lateral intercondylar ridge and the posterior articular margin. Threading and securing the drafts: the draft was threaded through the tibial tunnel into the femoral tunnel, the knee was hyper flexed 200, both ends were stretched, tendon was fixed to the tunnel. It was checked whether the drawer sign and the Lachman signs were no longer present. Drainage, closeed the incision, placeed knee brace. Rehabilitation included four stages [12].
Evaluation of surgical results: Early results include complications and surgical complications; later results were assessed according to the Lysholm scale (Very good: From 95-100 points, Good: From 84-94 points, Medium: From 65-83 points, Bad: Less than 65 points) [13].
Data processing
The data was processed by medical statistical method using SPSS software 15.0. and hypothesis test was done by the Chi- squared method.
Research ethics
Patients and family members who came for medical examination and surgery were consulted and agreed to participate in the study. Patients who disagreed were not included in the sample and did not receive any unfair treatment. The ethics committee of The 7A Military Hospital has approved the research content. Results
Age and gender
The youngest age was 18, the oldest 49, the average: 32.2 ± 8.8. The most common age group: 21-40 years old, accounting for 74.1%, male/female ratio =2.3. Men had ACL ruptures more often than women.
Causes
Traffic accidents and sport injuries were the most common causes, accounted for the 41 cases (48.2%) and 24 cases (28.2%), respectively. Daily life accidents and occupational accidents made up of 11 (13.0%) and 9 (10.6%) cases, respectively.
Time of surgery
Four patients (4.7%) had the surgery within less than one month after injury; 39 patients (45.9%) had the surgery at 1-3 months after the injury; 11 patients(12.9%) had at 4-12 months, and 31 patients (36.5%) had over 12 months. The average surgery time after the injury was 11.1 ± 18.9 months, the earliest was 0.6 months, the longest was 15 years; the majority was in group 1-3 months(39 patients, accounting for 45.9%), and after 12 months (31 patients, accounting for 36.5%).
Clinical symptoms included knee pain (94.1%), loose joints (70.6%), difficult moving (35.3%), joints swelling (24.7%), hydrarthrosis (17.6%), muscle atrophy (21.2%) and joint locks (2.4%) Eighty-two of 85 cases (96.5%) showed positive Lachmann signs, 71 cases (83.5%) positive front drawer sign, and in 42 cases (49.4%) positive Pivot shift test.
Completely ACL rupture on MRI accounted for a high proportion (56 patients, 65.9%) comparing to incomplet ACL rupture (29 patients, 34.1%). Ruptures of ACL with combined injuries (65 patients, 76.5%) accounted for a higher percentage than simple ACL rupture (20 patients, 23.5%). Combined injuries that commonly encountered were meniscus tear (81.5%): Lateral meniscus (33.8%), medial meniscus (23.1%), and both meniscus (24.6%); see Table 2.
Characteristics of knee injuries in arthroscopy
There were 72/85 cases of ACL completely rupture (84.7%), the remaining 13 cases (15.3%) had incomplete ACL rupture with lost tension.
ACL rupture with combined injuries: 66 patients (77.6%), ACL rupture alone: 19 patients (22.4%). Common combined injuries detected in arthroscopy were meniscus tear (80.3%), including lateral meniscus tear (36.4%), medial meniscus tear (22.7%), or both meniscus (21.2%); see Table 3.
Treatment
All 85 patients (100%) received spinal anesthesia. There were 67 damaged menisci in 53 patients (including 24 patients with lateral meniscus tears, 15 patients with medial meniscus tears, and 14 patients with both meniscus tears) were trimmed and reshaped, 15 patients had meniscus sutured, and in no case the meniscus was wholly removed.
There were 8 patients with cartilage injuries (femoral condyle and tibial plateau) treated by the cut off excessive broken pieces. Two patients with both femoral condyle and tibial plateau fractures were treated by removed cartilage fragments and microfracture drilled to stimulate cartilage formation.
All patients were collected gracilis and semitendinosus on the same side (100%).
The length of the draft after doubling was averaging 103.8 ± 7.1 mm, the shortest was 95 mm, and the longest was 120 mm. The 7.5 mm diameter of the drafts accounted for a high proportion (57.6%), ≤ 7 mm accounted for 31.8%, and ≥ 8 mm accounted for 10.6%.
For the diameter of femoral and tibial tunnels, an 8 mm diameter accounted for a high proportion of 80%, 7 mm diameter accounted for 18.8%, and 9 mm diameter accounted for 1.2%.
The fixation tool for the femoral tunnel was the anchor XO button (100%). The fixation tool for the tibial tunnel was a wedge screw (100%).
Early results
There were 83 patients (97.6%) with primary intention healing, the suture was removed after 7-10 days, and rehabilitated as instructed. Two patient (2.4%) with complications from incision superficial infection had to have suture removal, cleaning and treated with strong antibiotics till stable.
Two patient (2.4%) had incision expansion to avoid corrupting the draft due to sophisticated donor tendon connections.
Two patient (2.4%) had hematoma after surgery, stabilizing after drainage.
After three months of surgery, 85.0% of patients achieved very good and good points, only 12.5% of patients achieved a medium score, and 2.5% of patients achieved a bad score (Table 4).
Long-term outcome after surgery
We could only follow up 80 patients with the shortest follow-up time of 6 months, the longest of 18 months, average follow-up of 12.2 ± 2.5 months. The remaining 5 patients were followed up in the provincial hospitals (outside of Ho Chi Minh city). All patients had good surgical scar healing, no pain or paresthesia in the scar area.
Long-term results: After the surgery (12.2 months), 86.2% of patients achieved very good and good points, only 11.3% of patients achieved a medium score, and 2.5% of patients achieved a bad score (Table 4).
Before surgery: No patients achieved very good and good scores; only 37.5% of patients achieved a medium score; the remaining 62.5% of patients had poor motor function score. There was a significant improvement in the recovery of joint motor function after the surgery compared with the preoperative joint motor function (p <0.01).
Discussion
In terms of surgery time:
In our data, surgery 1-3 months after injury accounted for a large proportion of 45.9%. This was an appropriate time. Surgery, less than one month after injuries, had not been chosen. At this time, the knee joint would still be swollen with hematoma making it challenging to diagnose. The accompanying lesions (posterior ligament rupture) also had not been healed, limiting knee joints movement, and making it difficult for postoperative training.
The group that had surgery 12 months after injury also accounted for a high proportion (36.5%). Late surgery, when secondary lesions such as meniscus and cartilage degeneration had appeared, provided less ideal results. Therefore, timely diagnosis and appointment of operation are necessary.
About the value of clinical signs:
There are three clinical methods to detect ACL rupture.
The Lachman test is an easy-to-see, specific test that gives reliable results. The Lachman test has outweighed the previous drawer test in a folding position. The Lachman test is made in a slightly folded position so that the collateral ligaments are the least strain; the meniscus does not hinder the forward movement of the medial tibial plateau. At that time, the only component against the forward translational movement of the tibia on the femur was the ACL.
The previous drawer test is also a standard test for detecting ACL rupture, although with less sensitivity. According to Muller W., although every examiner has his or her routine, it is necessary to examine the drawer first in many degrees of knee flexion, because of the visible drawer mark one angle more than another angle. However, when flexed knee 900, only the anterior ligaments are strain, and posterior ligaments are loose; therefore, when only the anterior ligament ruptured, the drawer test is considered positive [14]. According to Tria AJ, the front drawer method is more sensitive to the anterior ligaments, and the Lachman test is more sensitive to the posterior ligaments. The front drawer test is more sensitive when there is combined damage in the posterior cruciate ligaments [15].
In our study, 100% of the patients had ACL rupture, the majority (82 of 85 patients, 96.5%) showed positive Lachmann signs while only 71 of 85 patients (83.5%) showed positive front drawer test. The results were aligned with literatures that Lachmann test is more sensitive than front drawer test.
The Pivot shift test (semi-rotation sign) is a complicated and specific solution for ACL rupture. This test involves the phenomenon of anterior dislocations of the tibial plateau compared to the femur. This test is a valuable test for the diagnosis of complete and late ACL rupture.
Complete ACL ruptures were in 84.7% of our patients but nearly a half of them received early treatments. That can explain the result of only 42 of 85 cases (49.4%) in our study that showed positive Pivot shift test results.
Characteristics of knee injury on MRI and in arthroscopy:
ACL rupture with combined lesions accounted for a higher proportion than ACL ruptures alone (77.6% compared to 22.4% from endoscopy in our study, n=66). Combined lesions detected during endoscopy or preoperative MRI scan, most commonly meniscus tear (81.5% from MRI, n=65 and 80.3% from endoscopy, n=66 in our study), including lateral meniscus tear, medial meniscus tear, or both meniscus tear. When comparing MRI with arthroscopic results, MRI is valuable in ACL fracture diagnosis with a sensitivity of 93.9%, specificity 83.3%, and accuracy of 91.1% [16]. MRI is quite sensitive to detect combined lesions, helping to detect multiple lesions, including cartilage, collateral ligaments, and surrounding tendons, in both primary and secondary injuries [16].
The incidence of combined meniscus injuries were 69%, according to Shelbourne KD [17]. The rate of combined lateral meniscus injuries was high (63.5%), medial meniscus injuries 36.7%, and both meniscus 0.9% [9]. According to Nguyen TB, the incidence of meniscus injury accounted for a high proportion and affected the surgical outcome, although it was not known whether the damage was primary or secondary [1]. In our study, the rates for lateral meniscus, medial meniscus, and both meniscus injuries were 36.4%, 22.7%, and 21.2%, respectively. The results were similar to other authors in that meniscus injuries accounted for a high proportion of combined ACL injuries but different in the percentages of each types, which might highly depend on the causes and the patient characteristics.
About surgical techniques:
When taking the graft, be careful to avoid damaging the nerves of the front branch patella. According to Lawhorn KW and Howell SM, the incision for tapering gracilis and semitendinosus tendon was a diagonal or small anterior incision on the tibial tuberosity to limit damage to the sural nerve [11]. We often slit the skin diagonally to remove tendons and to minimize damage to the sural nerve and to make the room into the tibial tunnel. When taking the tendon, should carefully peeled off, cut off all the sticking muscles to avoid breaking the tendon when using the tool to take it. The tool should be parallel to the line of the tendon. The braiding at both ends should also be done carefully so that the graft end could not be slipped out when screwing into the tunnel; the screw thread should not cut the graft.
The tibial tunnel plays an important role. The outer entry point is located on the upper edge of the goosefoot muscles, inside of the tibial tuberosity about 1.5 cm. The practitioner should avoid damaging the shallow part of the inner tendon and posterior tendon of the patella. The insertion point is just anteriorly between the tibia, slightly deviated to the inner side of the tibia, horizontal to the posterior edge of the lateral meniscus. The direction of the tunnel created with the tibial plateau at an angle of 45 – 550 and tilt 200 compared to the vertical plane. Careful preparation and shaping of the inter-condylar area should be made when the gap is narrow, giving a clear view of the highest position to guide the femoral tunnel drilling accurately and to help prevent the graft blockage when extending the knee. Always leave the 2 mm on the posterior side of condyles to avoid breaking. The position of the tibial tunnel has little effect of changing graft length when the knee joint moves than that of the femoral tunnel.
Prior clinical research suggested that the most common failure in ACL reconstruction was the malposition of the femoral tunnel. If the graft located in the femoral tunnel in a too forward position, it might be too stretch when knee flexed and too loose when knee extended. Conversely, when the position of the femoral tunnel is too backward or too high, the graft will be too stretch when extended and too loose when flexed. Both types of malpositions lead to the same consequence, causing the new ligament to become slacked or secondary rupture rapidly.
In our study, after an average of 12.2-month follow-up, 86.2% of patients had good and very good score according to the Lysholm scale, only 11.3% had average score and 2 patients accounted for 2.5% got poor score. Among those who had average and poor score, no one failed due to the malposition of the femoral tunnel and no secondary rupture was found during the observing time.
Conclusion
After studying 85 patients with ACL ruptures who had reconstruction using gracilis and semitendinosus tendons, we concluded as follow:
ACL ruptures were common in men in working age. Standard surgery periods were after injury 1-3 months for the early group and over 12 months after the injury for the late group. The prominent symptoms were loosened knee (positive Lachman sign and front drawer sign). ACL was usually completely ruptured, with combined lesions, commonly meniscus tears that could be detected on an MRI scan before surgery or encountered and treated during surgery.
Arthroscopic ACL reconstruction using gracilis and semitendinosus tendons had high efficiency. Before surgery, 38.2% of patients got a medium score; the remaining 61.8% of patients had a bad score. After 12.2 months of surgery, 86.2% of patients achieved very good and good results, 11.3% of patients achieved average results, and 2.5% of patients achieved bad results. There was an improvement in the recovery of joint motor function after surgery compared to preoperative function.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
1. Nguyen TB. Knee joint arthroscopic. Hanoi: Medical Publishing House; 2009. p. 154-246 (in Vietnamese).
2. Corry IS, Webb JM, Clingeleffer AJ, Pinczewski LA. Arthroscopic reconstruction of the anterior cruciate ligament. Am J Sports Med. 1999;;27(4):444-54.
3. Sanchis-Alfonso V, Martinez-Sanjuan V, Gastaldi-Orquin E. The value of MRI in the evaluation of the ACL deficient knee and in the post-operative evaluation after ACL reconstruction. Eur J Radiol. 1993;16(2):126-30.
4. Otsubo H, Shino K, Nakamura N, Nakata K, Nakagawa S, Koyanagi M. Arthroscopic evaluation of ACL grafts reconstructed with the anatomical two- bundle technique using hamstring tendon autograft. Knee Surg Sports Traumatol Arthrosc. 2007;15(6):720-8.
5. Ahn JH, Yoo JC, Yang HS, Kim JH, Wang JH. Second-look arthroscopic findings of 208 patients after ACL reconstruction. Knee Surg Sports Traumatol Arthrosc. 2007;15(3):242-8.
6. Jones KG. Reconstruction of the anterior cruciate ligament: A technique using the central one-third of the patellar ligament. J Bone Joint Surg. 1963;45-A(5): 925-32.
7. Ruiz AL, Kelly M, Nutton RW. Arthroscopic ACL reconstruction: a 5–9 year follow-up. The Knee. 2002;9(3):197-200.
8. Mickelsen PL, Morgan SJ, Johnson WA, Ferrari JD. Patellar tendon rupture 3 years after anterior cruciate ligament reconstruction with a central one-third bone-patellar tendon-bone graft. Arthroscopy. 2001;17(6): 648-52.
9. Buseck MS, Noyes FR. Arthroscopic evaluation of meniscal repairs after anterior cruciate ligament reconstruction and immediate motion. Am J Sports Med. 1991;19(5):489-94.
10. Patel S, Trehan RK, Railton GT. Successful ACL reconstruction with a variant of the pes anserinus. J Orthop Trauma. 2009;10(4):203-5.
11. Marcacci M, Zaffagnini S, Iacono F, Neri MP, Loreti I, Petitto A. Arthroscopic intra-and extra-articular anterior cruciate ligament reconstruction with gracilis and semitendinosus tendons. Knee Surg Sports Traumatol Arthrosc. 1998;6(2):68- 75.
12. Lawhorn KW, Howell SM. Hamstring tendon for ACL reconstruction. In: Miller MD, Cole BJ, Cohen SB, editors. Textbook of arthroscopy. Philadelphia: Saunders; 2004. p. 657-68.
13. D’Amato M, Bach BR. Knee injuries. In: Brotzman SB, Wilk KE, editors. Handbook of Orthopeadic Rehabilition. Second Edition, USA: Mosby; 2007; p. 375-546.
14. Lysholm J, Gillquist J. The evaluation of the knee ligament surgery with special emphasis to use of a knee scoring scale. Am J Sport Med. 1982;10(3):19-23.
15. Muller W. The knee: Form, function, and ligament reconstruction. Berlin: Springer-Verlag; 1983. p. 148-54, 222-66.
16. Tria AJ. Clinical examination of the knee. In: Scott WN, editor. Insall & Scott Surgery of the knee, vol. 1, 4th ed. PA: Churchill Livingstone Elsevier; 2006. p. 86-98.
17. Shelbourne KD, Pfenning C, Lawrance S. Anterior cruciate ligament reconstruction with patellar tendon autograft: Principles of rehabilitation. In: Johnson DH, Pedowitz RA, editors. Practical orthopaedic sports medicine & arthroscopy. PA: Lippincott Williams & Wilkins; 2007. p. 805-28.
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Minh-Hoang Nguyen, Quang-Tri Le. Assessment of anterior cruciate ligament (ACL) arthroscopic reconstruction using gracilis and semitendinosus tendon autograft. Ann Clin Anal Med 2020;11(5):374-378
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A description of bone density of osteoporosis patients with femoral neck fracture
Quang-Tri Le, Minh-Hoang Nguyen
Department of Orthopedics, 7A Military Hospital, 466 Nguyen Trai Street, Ward 8, District 5, Ho Chi Minh City, 72706, Vietnam
DOI: 10.4328/ACAM.20104 Received: 2020-01-03 Accepted: 2020-01-17 Published Online: 2020-01-20 Printed: 2020-09-01 Ann Clin Anal Med 2020;11(5):390-394
Corresponding Author: Quang Tri Le, Director of 7A MILITARY HOSPITAL, Head of Department of Orthopedics, 7A MILITARY HOSPITAL, 466 Nguyen Trai Street, Ward 8, District 5, Ho Chi Minh City, 72706, Vietnam. E-mail: lqtri@ntt.edu.vn P: (+084)0839241868 / (+084)0913126229 Corresponding Author ORCID ID: https://orcid.org/0000-0002-2777-0828
Aim: In this study, we aimed to describe clinical traits and bone density of osteoporosis patients with femoral proximal fractures on the Vietnamese elderly.
Material and Methods: This cross-sectional descriptive study included 152 patients over 65-year-olds with femoral neck fracture treated.
Results: Male/female ratio was 0.88, average age was 77.25 ± 8.64 years. Common clinical symptoms were pain or irritation across long bones (69.1%), reduced height at more than 3cm compared with earlier ages (38.2%). Radiographs show that 64.5% of patients had intertrochanteric fractures, 63.2% of patients had Grade 3 femoral neck condition according to Singh Index. Average bone density measured by the DEXA scan of the femoral neck was -2.87 ± 0.39 and of the lumbar spine was -3.74 ± 0.71. Bone density results of the Singh Index and DEXA scan had a rigid, positive correlation (p < 0.05).
Discussion: Aspects of gender, age, BMI index, lifestyles, menopause time and the number of children were discussed to show a correlation with results from Vietnam and others. Some initial clinical symptoms suggesting osteoporosis risks and types of hip fractures were assessed. Singh Index and DEXA scan mea- surements were compared and evaluated, showing a rigid correlation.
Conclusion: Osteoporosis and osteoporosis-related femoral neck fractures occurred more in female than in male patients. Risk factors included a sedentary lifestyle, long menopause and many children in female and unhealthy lifestyles in males. Some clinical symptoms might early suggest osteoporosis conditions. There was a correlation between bone density measured using the Singh Index and DEXA scan, implying that the Singh Index still a valuable tool for initial diagnostic of osteoporosis and bone fracture prevention.
Keywords: Femoral Neck; Fractures; Bone Density; Osteoporosis
Introduction
Osteoporosis is a bone disease with reducing bone mass and bone structure degeneration, which leads to an increase of bone fragility, i.e., fracture rate. Osteoporosis progresses naturally and silently with atypical clinical symptoms usually underestimated by the patients – 30% of the bone mass had already been lost when apparent symptoms or fractures occur. Risk factors of Osteoporosis include old age, gender (menopause in women increases bone loss), lifestyles (alcoholism, too little exercising, smoking), and some diseases and medication intake (hyperthyroidism, kidney disease, ovaries removal, corticoid, chemotherapy, etc.) [1-3].
In 1999 there were 1.7 million femoral neck fracture patients worldwide, and this number may reach 6.3 million in 2050, half of which occurred in Asia. Bone fractures due to osteoporosis were seen in 150000 patients annually in France, 70000 of them had femoral proximal fractures. Amongst patients, 80% did not fully recover after treatment, 40% required assistance in travel, and 25% died within one year. Treatment costs reached 1 billion euros. In America annually, there were 1.5 million bone fracture cases due to osteoporosis, 20% of whom got repeated fracture, 50% retain walking ability, 3 – 10% died in hospital, 14 – 36% died after one year. In Vietnam, it is estimated that 2.8 million people suffered from osteoporosis, accounted for 30% of women aged over 50 [5]. According to the initial survey data of the National Institute of Nutrition, osteoporosis affects about 1/3 of women and 1/8 of men over 50 years old. It is estimated that by 2030, the number of people with femoral neck fracture due to osteoporosis will be 41,000 cases (Bulletin of Ministry of Health, Mar 09, 2018, in Vietnamese).
Diseases should be prevented from the beginning, and for osteoporosis prevention, risk factors identification, early detection, and effective preventive care to avoid complications are considered critical. This study was carried out with the aim of a description of clinical traits and bone density of osteoporosis patients with femoral proximal fractures at the 7A Military Hospital, Hochiminh City, Vietnam.
Material and Methods
One hundred fifty-two patients diagnosed with osteoporosis according to WHO criteria (T-score ≤ -2,5) and femoral proximal fractures on radiographs in the 7A Military Hospital (Ho Chi Minh City, Viet Nam) from July 2015 to July 2019 were included in the study.
Participation in the study was voluntary. Criteria for rejection included cancer patients, patients unable to attend interviews. Research methods included description, study design, cross- section, case-by-case analysis, and total sample size. Clinical history, clinical examinations, and tests, bone density, were recorded for all patients with intertrochanteric fractures, data were collected using a unified form.
Research clinical criteria were as follows:
1. Interview: disease history, careers, lifestyles (sedentary or active), habits (smoking, drinking), menstruation (for females), fracture history, parental fracture history, drug-taking history, diabetes history (duration, treatment, complications).
2. Organs and full-body checkups, examinations of accompanying injuries. Measurements of blood pressure, height (low: < 1.47m for women, < 1.57m for men), weight (low: < 42kg for women, < 50kg for men), BMI calculation, detection of accompanying secondary fracture factors.
Research sub-clinical criteria were as follows:
1. Radiographs of hip joints from both sides in the supine position were recorded. Fractures were recorded and evaluated osteoporosis using Singh Index [4]. The Singh Index assesses bone condition based on gradual trabeculae losses shown on radiographs. Bone quality was classified into six grades in which grade 6 was the reasonable condition, and level 1 was severe osteoporotic bones.
a) Grade 6: All visible normal trabecular groups and fully occupied cancellous bone at the femoral proximal end.
b) Grade 5: Clear, prominent principal tensile and principal compressive trabeculae and Ward’s triangle.
c) Grade 4: Significantly reduced principal tensile trabeculae but traceable from the lateral cortex to the femoral neck upper part. d) Grade 3: Discontinuity of the principal tensile trabeculae opposite the greater trochanter. Indication of osteoporosis.
e) Grade 2: Only principal compressive trabeculae remain strongly visible; others have essentially vanished.
f) Grade 1: Principal compressive trabeculae are significantly reduced in number and are no longer prominent.
2. Bone density was measured by Dual-energy X-ray absorptiometry (DEXA) scan using MEDIX DR equipment (France) at femoral head, neck, greater and lesser trochanters, intertrochanteric line, Ward triangle, and lumbar spine (L1, L2, L3, L4). The final value was the averaged sum of all measured parameters.
3. Osteoporosis was diagnosed according to WHO criteria (Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of a WHO Study Group. World Health Organ Tech Rep Ser. 1994;843:1-129) based on bone density:
a) Normal: ≥-1 SD;
b) Osteopenia: -1 SD to -2.5 SD;
c) Osteoporosis: ≤-2.5SD;
d) Severe osteoporosis: ≤-2.5SD in the presence of one or more fractures.
Data analysis: The data were processed by the medical statistical method using SPSS software 16.0, and the hypothesis test was done by the Chi-squared method.
Results
Patients’ general information
There were more females than males in a total of 152 patients (53.3% to 46.7%), average age was 77.25 ± 8.64 years (min. 64, max. 95).
Patients’ historical records of several bones loss risk factors were presented in Figure 1. Among several different risk factors for bone loss, a sedentary lifestyle is most frequently occurred (79%), the second was alcohol drinking (37.5%), and the least was a natural loss due to old age and corticoid uptake (25% and 23%, respectively).
Most female patients gave birth more than thrice (55 patients, 67.9%) and were over 30 years postmenopausal (57 patients, 70.4%), and 14 patients were in their early menopause (17.3%) (n=81).
Many patients had one or more chronic diseases, including diabetes (20 patients, 13.2%), gastroduodenal diseases (26 patients, 17.1%), chronic kidney diseases (17 patients, 11.2%), chronic joint diseases (49 patients, 32.2%), chronic lung diseases (10 patients, 6.6%), and hypertension (51 patients, 33.6%). Chronic joint disorders and hypertension occurred at the highest rates amongst studied patients (32.2% and 33.6%, respectively).
Clinical traits and bone density
There were some osteoporosis-indicated clinical symptoms before bone fractures occurred; most patients had pain or irritation across long bones (105 patients, 69.1%). Other common symptoms were decreasing in height >3cm comparing to previous younger height (58 patients, 38.2%) and kyphosis and lordosis (46 patients, 30.3%).
When being examined in the hospital, most patients showed clinical symptoms of bone fractures, such as shooting pain (140 patients, 92.1%), shortened limb (122 patients, 80.3%), paralysis (116 patients, 76.3%), and impaired movement (42 patients, 27.6%).
On radiographs, the majority of femoral neck fractures were intertrochanteric, accounted for 64.5%; the remaining 35.5% were other types fractures.
Based on the Singh index, the majority of patients had bone condition grade 3 (96 patients, 63.2%), 45 patients had grade 2 conditions (29.6%), and 11 patients had grade 4 (7.2%). There were no patients with grade 1 or grade 5-6 bone conditions based on the Singh index.
DEXA scan results of bone density were collected, analysis, and presented in Table 2. In general, the measured average bone density at the femoral neck was higher than that at the lumbar spine (-2.87 ± 0.39 and -3.74 ± 0.71, respectively).
There was a strong, positive correlation between the lumbar spine and femoral neck bone density measured by the DEXA scan with radiographic osteoporosis conditions based on Singh Index.
Discussion
One hundred fifty-two patients were investigated in this study, 46.7% were males, and 53.3% were females; the average age was 77.25 ± 8.64 years. Intertrochanteric fractures took place in 64.5% patients, osteoporosis conditions of 92.8% patients were at Grade 2 and 3 according to Singh Index.
Many studies showed that obesity and excessive weight reinforces bone density. Survey of Dao et al. (2009) on osteoporosis in older women observed that for BMI < 23, the illness rate was significantly higher in the experimental group than in the control group (p < 0.001) [6]. Our research observed that patients with BMI < 23 took a significant portion in the study group (87.5%).
Effect of lifestyle on bone loss. Regular exercises are essential for the elderly since, after retirement, most of them choose to rest, stay at home more, and work lightly. Doing exercises at least five days a week, 30 minutes a day can promote health, increase bone density, improve circulation, reduce blood sugar; it also maintains muscular quality and reduces the chance of falling, thus more or less prevent osteoporosis and fractures in senior citizens [7,8]. In this study, 79% of the patients had a sedentary lifestyle making it the most frequently encountered risk factor. Other lifestyle risk factors for bone loss are smoking and alcoholism [2]. Most of the male patients in our study smoked (59.2%) and frequently consumed alcohol (78.9%) (n=71).
Effect of menopause on the loss of bone mass. Menopause is a natural physiological phenomenon in women. Postmenopausal estrogen level drastically decreases. Rapid bone loss occurs during the first 5 – 15 years after menopause, followed by a slow loss due to a lack of estrogen and old age. That means a higher period equal to longer postmenopausal time, which leads to more significant bone loss and higher risks for osteoporosis and osteoporotic bone fracture in women [7,9]. In this study, most female patients (n=81) menopause lasted over 30 years, accounted for 70.4% comparing to only 14 female patients who were in their early menopause (17.3%).
The number of offsprings is one essential trait of female reproduction. Reginster and colleagues (2005) [10] observed that mothers of many children had higher osteoporosis risks than mother of few since many births affected mother’s calcium metabolism due to transfer from mother to child during pregnancy and breastfeeding; without adequate calcium re-supplement in these periods, women with many births will suffer from high osteoporosis risks. Also, Vietnamese women tend to refrain from movement and eating during several first months after birth. Women with more than three children were also a majority in this study (67.9%).
Clinical traits and bone density
Osteoporosis is a silent disease without apparent symptoms. As a result of many patients, especially men, were not aware of their illness until bone fractures occurred. However, the senior patients in this study showed several symptoms such as pain or irritation across long bones (105 patients, 69.1%), decreasing in height >3cm comparing to previous younger height (58 patients, 38.2%), and kyphosis and lordosis (46 patients, 30.3%). Although no symptoms do not mean healthy or such signs always mean osteoporosis, the above mentioned signs, albeit not specific for this disease, may remind the clinicians of osteoporosis risks as such risks are very high in patients with these symptoms [11,12].
Senior people have a reduced bone quality, which, even in the case of simple falling with small impact, quickly leads to femoral proximal fractures [2]. In this study, intertrochanteric fractures were seen in 64.5% of cases, and other fractures accounted for 35.5% cases, compatible with the significant researches of Guyton (2003) [13] and Lorich (2004) [14]. Classification of intertrochanteric fractures may help in the selection of treatment equipment and methods.
Our study showed that bone density at the femoral neck was higher than that at the lumbar spine (-2.87 ± 0.39 and -3.74 ±
0.71, respectively), which is compatible with the literature since the lumbar vertebrae (L1 to L4) are spongy bones with higher annual bone loss than compact ones. Therefore osteoporosis in the lumbar spine took place earlier than in the femoral neck [12].
Osteoporosis levels, according to the Singh Index in this study, were mostly in Grade 3 (63.2%). There was a rigid, positive correlation between bone density measured by DEXA scan and osteoporosis assessment using the Singh Index. Some other authors otherwise reported that there was little to no correlation between Singh Index and DEXA scan bone density measuring [15]. Vietnam is still a developing country and expensive diagnostic tools as DEXA might not be readily available in many hospitals and be a financial burden to many patients. Based on our result, the Singh Index is still a valuable way to initially assess osteoporosis and give a useful hint about the patients’ bone conditions for further examination and treatment. Conclusion
Osteoporosis and osteoporosis-related femoral neck fractures occurred more in female than in male patients. The most frequently encountered risk factor, in general, was the sedentary lifestyle. Most female patients had long menopause and many children, while most male patients had unhealthy lifestyles such as smoking and alcoholism.
Although not significantly specific to osteoporosis, some clinical symptoms such as pain and irritation across long bones or highly decreasing in height might early suggest osteoporosis conditions.
There was a rigid, positive correlation between bone density measured using the Singh Index and DEXA scan, implying that the Singh Index is still a valuable tool for initial diagnostic of osteoporosis and bone fracture prevention.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
1. Zhu K, Prince RL. Lifestyle and osteoporosis. Curr Osteoporos Rep. 2015; 13(1):52-9. DOI: 10.1007/s11914-014-0248-6..
2. Golob AL, Laya MB. Osteoporosis: screening, prevention, and management. Med Clin North Am. 2015;99(3):587-606. DOI: 10.1016/j.mcna.2015.01.010.
3. Li G, Thabane L, Papaioannou A, Ioannidis G, Levine MA, Adachi JD. An overview of osteoporosis and frailty in the elderly. BMC Musculoskelet Disord. 2017; 18(1): 46. DOI:10.1186/s12891-017-1403-x
4. Singh M, Nagrath AR, Maini PS. Changes in trabecular pattern of the upper end of the femur as an index of osteoporosis. J Bone Joint Surg Am. 1970;52(3):457- 67.
5. Curtis EM, Moon RJ, Harvey NC, Cooper C. The impact of fragility fracture and approaches to osteoporosis risk assessment worldwide. Bone. 2017;104:29-38. DOI:10.1016/j.bone.2017.01.024
6. Dao TVK, Nguyen HTV, Nguyen THT. Assessment of osteoporosis in elderly women by quantity ultrasonic scan. J Prac Med. 2009;2:20-2. (In Vietnamese)
7. Luu NG, Nguyen TT. Relationship between osteoporosis and menopausal time of women in My Tho City. J Prac Med. 2011;2:21-4. (In Vietnamese)
8. Kanis JA, Hans D, Cooper C, Baim S, Bilezikian JP, Binkley N, et al. Interpretation and use of FRAX in clinical practice. Osteoporos Int. 2011;22(9) 2395-411. DOI: 10.1007/s00198-011-1713-z.
9. Ji M-X, Yu Q. Primary osteoporosis in postmenopausal women. Chronic Dis Transl Med. 2015;1(1):9-13. DOI:10.1016/j.cdtm.2015.02.006
10. Reginster JY, Delmas PD. Prevention and treatment of postmenopausal osteoporosis. In: Rizzoli R, editor. Atlas of postmenopausal osteoporosis. 2nd ed. London: Current Medicine Group Ltd.; 2005. p. 25-46.
11. Paolucci T, Saraceni VM, Piccinini G. Management of chronic pain in osteoporosis: challenges and solutions. J Pain Res. 2016;9:177-86. DOI:10.2147/ JPR.S83574
12. Burr J, Shephard R, Cornish S, Vatanparast H, Chilibeck P. Arthritis, osteoporosis, and low back pain: evidence-based clinical risk assessment for physical activity and exercise clearance. Can Fam Physician. 2012;58(1):59-62.
13. Guyton JL. Fractures of hip – Acetabulum, and Pelvis. Canae ST, editor. Campbells operative orthopaedics. 9th ed. Missouri: Mosby-Year Book, Inc.; 1998. p. 2181-262.
14. Lorich DG, Geller DS, Nielson JH. Osteoporotic pertrochanteric hip fractures. Management and current controversies. J Bone Joint Surg Am. 2004;86:398–410.
15. Qadir RI, Bukhari SI. Singh’s index accuracy with DEXA scan for evaluation of osteoporosis. J Med Sci. 2016:24(1):12-5.
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Minh-Hoang Nguyen, Quang-Tri Le. A Description of Bone Density of Osteoporosis Patients with Femoral Neck Fracture. Ann Clin Anal Med 2020;11(5):390-394
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Machine learning approaches for the histopathological diagnosis of prostatic hyperplasia
Syed Usama Khalid 1, Asmara Syed 2, Syed Sajid Hussain Shah 3
1 Department of Computer Science, University of Lahore – Islamabad Campus, 2 Department of Pathology, Faculty of Medicine, Northern Border University, Arar- Kingdom of Saudi Arabia, 3 Department of Pathology, College of Medicine, Northern Border University, Arar, Kingdom of Saudi Arabia
DOI:10.4328/ACAM.20105 Received: 2020-01-04 Accepted: 2020-01-26 Published Online: 2020-01-30 Printed: 2020-09-01 Ann Clin Anal Med 2020;11(5):425-428
Corresponding Author: Syed Sajid Hussain Shah, Professor of Pathology, College of Medicine, Northern Border University, Arar, Kingdom of Saudi Arabia. E-mail: prof.sajid99@gmail.com T: 00966537759649 Corresponding Author ORCID ID: https://orcid.org/0000-0003-3425-6293
Aim: The aim of the present study is to evaluate the effectiveness of computer vision-based system for the histopathological assessment of prostatic tissue and its diagnostic accuracy for the detection of hyperplasia of the glandular component of prostate.
Material and Methods: A total of 59 digital images have been acquired from the hematoxylin and eosin-stained sections of the prostatic tissue. In these 59 images, 169 regions were marked as sites of hyperplasia of the prostatic glandular component.
The entire dataset has been divided into three classes, which included the training set containing 41 images (70% of the total images), that had 109 marked regions as prostatic hyperplasia, validation set contained 6 images (10% of total images), that had 19 marked regions as prostatic hyperplasia and Testing set contained 12 images (20% of total images), that had 41 marked regions as the hyperplasia of the glandular component of the prostatic tissue.
Results: A total of fifty-nine digital images containing one hundred and sixty-nine marked regions of glandular hyperplasia of prostatic tissue are used in which 70% were employed for training, 10 % for validation, and 20% for testing. The computer vision-based system has diagnosed correctly with 96.3% f1-score.
Discussion: The application of artificial intelligence with the help of computer is emerging an important technique that will improve the diagnostic accuracy and will reduce the chance of human errors. The development of pattern recognition algorithms may be of great help in the histopathological diagnosis in the near future.
Conclusion: The present study revealed that computer vision-based system may be an effective adjunct tool for the histopathological assessment of benign prostatic hyperplasia.
Keywords: Prostatic Hyperplasia; Artificial Intelligence; Computer Vision
Introduction
Benign prostatic hyperplasia (nodular hyperplasia) is the most prevalent lesion among elderly men. With the advancing age, the prevalence of benign prostatic hyperplasia (nodular hyperplasia) rises in men. About fifty percent of the male population between the ages of 50 and 60 years revealed benign prostatic hyperplasia [1]. This lesion is characterized by more number of epithelial cells and stromal components in the prostate that are predominantly in the transitional zone which is the principal site for benign prostatic hyperplasia [2]. The increase in the number of cells has been attributed to decreased cell death. The increase in the number of cells increases the size of organ and this enlarged organ can compress and obstruct the urethra leading to urinary obstruction and urinary retention. The enlargement of prostate in case of benign prostatic hyperplasia (nodular hyperplasia) causes weak urinary stream, hesitancy, urgency, frequency, dysuria, and nocturia [3]. The risk of the development of lower urinary tract symptoms increases with the increase in the size of prostate [4].
The management of benign prostatic hyperplasia includes treatment with medicine (pharmacotherapy) and surgery (transurethral resection of the prostate or photoselective vaporization of the prostate using greenlight laser) if the urinary symptoms persist. The advancing age of the patients with benign prostatic hyperplasia is associated with a higher rate of surgeries [5]. With the increased life expectancy and rising prevalence of obesity, the number of prostatic surgeries has increased. After the surgery, the excised prostatic tissue is submitted to pathology laboratory for the histopathological examination in which multiple sections of the tissue are examined under a light microscope after the processing of the submitted tissue. The thorough microscopic examination of multiple sections of prostatic tissue is a very important but quite difficult and time-consuming task. The application of computer vision-based approach for the histological assessment of microscopic slides of the prostatic tissue may be evaluated for its usefulness in this regard.
The aim of the present study is to assess the usefulness and diagnostic accuracy of computer vision-based system for the histopathological examination of prostatic hyperplasia.
Material and Methods
Fifty-nine images from the hematoxylin and eosin-stained glass slides of the sections from prostatic tissue have been acquired. These images were used to mark the regions where hyperplastic prostatic glandular component was present. Though the histopathological examination of section from the prostatic tissue is a binary classification problem (hyperplasia of glandular component or normal prostatic gland), but in our case, not only we detect the hyperplastic prostatic glandular component but also the system returns the region of interest (ROI), clearly showing the boundary around the area where the system thinks contains the hyperplastic prostatic glandular component.
To develop the proposed method, we used the Mask-RCNN with Resnet 50. Our implementation of the Mask-RCNN model used the existing implementation by Matter-port Inc Abdulla.
We gathered a dataset of 59 images containing 169 regions with the hyperplastic prostatic glandular component. The data were split into training, validation and test sets. The train dataset had 70% of the total images, where we used 10% of total images for validation and 20% for total images for testing purpose.
Resnet takes an image of size 224×224 by default. As images in the dataset consisted of various sizes, all images were resized to fit the requirement of Resnet. To reduce the risks of overfitting we applied data augmentation on the images by flipping of images both left to right and up to down. All augmentation options were randomly applied with the probity of 33%.
We used the following parameters for our proposed deep learning algorithm
• Learning Rate = 1e-2
• Batch size = 4
• Epochs = 200
• Optimizer = Adam with default values for β1 and β2 • Metrics = Dice Similarity Coefficient (DSC)
Results
After training the proposed system, the prediction is done on the test dataset. As the problem was a segmentation problem hence DSC is used as a metric.
DSC= (A∩B) / (A+B), where A is the predicted region and B is ground truth region.
In our case, if the DSC value is greater than or equal to 0.75, then we consider this as a true detection. Using this, we generated confusion metrics. There were 41 regions with prostatic hyperplasia (glandular component) and the computer has identified 40 regions correctly. The results are depicted in Figure 1 and 2. One area has not been picked by the computer vision-based system while two regions were incorrectly identified as the hyperplastic glandular component of the prostate. The analysis of the data revealed that the sensitivity of computer vision-based system is 95.2% with a precision of 97.5%, F1-Score 96.3% and accuracy 93% respectively. The results are shown in Table 1.
Discussion
The use of computer programs to perform cognitive functions for the analysis of the data is emerging as a very important tool in the field of artificial intelligence for the solution of human health issues. The development of algorithms for the pattern recognition and advancement in the imaging processing techniques has revolutionized the computer-assisted complex task performance in the field of medicine. The computer with artificial intelligence programs can analyze the raw data for the extraction of important information which may help in yielding the appropriate solution of the problems.
The development of computer software based on machine learning may be able to assist in the performance of complex functions to find out the solution of vital medical issues such as diagnosis and treatment of various ailments and may reduce the burden on the medical consultants. These computer- based support systems may also contribute to the reduction of medical errors due to fatigability and may be quite helpful in reducing the cost and improving patient care.
For the appropriate drug therapy of the patients, computerized clinical decision supports systems have been developed which has reduced medication errors [6].
For appropriate treatment, an accurate diagnosis has got vital importance. Laboratory investigations help in reaching to the conclusive diagnosis of the particular ailment. An important laboratory test is the histopathological assessment of the tissue for the diagnosis which requires expertize in the histological assessment of various tissue for different diseases. With the rising trend in the prevalence of surgeries for prostatic lesions, the histopathology department is working under more burden. In this regard, the use of artificial intelligence with the help of machine learning may provide assistance in the accurate diagnosis and mitigate the chance of human errors. The digital image analysis of various pathological lesions by developing pattern recognition algorithms may be of great help in the histopathological diagnosis.
Many studies have been carried out for the characterization of prostatic lesion based on radiological images with the help of computer software and revealed quite impressive results [7-9]. But the biopsy and histopathological evaluation of the biopsy are gold standard for the diagnosis of prostatic lesions particularly the neoplasms [10]. In the present study, the computer vision- based system identified the areas with glandular hyperplasia of prostatic tissue correctly in 96% of the cases which have been confirmed by the two pathologists. These findings are a bit higher than the reported figures of 85% to 92.5% for the various lesions of the prostatic tissue by Bhattacharjee S et al [11]. Similar findings have been observed in other studies [12,13].
With the rising trend in the surgeries for the prostatic lesions, it becomes imperative to find out the computer- assisted systems for the sharing and reducing of the burden and stress of histopathologists. These computer vision- based programs can also reduce the chance of human errors and may prove to be more cost-effective. The present study has certain limitations but in the light of the present study, further research in this field is suggested with more extensive data of the various lesions. Conclusion: The present study revealed that computer vision- based software may be an effective adjunct tool for the histopathological assessment of benign prostatic hyperplasia.
Acknowledgment
The authors are thankful to Waleed Abdulla for the source code. (Mask R-CNN for object detection and instance segmentation on Keras and TensorFlow. http:// github.com/matterport/Mask_RCNN,2017,Github).
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
1. Vuichoud C, Loughlin KR. Benign prostatic hyperplasia: epidemiology, economics, and evaluation. Can J Urol;2015:22(Suppl.1):1-6
2. Aaron L, Franco O, Hayward SW. Review of Prostate Anatomy and Embryology and the Etiology of BPH. Urol Clin North Am. 2016; 43(3): 279–88. DOI:10.1016/j. ucl.2016.04.012.
3. Vasanwala FF, Wong MYC, Ho HSS, Foo KT. Benign prostatic hyperplasia and male lower urinary symptoms: A guide for family physicians. Asian J Urol. 2017;4(3):181–4. DOI:10.1016/j.ajur.2017.05.003
4. Simon RM, Howard LE, Moreira DM, Roehrborn C, Vidal AC, Castro-Santamaria R, et al. Does prostate size predict the development of incident lower urinary tract symptoms in men with mild to no current symptoms? results from the REDUCE trial. Eur Urol. 2016;69(5):885-91. DOI: 10.1016/j.eururo.2015.12.002.
5. Welliver C, Feinstein L, Ward JB, Fwu CW, Kirkali Z, Bavendam T, et al. Trends in Lower Urinary Tract Symptoms Associated with Benign Prostatic Hyperplasia, 2004-2013: The Urologic Diseases in America Project. J Urol. 2019; 203(1):171-8. DOI: 10.1097/JU.0000000000000499.
6. Jia P, Zhang L, Chen J, Zhao P, Zhang M. The Effects of Clinical Decision Support Systems on Medication Safety: An Overview. PLoS One. 2016;11(12):e0167683. DOI:10.1371/journal.pone.0167683
7. Lemaître G, Martí R, Freixenet J, Vilanova JC, Walker PM, Meriaudeau F. Computer-Aided Detection and diagnosis for prostate cancer based on mono and multi-parametric MRI: a review. Comput Biol Med. 2015;60:8-31. DOI: 10.1016/j. compbiomed.2015.02.009.
8. Toivonen J, Montoya Perez I, Movahedi P, Merisaari H, Pesola M, Taimen P, et al. Radiomics and machine learning of multisequence multiparametric prostate MRI: Towards improved non-invasive prostate cancer characterization. PLoS One. 2019;14(7):e0217702. DOI:10.1371/journal.pone.0217702.
9. Khalvati F, Wong A, Haider MA. Automated prostate cancer detection via comprehensive multi-parametric magnetic resonance imaging texture feature models. BMC Med Imaging. 2015;15:27. DOI:10.1186/s12880-015-0069-9
10. Thon A, Teichgräber U, Tennstedt-Schenk C, Hadjidemetriou S, Winzler S, Malich A, et al. Computer aided detection in prostate cancer diagnostics: A promising alternative to biopsy? A retrospective study from 104 lesions with histological ground truth. PLoS One. 2017;12(10):e0185995. DOI:10.1371/ journal.pone.0185995
11. Bhattacharjee S, Park HG, Kim CH, Prakash D, Madusanka N, Jae- Hong So JH, et al. Quantitative Analysis of Benign and Malignant Tumors in Histopathology: Predicting Prostate Cancer Grading Using SVM. Appl. Sci. 2019; 9(15): 2969; DOI:10.3390/app9152969.
12. Sahran S, Albashish D, Abdullah A, Shukor NA, Pauzi SHM. Absolute cosine- based SVM-RFE feature selection method for prostate histopathological grading. Artif Intell Med. 2018; 87:78–90. DOI:10.1016/j.artmed.2018.04.002
13. Tabesh A, Teverovskiy M, Pang HY, Kumar VP, Verbel D,Kotsianti A, et al. Multifeature Prostate Cancer Diagnosis and Gleason Grading of Histological Images. IEEE Trans Med Imaging. 2007; 26(10): 1366–78. DOI: 10.1109/ TMI.2007.898536
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Syed Usama Khalid, Asmara Syed, Syed Sajid Hussain Shah. Hybrid machine learning approaches for the histopathological diagnosis of prostatic hyperplasia. Ann Clin Anal Med 2020;11(5):425-428
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Effectiveness of kinesio taping in bicipital tendinitis treatment: A randomized controlled trial
Erdinç Genç 1 , Tomris Duymaz 2
1 Department of Orthopedics and Traumatology, Istanbul Bağcılar Training and Research Hospital, 2 Physiotherapy and Rehabilitation, Istanbul Bilgi University, Faculty of Health Sciences, Istanbul/Turkey
DOI: 10.4328/ACAM.20124 Received: 2020-02-01 Accepted: 2020-03-23 Published Online: 2020-04-07 Printed: 2020-09-01 Ann Clin Anal Med 2020;11(5):498-503
Corresponding Author: Tomris Duymaz, Istanbul Bilgi University, Faculty of Health Sciences, Physiotherapy and Rehabilitation, Pir Hüsamettin Sk No:20 34440 Beyoğlu, Istanbul/ Turkey. E-mail: tomrisduymaz@gmail.com GSM: +90 5446302676 Corresponding Author ORCID ID: https://orcid.org/0000-0003-0917-2098
Aim: Biceps tendinitis is characterized by inflammation of the biceps long head, and treatment options include various conservative and surgical methods. Kine- siotaping (KT) has benefited in reducing pain and providing motor control in various shoulder disorders. The aim of this study is to investigate the effectiveness of KT application in patients with biceps tendinitis in terms of pain, pain threshold, upper extremity functionality level and quality of life.
Material and Methods: Eighty patients with biceps tendinitis were divided into two groups randomly, each comprising 40 patients. The study group received KT with an exercise program, the control group received an exercise program only. Pre- and post-treatment evaluations were conducted. Pain threshold was evaluated with a digital algometer, pain severity with visual analog scale (VAS), functional capacity with the disabilities of the arm, shoulder and hand score (Q-DASH) and quality of life with Nottingham Health Profile (NHP).
Results: The mean duration of the symptoms was 4.5 months and the mean age was 45.80±8.48 years. Pain intensity decreased during activity (p<0.001) and pain thresholds increased (p<0.001) in the KT group. Q-DASH scores improved significantly in patients in the KT group, there was a less significance in the control group (p<0.001, 0.043). The NHP scores except social isolation improved in all sub-parameters of the KT group and there was no significance in control group (p>0.05, 0.003, 0.012, 0.023, 0.225, 0.035, 0.029, 0.006).
Discussion: KT application decreases pain and increases the functional capacity level and can also play a role in improving the general quality of life in biceps tendinitis treatment.
Keywords: Biceps tendinitis; Kinesio tape; Pain; Functional capacity; Quality of life
Introduction
The prevalence of shoulder pain in the general population is between 7-26% and the lifetime prevalence reaches 67% [1]. Biceps tendinitis is characterized by inflammation of the long head of the biceps and is one of the most common pathologies causingshoulderpain.Studiesspecifictothedefinitionofbiceps tendinitis were first performed by Codman in 1934. It often occurs as a result of mechanical irritation and degeneration of the tendon due to subacromial compression, trauma or excessive use [2]. Although it is frequently accompanied by degenerative rotator sheath lesions or impingement syndrome, primary biceps tendinitis occurs in 5% of cases [3]. Although there is no specific test with reliable positive predictive value in the clinical evaluation of biceps tendinitis, anterior shoulder pain, sensitivity in the bicipital groove, and Speed and Yergason tests can be seen positively [4]. In palpation, while the arm is at 10 degrees internal rotation, it is determined by the pain felt at the pressure applied approximately 7.5 cm below the acromion in the anterior of the shoulder. Magnetic resonance imaging is valuable for evaluating the biceps tendon, bicipital groove, bone osteophytes, and fluid [5].
Nonoperative approaches are preferred in the treatment of biceps tendinitis. Treatment methods include physiotherapy, rest, activity modification, nonsteroidal anti-inflammatories, corticosteroid injections and surgical interventions. Conservative physiotherapy methods include many multimodal approaches such as exercise, joint and soft tissue mobilizations, electrotherapeutic and thermal applications. In terms of exercise approaches, eccentric and eccentric-concentric exercises are used most frequently in the treatment of tendinitis. Although eccentric exercises have shown beneficial effects in patients with tendinitis by stimulating and organizing collagen synthesis [6,7], in recent years, concentric and eccentric exercise components have been reported to provide a process defined as ‘mechanotransduction’ that accelerates tissue healing with mechanical loading [8].
Kinesiotape (KT) application is a treatment method that has been used since 2007 and has become one of the current physiotherapy approaches in recent years. KT applications are recommended in rehabilitation protocols because they reduce pain and provide motor control [9]. KT stabilizes the muscles and joints with its elastic acrylic adhesive structure. KT increases interstitial space by creating skin lifting effect in manually stretched structures, facilitates tissue regeneration, and accelerates lymphatic and venous flow. It reduces pain by creating decompression in subcutaneous nociceptors in connective tissue [9]. Although its efficacy has been observed in various patient groups, no study evaluating its efficacy has been found specifically in patients with biceps tendinitis [5,9,10]. The aim of this study is to investigate the effectiveness of KT application in patients with biceps tendinitis in terms of pain, pain threshold, upper extremity functionality level and quality of life. Our hypothesis is that KT method applied in addition to exercise in biceps tendinitis will be more useful than exercise alone.
Material and Methods
This randomized prospective controlled trial was designed, conducted and reported in accordance with the standards of the CONSORT (Consolidated Standards of Reporting Trials) statement. The approval of the Istanbul Bilgi University Clinical Investigations Ethics Committee was obtained, and the enrolled subjects signed a free and informed consent form.
The study included 80 patients diagnosed with bicipital tendinitis. Biceps tendinitis was diagnosed with the Speed test, the Yergeson test, tenderness on bicipital groove, and MRI evaluation. The patients were divided into two groups, each comprising 40 patients. Patients were randomized using randomization software and divided into two groups. A randomized list was prepared in a computer environment by a statistician for randomization. In this list, odd numbers were given to the control group and the KT group were given even numbers. The group identification was printed on sequentially numbered cards placed in sealed envelopes. After enrollment, the numbered envelope was opened by the patient and the blinded investigator. KT and exercise were given to the patients in the first group, and the only exercise was given to the patients in the second group. Nonsteroidal anti-inflammatory therapy was applied to all patients. The exclusion criteria were full-thickness rotator cuff tears, shoulder girdle fracture, glenohumeral dislocation/subluxation, acromioclavicular sprain, concomitant cervical spine symptoms, a history of shoulder surgery within the previous 12 weeks, or shoulder pain for longer than 6 months.
Exercise protocol: All patients performed exercises 5 days per week over a 6-week period in the physical therapy clinic. Firstly, 1-repeat maximum values of the patients were found. Later, patients were in the sitting position, while the arm was in adduction near the body, elbow flexion and extension were performed with a weight of 50% of the maximum repeat values. Each repeat was controlled to be completed in 2-3 seconds. KT application: KT was applied twice a week, 12 times for a total of 6 weeks. KT was applied in combination with tonus reduction muscle application and fascia correction technique. In practice, 2 pieces of Y tape are used. The patient is seated in a resting position. The beginning of one of the tapes is applied below the inside of the elbow. The beginning of the tape is determined by shifting the skin. The 2 tails of the band surround the biceps brachii muscle body, then run parallel to the anterior edge of the deltoid muscle and end in the coracoid process. The beginning of the 2nd tape for fascia correction is in front of the pain point. The arm is in extension. The fascia is pulled in the transverse direction in the direction of the muscle fibers. It is pulled in the posterior direction to prevent compression of the biceps tendon. Tail tips are applied without tension (Figure 1). Measurements were performed twice before and after the treatment for all patients. Pain threshold with digital algometer, pain severity with visual analog scale (VAS), disability level with the DASH Scale, quality of life with the Nottingham Health Profile (NHP) were evaluated before and after treatment.
Pain threshold: Algometer is a tool that measures pressure pain threshold and pain tolerance in quantitative sensory tests. Measurements were taken from the inferior medial part of the biseps. Firstly, the application was explained to the patients. The probe of the algometer was placed vertically on the skin and after pressure was given, patients were asked to indicate and not try to withstand the first time they felt pain. The pressures at the time of the patients were measured. Measurements were performed 3 times giving rest intervals and their averages were recorded.
Pain severity: Pain severity was evaluated with VAS in activity. Participants were told how to do it and were asked to give a score between 0-100. Zero means no pain, 100 indicates severe pain.
Functional assessment: Upper extremity functional assessment was carried out with Q-DASH. Q-DASH is a regional result criterion that was developed for upper extremity musculoskeletal system disease. It evaluates all upper extremity functions, is filled out optionally and includes sport and musician modules. It contains eleven questions. To calculate the score of the criterion that can be used instead of Q-DASH, at least 10 questions out of 11 must be answered. Each question is graded on a 5-point- Likert scale. The total score of the questionnaire is calculated in such a way that the total number of points of the marked questions is divided by the number of questions marked, and then 1 is subtracted from the result, and the result is multiplied by 25. Point total between 0-20 indicates normal, 21-40 indicates slight, 41-60 indicates moderate, and 61-80 indicates severe disability. The business model investigation survey of Q-DASH contains 4 questions intended for the assessment of problems that the patient has with his/her arms while working. Difficulty level is scored between 1 and 5. The total score of the questions is divided by 4, then 1 is subtracted from the result and then this result is multiplied by 25. The validity and reliability of this scale was confirmed by Düger et al [11].
Quality of Life: The Nottingham Health Profile (NHP) was used to determine the quality of life of the participants. NHP is a general health status scale (health-related quality of life), which aims to measure a patient’s perceived emotional, social and physical health status. This scale consists of 38 items formed as yes-no questions that cover 6 subscales of the quality of life. These six subscales are sleep (5 item), energy level (3 item), emotional status (9 item), social isolation (5 item), physical mobility (8 item) and pain (8 item). Each section is scored from 0 to 100. Zero indicates the best health status, 100 indicates the worst health status. In the study, the sub-scores of NHP and total NHP scores were evaluated. Total NHP score was obtained from the sum of the sub-scores. NHP is an easy-to- use scale and the validity and reliability of the Turkish version was confirmed by Küçükdeveci at al [12].
Statistical analyses were conducted using SPSS for Windows version 22.0 (SPSS, Inc., Chicago, IL, USA). Continuous and categorical data are reported as mean ± standard deviation and number (percentages), respectively. The Kolmogorov- Smirnov test was performed to determine the suitability of the data for normal distribution. After descriptive statistics were recorded, the Mann-Whitney U test was used for inter-group comparisons of nonparametric data, and the Wilcoxon test was used to compare groups before and after treatment. P- value £ 0.05 was accepted as significant for all statistical levels.
Results
Eighty patients with a mean age of 45.80 ± 8.48 years and a body mass index of 27.90 ± 4.57 kg / m2 participated in the study; 62.5% of the patients in both groups were female and 37.5% were male. Biceps tendinitis was present in 61.9% of the patients in their right arm. There were no participants with biceps tendinitis in both arms. The mean symptom duration was 4.50±3.91 months since the onset of symptoms and the mean folllow-up period was 6.4 months (range 6-8 months). Demographic characteristics of the patients were similar (p>0.05) (Table 1).
Although the pain severity and pain thresholds of all patients were observed between the groups and within the groups, there was a statistically significant decrease in pain intensity (p<0.001) and significant increase in pain thresholds in KT group (p<0.001). No statistically significant difference was observed in the pain severity and pain thresholds of the patients in the control group after the treatment (p=0.889, 0.288). When the DASH scores were compared, it was observed that there was a statistically significant improvement in the functional level of the patients in the KT group (p<0.001), but there was a less significant improvement in the scores of the patients in the control group (p=0.043) (Table 2).
When the NHP results of the pre- and post-treatment patients were evaluated, significant improvement was observed in all sub-parameters except for social isolation of the KT group (p=0.003, 0.012, 0.023, 0.035, 0.029, 0.006, 0.225). No statistically significant change was observed in the parameters in the control group (p>0.05) (Table 3). In the comparison between the groups, all parameters of the NHP except sleep improved in the KT group (p=0.008, 0.026, 0.007, 0.008, <0.001, <0.001, 0.121) (Table 3). According to these results, KT application decreases pain and increases physical activity level but can also play a role in improving general quality of life.
Discussion
This randomized controlled prospective clinical trial is the first study in the literature to demonstrate the effectiveness of the KT method used in the treatment of patients with biceps tendinitis on pain, pain threshold, functionality and quality of life. As a result of our study, it was found that KT application applied in addition to exercise therapy was effective in reducing pain severity, increasing pain threshold, functional level and quality of life.
The long head of the biceps depresses the humerus head, providing stabilization in the glenohumeral joint. In cadaveric studies, contractions in which the biceps long head was stimulated significantly decreased anterior, superior, and inferior translation at the shoulder. In biomechanical analysis, the biceps long head has been shown to provide anterior stabilization of the glenohumeral joint during abduction and external rotation. In another cadaver study, Rodosky et al. found that when stimulating the biceps long head, the biceps muscle creates resistance against shoulder abduction and external rotational torsional force [13]. For these reasons, there is a significant limitation in shoulder functions in cases caused by pathological changes in the biceps tendon [5].
Treatment of biceps long head tendinitis often starts with non- surgical methods, as with most tendon conditions. Conservative treatment includes activity modification and non-steroidal anti-inflammatory therapy. Physical therapy applications are organized for scapular rhythm and accompanying shoulder pathologies. Studies have shown that tendons can respond to controlled loading after injury. In the systematic review by Malliaras et al., they reported that eccentric-concentric loading can be used alone or only instead of eccentric loading in tendinopathies [14]. The mechanism for the effectiveness of this exercise method is explained by loading the tendon resulting in localized tendon remodeling and tensile strength and providing lengthening in the neck. Therefore, in our study, we applied eccentric-concentric exercise combination to all our patients as exercise.
KT has been used in shoulder pathologies since 2007. Most of these studies include impingement syndrome and rotator cuff injuries. Specifically, there is no study with KT applied in biceps tendinitis. The KT is stated to have four basic functions in the tissue, including supporting the muscles, reducing the obstruction in the flow of body fluids, stimulating the endogenous analgesic system and correcting joint problems [15,16]. The most important feature of the KT is that it adapts to the flexing capacity of skin [15]. The tape minimises skin irritations and imparts greater elasticity to the skin. Its structure is similar to that of the epidermis layer of skin due to its thickness and weight. It can adapt to the tension and relaxation of the skin with movement, mimicking its thickness and flexibility. It has an elastic structure that allows it to stretch by 130%–140% of its original length [16]. Lim and Tay explained the effect of KT on pain reduction with neurophysiological and mechanical mechanisms [17]. According to these mechanisms, KT provides inhibition of the transmission of nociceptive signals, stimulates pain-reducing inhibitory mechanisms and reduces the pressure in subcutaneous nociceptors [17]. Shakeri et al. reported that the pain intensity decreased during movement immediately after the KT application [18]. Kaya et al. and Şimşek et al. compared the short-term results of KT and placebo KT in shoulder impingement syndrome, and found a reduction in pain with KT treatment [20,21]. Wilk et al. reported that KT may be beneficial in reducing symptomatic pain and pain during activity in biceps tendinitis [5]. Thelen et al. showed that half of 42 patients with rotator cuff tendinitis were treated with KT and the other half received the placebo treatment, which resulted in pain-free shoulder abduction in the short term. However, they reported that it had no effect on pain functionality in the long term [10]. Kaya et al. divided patients with subacromial impingement syndrome into 2 groups, and applied KT and exercise to one group for 6 weeks, and manual therapy and exercise to the other group. In both groups, they did not find any difference between the groups seeing improvement in pain and disability [18]. Reynard et al. found that after KT application of rotator cuff surgery, compared to the placebo group, the KT has no clinical benefit on shoulder joint range of motion, pain, and muscle strength [9]. In our study, we found that KT treatment has beneficial results in the short term in terms of pain and functional scores in patients with biceps tendinitis. For better evaluation of patients with biceps tendinitis and to show treatment results, we did not include patients with full- thickness rotator cuff tears.
Benefits of KT include increase in the functionality in the joints by providing the correct alignment, development of the joint position feeling and kinesthetic awareness. There are researches reporting that KT enhances upper extremity functionality and quality of life in shoulder pathologies [9]. Oliveira et al. divided 52 patients with rotator cuff tendinopathy into 2 groups. For 6 weeks, they applied only one rehabilitation program to one group and KT to the other group twice a week in addition to the rehabilitation program. They reported that symptoms and functional limitations decreased in their evaluations with DASH after 3 months and 6 months after treatment [22]. Frassanito et al. performed treatment of rotator cuff calcific tendinopathy only with ESWT in half of 42 patients and ESWT with KT in the other half. They reported greater improvement in the group that applied KT when they evaluated pain with VAS in short, medium, and long term, and disability with DASH [23]. It is thought that KT provides this healing effect by providing biomechanical correction in the joint, increasing neurological activation in muscles, decreasing wrong positioning and mechanical stress [19]. Miccinilli et al. reported that the KT applied to patients with rotator cuff tendinopathy decreases pain, increases functional recovery and muscle strength, but there is not enough evidence for KT application, and randomized controlled studies with larger groups are needed [24].
Among the limitations of the study, the first is that the diagnosis of biceps tendinitis cannot be made using arthroscopic method. Due to the fact that the diagnosis and treatment of all patients are performed by non-invasive methods, arthroscopic diagnosis has not been made. However, it has been stated in the literature that clinical diagnostic tests and magnetic resonance imaging are sufficient for diagnosis in the diagnosis of biceps tendinitis [4]. Another limitation of the study is the short follow-up time. As a result, in our study, the application of kinesio tape in addition to exercise therapy in biceps tendinitis has been shown to provide significant benefits in terms of both pain and functionality. Larger patient groups and longer follow-up clinical studies are needed to investigate the efficacy of KT application in biceps tendinitis and other shoulder pathologies.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
1. Luime J, Koes B, Hendriksen I, Burdorf A, Verhagen A,Miedema H, et al. Prevalence and incidence of shoulder pain in the general population; A systematic review. Scand J Rheumatol. 2004;33(2):73–81.
2. Sethi N, Wright R, Yamaguchi K. Disorders of the long head of the biceps tendon. J Shoulder Elbow Surg 1999; 8(6):644-654.
3. Maier D, Jaeger M, Suedkamp NP, Koestler W. Stabilization of the long head of the biceps tendon in the context of early repair of traumatic subscapularis tendon tears. J Bone Joint Surg Am. 2007;89(8):1763-9.
4. Nho SJ, Strauss EJ, Lenart BA, Provencher MT, Mazzocca AD, Verma NN, et al. Long head of the biceps tendinopathy: diagnosis and management. J Am Acad Orthop Surg. 2010;18(11):645-56.
5. Wilk KE, Hooks TR. The Painful Long Head of the Biceps Brachii: Nonoperative Treatment Approaches. Clin Sports Med. 2016;35(1):75–92.
6. Bernhardsson S, Klintberg IH, Wendt GK. Evaluation of an exercise concept focusing on eccentric strength training of the rotator cuff for patients with subacromial impingement syndrome. Clin Rehabil. 2011; 25(1): 69–78.
7. McDevitt AW, Snodgrass SJ, Cleland JA, Leibold MBR, Krause LA, Mintken PE. Treatment of individuals with chronic bicipital tendinopathy using dry needling, eccentric-concentric exercise and stretching; a case series. Physiother Theory Pract. 2018;1–11.
8. Khan KM, Scott A. Mechanotherapy: how physical therapists’ prescription of exercise promotes tissue repair. Br J Sports Med. 2009; 43(4): 247–52.
9. Reynard F, Vuistiner P, Léger B, Konzelmann M. Immediate and short-term effects of kinesiotaping on muscular activity, mobility, strength and pain after rotator cuff surgery: a crossover clinical trial. BMC Musculoskelet Disord. 2018;19(1):305.
10. Thelen MD, Dauber JA, Stoneman PD. The clinical efficacy of kinesio tape for shoulder pain: a randomized, double-blinded, clinical trial. J Orthop Sports Phys Ther. 2008; 38(7): 389–95.
11. Düger T, Yakut E, Öksüz Ç, Yörükan S, Bilgütay BS, Ayhan Ç, et al. Kol, Omuz ve El Sorunları Anketi Türkçe uyarlamasının güvenirliği ve geçerliği (Reliability and authenticity of the Turkish version of the DASH (Disabilities of the Arm, Shoulder and Hand) questionnaire). Fizyoter Rehabil. 2006;17(3):99-107.
12. Kücükdeveci AA, McKenna SP, Kutlay S, Gürsel Y, Whalley D, Arasil T. The development and psychometric assessment of the Turkish version of the Nottingham Health Profile. Int J Rehabil Res. 2000;23(1):31–38.
13. Rodosky MW, Harner CD, Fu FH. The role of the long head of the biceps muscle and superior glenoid labrum in anterior stability of the shoulder. Am J Sports Med. 1994;22(1):121–30.
14. Malliaras P, Barton C, Reeves N, Langberg H. Achilles and patellar tendinopathy loading programmes: A systematic review comparing clinical outcomes and identifying potential mechanisms for effectiveness. Sports Med. 2013; 43(4): 267–86.
15. Kim JH, Cho MR, Park JH, Shin JC, Cho JH, Park GC, et al. The effects of Kinesiotape on acute lateral ankle sprain: study protocol for a randomized controlled trial. Trials. 2018; 19(1):125.
16. Basset KT, Lingman SA, Ellis RF. The use and treatment efficacy of kinaesthetic taping for musculoskeletal conditions: a systematic review. New Zealand Journal of Physiotherapy 2010; 38(2):56–62.
17. Lim EC, Tay MG. Kinesio taping in musculoskeletal pain and disability that lasts for more than 4 weeks: is it time to peel off the tape and throw it out with the sweat? A systematic review with meta-analysis focused on pain and also methods of tape application. Br J Sports Med. 2015;49(24):1558–66.
18. Shakeri H, Keshavarz R, Arab AM, Ebrahimi I. Clinical effectiveness of kinesiological taping on pain and pain-free shoulder range of motion in patients with shoulder impingement syndrome: a randomized, double blinded, placebo- controlled trial. Int J Sports Phys Ther. 2013; 8(6):800–10.
19. Kaya E, Zinnuroglu M, Tugcu I. Kinesio taping compared to physical therapy modalities for the treatment of shoulder impingement syndrome. Clin Rheumatol. 2011;30(2):201–7.
20. Simsek HH, Balki S, Keklik SS, Ozturk H, Elden H. Does Kinesio taping in addition to exercise therapy improve the outcomes in subacromial impingement syndrome? A randomized, double-blind, controlled clinical trial. Acta Orthop Traumatol Turc. 2013;47(2):104–10.
21. Kaya DO, Baltaci G, Toprak U, Atay AO. The clinical and sonographic effects of kinesiotaping and exercise in comparison with manual therapy and exercise for patients with subacromial impingement syndrome: a preliminary trial. J Manipulative Physiol Ther. 2014; 37(6):422–32.
22. Oliveira FCL, de Fontenay BP, Bouyer LJ, Desmeules F, Roy JS. Effects of kinesiotaping added to a rehabilitation programme for patients with rotator cuff tendinopathy: protocol for a single-blind, randomised controlled trial addressing symptoms, functional limitations and underlying deficits. BMJ Open. 2017;7(9). DOI: 10.1136/bmjopen-2017-017951.
23. Frassanito P, Cavalieri C, Maestri R, Felicetti G. Effectiveness of Extracorporeal Shock Wave Therapy and kinesio taping in calcific tendinopathy of the shoulder: a randomized controlled trial. Eur J Phys Rehabil Med. 2018; 54: 333-40.
24. Miccinilli S, Bravi M, Morrone M, Santacaterina F, Stellato L, Bressi F, et al. A Triple Application of Kinesio Taping Supports Rehabilitation Program for Rotator Cuff Tendinopathy: a Randomized Controlled Trial. Ortop Traumatol Rehabil. 2018;20(6):499–505.
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Erdinç Genç, Tomris Duymaz. Effectiveness of kinesio taping in bicipital tendinitis treatment: A randomized controlled trial. Ann Clin Anal Med 2020;11(5):498-503
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Perceptions of parental acceptance-rejection in type 1 diabetic and healthy children
Şaziye Senem Başgül 1, Erol Kurt 1, Melek Gözde Luş 2
1 Department of Psychology, Faculty of Economy, Administration and Social Sciences, Hasan Kalyoncu University, Gaziantep, 2 Department of Child and Adolescent Psychiatry, University of Health Science, Haydarpaşa Numune Training and Research Hospital, İstanbul, Turkey
DOI: 10.4328/ACAM.20125 Received: 2020-02-03 Accepted: 2020-05-05 Published Online: 2020-05-12 Printed: 2020-09-01 Ann Clin Anal Med 2020;11(5):504-509
Corresponding Author: Melek Gözde Luş, Department of Child and Adolescent Psychiatry, University of Health Science, Haydarpaşa Numune Training and Research Hospital, İstanbul, Turkey. E-mail: gozdelus@yahoo.com GSM: +90 5322053556 Corresponding Author ORCID ID: https://orcid.org/0000-0002-0430-9289
Aim: The present study aimed to comparatively investigate the parental acceptance-rejection perceived by type 1 diabetic and healthy children and reported by their mothers. The number of studies investigating how mothers of children with chronic diseases cope with this situation is limited.
Material and Methods: The study included 52 children (aged 8-15 years) with type 1 diabetes mellitus who were followed-up in an outpatient clinic of a state hospital in Gaziantep province and their mothers (n=52). A control group was formed of 52 healthy children (aged 8-15 years) who had no chronic diseases and were residents of Gaziantep province and their mothers (n=52). The perception of parental acceptance and rejection was assessed using the Parental Acceptance-Rejection Questionnaire (PARQ; child and mother versions).
Results: The results of this study revealed that diabetic children felt lower levels of warmth/affection and higher levels of undifferentiated rejection as compared with healthy children. In addition, the undifferentiated rejection perception of mothers of diabetic children was higher than that of mothers of healthy children. Moreover, a significant inverse correlation was found between the parental attitude perceived by diabetic children and the parental attitude perceived by their mothers.
Discussion: Diabetic children felt lower levels of warmth/affection and higher levels of undifferentiated rejection as compared with healthy children. Establishing further supportive and preventive studies within the frame of parental attitude, in particular, would enable effective management of a chronic disorder.
The outcomes of this study, which investigated acceptance-rejection attitudes of mothers of type 1 diabetic children, may contribute to establish efficient and beneficial training programs for children with chronic diseases and for their families to maintain well-being and functionality.
Keywords: Chronic illness; Diabetes; Parenting
Introduction
Diabetes mellitus (DM) is a highly prevalent chronic disease involving individuals of all ages in the population. Type 1 DM, also called as young type diabetes, is the type of diabetes seen in young adults and children. Type 2 DM is defined as adult- type diabetes [1]. Type 1 DM is a challenging disease requiring daily and life-long therapy adherence to insulin regimen and blood glucose measurement in addition to diet and physical exercise. Mental disorders and cognitive problems are common among adolescents with type 1 DM [2, 3] and psychiatric disorders associated with poor therapy adherence have been reported [4]. Parents of pediatric patients are responsible for the treatment of DM in their children; adolescents, however, manage this situation independently in a gradual manner [5]. Within this context, parents are the subjects directly witnessing the situation which the adolescents are in; thus, the process is challenging also for them. The presence of a child with a chronic disease leads to a significant burden on the family concerning care, increased demands, and rearrangement of the roles [6]. It is observed that parents are in need of better supporting tools that would help their children in coping with the difficulties they meet [7]. It is thought that mothers, the ones who take care of child particularly in our population, witness this situation [8]. The Parental Acceptance-Rejection (PAR) theory was first introduced in 1975 by Ronald Rohner and then restructured in 1986 [9, 10]. This theory existing in the literature as “PAR Theory” was developed based on the hypothesis that children’s behavior is structured within the scope of the degree of parental warmth they perceive [10]; it is a “socialization” theory investigating the effects of parental acceptance or rejection perceived in childhood on the overall compliance of a child. Acceptance is defined as warmth, affection, care, attention, and support displayed by parents towards their children and the physical and verbal behaviors of parents while they are expressing these emotions. Rejection is defined as the absence or apparent denial of these emotions and, in addition, displaying various physical or psychological behavior or emotions that hurt the child. The warmth (acceptance-rejection) and the control dimensions of the theory have been confirmed in the studies from 186 different cultures [11]. In particular, given that chronic disorders could affect the functionality of a family, it is estimated that parental acceptance-rejection perception may present data that would provide hints on this subject. Studies in this field have revealed that parental attitudes, either maternal or paternal, perceived by adolescents have distinctive outcomes in terms of social competence, self-efficacy, and sympathy [12]. Rohner and Rohner [13] defend that rejection dimension manifests itself in four different features: 1) cold and unaffectionate is defined as the overall parental behavior comprising attention or inattention given to the child; 2) hostility and aggression are defined as the states of parental hate and hostility leading to aggression of a child; 3) indifference and neglect is defined as the state of child’s needs not being met by parents and the child’s feeling him/herself as neglected; and 4) undifferentiated rejection is defined as the child’s feeling him/ herself as rejected despite the absence of apparent parental attitude of rejection.
Positive and negative feedbacks are received by the subjects from people who are responsible for their care and who can be considered as the attachment figure also have an impact on the subject’s functionality [13]. Based on these findings, it is estimated that opinions of diabetic subjects and their families on parental attitude would provide contributive information. The present study aimed to investigate the parental attitudes perceived by type 1 diabetic children and reported by their mothers comparing with parental attitudes perceived by healthy children and reported by their mothers using the Parental Acceptance-Rejection Questionnaire (PARQ) as well as to evaluate the relationship of personal and clinical variables with parental attitudes.
Material and Methods
Study sample
The study included children/adolescents aged between 8 and 15 years with type 1 DM diagnosis, who were admitted to, treated, and followed-up in an Outpatient Clinic of a State Hospital in Gaziantep province, and their mothers. A control group was formed of healthy children/adolescents aged between 8 and 15 years who had no chronic diseases and were residents of Gaziantep province and their mothers. The participants were included only if both the mother and the child had an education level of literacy at least being able to complete the scales on their own. Children/adolescents who had a diagnosis of an endocrine disorder such as thyroid disorder, obesity, developmental problems other than type 1 DM were excluded. The study was approved by the Ethics Committee of Hasan Kalyoncu University with an approval number of 06 dated May 26, 2016. Required permissions were also obtained by consulting with the relevant outpatient clinic in the hospital. Written informed consents were obtained from the mothers both for themselves and for their children.
Data collection tools
Data collection form developed by the researchers as well as the Parental Acceptance-Rejection Questionnaire (PARQ) (mother version-Short form and child version-Short form) were applied to both diabetic and control groups.
Data collection form: Data collection form developed by the researchers is a form that includes questions inquiring information about age and gender of children, maternal age, variables concerning family life, occupational status of mothers, number of children of the mother, income level, and child’s school success. The form was developed to include different number of items for the diabetic and control groups; while the form for the control group did not include questions about any diagnosed disease, the form for the diabetic group also included DM-related questions.
The PARQ (Mother version-Short form): The PARQ is a self- report scale developed by Rohner in 1986 [14] and includes questions aiming at assessing the acceptance and rejection attitudes of parents towards their children. The initial version of PARQ consists of 73 items and 4 sub-dimensions. While 60 of 73 items assess parental acceptance and rejection, the remaining 13 items assess the behavioral control dimension. The acceptance-rejection dimension has the following 4 sub- dimensions: 1) warmth/affection, 2) hostility/aggression, 3) indifference/neglect, and 4) undifferentiated rejection. The participants are required to respond to the questions on a 4-point Likert-scale from 1 (almost never true) to 4 (almost always true). The total score is calculated by subtracting the scores of all sub-dimensions other than the score of Warmth/ Affection sub-dimension from 100. The lowest and highest scores of this scale are 60 and 240, respectively. The scale used in the present study was the short form of the original questionnaire and consists of 30 items. Higher scores indicate a rejectionist parental attitude. In the study conducted to identify the psychometric features of the questionnaire [15], the internal consistency was found as 0.75 for the maternal form and as 0.79 for the paternal form. The test-retest reliability of the questionnaire was 0.93. The Turkish validity and reliability study of the questionnaire was performed in 2003 in an unpublished study and the internal consistency coefficient was found to change from 0.86 to 0.96 both for the paternal and maternal forms. Additionally, the internal consistency coefficient of the control sub-dimension was 0.84 for maternal form and 0.83 for paternal form.
The PARQ (Child version-Short form): The PARQ-Child Form, which was first developed in 1971 by Rohner [9], aims at assessing parental attitudes perceived by children. Distribution of the items among sub-dimensions of the scale is as follows: 6 items in the Warmth/Affection sub-dimension, 6 items in the Hostility/Aggression sub-dimension, 6 items in the Indifference/ Neglect sub-dimension, and 4 items in the Undifferentiated Rejection sub-dimension. The 24-item short form of the questionnaire was developed in line with the distribution of these items. This short form of the PARQ Child Form was used in the present study. As is in the parental form, the participants are required to respond to the questions on a 4-point Likert- scale from 1 (almost never true) to 4 (almost always true). The 13th item in the short form is scored reversely; higher scores obtained from this questionnaire indicate rejectionist parental attitude perceived by the children. The reliability study of the Turkish version of the PARQ-Child Short Form was performed by Yılmaz and Erkman (2008) [16].
Statistical Analysis
Data analysis was performed using the Statistical Package for the Social Sciences (SPPS Inc., Chicago, IL, USA) for Windows version 16.0. The Chi-square analysis was performed in order to determine the differences between two groups in terms of personal and demographic variables. The normality of variables was tested and it was observed that the scale scores and variables were distributed normally; thus, the parametric tests were used. Accordingly, the independent samples t-test and the Analysis of Variance [ANOVA] were used to test differences between the variables and a correlation analysis was performed to investigate the relationship between the variables. A p-value of <0.05 was considered statistically significant.
Results
A total of 120 children returned their forms and 16 forms were excluded due to missing data. In order to validate data analysis, the number was equalized. Accordingly, the present study included 52 diabetic children who composed the diabetic group and their mothers (n=52) and 52 healthy children who composed control group and their mothers (n=52). The general characteristics of the diabetic and healthy control groups as well as disease-related characteristics of the diabetic group are presented in Table 1. The distribution of girls and boys was similar in the diabetic group, whereas the number of girls was much higher than the number of boys in the healthy control group. In the diabetic group, the age distribution of the children ranged from 8 to 15 years, with the highest percentage of children being at the age of 9 years. In addition, the age distribution of the mothers ranged from 25 to 59 years in the diabetic group. In the healthy control group, the age distribution of the children ranged from 8 to 15 years, with the highest percentage of children being at the age of 12 years. Moreover, the age distribution of the mothers ranged from 25 to 60 years with the highest percentage of mothers being in the age range of 36-45 years. Evaluation of the clinical variables relevant to DM revealed that the majority of children were hospitalized twice for treatment. Based on the mothers’ self-report, the rate of absence from school for diabetic children due to their disease was 75%. The time elapsed after the diagnosis of diabetes was ≥5 years in 23.1% of the diabetic group. All children in the diabetic group were receiving insulin therapy; the majority of the children were performing their own insulin injection. The PARQ scores according to the age of children in the diabetic and control groups are presented in Table 2.
The comparison of the PARQ score according to gender, maternal age, and the variable “family member performing the insulin injection” in the diabetic and control groups are presented in Table 3. In the diabetic group, the mean score of the PARQ- Mother version of the girls was significantly higher than that of the boys (p=0.004). The parental attitude perceived by the children did not differ according to child gender (p=0.326). In the diabetic group, the parental acceptance-rejection attitude of the mothers did not change according to the maternal age (p=0.579). Likewise, the parental acceptance-rejection attitude perceived by the children did not differ according to the maternal age (p=0.547). In the control group, the parental acceptance- rejection attitude of the mothers and perceived by the children did not significantly differ according to the maternal age (p=0.838 and p=0.191). The parental attitude of the mothers and perceived by the children did not differ according to family member performing insulin injection (p=0.267 and p=0.744, respectively) in the diabetic group. According to the results of “independent samples t-test” performed to compare the scores of sub-dimensions of the PARQ between the diabetic and control groups, there was a significant difference between the groups in terms of “Undifferentiated Rejection” sub-dimension of the PARQ-Mother version with a significantly higher level of undifferentiated rejection determined in the diabetic group than in the control group (p=0.003). In addition, a significant difference was determined between the diabetic and control groups in terms of the “Warmth/Affection” sub-dimension of the PARQ-Child version (p=0.004). Accordingly, the mean score of “Warmth/Affection” sub-dimension of the PARQ-Child version was significantly higher in the diabetic group than in the control group. Since this sub-dimension is scored inversely while calculating the total score, the warmth/affection attitude was significantly lower in the diabetic group than in the healthy control group. “Undifferentiated Rejection” in the PARQ-Child version was another sub-dimension showing a significant difference between the groups. Accordingly, the mean score of the undifferentiated rejection sub-dimension was significantly higher in the diabetic group than in the control group (p=0.003). According to the results of the correlation analysis of the sub- dimensions of the Parental Acceptance-Rejection Questionnaire for both Mother and Child versions for the control group and for the diabetic group, different levels of significant correlation were determined between the sub-dimensions.
Discussion
The present study aimed to determine whether there was a difference between parental acceptance-rejection perceived by diabetic children and perceived by their mothers concerning the diagnosis of DM, whether there was a difference between the maternal attitude perceived by the diabetic children and the maternal attitude perceived by the healthy children, and whether there was a significant difference between the parental attitude perceived by the healthy children and the parental attitude reported by their mothers. Accordingly, significant differences were determined between the diabetic and healthy control groups in terms of the scores of “Warmth/ Affection”, “Undifferentiated Rejection” sub-dimensions of the PARQ-Child version and in terms of “Undifferentiated Rejection” sub-dimensions of the PARQ-Mother version. Hence, the diabetic children were determined to feel lower levels of warmth/affection and higher levels of undifferentiated rejection as compared with healthy children. In addition, in terms of mothers’ perception on parental attitude, the mean score of “Undifferentiated Rejection” sub-dimension was significantly higher in the mothers of diabetic children than in the mothers of healthy children.
Treatment of type 1 DM is a multifactorial approach requiring the active involvement of all family members [17]. Williams et al. [18] carried out a study on 187 patients aged between 10 and 17 years to investigate diabetes-specific family conflict, adolescent depression, and depression and anxiety in the family. They reported increased diabetes-specific family conflict with psychological stress existing in the parents, children, and adolescents. They also stated that pediatric type 1 DM was usually defined as “family disease” due to the critical role of family interaction and parental support [18]. Noueiri et al. [19] conducted a study in the families of 37 type 1 diabetic patients and reported that 75.7% of the families felt guilty about their children’s condition and that 97.3% of the mothers needed to be with diabetic children longer than necessary. Cavini et al. [20] attributed this behavior to the fact that mothers take the responsibility of home care and accordingly blame themselves when their children get sick and balance this feeling with providing the most intensive care to their children. In another study, 132 type 1 diabetic children with a mean age of 12 years were interviewed once in a year for five years and the level of perceived stress by the families due to the child’s illness was investigated with one of the parents completing the questionnaire [21]. It was determined that the stress experienced by the parents has an impact on their quality of life and wellness and might be negatively influenced during the child’s disease process [21].
In the present study, the type 1 diabetic and healthy control children, as well as their mothers, were separately evaluated to assess parental attitude perceived by the children and by the mothers. The age of the children ranged from 8 to 15 years both in the diabetic group and in the healthy control group. The ratio of children was the highest at the age of 9 years in the diabetic group and at the age of 12 years in the control group. There was no child at the age of 8 or 9 years in the healthy control group.
In the healthy control group, no difference was observed in the parental acceptance-rejection attitude perceived by the mothers according to child age (p=0.630). Likewise, there was also no difference in the parental attitude perceived by the children according to child age (p=0.718). In the diabetic group, the parental acceptance-rejection perceived by the mothers significantly differed according to child age (p=0.004), whereas the parental attitude perceived by the children did not differ according to child age (p=0.081). These outcomes appear to be consistent with those in the literature. In the literature, it was reported that the families of 13-17-year-old adolescents with type 1 DM were less frequently involved in blood glucose monitoring and insulin injection as compared with the families of the younger diabetic patients aged 8-12 years, resulting in adolescents’ having the risk of not receiving adequate parental support concerning care and adherence to treatment from the beginning of the diagnosis of diabetes [22, 23]. Nevertheless, in the present study, it was observed that the parental acceptance- rejection perceived by the mothers did not differ according to the family member performing insulin injection (p=0.267). Likewise, the parental acceptance-rejection perceived by the child did not differ according to the family member performing insulin injection [p=0.744]. Moreover, in the diabetic group, the mean score of the PARQ-Mother version was significantly higher in the mothers of the girls than in those of the boys (p=0.004).
Study Limitations
The outcomes of the present study include findings that may contribute to the support and trainings required particularly for the children and adolescents diagnosed with Type 1 DM and for their families. Nevertheless, the study has limitations in terms of methodology and study sample. First, the study sample was selected from a single province and was thereby considered limited in terms of the probability of providing data to make a conclusion for the overall population in Turkey. In addition, the questionnaires used in the present study are limited to the items they contain in measuring the study variables. This poses a limitation in terms of the likelihood of the presence of different factors that were not evaluated. Another limitation was the outcomes obtained in the study, which were based on participants’ answers to the questions. The age of the diabetic and healthy control children ranged from 8 to 15 years and they answered the questionnaires after the informed consent was obtained from their parents. The answers given by the children, who can be considered as a sensitive population, are thought to pose a limitation to the study outcomes.
Conclusions
The results of the present study revealed that the diabetic children felt lower levels of warmth/affection and higher levels of undifferentiated rejection compared with healthy children. In addition, the undifferentiated rejection perception of the mothers of diabetic children was higher than that of the mothers of healthy children. An inverse correlation was found between the parental attitude perceived by the diabetic children and the parental attitude perceived by their mothers. It was determined that the parental attitude perceived by the children was much closer to the rejection as compared with that reported by the mothers. In the control group, the parental attitude perceived by the children with that perceived by their mothers revealed a correlation in the same direction with those of the diabetic group but in different sub-dimensions.
Establishing further supportive and preventive studies within the frame of family living and parental attitude, in particular, would enable effective management of a chronic disorder such as diabetes, which has a high prevalence and requires rearrangement of living conditions of children and adolescents. It is thought that measurement tools that would assess the compliance process and wellbeing of not only children/ adolescents but also families could be included in future studies. Moreover, personal and clinical variables considered to be potentially associated with DM such as depression, anxiety, negative thought patterns and eating attitude, which might reflect the psychopathology in children and adolescents, are also assumed to be included in future studies. Accordingly, this may allow discussing the factors considered to be challenging for children, adolescents, and their parents during the disease process in different aspects.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
1. American Diabetes Association. Classification and diagnosis of diabetes. Diabetes Care. 2015;38(Suppl. 1):S8-16.
2. Northam EA, Matthews LK, Anderson PJ, Cameron FJ, Werther GA. Psychiatric morbidity and health outcome in Type 1 diabetes-perspectives from a prospective longitudinal study. Diabet Med. 2005;22(2):152-7.
3. Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study Research Group, Jacobson AM, Musen G, Ryan CM, Silvers N, Cleary P, et al. Long-term effect of diabetes and its treatment on cognitive function. N Engl J Med. 2007;356(18):1842-52.
4. Kovacs M, Mukerji P, Iyengar S, Drash A. Psychiatric disorder and metabolic control among youths with IDDM. A longitudinal study. Diabetes Care. 1996;19(4):318-23.
5. Nardi L, Zucchini S, D’Alberton F, Salardi S, Maltoni G, Bisacchi N, et al. Quality of life, psychological adjustment and metabolic control in youths witht type 1 diabetes: A study with self- and parent-report questionnaires. Pediatr Diabetes. 2008;9(5):496-503.
6. dePaula ES, Nascimento LC, Rocha S.M. Roles assessment in families of children with chronic renal failure on peritoneal dialysis. Int J Nurs Pract. 2008;14:215-20.
7. Morrow AM, Hayen A, Quine S, Scheinberg A, Craig JC. A comparison of doctors’, parents’ and children’s reports of health states and health-related quality of life in children with chronic conditions. Child Care Health Dev. 2012;38:186-95.
8. Khanna AK, Prabhakaran A, Patel P, Ganjiwale JD, Nimbalkar S.M. Social, psychological and financial burden on caregivers of children with chronic illness: A cross-sectional study. Indian J Pediatr. 2015;82:1006-11.
9. Rohner RP, Saavedra JM, Granum EO. Development and validation of the parental acceptance-rejection questionnaire: Test manual. Catalog of Selected Documents in Psychology. 1978; 8:17-48.
10. Rohner RP, Khaleque A, editors. Handbook for the Study of Parental Acceptance and Rejection. Storrs, C.T. 4th ed. Rohner Research Publications; 2005.p:75-81.
11. Khaleque A, Rohner RP. Perceived parental acceptance-rejection and psychological adjustment: A meta-analysis of cross cultural and intra cultural studies. J Marriage Fam. 2002;64:54-64.
12. Bariola E, Gullone E, Hughes EK. Child and adolescent emotion regulation: the role of parental emotion regulation and expression. Clin Child Fam Psychol Rev. 2011;14(2):198-212.
13. Rohner R.P, Rohner EC. Parental acceptance-rejection and parental control: cross-cultural codes. Ethnology. 1981;20:245-60.
14. Rohner R.P, editor. The Warmth Dimension: Foundations of Parental Acceptance Rejection Theory. Newbury Park: Sage Publications; 1986.p:98-110
15. Rohner R.P. Personality assessment questionnaire: Test manual. In: Rohner RP, Khaleque A, editors. Handbook for the Study of Parental Acceptance and Rejection. Storrs, CT, Rohner. Research Publications; 2005.p:67-81
16. Yılmaz B, Erkman F. Understanding Social Anxiety Through Adolescents’ Perceptions of Interparental Conflict and Parental Rejection. In: Erkman F, editors. Acceptance: The Essence of Peace. Istanbul: Turkish Psychological Association; 2008.p.67-96.
17. de Brito TB, Sadala ML. Juvenile diabetes: the family’s experience with diabetic adolescents and pre-adolescents. Cien Saude Colet. 2009;14:947-60. [Article in Portuguese]
18. Williams LB, Laffel LM, Hood KK. Diabetes-specific family conflict and psychological distress in paediatric Type 1 diabetes. Diabet Med. 2009;26(9):908- 14.
19. Noueiri B, Nassif N. Impact of diabetes mellitus type 1 on Lebanese families’ quality of life. Int J Clin Pediatr Dent. 2018;11(2):61-65.
20. Cavini FL, Gonçalves KA, Cordeiro SM, da Silva Moreira D, Resck ZMR. Experiences of diabetic adolescents: A phenomenological approach. Journal of nursing UFPE. 2016; 10(Suppl. 2):805-13.
21. Helgeson V, Becker D, Escobar O, Siminerio L. Families with children with diabetes: implications of parent stress for parent and child health. J Pediatr Psychol. 2012;37(4):467-78.
22. American Diabetes Association. Diabetes Statistics. In: Raynor J, editors. Diabetes 2001 Vital Statistics. Alexandria: VA, American Diabetes Association. 2001;13-27.
23. Wysocki T, Taylor A, Hough BS, Linscheid R, Yeates KO, Naglieri JA. Deviation from developmentally appropriate self-care autonomy. Association with diabetes outcomes. Diabetes Care 1996;19(2):119-25.
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Şaziye Senem Başgül, Erol Kurt, Melek Gözde Luş. Perceptions of parental acceptance-rejection in type 1 diabetic and healthy children. Ann Clin Anal Med 2020;11(5):504-509
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Analysis of outcomes of anesthesia management in renal transplant patient
Hulya Ozden Terzi 1, Aysu Hayriye Tezcan 2, Baris Dogu Yildiz 3, Dilsen Hatice Ornek 1
1 Department of Anesthesiology and Reanimation, Ankara Numune Education and Research Hospital, Ankara, 2 Department of Anesthesiology and Reanimation, Kafkas University, School of Medicine, Kars 3Department of General Surgery, Numune Education and Research Hospital, Ankara, Turkey
DOI: 10.4328/ACAM.20131 Received: 2020-02-05 Accepted: 2020-02-28 Published Online: 2020-03-14 Printed: 2020-09-01 Ann Clin Anal Med 2020;11(5):467-473
Corresponding Author: Dilsen Hatice Ornek, Bilkent City Hospital Department of Anesthesiology and Reanimation, Ankara, Turkey. E-mail: dilsenbaris@gmail.com GSM: +90 505 737 3828 Corresponding Author ORCID ID: https://orcid.org/0000-0002-3300-4839
Aim: This study aimed to investigate the effects of anesthesia on organ functions in patients undergoing renal transplantation in our center.
Material and Methods: Data of patients undergoing renal transplantation at Ankara Numune Training and Research Hospital between 2011 and 2014 were retrospectively reviewed. Data of patients were accessed through the analysis of organ transplant follow-up charts, anesthesia follow-up forms and their electronic records at the system.
Results: Of the 42 renal transplantation patients, 17 (40%) had living donors and 25 (60%) had a transplant from a cadaver. None of the patients had com- plications at the time of anesthesia induction; sevoflurane was the most commonly used anesthetic gas, and no statistically significant relationship was found between types of anesthetic gas and postoperative renal functions. Cold ischemia time was found to be statistically longer in patients with delayed graft function, and the incidence of delayed graft function was higher in cadaveric renal transplant recipients than in patients receiving living donor renal transplant. The development of delayed graft function was not found to be statistically related to the administered anesthetic gases. There was no significant difference for patients in terms of anesthetic agent with regard to post-renal transplant laboratory values.
Discussion: In this patient group, where many factors play a role in the survival of the renal graft and the kidney recipient, there is no single proven technique for anesthesia management. The anesthesia and surgery management techniques in our study had no adverse effect on patient and graft survival.
Keywords: Anesthesia; Renal; Transplant
Introduction
Chronic kidney disease is an important health problem all around the world with increasing rates of incidence. Patients with end statege renal failure (ESRF) need a renal replacement treatment (hemodialysis, peritoneal dialysis or renal transplantation) to survive. Renal transplantation is the ideal renal replacement treatment option for ESRF patients because it provides higher survival rates and a better quality of life than hemodialysis and peritoneal dialysis [1]. Anesthesia in renal transplantation was defined in the early 1960s. Much progress has been achieved today through changes in anesthesia management compared to those times when the recipient was administered spinal anesthesia and only provided non-invasive blood pressure and electrocardiogram (ECG) monitorization. ESRF often results in dysfunction in other organs and systems, and responses to anesthetic agents in such patients cannot be fully anticipated. In addition, these patients are at high risk for perioperative complications due to their underlying diseases [1-3].
In this study, we aimed to evaluate the anesthesia and surgery management, early and late anesthetic and surgical complications, patient and graft survival rates for the patients undergoing renal transplant at our hospital and present their relationship with the administered anesthesia method.
Material and Methods
Forty-two patients undergoing renal transplantation at Ankara Numune Training and Research Hospital between May 2011 and October 2014 were included in the study. Data were accessed through the analysis of patient files, patient information recorded at the computer system of our hospital, and anesthesia follow-up forms. Based on the renal transplantation date, patient data including age, gender, body weight, American Society of Anesthesiologists (ASA) score, comorbid diseases, reason for kidney failure, type of dialysis, duration of dialysis, type of donor, duration of surgery, applied interventional procedures, administered anesthetic agents, diuretic drugs, vasoactive drugs, administered fluid therapies, central venous pressure (CVP) values right before and after surgery, cold ischemia times, urination after intraoperative anastomosis, postoperative infections, postoperative complications of anesthesia and surgery, rejection development, length of hospital stay, mortality information and laboratory values for hemogram and biochemistry in the preoperative period, on the 1st, 3rd, and 5th postoperative days and at the time of discharge were retrospectively reviewed.
Statistical data were analyzed with SPSS 20 package program. Friedman’s Two-Way ANOVA was used in the analysis of more than two independent variables as they were non-normally distributed, and when significant differences were observed, Multiple Comparison Tests were used to determine the variables differing from each other. In the analysis of differences between groups, the Mann-Whitney U test and the Kruskal-Wallis H Test were used when the variables were not normally distributed. Since the number of units was over 20, standardized z-values were given for the Mann- Whitney U Test. When significant differences were detected with the Kruskal-Wallis H test, the Post-Hoc Multiple Comparison Test was applied to identify the groups with differences. The Pairedt- test was used to analyze the difference between two dependent variables if they were normally distributed. The Chi-square analysis was applied to examine the correlation between the groups of nominal variables. If the expected values in the cells did not have enough volume, the Pearson Chi-Square analysis was applied with the help of Monte Carlo Simulation. Spearman’s Correlation Coefficient was used to investigate the relationships between non-normally distributed variables.
For the interpretation of the results, 0.05 was accepted as the level of significance, and while p<0.05 indicated a significant difference/correlation, p>0.05 showed no significant difference/ correlation.
Results
Twenty-five patients received kidneys from deceased donors. Of the 17 patients who had kidneys from living donors, 3 received from his/her spouse, 8 received from his/her mother, 2 received from his/her father, 4 received from his/her sibling (i.e 14 living related and 3 living unrelated donors). The demographic data of the patients are summarized in Table 1.
When the patients were analyzed in terms of their comorbidities, 18 patients (42.8%) were found to have essential hypertension and 4 patients (9.5%) had goiter. Four (9.5%) patients underwent preemptive renal transplantation without renal replacement therapy, 10 (23.8%) underwent peritoneal dialysis in the pre- transplant period, 23 (54.7%) underwent hemodialysis and 6 (14.2%) patients underwent both peritoneal dialysis and hemodialysis in various periods during their follow-up. The donor source was living in 17 patients (40.4%) and 25 patients (59.5%) had a renal transplant from a cadaver.
While hypertensive nephropathy was the most common etiology in the patient group, the etiology was idiopathic in half of the patients. The etiology for renal failure of the patients is presented in Table 2.
Standard noninvasive monitoring and invasive central venous pressure (CVP) monitoring via an internal jugular vein catheter were applied to the patients who were taken to the operation table. Invasive blood pressure monitoring was performed through the radial artery in 20 (47.6%) patients. As a premedication, 2 mg midazolam was administered intravenously and operations were performed under general anesthesia. The drugs used for anesthesia induction and maintenance are shown in Table 3. The dose of fentanyl used in the induction of anesthesia was 101±50.9 μg. Propofol and remifentanil infusion and a mixture of 50% air + 50% oxygen were administered to patients in the total intravenous anesthesia (TIVA) group. It was observed that while 50% nitrogen protoxide + 50% oxygen mixture was used in 32 patients (76.1%) who received inhalation anesthesia, 50% air + 50% oxygen mixture was preferred in 8 patients (19%). All patients received atropine and neostigmine to reverse the muscle relaxant effect.
The mean operation time of the patients was 239±49.9 minutes (min: 150, max: 394).
No patient had anesthesia-related complications during the perioperative period. No statistically significant relationship was found between the anesthetic gases used for the patients and the postoperative change in renal functions and biochemical values (p>0.05). Intraoperative fluid management was found that Crystalloid (0.9 % NaCl, Isolyte-S, Ringer lactate, 5% Dex 0.45% NaCl; mean (ml)-Std (ml)4238-1358, 83-290, 161- 382,36-171, Total;4530-1339) Colloid (Hydroxyethyl starch; mean (ml)-Std (ml) 50-185) were used.
It was found that 35.24±9.69 mg mannitol and 84.05±28.03 mg furosemide were administered to the patients in the intraoperative period. The relationship between urine output and mannitol or furosemide dose after intraoperative anastomosis was not found to be statistically significant (p>0.05). Intraoperative urine output was not observed in five patients after anastomosis and 14 patients (33.3%) required postoperative hemodialysis.
The mean duration of cold ischemia was 406.6±226 minutes (min: 73, max: 883). The need for postoperative hemodialysis is defined as delayed graft function. Longer ischemia time and cadaveric donor source are thought to be effective in its development. In our study, the duration of cold ischemia was found to be statistically longer in patients with delayed graft function (p<0.01). In addition, while delayed graft function was detected in 52% of cadaveric renal transplant patients, it occurred in only 5.9% of renal transplant patients with living donors (p<0.01).
There was no statistically significant difference in the analysis of anesthetic gas groups due to delayed graft function development (p>0.05).
Intraoperative follow-up revealed high blood pressure requiring treatment in 3 patients, two of whom were treated with esmolol infusion and the other with perlinganitis infusion. One patient was given insulin infusion upon the detection of hyperglycemia. Central venous pressure (CVP) values of patients at the end of the operation (12.07±5.01 mmHg) were significantly higher than those measured right before the operation (7.21±4.6 mmHg) (p<0.01). In the statistical analysis, it was found that the increase in CVP value had a statistically significant positive correlation with the intraoperative crystalloid amount (r=0.411, p=0.007).
In the postoperative period, only one patient was followed up in the post-anesthesia care unit while all the other patients were transferred to the nephrology unit. In the postoperative follow-up, one patient was transferred to the ICU on the 7th postoperative day due to multiple organ dysfunction syndrome (MODS) and died on the 9th day. This patient was thought to have developed cytokine storm due to Rituximab given for rejection therapy, resulting in MODS.
In our study, rejection was observed in 10 patients (23.8%). Seven of them responded to immunosuppressive therapies while 2 patients had to undergo nephrectomy through reoperation. One patient developed rejection approximately one year after the operation and returned to the dialysis program. Postoperative follow-up revealed surgical complications (hematoma, renal artery stenosis) in 11 patients (26.2%). Postoperative renal artery stenosis was detected in 7 patients during the first five months. Four of these patients were treated with stent placement by interventional radiology, and three of them underwent reoperation and reanastomosis due to the detection of low flow rate in the renal artery at the doppler ultrasonography on the first postoperative day, with no additional pathologies in their follow-up. In addition, 4 patients developed perirenal collection drained from the incision at the operated area and were treated with a vacuum-assisted closure device.
One patient had nephrostomy secondary to the development of BK virus-induced ureteral stricture after the 6th month. This late complication was not included in the surgical complications. The patient is being followed up without the need for hemodialysis.
Of the 42 patients we examined, 6 had to undergo reoperation for various reasons: Three patients had renal artery stenosis, one had suspected parenchymal necrosis (diagnosed as acute tubular necrosis and underwent no additional intervention), and two had rejection.
Fever was detected in the postoperative follow-up of 17 patients. In 7 patients, the fever responded to prophylactic antibiotic therapy despite negative culture results, 7 other patients had urinary tract infection and 3 patients had both urinary tract infection and respiratory tract infection. While nine patients recovered with antibiotherapy, 1 patient with urinary tract infection was admitted to the intensive care unit with MODS findings on the postoperative 7th day and died on the 9th day.
In our study, the mortality rate in renal transplantation at our hospital was found to be 2.38%.
It was analyzed whether the morbidity observed in the patients in the postoperative period differed according to the type of donor. The relationship between donor source and morbidity was statistically significant (p<0.05). While morbidity was observed in 29.4% of patients who underwent renal transplantation from living donors, morbidity rate was 72% in patients undergoing renal transplantation from cadaver. As seen, the morbidity rate is higher in cases where the donor is a cadaver (p<0.05). Postoperative morbidities were found that ; renal artery stenosis (living donor 3 and cadaveric 4), infection (positive culture result: living donor 1 and cadaveric 9), rejection (living donor 2 and cadaveric 8), nephrectomy secondary to rejection (living donor 0 and cadaveric 2), hematoma at the operated area (living donor 2 and cadaveric 2), ureteral stricture( living donor 0 and cadaveric 1), anemia (requiring ES replacement) ( living donor 3 and cadaveric 5), MODS (resulting in death) (living donor 1 and cadaveric 0), Fever (negative culture result) (living donor 3 and cadaveric 4).
Discussion
Between May 2011 and October 2014, 42 patients underwent renal transplantation in our hospital. In our study population, 4 (9.5%) of 42 patients had undergone preemptive renal transplantation. In preemtive transplantations, patient and graft survival is better due to the fact that the recipient has not yet started dialysis and the systemic changes caused by renal failure are still minimal. In our study, renal transplantation in 17 (40.4%) patients was from living donors and in 25 (59.5%) patients from cadavers. The reason why cadaver transplants are more common in our hospital in comparison to the country average is the socio-cultural-economic characteristics of the patients admitted to our hospital. Namely, our patients cannot find living donors. However, the higher percentage of cadaver transplantation in our hospital should be acknowledged as the desired rate required for our country.
In our study, hypertensive nephropathy was detected in 5 patients (11.9%), primary renal disease in 16 patients (38%) and ESRF with unknown primer in 21 patients (50%) as etiological reasons. However, hypertension was detected in 10 of these patients with unknown primer.
When comorbidities were investigated, preoperative hypertension was seen in 18 patients (42.8%). Diabetes mellitus and ischemic heart disease are also common comorbidities. However, none of the patients in our study had preoperative diabetes or ischemic heart disease. Although goiter is not a common comorbidity with chronic renal failure, in our study, preoperative goiter was detected in 4 patients (9.5%). Anemia is common in patients with ESRF. In our study, 25 patients (59%) had hemoglobin values of 12 g/dL and lower. The number of patients with hemoglobin concentration of 8 g/dL and lower was 3 (7.1%).
Prolonged cold ischemia time in transplantation preparation is an important risk factor for delayed graft function and graft loss [2]. The risk of delayed graft function increases by 23% every 6 hours during the period of cold ischemia [2]. Cold ischemia time should be kept as short as possible and should not exceed 24 hours [4]. In our study, the mean duration of cold ischemia was found to be 406.6±226 minutes. In a study by Aydoğan et al. [5], ischemia time was 158±110 seconds, total ischemia time was 450±178 minutes, and cold ischemia time was not fully specified. In our study, the duration of cold ischemia (524.64±138.88 minutes) was found to be statistically longer in patients with delayed graft function (p<0.01). The major reasons why cold ischemia time could not be shortened in our center are that organs are brought to our hospital from a long distance by land transport, most of our patients travel to the hospital from rural areas outside our province and have to wait for at least 5-6 hours for immunological matching analyses. Immunosuppressive therapy, which starts in the preoperative period in renal transplantation, continues in the intraoperative period. All patients included in our study were treated with intraoperative anti-thymocyte globulin (ATG) and methylprednisolone. ATG could rarely have side effects due to cytokine release syndrome or possible anaphylaxis [6,7]. In our study, no side effects related to ATG were observed in patients in the intraoperative period.
For renal transplantation, most centers prefer general anesthetic techniques as they offer better hemodynamic stability, muscle relaxation and foreseeable anesthetic depth. All patients in our study had general anesthesia. There have been studies comparing anesthesia methods, none of these anesthesia methods seem to affect the success of transplantation more positively than the other [8]. In our study, total intravenous anesthesia was applied in 2 patients and inhalation anesthesia was used in 40 patients for the maintenance of anesthesia. In our study, no statistically significant relationship was found between postoperative renal function and anesthetic gases administered to the patients (p>0.05). In addition, in our study, no statistically significant relationship was found between the types of anesthesia administered to the patients in terms of laboratory values followed up according to days after renal transplantation (p>0.05). Our findings were not different from those in other studies in terms of anesthetic substances. Arterial cannulation is rarely needed in perioperative blood pressure monitoring because preoperative preparation of renal transplantation patients is well- performed and excessive blood loss is seldom observed. However, serious fluctuations in blood pressure may be observed in some patients due to their coexistingdiseases,whichmayrequireinvasivearterialblood pressure monitoring [1,8]. In our study, arterial cannulation was performed in 22 patients (52.4%) for intraoperative blood pressure monitoring. Hypertension in 6 patients and morbid obesity in one patient were the only co-morbid diseases. The arterial cannulation rate of 52.4% may be attributed to the anesthesiologist’s personal preference or to the fact that anesthesiologists may request a stricter follow-up for blood pressure since cadaveric renal transplants are performed in emergency conditions and there is limited time for preoperative preparation.
In patients with hypertension, there might be fluctuations in peroperative blood pressure. In our study, 3 patients had high blood pressure requiring intraoperative treatment. In a large case series, the incidence of hypotension (49.6%) was reported to be higher than hypertension (26.8%) in the intraoperative period [1]. In our study, no patient had intraoperative hypotension requiring treatment.
Central venous pressure (CVP) measurement is as important as blood pressure measurement in renal transplantation patients. The aim of CVP monitoring is to keep CVP between the values of 10-15 mmHg in order to optimize cardiac output and renal blood flow [1]. In our study, central venous pressure (CVP) values of the patients at the end of the operation (12.1±5.0 mmHg) were significantly higher than those measured right before the operation (7.2±4.6 mmHg) (p<0.01). The statistical analysis showed that the increase in CVP value showed a significant positive correlation with intraoperative fluid regimen (r=0.411, p=0.007).
Furosemide is known to reduce the activity of the antidiuretic hormone and increase resistance to ischemia. Mannitol, on the other hand, is known to increase renal blood flow and act as a protection against tubular necrosis and free radicals. Loop diuretics and mannitol can be used to increase diuresis in the kidney [8]. In our study, it was found that mannitol and furosemide, a loop diuretic, were administered together and 35.2±9.8 g mannitol and 84±28 mg furosemide were administered to all patients. In 37 patients, urine output was observed after intraoperative anastomosis, while no urine output was observed in 5 patients, and no statistically significant result was found between mannitol or furosemide dose and urine output after anastomosis (p>0.05). This finding is different from those previously published in the literature [9,10].
In addition to the use of mannitol and diuretics to generate diuresis, it is also important to ensure adequate circulation volume [8]. Dawidson et al. [11] reported that urine output was delayed after reperfusion in patients with a blood volume under 70 mL/kg. In recent years, there have been controversies about whether a certain crystalloid fluid is better than others for postoperative renal function. An extensive survey study conducted at 49 hospitals in the USA showed that normal saline-based solutions were used during transplantation in more than 90% of the patients [12,13]. However, in a prospective, randomized, controlled and double-blind study comparing the use of normal saline and Ringer’s lactate solution in intraoperative fluid management for renal transplantation, a higher rate of severe hyperkalemia and metabolic acidosis was observed in the normal saline group. In their study, Aydoğan et al. [5] reported that 2129±1024 ml 0.9% sodium chloride solution was administered to the patients on average. In our study, it was found that patients were intraoperatively given an average of 4530±1339 ml crystalloid solution in total, and the value for each type was as follows: 4238±1358 ml 0.9% sodium chloride, 83±290 ml isolyte-s, 161±382 ml Ringer’s lactate and 36±171 ml 0.45% sodium chloride + 5% dextrose solution. It was found that the most frequently used solution by anesthesia specialists in our clinic for renal transplantation cases was 0.9% sodium chloride solution, followed by Ringer’s lactate solution. No statistically significant hyperkalemia was observed in the patients (p>0.05).
In total, a colloid solution containing hydroxyethyl starch was used in only three patients, at a mean amount of 50±185 ml. In one of these patients, renal vein thrombosis developed on the first postoperative day and the allograft was lost. Heta starch has a side effect of nephrosis and there are opinions that it should not be administered in renal transplantation [14].
Since blood loss is usually minimal in renal transplantation, the need for transfusion is rare [8]. No patient in our study received blood or blood product replacement.
Following transplantation, urine output is observed in more than 90% of renal transplants from living donors and in 40 % to 70 % of cadaveric renal transplant recipients [1]. In our study, 37 patients had diuresis after anastamosis and 5 patients had no urine output in the intraoperative period after anastamosis. All of these 5 patients had renal transplantation from cadaver. One patient was found to have severe renal artery stenosis with postoperative Doppler ultrasonography (Doppler USG), and had to be reoperated to renew the anastomosis. Urine output was observed after the second operation. Another patient developed acute antibody-mediated rejection, failed to respond to treatment, and underwent graft nephrectomy. The other three patients required postoperative intermittent hemodialysis. In these patients who were considered to have delayed graft function, renal functions recovered later on, and they are still followed up with functional kidneys.
The incidence of postoperative admission of renal transplantation patients to ICU is generally low, found to be around 1% in a large series. Sepsis or excessive fluid load was observed in patients who had to be transferred to ICU [15]. In our study, it was found that one patient was admitted to the ICU due to MODS on the postoperative 7th day and died on the 9th day. One patient was admitted to the post-anesthesia care unit due to late postoperative recovery and low oxygen saturation, and transferred to the ward after oxygen treatment with a mask for about 4 hours.
Postoperative pain in patients after renal transplantation is usually mild to moderate [1]. It is recommended to avoid the use of NSAI in patients undergoing transplantation and in all patients with renal dysfunction [8]. In our study, it was seen that NSAI was not preferred, instead, tramadol was used for postoperative analgesia in patients. However, since there is no routine evaluation with a pain scale, statistical data are not available.
The success of long-term outcomes of renal transplant recipients depends on the successful management of perioperative and early postoperative periods [16]. Early surgical complications such as delayed graft function, acute rejection attacks, urinary leakage or vascular complications and sepsis are among the important factors affecting long-term outcomes [16].
Delayed graft function is the most common complication in the early postoperative period [17]. In an analysis of 107787 cadaveric renal transplantations between 1987 and 2001, the incidence of delayed graft function was found to be approximately 23% in cases with standard donor criteria and approximately 34% in those with expanded donor criteria [18]. In our study, delayed graft function was found in 14 patients (33.3%). The reason for this high rate is that transplantations in our center are mostly from cadavers, and the cadaver donors are mainly composed of expanded criteria donors. Three of these patients had acute tubular necrosis, 6 had acute antibody- mediated rejection, 1 had acute T-cell mediated rejection and another had renal artery stenosis. One patient died due to MODS on the 9th postoperative day. Graft nephrectomy was performed in 2 of the patients who had rejection, and a patient who developed acute T-cell rejection about one year after the operation had to restart dialysis. Except for these 3 patients and 1 exitus patient, renal functions in the other 10 patients returned to normal with the appropriate treatment, and these patients are still followed up with functional grafts. In our study, while delayed graft function was detected in 52% of cadaveric renal transplant patients, the incidence rate was 5.9% in renal transplant patients with living donors (p<0.01). In our analysis, the difference between the administered anesthetic gases in terms of delayed graft function development was not found to be statistically significant (p>0.05).
In our study, rejection was observed in 10 patients (23.8%). While two of these developed acute T-cell mediated rejection, the other 8 patients had acute antibody-mediated rejection. It was found that 7 patients who developed rejection were discharged with functional grafts whereas 2 patients underwent graft nephrectomy through reoperation. One patient who developed rejection approximately one year after the operation had to return to the dialysis program.
Surgical complications such as hematoma and renal artery stenosis were observed in 11 patients (26.2%) in the postoperative period. Renal artery stenosis is the most common vascular complication after renal transplantation, with an incidence ranging between 1% and 23% [19]. In our study, renal artery stenosis was detected in 7 patients (16.6%) in the first five postoperative months. Hematoma at the operation area was detected in 4 patients (9.5%) and treated with vacuum drainage.
In developed countries, post-transplant infection rates have dramatically decreased from 70% to 40%, accompanied by a decrease in mortality rates from 40% to 5%. However, developing countries are still fighting against these problems [20]. Infections worsen the course after transplantation in 50% to 75% of recipients and cause mortality at rates ranging between 20% and 60% [20]. Most of the infections seen in the early postoperative period are associated with surgery. Generally, wound site infection, central catheter-induced bacteraemia, urinary tract infection or pneumonia is observed [21]. In India, the incidence rate of pneumonia in the early period after renal transplantation was reported to be 18% [22]. In our study, the incidence of infection in patients was 23.8% in the post-transplant period until discharge from the hospital; 70% of these were urinary tract infections and in 30% of them, urinary tract infection was accompanied by respiratory tract infection. Seven patients (16.6%) with fever but negative culture results were not included in this rate of 23.8%.
Postoperative complications in the patients were reviewed and considered as morbidity, and it was analyzed whether they differed according to donor type. There was a statistically significant relationship between donor source and morbidity (p<0.05). While 29.4% of patients undergoing renal transplantation from living donors had morbidity, this rate was 72% in cadaveric renal transplant recipients.
In our study, one patient died on the 9th postoperative day and the mortality rate was calculated as 2.3%. In many recent series, it has been reported to range between 0.03% and 0.6% [16].
In studies by Aydoğan et al. [5], Dogukan et al. [23], and Sağıroğlu et al. [24], 32 out of 33 (96.9%), 20 of 30 (66.6%), and 52 (92.8%) of 56 renal transplant patients, respectively, were reported to have functional grafts. Of the 42 patients who underwent renal transplantation in our hospital between May 2011 and October 2014, 38 (90.4%) still have functional grafts. Outcomes of renal transplantation are affected by factors such as differences in the experience of centers, patient diversity, donor source, immunosuppressive treatment regimens, follow- up periods and patient compliance. In many countries, 1-year survival rates in renal transplantation patients have been reported to be over 90% in the 1990s and since 2000s [25]. The survival rate of 42 renal transplant patients treated in our hospital between May 2011 and October 2014 has been 97.6%. Conclusion
The successful management of the problems that may be encountered in the perioperative period in renal transplant surgery plays an essential role in preventing graft and patient loss.
There is no single method and drug group for effective and reliable anesthesia management in renal transplantation patients. We believe that our main aim is to stabilize the hemodynamic parameters of the patients independent of the anesthetic agents used, and thus, to ensure adequate perfusion of the graft kidney.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
1. Yost CS, Niemann CU. Anesthesia for Abdominal Organ Transplantation. In: Miller RD, editors. Miller’s Anesthesia. 7th ed. Philadelphia: Elsevier Churchill Livingstone; 2010. Chapter: 67, p. 2155-84.
2. Ojo AO, Wolfe RA, Held PJ, Port FK, Schmouder RL. Delayed graft function: Risk factors and implications for renal allograft survival. Transplantation. 1997;63(7):968-74.
3. Shoskes DA, Cecka JM. Deleterious effects of delayed graft function in cadaveric renal transplant recipients independent of acute rejection. Transplantation. 1998; 66:1697-701.
4. Gibbs P. Surgical procedure. In: Klein AA, Lewis CJ, Madsen JC, editors. Organ Transplantation: A Clinical Guide. Cambridge (UK): Cambridge University Press; 2011. Section 5, Chapter 30, p. 253-7.
5. Aydoğan MS, Çolak YZ, Pişkin T, Ünal B, Toprak Hİ, Durmuş M. Anaesthetic management of renal transplanted patients. Ann Med Res. 2013;20(4):318-21.
6. Issa FG, Goto R, Wood KJ. Immunological principles of acute rejection. In: Klein AA, Lewis CJ, Madsen JC, editors. Organ Transplantation: A Clinical Guide. Cambridge (UK): Cambridge University Press; 2011. Section 1, Chapter 2, p. 9-18.
7. Kumar V, Gaston RS. Immunosuppression: Past, present, and future. In: Klein AA, Lewis CJ, Madsen JC, editors. Organ Transplantation: A Clinical Guide. Cambridge (UK): Cambridge University Press; 2011. Section 1, Chapter 3, p. 19-30.
8. Sear JW, Dyar OJ. Anesthesia for Patients Undergoing Renal Transplantation. In: Morris PJ, Knechtle SJ, editors. Kidney Transplantation: Principles and Practice. 6th ed. Philadelphia: Saunders Elsevier; 2008. Chapter 13, 187-209.
9. Sprung J, Kapural L, Bourke DL, O’Hara JF Jr. Anesthesia for kidney transplant surgery. Anesthesiol Clin North Am. 2000;18(4):919-51.
10. Lemmens HJ. Kidney transplantation: recent developments and recommendations for anesthetic management. Anesthesiol ClinNorth Am. 2004;22(4):651-62.
11. Dawidson I, Berglin E, Brygner H, Reisch J. Intravascular volumes and colloidal dynamics in relation to fluid management in living related kidney donors and recipients. Crit Care Med. 1987;15(7):631-6.
12. O’Malley CMN, Frumento RJ, Bennett-Guerrero E. Intravenous fluid therapy in renal transplant recipients: Results of a US survey. Transpl Proc. 2002;34(8):3142- 5.
13. O’Malley CMN, Frumento RJ, Hardy MA, Benvenisty AI, Brentjens TE, Mercer JS, et al. A randomized double-blind comparison of lactated Ringer’s solution and 0.9% NaCl during renal transplantation. Anesth Analg. 2005;100(5):1518-23.
14. Ebcioglu Z, Cohen DJ, Crew RJ, Hardy MA, Ratner LE, D’Agati VD, et al. Osmotic nephrosis in a renal transplant recipient. Kidney Int. 2006;70(10):1873-6.
15. Kogan A, Singer P, Cohen J, Grozovski E, Grunberg G, Mor E, et al. Readmission to an intensive care unit following liver and kidney transplantation: A 50-month study. Transplant Proc. 1999;31(4):1892-3.
16. Knechtle SJ, Pirsch JD. Early Course of the Patient with a Kidney Transplant. In: Morris PJ, Knechtle SJ, editors. Kidney Transplantation: Principles and Practice. 6th ed. 6th ed. Philadelphia: Saunders Elsevier; 2008. p. 210-9.
17. Cecka JM. The UNOS Scientific Renal Transplant Registry. In: Cecka JM, Terasaki PI, editors. Clinical Transplants 1998. Los Angeles: UCLA Tissue Typing Laboratory; 1999. p. 421-36.
18. Cecka JM. The UNOS Renal Transplant Registry. In: Cecka JM, Terasaki PI, editors. Clinical Transplants 2002. Los Angeles: UCLA Immunogenetics Center; 2003. p. 1-20.
19. Fervenza FC, Lafayette RA, Alfrey EJ, Petersen J. Renal artery stenosis in kidney transplants. Am J Kidney Dis. 1998;31(1):142-8.
20. Jha V, Chugh KS. Posttransplant infections in the tropical countries. Artif Organs. 2002;26(9):770-7.
21. Rubin RH. Infectious diseases in transplantation/pre- and post- transplantation. In: Norman DJ, Suki WN, editors. Primer on Transplantation. Thorofare, NJ: American Society of Transplant Physicians; 1998. p. 141-52.
22. Moosa MR. Renal Transplantation in Developing Countries. In: Morris PJ, Knechtle SJ, editors. Kidney Transplantation: Principles and Practice. 6th ed. Philadelphia: Saunders Elsevier; 2008. Chapter 36, p. 630-56.
23. Doğukan A, Tokgöz B, Oymak O, Taşkapan H, Sözüer E, Yılmaz Z, et al. Outcome of Renal Transplantation at Erciyes University Medical Faculty: Analysis of 5 Year Results. Erciyes Med J. 2003;25(2):86-91.
24. Sağıroğlu T, Yıldırım M, Meydan B, Çobanoğlu M. Retrospective analysis of kidney transplanted patients. Dicle Med J. 2009;36(2):75-9.
25. Knechtle SJ, Morris PJ. Results of Renal Transplantation. In: Morris PJ, Knechtle SJ, eds. Kidney Transplantation: Principles and Practice. 6th ed. Philadelphia: Saunders Elsevier; 2008. Chapter 37, p. 657-75.
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Hulya Ozden Terzi, Aysu Hayriye Tezcan, Baris Dogu Yildiz, Dilsen Hatice Ornek. Analysis of outcomes of anesthesia management in renal transplant patient. Ann Clin Anal Med 2020;11(5):467-473
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The effect of Urtica Urens on A549 lung cancer cell line
Ulfat Omar 1, 2, Akram Aloqbi 3
1 Department of Biochemistry, Faculty of Science, King Abdulaziz University, 2 Immunology Unit, King Fahad Medical Research Center, King Abdulaziz University, 3 Department of Biology, Faculty of Sciences and Arts-Alkamel, University of Jeddah, Jeddah, KSA
DOI: 10.4328/ACAM.20133 Received: 2020-02-12 Accepted: 2020-03-17 Published Online: 2020-03-30 Printed: 2020-09-01 Ann Clin Anal Med 2020;11(5):510-514
Corresponding Author: Ulfat Omar, Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, PO Box 40288, zip code, 21499, Saudi Arabia. E-mail: uomer@kau.edu.sa Corresponding Author ORCID ID: https://orcid.org/0000-0002-9751-8476
Aim: Urtica Urens is expected to produce effective results in reducing cancer cell growth as it exhibits anti-oxidant properties. The present study aims to investigate the effect of Urtica Urens on A549 lung cancer cell line.
Material and Methods: Leaves of Urtica Urens were obtained from a local market and its freeze-dried mixture was stored at -20oC. A549 lung cancer cells were incubated with either 5 or 10 μg/ml of aqueous extract of dried leaves or freeze-dried leaves preparations of Urtica Urens for 24 hours. The obtained data were analyzed using Graph Pad Prism software version 6.
Results: The freeze-dried Urtica Urens showed a significant rise in late apoptosis phase and necrosis, respectively, as compared to the use of 5 μg/ml of aqueous extract of dried and the freeze-dried Urtica Urens. The cells were arresting either in G0/G1 phase (in freeze-dried leaves extract) or in G2/M phase (in dried leaves extract), under 10μg/ml concentration.
Discussion: Urtica Urens was significantly producing more cellular and mitochondrial ROS, as compared to the untreated A549 cells control. The study concluded that cytotoxic effects are produced by dried extracts of Urtica Urens leaves on cancer cell lines, under certain concentrations.
Keywords: Apoptosis; Cell line; Necrosis; ROS
Introduction
Cancer is known as an important health problem across the world. In 2008, 13% (7.6 million) of all the deaths occurred because of cancer and this number is likely to rise over 11 million in the year 2030 [1]. The most prevalent type of cancers includes lung cancer, breast cancer, and colorectal cancer. The prevalence of lung cancers has increased in developing countries because of its increased incidence, rapid progression, and poor prognosis [2,3]. Lung cancer has emerged as a life-threatening disease and it is the most significant type of cancer that increases mortality rate across the world [4]. There is a 5-year survival rate of 15% among the patients suffering from lung cancer. However, the risk of developing lung cancer or increased mortality rates associated with lung cancer can be prevented through timely detection, diet and food supplements. Recently, different types of cancers have been treated effectively through chemotherapy procedure; however, there is a wide range of side effects associated with the anti-tumor chemotherapies. Therefore, the researchers are exploring an alternative treatment for treating cancer with minimum or no side effects [2]. Cancer is considered an aggressive killerdespite considerable efforts exerted to minimize its occurrence and produce an effective treatment. A considerable amount of cost has been invested for developing the novel synthetic chemotherapeutic agents; however, its clinical use has failed to fulfill the desired expectations during the last decade. This increases the demand for developing new, affordable, and effective anti-cancer drugs [5].
On the contrary, natural remedies along with the medicinal plants have been used for ages to treat different diseases as they have the capability to cure a wide range of illnesses [6]. The chemical compounds derived from plants are extensively used for treating human illnesses since the emergence of ancient medicine [7].
Previous studies have shown that naturally derived therapeutic drugs having the potential to treat cancer have received increased attention over the past 30 years [8,9]. Underlying the significance of these therapeutic compounds, the use of plant- derived products inhibiting various stages of tumorigenesis and associated inflammatory processes has become evident.
The majority of the drugs i.e. 60% of the drugs isolated from the natural products are used for treating cancer, currently [10]. The plants used for deriving these natural products include Camptotheca alkaloids, Podophyllum lignans, Taxus diterpenes, and vinca alkaloids [7].
A study conducted by Saklani and Kutty [11] tested the effectiveness of 16 new plant-derived compounds in treating cancer. The results demonstrated that meisoindigo, isolated from the Chinese plant Indigofera tinctoria and flavopiridol, isolated from the Indian tree Dysoxylum binectariferum produced effective results for treating cancer with lesser side effects and level of toxicity. Studies have also demonstrated the significance of medicinal plants that are used as an alternative for treating cancers in many countries [13,13]. A total of 3000 plants account for exhibiting anti-cancer properties [7].
It has been shown that there are certain compounds derived from plants are used as anti-cancer agents [6,14].
For instance, Urtica Urens, also known as small nettle and belonging to genus Urtica is a semi-woody plant that grows annually. Previously, it was reported that the herb Urtica Urens is used for treating skin inflammations and fever [6]. Flavonoids, caffeic acid, sitosterol, caffeoyl-esters, scopoletin, fatty acids, minerals, and polysaccharides are known as the main constituents of Urtica Urens. It is anticipated that Urtica Urens may produce effective results in reducing cancer cell growth because it consists of flavonoids and other compounds exhibiting antioxidant properties. The pharmacological data supporting the effective use of Urtica Urens is lacking, despite its widespread use in traditional plant medicines. Therefore, the present study aims to investigate the effect of Urtica Urens on A549 lung cancer cell line. The study holds significance as it is the first study investigating the effectiveness of Urtica Urens on A549 lung cancer cell line. In clinical practice, the study results would be helpful for the oncologists as they are exploring an alternative treatment for treating cancer with minimum or no side effects, as compared to the chemotherapeutic drugs.
Material and Methods
Chemicals
The chemicals used in this study for tissue culture, detecting cytotoxic assay, detecting cells cycle assay, and determining reactive oxygen species production assays have been listed below.
• Tissue culture: high glucose Dulbecco’s Modified Eagle’s Medium powder (DMEM) (Hyclone, USA), foetal bovine serum (FBS) (Hyclone, USA), L-glutamine (Sigma-Aldrich Chemical Co, UK), trypsin/EDTA (Gibco, Canada), antibiotic (penicillin/ streptomycin) (Gibco, Canada), and non-essential amino acids (NEAA) (Gibco, Canada).
• Detection of cytotoxicity assay: 3-(4, 5–dimethylthiazol-2-yl) and 2,5- diphenyltetrazolium Bromide (MTT) (Sigma-Aldrich chemical Co, UK).
• Detection of cell cycle arrest: Phosphate buffered saline (PBS) tablets (Oxoid, UK) and the RNase (Abcam, UK).
• Detection of cell death mechanism assays: propidium iodide (PI) (Sigma-Aldrich Chemical Co, UK) and Annexin V-FITC apoptosis detection kits (Abcam, UK).
•Determination of reactive oxygen species (ROS) production assays: MitoSox red dye (Invitrogen, UK) and di- hydrodichlorofluorescein diacetate (CM-H2DCFDA) (Invitrogen, UK).
Preparation of Urtica Urens for Treatments
The leaves of Urtica Urens were obtained from a local market in Jeddah. The leaves were washed, dried, and crushed. Around 50 g of the crushed leaves were soaked in 1.5 L of boiling water for 30 minutes at room temperature for preparing freeze-dried leaves. The mixture while boiling was occasionally stirred. After boiling, the extract was filtrated. The filtrate obtained after filtration was freeze-dried and stored at -20°C.
Cell Culture and Cytotoxicity Analysis of Urtica Urens on A549 Cells
Human (A549) lung cancer cell line was obtained from the immunology laboratory at King Fahad Medical Research Center (KFMRC) at King Abdul-Aziz University (KAU) in Jeddah, Kingdom of Saudi Arabia (KSA). The cells were cultured in DMEM supplemented with 10% fetal bovine serum (FBS), 1% L-glutamine, 1% penicillin/streptomycin, and 1% non-essential amino acids under standard cell culture conditions (5% CO2 at 37°C). The cell cytotoxicity was assessed through three independent experiments of MTT assay.
Determination of Apoptosis by Annexin-V dye
A549 lung cancer cells were incubated with either 5 or 10 μg/ ml of aqueous extract of dried leaves or freeze-dried leaves preparations of Urtica Urens for 24 hours when these cells were 70% confluent in 25 cm2 flasks. Then, flow cytometry was performed following the manufacture’s instructions and 10,000 events in the gated regions were acquired using an emission wavelength of 520 nm for cells labeled with Annexin V-FITC and 620 nm for cells labeled with propidium iodide (PI) on Beckman Coulter flow cytometer.
Detection of Cell Cycle Arrest and DNA Fragmentation
In 25 cm2 flasks, 70% confluent A549 cells were incubated with 5 or 10 μg/ml of aqueous extract of dried leaves or freeze-dried leaves preparations of Urtica Urens for 24 hours. After that, cells were trypsinized and pellets were washed twice with PBS, fixed with 1 ml of ice-cold fixing buffer (70% ethanol in PBS), and incubated at 4oC overnight. Then, the cells were incubated for 30 min at 37oC. Following the incubation, 500 μl PBS followed by 5 μl of 5 mM RNase were added to re-suspend the cells. Five μl of PI (1 mg/ml) was added and cells were examined on BD FACSCalibur flow cytometer to acquire 10,000 events at an emission wavelength of 620 nm, to capture the changes in the cell cycle.
Determination of Cellular and Mitochondrial Response of Cells to Reactive Oxygen Species (ROS)
Di-hydrodichlorofluorescein diacetate (H2-DCFDA) dye and Mitosox red dye assays were performed to assess cellular and mitochondrial ROS levels, respectively in lung A549 cancer cells. For cellular ROS measurement, cells were first cultured in a 96-well plate and then treated with 5 or 10 μg/ml of aqueous extract of freeze-dried leaves preparations of Urtica Urens for 24 hours. After that, 5 μl of DCFDA was added to each well and incubated in the dark for 30 min at 37oC/ 5% CO2. The resulted DCF fluorescence was read in a BioTek Fluorescence microplate reader at excitation and emission wavelengths of 485 nm and 528 nm, respectively. For the mitochondrial ROS (mtROS) measurements, cells were treated with 5 or 10 μg/ml of aqueous extract of freeze-dried leaves preparations of Urtica Urens under the same culture conditions as cellular ROS experiments. Then, the resulted red fluorescence that represents the level of superoxide produced in the cells was measured with BioTek fluorescence microplate reader according to the manufacture instructions (was read at an excitation wavelength of 530 nm and at an emission wavelength of 590 nm). For each assay, three independent experiments were performed to ensure reproducibility.
Statistical Analysis
Graph Pad Prism software version 6 was used to analyze the data obtained from all assays. The significant differences were evaluated using a one-way analysis of variance (ANOVA) followed by Bonferroni’s test correction. A p-value ≤ 0.01 was considered significant. The untreated A549 cells in this study represent the control and it was used to compare the results of all experiments with treated A549 cells.
Results
Cytotoxicity Analysis of Urtica Urens on A549 Cells
The cytotoxic effect of 5 and 10 μg/ml of aqueous extract of dried leaves or freeze-dried leaves preparations of Urtica Urens on lung A549 was assessed by MTT assay. Data revealed that at 10 μg/ml of both aqueous extract of dried leaves and freeze- dried leaves of Urtica Urens has a significant effect on the cell viability of A549 compared to untreated control cells (Figure 1). The cell viability percentage of HCT-116 cells under dried leaves and freeze-dried leaves of Urtica Urens (10 μg/ml) was reduced to 72.18% and 74% compared to untreated HCT-116 (control).
Determination of Apoptosis by Annexin-V Dye in A549 Cells
Apoptosis (programmed cell death) mechanism and necrosis were investigated in A549 cell line under the treatment of two concentrations (5 & 10 μg/ml) of aqueous preparations of dried leaves and freeze-dried leaves of Urtica Urens. The results showed that treated A549 cells did not respond to both aqueous preparations of Urtica Urens at the early and late phase of apoptosis at 5μg/ml (Figure 2), as compared to the untreated control. Moreover, cells did not go under necrosis process. In contrast, 10 μg/ml of aqueous extract of dried and the freeze-dried Urtica Urens showed a significant rise in late apoptosis phase and necrosis, respectively indicating that A549 cells respond only to high concentration of Urtica Urens.
Detection of Cell Cycle Arrest and DNA Fragmentation in A549 Cells
Figure 3 represents the A549 cell cycle phases after treatment with 5 or 10μg/ml of aqueous extracts of dried leaves or freeze- dried leaves of Urtica Urens. Under 5μg/ml concentration, the cell cycle did not show any arrest at any phase for both aqueous extracts of dried leaves or freeze-dried leaves of Urtica Urens. Under 10μg/ml concentration, cells were arresting either in G0/ G1 phase (in freeze-dried leaves extract) or in G2/M phase (in dried leaves extract).
Determination of Cellular and mitochondrial response of A549 cells to Reactive Oxygen Species (ROS)
The calculated cellular or mitochondrial ROS formation intensity showed no significant difference in the cellular or mitochondrial ROS production in lung A549 cells treated with 5 μg/ml compared to the control in both aqueous extracts (dried leaves and freeze-dried) of Urtica Urens (Figure 4). In contrast, cells treated with 10 μg/ml aqueous extract of both aqueous extract of dried leaves and freeze-dried leaves of Urtica Urens was significantly producing more cellular and mitochondrial ROS, as compared to the untreated A549 cells control.
Discussion
Over the past 30 years, there is a dramatic increase in the use of herbal medicine for treating cancer. These medicines are not only used for treating cancer, rather they are used for reducing the toxicity induced after the use of chemotherapeutic drugs [16].
The present study has illustrated the cytotoxic effect of dried and freeze-dried leaves of Urtica Urens on A549 lung cancer cell lines. The ability of cytotoxic agent to destroy the living cells is termed as cell cytotoxicity. This results in either necrosis or apoptosis of the normal cells. Measurement of cell toxicity holds significant importance as it is an important factor in the development of therapeutic anti-cancer drugs.
The present study conducted MTT experiments to investigate the effect of Urtica Urens on A549 cells tackled with different concentrations for an entire day. Minimum of three independent MTT experiments were conducted, whereas, the outcome was made using one way that has been persuaded by Bonferroni’s test. The cell viability was considerably declined in juxtaposition with the untreated cell at 10ug/ml of either the dried leaves or freeze-dried ones of Urtica Urens. It has been noted that the cell death mechanism of the A549 cells that have been dealt with Urtica Urens for 24 hours elucidated that Urtica Urens has no impact on A 549 cells early and late apoptosis or necrosis at 5 μg/ml of both dried and freeze- dried preparation. Whereas, the lung A549 cells retort to the Urtica Urens treatments with 10μg/ml l concentration in late apoptosis (at the dried leaves extract) and necrosis (freeze- dried leaves extract) respectively. The results of the present study revealed that using dried and freeze-dried extracts of Urtica Urens in high concentration significantly reduced the cell viability of the A549 lung cancer cell lines. A similar study conducted by Shofian et al. [16] studied the impact of freeze-dying on the antioxidant activity of different compounds. The results demonstrated that the antioxidant power value of the freeze-dried leaves is significantly low. However, the cell viability was significantly reduced in the three types of cancer cells without resistance in the lung cancer cell line at a high concentration of freeze- dried leaves. These results contradict with the results of the present study. The results stated that freeze-dried Urtica Urens shows a significant difference in the intensity of cellular ROS and mtROS production when they are treated with 10μg/ml. The values of 3 independent flow Cytometry experiments were considered based on cell cycle arrest and DNA fragmentation in A549 cells treated with 5 and 10μg/ml of Urtica Urens. The functional method followed by the Bonferroni’s test namely clarified that the concentration of 5μg/ml did not lead to any arrest. However, at 10μg/ml cells started to arrest either at the phase of G0/G1 at dried leaves extract or at G2/M phase as freeze- dried leaves, respectively. Accordingly, the given results pointed that HCT-116 cells have been treated with the aqueous preparation of dried leaves or freeze-dried Urtica Urens indicating a substantial difference in the intensity of both the cellular ROS and MT ROS production, as they were tackled by 10μg/ml that merely contrast with control the untreated cells. Like Urtica Urens, Urtica Dioica being a member of Urticaceae family is known to be interchangeable, therapeutically. The cytotoxic activity of Urtica Dioica on cancer cell lines has also been investigated [17].
For instance, a study conducted by Fattahi et al. [18] showed a significant effect of Urtica Dioica on BT-474 and Hela cell lines. Moreover, another study showed a significant effect of Urtica Dioica on human prostate carcinoma LNCaP cells [17].
In a similar context, few of the previous studies have shown a decrease in the proliferation of MCF-7 cell line after being treated with aqueous extracts of Urtica Dioica leaves. Multiple mechanisms are developed by the cancer cells that help avoid apoptosis and escape the regulated growth of cells [7]. Therefore, it is stated that there is an advantage of using whole- cell extracts containing several components, as compared to an isolated plant product. There is a significant effect of using whole plant extracts in combination with other medications, as plant species like Urtica and Origanum have a long history of oral use.
Conclusion
The present study has investigated the effect of Urtica Urens on A549 lung cancer cell line. The results demonstrated that 10 μg/ml of both aqueous extract of dried leaves and freeze- dried leaves of Urtica Urens had a significant effect on the cell viability of A549 compared to untreated control cells. It was indicated that A549 cells respond only to a high concentration of Urtica Urens as 10 μg/ml of dried and the freeze-dried Urtica Urens showed a significant rise in late apoptosis phase and necrosis, respectively. Moreover, Urtica Urens was significantly producing more cellular and mitochondrial ROS, as compared to the untreated A549 cells control. The study concluded that freeze-dried extracts of Urtica Urens leaves have cytotoxic effects on cancer cell lines, under certain concentrations. Additional in vivo studies on animal models and human clinical trials are needed for further testing of human specific use of these plants for treating cancer cell lines.
Acknowledgment
The authors are thankful to all the associated personnel who contributed for this research.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
1. Thun MJ, DeLancey JO, Center MM, Jemal A, Ward EM, The global burden of cancer: priorities for prevention. Carcinogenesis. 2010; 31(1):100-10. DOI:10.1093/carcin/bgp263.
2. Wei Y, Xu Y, Han X, Qi Y, Xu L, Xu Y, et al. Anti-cancer effects of dioscin on three kinds of human lung cancer cell lines through inducing DNA damage and activating mitochondrial signal pathway. Food Chem Toxicol. 2013;59:118-28. DOI:10.1016/j.fct.2013.05.054
3. Yin SY, Wei WC, Jian FY, Yang NS. Therapeutic applications of herbal medicines for cancer patients. J Evid Based Complementary Altern Med. 2013;2013. DOI:10.1155/2013/302426
4. Lan D, Zhang X, He R, Tang R, Li P, He Q, et al. MiR-133a is downregulated in non-small cell lung cancer: a study of clinical significance. Eur J Med Res. 2015;20(1):50. DOI:10.1186/s40001-015-0139-z
5. Coseri S. Natural products and their analogues as efficient anticancer drugs. Mini Rev Med Chem. 2009;9(5):560-71. DOI:10.2174/138955709788167592
6. Al Doghaither HA, Omar UM, Rahimulddin SA, Al-Ghafari AB. Cytotoxic Effects of Aqueous Extracts of Urtica urens on Most Common Cancer Types in Saudi Arabia. J Biol Sci. 2016;16(6):242-6. DOI:10.3923/jbs.2016.242.246
7. Solowey E, Lichtenstein M, Sallon S, Paavilainen H, Solowey E, Lorberboum- Galski H. Evaluating medicinal plants for anticancer activity. Sci World J. 2014;2014. DOI:10.1155/2014/721402
8. Newman DJ, Cragg GM, Snader KM. Natural products as sources of new drugs over the period 1981-2002. J Nat Prod. 2003;66(7):1022-37. DOI:10.1021/ np030096l
9. Newman DJ. Natural products as leads to potential drugs: an old process or the new hope for drug discovery? J Med Chem. 2008;51(9):2589-99. DOI:10.1021/ jm0704090
10. Gordaliza M. Natural products as leads to anticancer drugs. Clin Transl Oncol. 2007;9(12):767-76. DOI:10.1007/s12094-007-0138-9
11. Saklani A, Kutty SK. Plant-derived compounds in clinical trials. Drug Discov Today. 2008;13(3-4):161-71. DOI:10.1016/j.drudis.2007.10.010
12. Gerson-Cwillich R, Serrano-Olvera A, Villalobos-Prieto A. Complementary and alternative medicine (CAM) in Mexican patients with cancer. Clin Transl Oncol. 2006;8(3):200-7. DOI:10.1007/s12094-006-0011-2
13. Tascilar M, de Jong FA, Verweij J, Mathijssen RH. Complementary and alternative medicine during cancer treatment: beyond innocence. Oncologist. 2006;11(7):732-41. DOI:10.1634/theoncologist.11-7-732
14. Cragg GM, Newman DJ. Plants as a source of anti-cancer agents. J Ethnopharmacol. 2005;100(1-2):72-9. DOI:10.1016/j.jep.2005.05.011
15. Doukkali Z, Taghzouti K, Bouidida EH, Nadjmouddine M, Cherrah Y, Alaoui K. Evaluation of anxiolytic activity of methanolic extract of Urtica urens in a mice model. Behav Brain Funct. 2015;11(1):19. DOI:10.1186/s12993-015-0063-y
16. Shofian NM, Hamid AA, Osman A, Saari N, Anwar F, Pak Dek MS, et al. Effect of freeze-drying on the antioxidant compounds and antioxidant activity of selected tropical fruits. Int J Mol Sci. 2011;12(7):4678-92. DOI:10.3390/ ijms12074678
17. Levy A, Sivanesan D, Murugan R, Jornadal J, Quinonez Y, Jaffe M, et al. Urtica dioica Induces cytotoxicity in human prostate carcinoma LNCaP Cells: involvement of oxidative stress, mitochondrial depolarization and apoptosis. Trop J Pharm Res. 2014;13(5):711-7. DOI:10.4314/tjpr.v13i5.9
18. Fattahi S, Zabihi E, Abedian Z, Pourbagher R, Ardekani AM, Mostafazadeh A, et al. Total phenolic and flavonoid contents of aqueous extract of stinging nettle and in vitro antiproliferative effect on hela and BT-474 Cell lines. Int J Mol Cell Med. 2014;3(2):102. DOI:10.7314/apjcp.2013.14.9.5317
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Ulfat Omar, Akram Aloqbi. The effect of Urtica Urens on A549 lung cancer cell line. Ann Clin Anal Med 2020;11(5):510-514
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Biophysical properties of skin in pregnancy: A controlled study
Kıymet Handan Kelekci 1, Rahime İnci 2, Ali Karakuzu 1, Şemsettin Karaca 1
1 Department of Dermatology, İzmir Katip Çelebi University, College of Medicine, 2 Department of Dermatology, Atatürk Research and Training Hospital, İzmir, Turkey
DOI: 10.4328/ACAM.20138 Received: 2020-02-21 Accepted: 2020-04-22 Published Online: 2020-04-25 Printed: 2020-09-01 Ann Clin Anal Med 2020;11(5):438-442
Corresponding Author: Kıymet Handan Kelekci, Department of Dermatology, İzmir Katip Çelebi University, College of Medicine, İzmir, Turkey. E-mail: drhandankelekci@yahoo.com GSM: +90 505 312 41 00 Corresponding Author ORCID ID: https://orcid.org/0000 000239875627
Aim: It is well-known that there are some physiologic changes in the skin during pregnancy. In this study, we aimed to compare the biophysical changes in the skin of pregnant women with healthy non-pregnant women’s skin.
Material and Methods: A total of 60 pregnant women in the third trimester and 30 age-matched healthy volunteers as a control group were included in our study. Stratum corneum hydration, erythema, melanin of forearm and sebum content of forehead of skin were measured with noninvasive cutometer and compared between groups with the use of IBM’s SPSS software (SPSS version 17.0 for Windows).
Results: We found a moderate but significant disturbance of melanin and erythema on the forearm between pregnant women and healthy volunteer women. There was no significant correlation between baby gender and skin parameters of pregnant women.
Discussion: We conclude that even the clinically normal- appearing skin of pregnant women compared with healthy volunteers have increased melanin secretion and erythema properties.
Keywords: Erythema; Humidity; Melanin; Pregnancy; Sebum; Striae distensae
Introduction
The period during which an organism experiences immunological, metabolic, endocrine and vascular changes in a complex but a perfect balance is called pregnancy [1,2]. In normal pregnancy, these are characterized by protein hormones such as high elevations of human chorionic gonadotropin (HCG), somatomammoprotein, chorionic thyrotropin, chorionic corticotropin as well as prolactin, progesterone, estrogen hormones and mediators that completely alter the body’s functions [3]. Although pregnancy changes vary from person to person, many women find that their skin is one of the most noticeable affected areas [4]. However, it is not exactly known how pregnancy hormones affect the physiology, immunology and inflammatory response of the skin [5]. The skin constitutes the largest non-reproductive organ targeted by estrogen. Even if the effects of estrogen on the skin are still unclear, it is known that in women, declining estrogen levels are associated with a variety of cutaneous changes. Skin function and quality with various stages of life accompany the changes in estrogen production and it is clear that estrogen replacement can symptomatically treat many menopausal symptoms [6]. Evidence suggests that skin biophysical properties in predicting and developing of disease are important for appropriate skincare [7]. It is critical to consider the influence of genetic and environmental factors on most of the skin characteristics [8]. Physiological skin changes due to pregnancy are often ignored by health professionals [3]. There are few comprehensive studies on the physiological functions of the skin during pregnancy. In this study, we aimed to determine physiologic barrier changes of the skin, comprising melanin, stratum corneum (SC) hydration, erythema, surface sebum content at the pregnancy time period.
Material and Methods
Study subjects
This cross-sectional controlled clinical study was performed in our hospital and study protocol was approved by the ethics committee (2013/101) and was performed according to the Declaration of Helsinki principles. All of the participants were instructed about the investigation and informed consent was obtained from each one.
Sixty primiparous pregnant women whose ages ranged from 18 to 40 years and 30 healthy volunteers whose ages ranged from 20 to 38 years old were enrolled in the study. Pregnant women who were in the third trimester of their pregnancy, experienced pregnancy for the first time and single pregnancy were included in the study. This period was chosen because physiological changes in pregnancy were seen more in the 3rd trimester. Of the subjects, 55 had Fitzpatrick’s skin type III, three had II and two had IV.
Participants having the habit of smoking, alcohol etc., getting systemic and topical medicine treatment (except iron and vitamin supplements), suffering from systemic or dermatologic disease, applying oil (almond, olive oil, etc.) or moisturizers were excluded from the study. No skin care products had been applied to the measured sites for at least 24 hours prior to the measurement, and the measured sites had not been washed with a cleanser for at least 2 hours prior to the measurement. Skin biophysical measurements were performed at two different locations of the body, i.e. the right volar surface of the forearm (hydration, melanin, erythema) and in the middle of the forehead (sebum) by staff physician (R.I). Detailed medical history of pregnant women who met the inclusion criteria of the study was taken, the data of these women such as dermatological examination, received total weight gain, waist circumference, the gender of their babies (depending on the results late USG) and striae distensae (SD) existence were recorded. Noninvasive measurements of the stratum corneum
The epidermal barrier function was measured using the device MPA 580 (Courage & Khazaka, Germany) with respective probes of Sebumeter, Corneometer, Mexameter. The capacity of stratum corneum hydration was measured using the Corneometer 825, the measuring principle of which is based on the high degree of polarity of the water molecule because it uses the high dielectric constant of water for analyzing the water-related changes in the electrical capacitance of the skin. The measuring range of the device is 0 – 130 arbitrary units (a.u.). The amount of the targeted skin sebum secretion was measured using the Sebumeter 815; the measuring principle of which is based on the difference of light intensity through a plastic strip in contact with the skin for 30 seconds to indicate the amount of absorbed sebum. The measuring range of the device is 0 – 350 μg/cm2.
Erythema and skin pigmentation were measured using Mexameter 18 probe; the measurement of which is based on the absorption and reflexion. The Mexameter shows that the melanin and erythema values range from 0 to 999. The mean value of three recordings for each participant was used for analysis. Measurements were obtained between 9:00 am and 12:00 am due to diurnal variations and measured in a room at a temperature of 20–25°C and relative humidity of 30–40%. Statistical Methods
Categorical variables were described in frequencies and percentages; numerical variables were described in means and standard deviations or medians and IQRs (interquartile range). The Shapiro-Wilk test was used to check the normality distribution of numerical variables. Two independent means were compared with the Student’s t-test, and two independent medians were compared using the Mann-Whitney U test in pregnant women and controls. The relationship between numeric parameters was tested by the Spearman Correlation Analyses. A p-value less than 0.05 was accepted statistically significant. All analysis was conducted by SPSS17.0 statistical software.
Results
The baseline characteristics of the 60 pregnant women included in this study are shown in Table 1. A significant relation between pregnant women and a control group was determined in terms of the value of melanin and erythema (P<0.05). Erythema increase in pregnant women led to an increase in the level of melanin. No significant impairment in the skin sebum secretion and capacity of stratum corneum hydration were detected between pregnant and non-pregnant women (p >0.05) (Table 2). Overall, the Spearman’s rank test showed a positive linear correlation between skin melanin and erythema (r=0.386, p=0.002) (Figure 1), although linear correlation between skin melanin and hydration was negative (r = -0.414, p=0.001) (Figure2). SC hydration on the forearm in the pregnant women with SD was significantly different from that in the pregnant women without SD (p<0.05) (Table 3). When comparing index values between pregnant women with male and female fetus, this difference was not statistically significant.
Discussion
During pregnancy, physiologic skin changes are often markedly revealed because of the numerous metabolic, mechanical, and hormonal adjustments of this state. The most common physiologic changes are seen more in the 3rd quarter [3]. Physiologic changes in the skin during pregnancy can be complex and confusing [2].
In the present study, we found that physiological state of pregnancy had a significant effect on changes in basal skin physiology parameters especially melanin and erythema in the pregnant women at the third trimester rather than in non-pregnant healthy volunteer. These changes, especially melanin content are correlated with erythema and skin hydration. Hyperpigmentation in pregnancy is attributed to the increased output of some combination of pituitary, and ovarian hormones (melanocyte- stimulating hormone, estrogen, progesterone), and bioactive sphingolipids derived from the placenta. These hormones were thus suggested to be strong stimulants of melanogenesis [9]. Seite S et al. found 177±37 on the forehead, 193±34 on chine, 147±28 on the right malar area, 150±27 on the left malar area in pregnant women [10]. However, we found melanin value as 133.07±44.30 on the right inner forearm. Although we identify lower melanin value in our pregnant women, it was significantly higher than the control group. In this study, the average age of the group was younger (26 years) and all of them were having their first baby, single pregnancy, measured from forearm. These reasons may explain the low melanin level occurrence rate noticed in the study. Vascular changes during pregnancy frequently occur to a variable extent in all women. They are thought to be caused by high levels of circulating estrogens, angiogenesis factors associated with hyperkinetic circulation, the marked rise in blood volume, and genetic predisposition [9]. Vascular endothelial growth factor (VEGF) could have a direct influence on melanocyte behavior through its receptor on them [11]. Similarly, we found that skin parameters increased significantly especially erythema index and melanin index in pregnant women. Interestingly, we found that the average erythema index of forearm is higher in the pregnant women with SD. Also, it may be explained that striae formation could be associated with erythema increase. We demonstrated that the skin erythema index was higher in pregnant women than control group but was not significantly different among pregnant groups.
SC hydration was essential to maintain the properties of cutaneous functions such as regulating epidermal proliferation, differentiation or inflammation [12]. The SC hydration status is known to be regulated mainly by water-soluble natural moisturizing factors chiefly consisting of amino acids, intercellular lipids and sebum lipids in the SC [13,14]. One study reported that elevated endogenous estrogen increased dermal hydroscopic qualities. The dermis contributes to the water-holding capacity through its content of hydrophilic glycosaminoglycans [15]. However, we found that the hydration status of the SC decreased in pregnant women. There may be several factors contributing to the reduced SC hydration in the pregnancy group. The increase of eccrine gland activity as a result of the hormonal effects of pregnancy can cause hyperhidrosis. Vasomotor change and hyperhidrosis in pregnancy may cause increased transepidermal water loss (TEWL) in our patients. Higher TEWL values are believed to indicate a compromised barrier function and increased dry skin [16]. Our study revealed a reduction in the degree of stratum corneum hydration in all pregnant women. Disruption of the epidermal barrier consisting in reducing humidity and increasing TEWL value and reductions of these natural moisturizers values may be responsible for the skin dryness are confirmed by pregnant women. Hydration of the skin is also influenced by ethnicity and environmental variations [17,18]. In this study, environmental factors can influence humidity, certain personal and habitual factors, such as the increased hyperhidrosis, wearing closed clothes, frequent bathing, frequent soaping of face and forearm. In spite of some contradictions, it is estimated that sebaceous gland function increases in the last period of pregnancy [9]. Normally, the effect of estrogen on the sebaceous gland secretion is blocked, but it suggested that the sebum excretion rate is in fact increases in pregnancy. It may be explained by the presence of unknown powerful sebotrophic factors [19]. Some factors such as hormones, age, sex, and ethnicity (race) could affect the sebum secretion [20]. In one study including 10 pregnant women, sebum excretion rates from forehead skin were measured during and after pregnancy. They have been determinated minor fluctuations during the middle and last trimesters of pregnancy [19]. We found that sebum secretion increased in pregnant women compared to control groups, but it was not significant. Cunliff et al. reported that sebum excretion increases by 10% as local temperature increases by one degree Celsius [21]. There are regional differences in the skin parameters. Sebum secretion is expecially higher on the forehead [22].The resulting increase of sebum secretion due to increased metabolism with high temperature in pregnancy can be the cause of this situation. Overall, both our pregnant women and control group had higher sebum value. The difference may be due to measurement of the forehead, environmental factors and/or our subjects’ ethnicities.
Undoubtedly, SC surface change in pregnancy may disrupt skin function and structure. Fluctuation in hormone levels in pregnancy will be reflected in the physiology of the skin, but it is impossible to predict precisely how individuals will react. The decrease in the SC hydration induced by pregnancy may be more serious in pregnant women without SD than in pregnant women with SD. The cause of SD in pregnancy is still unknown, but it is a combination of distension and adrenocortical activity, genetic factors. Skin distension may lead to excessive mast cell degranulation with subsequent damage of collagen and elastin [23]. In the study by Stamatas et al., SD sites were very slightly more hydrated compared to control skin [24]. Our pregnants with SD showed an increased SC hydration, sebum, and erythema status, but it was only correlated with SC hydration. This, moisture and other unknown reasons may affect formation of collagen and elastin. Notably, pregnant women with SD showed also significantly positive correlation by increasing the waist circumference.
To our knowledge, this is the first study of its kind to provide evidence that physiological skin changes encompassed melanin, erythema, and skin surface lipids caused by pregnancy at the third trimester. These findings suggest that pregnancy is required for the exclusive homeostasis of the skin biophysical properties. The main limitation of this study is the limited number of subjects and it is not comparing the environmental and ethnic factors.
Conclusion
Our present study demonstrated that erythema and melanin content of the skin in pregnant women were statistically different from non-pregnant women. Moreover, these results suggest that special care should be given to the skin in pregnant women, particularly with hyperpigmentation prone skin. The use of regular sun blocking cream containing higher protection factor on sun-exposed part of body and moisturizers with lower water-based content may be more appropriate in pregnancy. Regarding skin sensitivity in pregnancy, in order to avoid striae distensae, formulation of oily skincare products should be recommended. Future research will hopefully shed light affecting on the skin function and structure of hormonal and physiologic changes during pregnancy.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
1. Kroumpouzos G, Cohen LM. Dermatoses of pregnancy. J Am Acad Dermatol. 2001;45(1):1-19; quiz 19-22.
2. Barankin B, Silver SG, Carruthers A. The skin in pregnancy. J Cutan Med Surg 2002; 6(3):236-40.
3. Fernandes LB, Amaral WN. Clinical study of skin changes in low and high risk pregnant women. An Bras Dermatol. 2015;90(6):822-828.
4. Scott R. Skin changes induced by pregnancy. The Biomedical Scientist. 2011;8:523-4.
5. Maharajan A, Aye C, Ratnavel R, Burova E. Skin eruptions specific to pregnancy: an overview. The Obstetrician and Gynaecologist. 2013;15:233-40.
6. Hall G, Phillips TJ. Estrogenand skin: The effects of estrogen, menopause, and hormone replacement therapy on the skin. J Am Acad Dermatol. 2005;53:555-68.
7. Man MQ, Xin SJ, Song SP, Cho SY, Zhang XJ, Tu CX, et al. Variation of skin surface pH, sebum content and stratum corneum hydration with age and gender in a large Chinese population. Skin Pharmacol Physiol. 2009;22:190-9.
8. Chu M, Kollias N. Documentation of normal stratum corneum scaling in an average population: features of differences among age, ethnicity and body site. Br J Dermatol. 2011; 164(3): 497-502.
9. Ingber A. Physiologic glandular changes during pregnancy. Obstetric dermatology: Practical guide. 1st ed. Berlin: Springer-Verlag , Heidelberg; 2009.p.46.
10. Seité S, Park SB. Effectiveness of a broad-spectrum sunscreen in the prevention of melasma in Asian pregnant women. Journal of Cosmetics, Dermatological Sciences and Applications. 2013; 3: 4-7.
11. Kim EH, Kim YC, Lee ES, Kang HY. The vascular characteristics of melasma. J Dermatol Sci. 2007;46(2): 111-16.
12. Engelke M, Jensen JM, Ekanayake-Mudiyanselage S, Proksch E. Effects of xerosis and ageing on epidermal proliferation and differentiation. Br J Dermatol 1997; 137(2): 219-25.
13. Seirafi V, Farsinejad K, Firooz A, Davoudi SM, Robati RM, Hoseini MS, et al. Biophysical characteristics of skin in diabetes: a controlled study. J Eur Acad Dermatol Venerol. 2009; 23(2):146-9.
14. Sakai S, Kikuchi K, Satoh J, Tagami H, Inoue S. Functional properties of the stratum corneum in patients with diabetes mellitus: similarities to senile xerosis. Br J Dermatol 2005;153(2):319-23.
15. Hall G, Phillips T J. Estrogen and skin: The effects of estrogen, menopause, and hormone replacement therapy on the skin. J Am Acad Dermatol. 2005; 53(4):555-68.
16. Fluhr JW, Feingold KR, Elias PM. Transepidermal water loss reflect permeability barrier status: validation in human and rodent in vivo and exvivo models. Exp Dermatol. 2006;15(7):483-92.
17. Sato J, Denda M, Nakanishi J, Koyama J. Dry condition affects desquamation of stratum corneum in vivo. J Dermatol Sci. 1998; 18(3):163-9.
18. Caspers PJ, Lucassen GW, Carter EA, Bruining HA, Puppels GJ. In vivo confocal Raman microspectroscopy of the skin: noninvasive determination of molecular concentration profiles. J Invest Dermatol. 2001; 116(3):434-42.
19. Burton JL, Cunliffe WJ, Millar DG, Shuster S. Effect of pregnancy on sebum excretion. Br Med J. 1970; 2(5712): 769-71.
20. Marrakchi S, Maibach HI. Biophysical parameters of skin: map of human face, regional, and age-related differences. Contact Dermatitis. 2007;57(1):28-34.
21. Cunliffe WJ, Burton JL, Shuster S. The effect of local temperature variations on the sebum excretion rate. Br J Dermatol. 1970;83(6):650-4.
22. Machková L, Švadlák D, Dolečková. A comprehensive in vivo study of Caucasian facial skin parameters on 442 women. Arch Dermatol Res. 2018;310(9):691-9.
23. Al-Himdani S, Ud-Din S, Gilmore S, Bayat A. Striae distensae: A comprehensive review and evidence-based evaluation of prophylaxis and treatment. Br J Dermatol. 2014;170(3):527-47.
24. Stamatas GN, Lopes-DaCunha A, Nkengne A, Bertin C. Biophysical properties of striae distensae evaluated in vivo using non-invasive assays. Skin Res Technol. 2014;1-5.
Download attachments: 10.4328ACAM.20138
Kıymet Handan Kelekci, Rahime İnci, Ali Karakuzu, Şemsettin Karaca. Biophysical properties of skin in pregnancy: A controlled study. Ann Clin Anal Med 2020;11(5):438-442
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Relationship between physical activity and constipation in university students
Feride Yarar 1, Melike Akdam 2, Nesrin Yağcı 1
1 School of Physical Therapy and Rehabilitation, Pamukkale University, Denizli, 2 School of Physical Therapy and Rehabilitation, KTO Karatay University, Konya, Turkey
DOI: 10.4328/ACAM.20147 Received: 2020-03-10 Accepted: 2020-04-07 Published Online: 2020-04-17 Printed: 2020-09-01 Ann Clin Anal Med 2020;11(5):515-518
Corresponding Author: Feride Yarar, School of Physical Therapy and Rehabilitation, Pamukkale University, Denizli, Turkey. E-mail: feridebeydemir@hotmail.com T: +90(258)2964291 F: +90(258)2964494 Corresponding Author ORCID ID: https://orcid.org/0000-0001-9938-7513
Aim: This study investigates the relationship between the physical activity level and constipation severity in university students.
Material and Methods: The study included 155 females with a mean age of 20,93 ± 1,8 years. Mini Nutritional Questionnaire-Short Form (MNQ-SF), International Physical Activity Questionnaire-Short Form (IPAQ-SF), The Constipation Severity Instrument (CSI) were used for evaluation. Female students between the ages of 18 and 25 years who received more than 12 points, which means normal nutritional status, from the MNQ-SF were included in the study.
Results: The physical activity levels of the cases were compared and we found out that there was no significant difference between groups in the sub-scales and total score of CSI (p>0.05). There was no relationship between subgroups and total score of IPAQ-SF and sub-scales and total score of CSI (p>0.05)
Discussion: In conclusion, we couldn’t find a relationship between physical activity level and constipation severity in individuals included in the study. Although this research provides insights into the relationship between the physical activity level and constipation severity in the university student, studies with samples including different age groups should be planned in the more widespread population for future research.
Keywords: Constipation; Students; Female
Introduction
Constipation, which negatively affects health-related quality of life affecting physical, mental and social well-being, is a very common health problem in the community [1]. While healthcare professionals define constipation as defecation less than three times a week, patients often describe incomplete discharge sensation, strain, hard stool, defecation that requires inadequate effort in bowel movements [2].
There are so many studies all around the world about prevalence of constipation, for instance, USA, Sweden, Taiwan, Germany, France, China, Hong Kong, Spain, South Korea, and Iran. According to these studies, prevalence of constipation varies from %2 to %35 [3,4,5]. The prevalence rate of constipation in our country was found to be between 22-40% [6].
Several studies have reported that female gender, older age, low socioeconomic level, experiencing anxiety, depression, increased body mass index, low dietary fiber intake, positive family history, stressful life events, and decreased physical activity level are more related to constipation [7,8].
Physical activity is a life-long, complex behavior that provides protection and improvement of cardiorespiratory resistance, reduces obesity and related diseases, resulting in a longer life span [9]. Many studies have shown that walking is positively associated with bowel movements [10,11]. Exercise, which is one of the subgroups of physical activity, includes planned, structured, repetitive body movements aimed at improving one or more components of physical fitness; It is negatively related to constipation in adults [3,8,12].
It has been stated that daily moderate- intensity exercise reduces constipation by 44% in women. The inability to define constipation in a homogeneous way in the literature results in contradictions and many difficulties in its interpreting [8].
The aim of this study is to examine the relationship between the level of physical activity and constipation severity in university students.
Material and Methods
This study was carried out on 155 female (mean age 20,93 ± 1,8 years) students studying at Pamukkale University, Physical Therapy and Rehabilitation Department and volunteering to participate in the study.
Informed consent was obtained from the individuals who accepted to participate in the study and participants were informed about the study based on the Helsinki Declaration. This study was approved by Pamukkale University, Faculty of Medicine, Non-Interventional Clinical Research Ethics Committee (60116787-020/1693).
Female students aged between 18 and 25 years who received more than 12 points, which means normal nutritional status, from the Mini Nutritional Questionnaire-Short Form were included in the study. Exclusion criteria were individuals who used regular medication and underwent surgery related to the digestive system, and did not satisfy the inclusion criteria. Instruments
Age, gender, height, body weight and health information of the students participating in the study were obtained. In addition, the amount of meals consumed daily and water consumption were also recorded. The existence of constipation was determined by students’ self-assessment such as “I have constipation or not”.
Mini Nutritional Questionnaire-Short Form
Mini Nutritional Questionnaire-Short Form is a nutritional screening tool which is short and valid for older populations. It takes 10-15 minutes to complete. This questionnaire contains Screening and Evaluation sections. Scan section consists of 6 questions ranging from 0-14 points. Points from 0 to 7 are evaluated as “Malnutrition”, 8-11 points as “At risk of malnutrition” and 12-14 points are evaluated as “Normal nutritional status” [13]. Mini Nutritional Questionnaire was found valid by Sarıkaya et al [14].
The International Physical Activity Questionnaire- Short Form (IPAQ-SF)
Physical activity levels of the participants were evaluated using the International Physical Activity Questionnaire-Short Form. In this questionnaire, the individual fills his/her vigorous physical activity, moderate physical activity and walking activities with the duration and frequency for the last 7 days [15]. The metabolic equivalent (MET) values (vigorous-intensity activity = 8 MET, moderate- intensity activity = 4 MET, walking = 3.3 MET) assigned to the activities are multiplied by duration (min) and frequency (days) and the total score is calculated. Accordingly, weekly MET-min scores of individuals are obtained. According to the scores obtained, individuals are categorized as inactive, minimally active and very active [9]. Turkish reliability and validity study was done by Saglam et al [16].
The Constipation Severity Instrument(CSI)
The Constipation Severity Instrument was developed by Varma et al [17]. This questionnaire evaluates individuals’ frequency of defecation, stool density, and difficulty during defecation. This scale can also be used to measure constipation symptoms. It has 3 subscales (Obstructive Defecation, Colonic Inertia, Pain). The points that can be obtained from the scale vary between 0 and 73. As the score increases, constipation severity increases. Turkish validity and reliability version was done by Kaya and Turan [18].
Statistical Analysis
The data were analyzed with the SPSS 25.0 package program. The normality test was done with the Kolmogorov-Smirnov or with the Shapiro-Wilk tests. Quantitative data were presented by the mean and standard deviation values (X±SD) and median (min-max). Number (n) and percentage (%) were used for the presentation of the qualitative data. Comparisons between groups were made using one-way ANOVA and the Kruskal- Wallis test. Correlation coefficients and statistical significance were calculated with the Spearman correlation coefficient. The statistical significance level was p <0.05.
Correlation coefficient of 0.00-0.19 means “no or negligible relationship”, 0.20-0.39 is “weak”, 0.40-0.59 is “moderate”, 0.60-0.79 is “strong” and 0.80-1.0 is “very strong correlation” [19].
Results
One hundred fifty-five females with the mean age 20.93±1.8 years were included in this study. Demographic data of the cases participating in the study are shown in Table 1.
In this study, no significant relationship was found between age and constipation severity obtained from the total score of CSI (r = – 0.051, p = 0.528). In addition, no relationship was found between smoking frequency and daily water consumption (r = 0.149 p = 0.065, r = -0.112, p = 0.164).
Students’ IPAQ-SF score was calculated as 1377 MET x min/ week. According to scores, 21.9% were inactive, 60% were minimally active and 18.1% were very active.
When physical activity levels of the cases were compared, there was no significant difference between groups in the subscales and total score of CSI (p>0.05) (Table 2).
There was no relationship between sub-groups and the total score of IPAQ-SF and sub-scales and the total score of CSI (p>0.05) (Table 3).
Discussion
According to the results obtained from our study, although the cases who have constipation were young population, the physical activity level of them was low. No correlation was found between physical activity level and constipation severity. The mean age of individuals who participated in our study was 20.93 years. Studies have reported that women experience constipation problems more frequently than men do, and this rate is 2 times more common in women [20,21]. There is no study that clearly explains this difference.
Some studies link higher prevalence in women to factors such as gut function differences [22] and nutritional habits [23] . In our study, the presence of constipation was asked according to self-reported cases, not based on any criteria. But nutritional states are specifically questioned and cases who get 12 or more scores from the MNQ-SF are included in the study. This shows that our study is different from other studies.
Chaud et al. [24] reported that constipation is associated with daily fluid consumption in university students. In the study by Chang et al. [23], they found that constipation is related to fast food and snack eating habits, frozen food consumption, daily water consumption and physical activity level. In our study, no relation was found between daily water consumption and CSI. According to Karakaya et al. [25], there is a relation between physical activity level and constipation. But we could not find any relationship between subgroups and total score of IPAQ- SF and subscales and total score of CSI. Moreover, we could not find any significant difference between the sub-parameters of the physical activity level (inactive, minimally active, very active) in terms of CSI sub-scales and total score.
Consequently, we couldn’t find a relationship between physical activity level and constipation severity in individuals included in our study. We think that the age of the individuals is young and the nutrition level is normal, which affects this result. In the literature, we did not find any other study which evaluates the relationship between the constipation severity and physical activity level and in which only one gender is included and nutrition levels of cases are normal. In the future, studies with samples including different age groups should be planned in a more widespread population.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
1. Lembo A, Camilleri M. Current concepts: Chronic constipation. N Engl J Med. 2003;349(14):1360-8.
2. Leung L, Riutta T, Kotecha J, Rosser W. Chronic constipation: An evidence- based review. J Am Board Fam Med. 2011;24(4):436-51.
3. Everhart JE, Go VLW, Johannes RS, Fitzsimmons SC, Roth HP, White LR. A longitudinal survey of self-reported bowel habits in the United States. Dig Dis Sci. 1989;34(8):1153–62.
4. Walter S, Hallböök O, Gotthard R, Bergmark M, Sjödahl R. A population-based study on bowel habits in a Swedish community: Prevalence of faecal incontinence and constipation. Scand J Gastroenterol. 2002;37(8):911–6.
5. Frexinos J, Denis P, Allemand H, Allouche S, Los F, Bonnelye G. Descriptive study of digestive functional symptoms in the French general population [Article in French]. Gastroenterol Clin Biol. 1998;22(10):785–91.
6. Cevik K, Cetinkaya A, Yigit Gokbel K, Menekse B, Saza S, Tıkız C. The effect of abdominal massage on constipation in the elderly residing in rest homes. Gastroenterol Nurs. 2018;41(5):396–402.
7. Mugie SM, Benninga MA, Di Lorenzo C. Epidemiology of constipation in children and adults: A systematic review. Best Pract Res Clin Gastroenterol. 2011;25(1):3–18.
8. Dukas L, Willett WC, Giovannucci EL. Association between physical activity, fiber intake, and other lifestyle variables and constipation in a study of women. Am J Gastroenterol. 2003;98(8):1790–6.
9. Orhan C, Akbayrak T, Kaya S, Kav T, Kerem Günel M. Fiziksel aktivite seviyesi ile konstipasyon şiddeti arasındaki ilişkinin incelenmesi (Examination of the relationship between physical activity level and severity of constipation). JExerc Ther Rehabil. 2016;2(2):66-73.
10. Kim HS, Park DH, Kim JW, Jee MG, Baik SK, Kwon SO, et al. Effectiveness of walking exercise as a bowel preparation for colonoscopy: A randomized controlled trial. Am J Gastroenterol. 2005;100(9):1964–9.
11. Kinnunen O. Study of constipation in a geriatric hospital, day hospital, old people’s home and at home. Aging (Milano). 1991;3(2):161–70.
12. Caspersen CJ, Powell KE, Christenson GM. Physical activity, exercise, and physical fitness: definitions and distinctions for health-related research. Public Health Rep. 1985;100(2):126-31.
13. Kaiser MJ, Bauer JM, Ramsch C, Uter W, Guigoz Y, Cederholm T, et al. Validation of the Mini Nutritional Assessment short-form (MNA®-SF): A practical tool for identification of nutritional status. J Nutr Heal Aging. 2009;13(9):782–8.
14. Sarikaya D, Halil M, Kuyumcu ME, Kilic MK, Yesil Y, Kara O, et al. Mini nutritional assessment test long and short form are valid screening tools in Turkish older adults. Arch Gerontol Geriatr. 2015;61(1):56–60.
15. Craig CL, Marshall AL, Sjöström M, Bauman AE, Booth ML, Ainsworth BE, et al. International Physical Activity Questionnaire: 12-Country Reliability and Validity. Med Sci Sport Exerc. 2003;35(8):1381–95.
16. Saglam M, Arikan H, Savci S, Inal-Ince D, Bosnak-Guclu M, Karabulut E, et al. International physical activity questionnaire: Reliability and validity of the Turkish version. Percept Mot Skills. 2010;111(1):278–84.
17. Varma MG, Wang JY, Berian JR, Patterson TR, McCrea GL, Hart SL. The constipation severity instrument: A validated measure. Dis Colon Rectum. 2008;51(2):162–72.
18. Kaya N, Turan N. Reliability and validity of constipation severity scale. Turkiye Klin J Med Sci. 2011;31(6):1491–501.
19. Schober P, Boer C, Schwarte LA. Correlation coefficients: Appropriate use and interpretation. Anesth Analg. 2018;126(5):1763-8.
20. Pare P, Ferrazzi S, Thompson WG, Irvine EJ, Rance L. An epidemiological survey of constipation in canada: definitions, rates, demographics, and predictors of health care seeking. Am J Gastroenterol. 2001;96(11):3130-7.
21. Sandler RS, Jordan MC, Shelton BJ. Demographic and dietary determinants of constipation in the US population. Am J Public Health. 1990;80(2):185-9.
22. Brandt LJ, Prather CM, Quigley EM, Schiller LR, Schoenfeld P, Talley NJ. Systematic review on the management of chronic constipation in North America. Am J Gastroenterol. 2005;100(Suppl. 1):S5-21.
23. Chang LL, Lin YC, Lo TC, Chen MC, Kuo HW. Understanding the lifestyle correlates with chronic constipation and self-rated health. Food and Nutrition Sciences. 2015;6(4):391-8.
24. Chaud D, Olivon E, Machado A, Abreu E. Prevalence of functional constipation and its risk factors among university students LB328. FASEB J. 2014; 28: 328.
25. Karakaya IC, Kilic Z, Yilmaz U, Karakaya MG. Relation of constipation problem and physical activity level in university students. TAF Preventive Medicine Bulletin. 2015;14(4):329-32.
Download attachments: 10.4328ACAM.20147
Feride Yarar, Melike Akdam, Nesrin Yağcı. Relationship between physical activity and constipation in university students. Ann Clin Anal Med 2020;11(5):515-518
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Angiographic predictors of left ventricular thrombus after anterior myocardial infarction
Abdulkadir Kırış 1, Hüseyin Bektaş 1, Zeydin Acar 1, 2, Gülhanım Kırış 3
1 Department of Cardiology, Medicalpark Karadeniz Hospital, 2 Avrasya University Faculty of Health Sciences, 3 Department of Cardiology, Ahi Evren Cardiovascular and Thoracic Surgery Training and Research Hospital, Trabzon, Turkey
DOI: 10.4328/ACAM.20152 Received: 2020-03-07 Accepted: 2020-04-02 Published Online: 2020-04-11 Printed: 2020-09-01 Ann Clin Anal Med 2020;11(5):479-484
Corresponding Author: Zeydin Acar, Department of Cardiology, Medicalpark Karadeniz Hospital, 61040, Trabzon, Turkey. E-mail: drzeydin@yahoo.com T: +90 462 2297070 Corresponding Author ORCID ID: https://orcid.org/0000-0002-0288-7499
Aim: Left ventricular thrombus (LVT) formation after anterior acute myocardial infarction (AMI) leads to increased morbidity and mortality rate. Therefore, a variety of studies were performed to find the predictors of LVT formation. However, the relationship between full angiographic features and LVT was not comprehensively investigated. The goal of the study is to assess the relationship between angiographic variables and LVT formation
Material and Methods: A total of 87 patients with AMI were enrolled in the study. Patients who met exclusion criteria were excluded, and 75 patients were included in the final statistical analysis. Full angiographic data such as antegrade and retrograde filling, right-left coronary dominance, no-reflow phenomenon, and syntax (SX) score were obtained from all patients in both baseline and during the primary percutaneous coronary intervention (PCI). Then, two multivariate analysis models were created to find the angiographic predictors of LVT. Baseline angiographic findings were analyzed by Model 1 and data associated with PCI were used in Model 2.
Results: Primary PCI was performed in sixty-four patients (85.3%) and 57 patients(%89) were successfully revascularized. LVT developed in 18 (24%) patients (Group 1) and did not develop in 57 (76%) patients (Group 2). The prevelance of RCA ectasia, total occlusion, and baseline syntax (SX) score was higher in Group 1 than Group 2. Other angiographic features were similar in both groups. In multivariable models, RCA ectasia and baseline SXscore were found to be independent angiographic predictors of LVT formation.
Discussion: The presence of right coronary artery ectasia and baseline SX score are independent angiographic predictors of LVT formation in patients with first anterior AMI. They can be used as simple and practical tools to predict the development of LVT.
Keywords: Ventricular thrombus; Myocardial infarction; Coronary angiography
Introduction
Left ventricular thrombus (LVT) formation is a major complication of acute myocardial infarction (AMI) because it is associated with higher mortality and morbidity due to systemic embolism. Therefore, a large number of studies were performed to find the factors associated with LVT formation during the last three decades. Initially, the effects of anticoagulant and fibrinolytic therapy on LVT formation were investigated in various studies [1-3]. Later, echocardiographic and biochemical predictors of LVT formation were sought [4-7]. In the last decade, the effect of primary percutaneous coronary intervention (PCI) on the development of LVT was specifically examined in five studies [8,9].
The extent of myocardial damage is an important predictor of LVT formation [5,8,10]. It was reported that some angiographic features may be associated with myocardial damage. For example, coronary artery ectasia (CAE) leads to the impairment of coronary flow reserve [11], ischemia [12] and left ventricular (LV) dysfunction [13]. Similarly, the presence of retrograde coronary collateral circulation reduces the myocardial damage in patients with AMI [14]. In addition, some other angiographic features such as thrombolysis in myocardial infarction (TIMI) frame count and syntax (SX) score were suggested to be associated with no-reflow phenomenon mortality in patients with AMI [15,16]. Thus, we hypothesized that angiographic features such as presence of ectatic vessel, SXscore, and retrograde filling of infarct-related artery may affect the extent of myocardial damage and may contribute to the LVT formation.
To date, although the relationship between LVT formation and some angiographic parameters such as door-to-balloon time and TIMI flow grade were evaluated in prior studies, full angiographic data has not been evaluated [9]. Therefore, in this prospective observational study, we aimed to comprehensively assess the relationship between angiographic findings and LVT formation.
Material and Methods
Patients Selection
The study population consisted of 87 consecutive patients with anterior AMI. The anterior AMI was diagnosed as the presence of anginal chest pain >30 min, ST segment elevation >2 mm in consecutive two derivations in electrocardiography (ECG) and/or cardiac-Troponin I (c-Trop I) elevation. Exclusion criteria were defined as the presence of in-hospital death, previous or emergency coronary artery by-pass graft operation (CABG-op) and inadequately echocardiographic follow-up. But, subjects with thrombus detected before elective CABG operation or in- hospital death were not excluded. The use of antihypertensive and antidiabetic drugs (or insulin) was accepted for the diagnosis of hypertension (HT) and diabetes mellitus (DM), respectively. The study was conducted in accordance with the guidelines in the Decleration of Helsinki. The Local Ethics Committee approved the study protocol. The informed consent was obtained for all of the study participants.
Coronary angiography and revascularization procedures
Selective coronary angiography (CA) was performed by the Judkins technique using right or left femoral artery. Primary percutaneous coronary intervention (PCI) was considered as the main treatment method for the patients who presented to our hospital with AMI. Before primary PCI, 600 mg clopidogrel and 300 mg acetylsalicylic acid were given to all patients. If a patient was not a candidate for primary PCI, fibrinolytic therapy was used for revascularization. Patients who were reperfused by fibrinolytic therapy in other centers underwent elective CA or rescue PCI according to clinical status. All angiographic records in both baseline and during PCI were assessed by two experienced interventional cardiologists who were blinded to the patient’s data. If there was a disagreement, the final decision was obtained by consensus with the third cardiologist’s assessment.
Antegrade filling and retrograde filling of infarct- related artery
Antegrade filling determined by thrombolysis in myocardial infarction (TIMI) flow grade was assessed using baseline CA records. TIMI flow grade was assessed using a predefined method [17]. The presence of TIMI flow grade 2 or 3 distal to the culprit lesion in the main branch of the left anterior descending artery (LAD) was accepted as antegrade filling (spontaneous revascularization). The presence of TIMI 0-1 flow was considered as total occlusion. Retrograd filling was evaluated using baseline CA records. The presence of collateral circulation from RCA or Cx to LAD artery was accepted as retrograde filling and was graded using a method predefined by Rentrop et al [18].
Right-left dominance of coronary circulation
Right or left dominance was assessed according to the origin of the posterior descending artery (PDA) and posterolateral artery (PLA). Right dominant circulation was considered if the PDA and PLA have originated from the RCA, and left dominant circulation was considered when they originated from Cx artery. Coronary artery ectasia
The presence of localized or diffuse dilation of the coronary arteries with a luminal dilation exceeding the 1.5-fold of normal adjacent segment or vessel diameter has been accepted coronary artery ectasia (CAE) [19]. Cases that are not accompanied by critical stenosis (≥50%) have been considered as isolated ectasia. In this study, we accepted as CAE only isolated form because of two reasons that may lead to conflicting data about the impact of ectasia on LVT formation. First, the presence of critical stenosis in the ectatic vessel may influence the effect of ectasia on coronary flow and myocardial function. Secondly, critical stenosis in ectatic vessel also increases the SXscore. Thus, data overlapping may occur.
SYNTAX score
SX score was calculated using the SXscore algorithm [20] at two stages. According to this algorithm, each coronary stenosis (≥50%) in vessels (≥1.5 mm) was scored separately for LAD, RCA, and Cx artery. Then, they were added together to obtain the overall SXcore.
SXscore in baseline: It was obtained from baseline coronary anatomy. The presence of TIMI 0 or 1 flow in LAD was scored as a total occlusion (<3 months) with thrombus.
SXscore after wiring/ballooning: This score was computed using coronary anatomy after wiring/ballooning. If reperfusion was obtained, SXscore was computed according to new coronary anatomy. But, if there was no reperfusion, the lesion was scored as a total occlusion (<3 months) with thrombus.
Successful primary PCI, no-reflow phenomenon and TIMI frame count
The presence of TIMI 3 flow grade and <%30 residual lesion in LAD artery was accepted as successfully PCI; whereas, TIMI 0 or 1 flow grade in target vessel after PCI was considered no-reflow phenomenon. In addition, to obtain a more objective evaluation of coronary blood flow, TIMI frame count (TFC) after PCI was calculated using a method which was firstly described by Gibson et al [21]. TFC for LAD (corrected by dividing by 1.7), circumflex (Cx), and right coronary artery (RCA) were separately calculated. Then, the mean TFC was obtained by dividing the sum of TFC of three vessels by three in only patients with antegrade TIMI 2-3 flow after PCI.
Echocardiography and Thrombus detection
Echocardiographic evaluation was serially performed on 1,3,7 and 30 days according to the recommendations of the American Society of Echocardiography using a commercially available system (Vivid 3, GEMS Ultrasound, Tirat, Carmel, Israel) [22]. LV dimensions were measured by two dimensional guided M mode echocardiography. LV function was assessed by left ventricular ejection fraction (LVEF) using the modified biplane Simpson’s rule. LVT was diagnosed by the presence of an echodense mass with a margin distinct from the LV wall. The wall motion score index (WMSI) was calculated using the 16 segments model [23]. The motion of each segment was coded as follows: 1=normal, 2=hypokinesis, 3=akinesis, 4=dyskinesis, and 5=aneurysmal. Then, WMSI was computed by dividing the sum of scores of all segments by sixteen.
Statistical analysis
Continuous variables were described as mean ± standard deviation (SD). Normal distributions of values were assessed using the Kolmogorov-Smirnov test and histogram. The Mann- Whitney U test was used for the analysis of continuous variables. Categorical variables were expressed as percentage values. They were analyzed using the Chi-squared or the Fischer’s exact test. A multivariable logistic regression analysis was performed to determine the independent predictors of LVT formation. The variables which have a p-value <0.1 in univariate analysis were included in the multivariable analysis. Two multivariable logistic regression models were created. Model 1 analyzed the baseline angiographic findings and model 2 used the angiographic data during PCI. A p-value <0.05 was considered statistically significant. All statistical analyses were performed by the SPSS software program (SPSS, 13.0, Inc, Chicago, Illinois).
Results
Baseline Characteristics
Eighty-seven consecutive patients were included in the study. Patients who met exclusion criteria (4 patients died in hospital, 3 patients underwent CABG-op, and 5 patients have insufficient echocardiographic follow-up) were excluded. Seventy-five subjects (mean age 59.6±12.7 years) were included in the statistical analysis. LVT was detected in 18 of 75 patients (24%, Group 1) and was not detected in 57 patients (76%, Group 2). Both groups had similar baseline demographic findings including age (61.3±14.2 vs 59.1±12.25, p=0.58), gender (male/ female ratio =16/2 vs 45/12, p=0.5), smoking (55.6% vs 33.3%, p=0.09), rates of HT and DM (50% vs 42.1%, p=0.56 and 22.2% vs 12.3%, p=0.44, respectively). Systolic blood pressure was similar in both groups (112.8±21 mmHg vs 120.9±23.9 mmHg, p>0.05) but diastolic blood pressure was higher in Group 2 than Group 1 (77.1±15.3 vs 67.3±12.2, p=0.02).
Angiographic features
All angiographic findings of both groups were presented in Table 1. The primary PCI was performed to sixty-four patients (85.3%) and 57 patients (%89) were successfully revascularized by primary PCI. Six patients (8%) received fibrinolytic therapy and 2 patients (2.7%) underwent rescue PCI. No-reflow phenomenon developed in 4 of 75 patients (5.3%). There was no difference between both groups for the development of no-reflow (14.3% vs 3.8%, respectively, p=0.19). TIMI frame counts were similar in both groups. The rate of total occlusion in baseline was higher in Group 1 than Group 2; but, retrograde filling and right-left dominance were similar in both groups. The prevalence of coronary ectasia in LAD and Cx artery was similar in both groups. But, the prevalence of both overall and isolated RCA ectasia was higher in Group 1 than Group 2. Baseline SXscore was higher in Group 1 than Group 2. But, SXscore after wiring/ballooning was similar in both groups.
Parameters of Echocardiography
There were significant differences in baseline echocardiographic parameters of both groups. Systolic and diastolic diameters were higher in Group 1 than Group 2 (38.6±8.9 mm vs 31.7±4 mm, p=0.002 and 53.1±7 mm vs 47.9±4.8 mm, p=0.003; respectively). WMSI also were higher in Group 1 than Group 2 (1.86±0.37 vs 1.5±0.37, p=0.005). But, ejection fraction was lower in Group 1 compared with Group 2 (32.8±9.4 vs 42.8±10.1, p=0.002).
Relationship between LVT formation and other factors
This relationship was assessed with two different models. Model 1 was created using the baseline angiographical data obtained from all patients (Table 2). In this model, smoking, LVEF, the presence of total occlusion in presentation, RCA ectasia and baseline SXscore were associated with LVT formation in univariate analysis. RCA ectasia, SXscore, smoking, and WMSI were found to be an independent predictor of LVT by multivariable analysis. In addition, RCA ectasia and baseline SXscore were similarly found to be independent predictors when data of patients who underwent only PCI were analyzed in this model.
In model 2, the data of patients who underwent PCI were analyzed (Table 3). Smoking, WMSI, RCA ectasia, SXscore after wiring/ballooning and the success of PCI were related to LVT formation in univariate analysis. However, only RCA ectasia was independently associated with LVT formation in multivariable analysis.
Discussion
In this study, angiographic factors associated with LVT formation comprehensively were firstly investigated in patients with anterior AMI. RCA ectasia and baseline SXscore were found to be independent predictors of LVT formation. However, other angiographic data were not related to the LVT.
LVT is an important complication of AMI which leads to morbidity and mortality because of embolism. Therefore, factors associated with LVT formation have always been the focus of attention and a large number of studies were performed to find these factors. Initially, the effects of acetylsalicylic acid, heparin, streptokinase or tissue plasminogen activator on LVT formation were investigated in various studies [1-3]. Later, many of biochemical and echocardiographic parameters such as LV wall motion score and C-reactive protein were found to be associated with LVT formation [4-7]. In the last decade, primary PCI was the first-line therapy for AMI and its effect on the development of LVT was sought by five studies [8,9]. According to the results of these studies, the extent of myocardial damage and regional inflammation are the most important predictors of LVT formation [4-7,10]. It has been reported that some angiographic features such as presence of retrograde filling and CAE have affected the myocardial damage [11-14]. SXscore has also recently raised as a predictor of no- reflow phenomenon and mortality in ST segment elevation myocardial infarction [16]. However, to date, all angiographic data were not evaluated, although the relationship between LVT formation and some angiographic factors such as door- to- balloon time and TIMI flow grade were evaluated in prior studies [9]. Therefore, we comprehensively assessed the relationship between LVT formation and all angiographic data which may affect the extent of myocardial damage in this study.
We found only two independent angiographic predictors for LVT: the presence of RCA ectasia and baseline SXscore. Coronary ectasia has some adverse effects on coronary circulation and myocardium. For example, Akyürek et al. [11] reported impaired coronary flow in patients with diffuse coronary artery ectasia. Markis et al. [12] suggested myocardial ischemia caused by CAE. In addition, Ceyhan et al. [13] have recently shown that CAE leads to the impairment of LV myocardial performance in patients without critical stenosis. In our study, the prevelance of RCA ectasia was higher in Group 1 than Group 2. Also, there was a relationship between CAE and RCA TIMI frame count (B=0.73, 95% CI=1.023-1.131, p=0.004, not given in results) which suggests impaired coronary flow and myocardial ischemia in non-infarcted RCA area. Ventricular remodeling results from the loss of the necrotic myocardial tissue and myocardial disruption within the non-infarcted area. Therefore, it has been proposed that the presence of RCA ectasia may contribute to LVT formation by means of myocardial ischemia and accelerated remodelling.
SXscore is a scoring system which suggests lesion complexity based on anatomical and functional characteristics of each critical coronary stenosis (>50%) in the vessel larger than 1.5 mm. Basically, this system was developed to choose the optimal treatment strategies in elective patients who have three-vessel or left main artery disease. To date, the relationship between SXscore and LVT formation in patients with ST-elevation MI has not been assessed. This relationship was firstly evaluated in this study and baseline SXscore was found to be an independent predictor for LVT. In our study, the baseline SXscore was significantly correlated with LVEF (r= -0.40, p<0.001) and LVESD (r=0.28, p=0.014). Therefore, we considered that baseline SXscore may affect the ventricular remodelling and LVT formation. On the other hand, SXscore after wiring/ ballooning was not an independent predictor for LVT formation in our study. A possible explanation of this situation is that SXscore after wiring/ballooning may not affect the remodelling process, because, we could not find any relationship between SXscore after wiring/ballooning and LV function or diameters in this study.
Smoking, is another independent predictor of LVT in this study, has a variety of the adverse effects on the cardiovascular system such as increased levels of adhesion molecules, fibrinogen and homocysteine and endothelial dysfunction [24]. Additionally, Zornoff et al. reported that smoking has aggravated the ventricular remodelling after myocardial infarction [25]. They also reported that the loss of anti-thrombotic property of the surface of the infarcted region and ventricular remodelling are two main mechanisms for LVT formation. Therefore, it has been considered that smoking may affect the LVT formation by means of both changing the surface of the infarcted area to a thrombogenic layer and aggravating the ventricular remodeling. On the other hand, we could not find a relationship between LVT formation and other angiographic data such as antegrade and retrograde filling, TIMI flow grade, TIMI frame count, successful primary PCI, door- to- balloon time. Actually, some angiographic findings including the success of the primary PCI and door-to- balloon time were found to be unrelated to LVT in previous studies. However, other angiographic findings including the presence of total occlusion and retrograde filling in baseline, right-left dominance of coronary circulation, coronary ectasia, TIMI frame count and no-reflow were firstly evaluated in our study and they were not related to LVT.
Our results are consistent with and support previous studies. Additionally, our results may suggest that the presence of a pathology that leads to more globally affected myocardium plays a role in the development of LVT after AMI. For example, RCA ectasia may affect a non-infarcted region of myocardium and may lead to more global impairment of ventricle in anterior AMI. Similarly, overall SXscore accounts the effect of all vessel. Therefore, it may suggest a more globally affected myocardium. The indexes of globally myocardial dysfunction such as myocardial performance (Tei) index and WMSI were found to be associated with LVT formation in previous echocardiography studies supports this consideration.
Study limitation
The small sample size is the main limitation of our study.
However, our study has some advantages. First, our study was performed prospectively. Secondly, the study population consisted of consecutive patients instead of selective patients. Therefore, the results of this study may reflect the real world. Conclusion
The presence of RCA ectasia and baseline SXscore are associated with LVT formation in patients with anterior AMI. Both can be easily assessed using coronary angiography and they can be used as a practical tool for determining patients at a higher risk of developing LVT.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
1- Eigler N, Maurer G, Shah PK. Effect of early systemic thrombolytic therapy on left ventricular mural thrombus formation in acute anterior myocardial infarction. Am J Cardiol. 1984;54(3):261-3.
2- Nordrehaug JE, Johannessen KA, von der Lippe G. Usefulness of high-dose anticoagulants in preventing left ventricular thrombus in acute myocardial infarction. Am J Cardiol. 1985;55 (13 Pt. 1):1491-3.
3- Grambow DW, Valentini VV, Armstrong WF. Thrombolytic therapy and intravenous heparin in acute myocardial infarction do not affect the incidence of left ventricular mural thrombus formation. Am Heart J. 1994;127(5):1424-6.
4- Celik S, Baykan M, Erdöl C, Gökce M, Durmus I, Orem C, et al. Doppler-derived mitral deceleration time as an early predictor of left ventricular thrombus after first anterior acute myocardial infarction. Am Heart J. 2000;140(5):772-6.
5- Yılmaz R, Celik S, Baykan M, Orem C, Kasap H, Durmus I, et al. Pulsed wave tissue Doppler-derived myocardial performance index for the assessment of left ventricular thrombus formation risk after acute myocardial infarction. Am Heart J. 2004;148(6):1102-8.
6- Celik S, Baykan M, Erdöl C, Kilinç K, Orem A, Orem C, et al. C-Reactive protein as a risk factor for left ventricular thrombus in patients with acute myocardial infarction. Clin Cardiol. 2001;24(9):615-19.
7- Celik S, Baykan M, Orem C, Kilinç K, Orem A, Erdöl C, et al. Serum lipoprotein(a) and its relation to left ventricular thrombus in patients with acute myocardial infarction. Jpn Heart J. 2001;42(1):5-14.
8- Zielinska M, Kaczmarek K, Tylkowski M. Predictors of left ventricular thrombus formation in acute myocardial infarction treated with successful primary angioplasty with stenting. Am J Med Sci. 2008;335(3):171-6.
9- Solheim S, Seljeflot I, Lunde K, Bjørnerheim R, Aakhus S, Forfang K, et al. Frequency of left ventricular thrombus in patients with anterior wall acute myocardial infarction treated with percutaneous coronary intervention and dual antiplatelet therapy. Am J Cardiol. 2010;106(9):1197-200.
10- Orhan AL, Okuyan E, Okcun B, Nurkalem Z, Sayar N, Soylu O, et al. Plasma homocysteine level and left ventricular thrombus formation in acute anterior myocardial infarction patients following thrombolytic therapy with t-PA. Thromb Res. 2009;124(1):65-69.
11- Akyürek O, Berkalp B, Sayin T, Kumbasar D, Kervancioğlu C, Oral D. Altered coronary flow properties in diffuse coronary artery ectasia. Am Heart J. 2003;145(1):66-72.
12- Markis JE, Joffe CD, Cohn PF, Feen DJ, Herman MV, Gorlin R. Clinical significance of coronary arterial ectasia. Am J Cardiol. 1976;37(2):217-22.
13- Ceyhan K, Koc F, Ozdemir K, Celik A, Altunkas F, Karayakali M, et al. Coronary Ectasia Is Associated with Impaired Left Ventricular Myocardial Performance in Patients without Significant Coronary Artery Stenosis. Med Princ Pract. 2012;21(2):139-44.
14- Sasayama S. Effect of coronary collateral circulation on myocardial ischemia and ventricular dysfunction. Cardiovasc Drugs Ther. 1994; 8 (Suppl. 2):S327-34.
15- Gibson CM, Murphy SA, Rizzo MJ, Ryan KA, Marble SJ, McCabe CH, et al. Relationship between TIMI frame count and clinical outcomes after thrombolytic administration. Thrombolysis In Myocardial Infarction (TIMI) Study Group. Circulation. 1999;99(15):1945-50.
16- Magro M, Nauta ST, Simsek C, Boersma E, van der Heide E, Regar E, et al. Usefulness of the SYNTAX Score to Predict “No Reflow” in Patients Treated With Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction. Am J Cardiol. 2012;109(5):601-6.
17- The TIMI Study Group. The Thrombolysis In Myocardial Infarction (TIMI) Trial. N Engl J Med. 1985;312(14):932-6.
18- Rentrop KP, Cohen M, Blanke H, Phillips RA. Changes in collateral channel filling immediately after controlled coronary artery occlusion by an angioplasty balloon in human subjects. J Am Coll Cardiol. 1985;5(3):587-92.
19- Swaye PS, Fisher LD, Litwin P, Vignola PA, Judkins MP, Kemp HG, et al. Aneurysmal coronary artery disease. Circulation. 1983;67:134–8.
20- Sianos G, Morel MA, Kappetein AP, Morice MC, Colombo A, Dawkins K, et al. The SYNTAX Score: an angiographic tool grading the complexity of coronary artery disease. EuroIntervention. 2005;1(2):219-27.
21- Gibson CM, Cannon CP, Daley WL, Dodge JT Jr, Alexander B Jr, Marble SJ, et al. TIMI frame count: A quantitative method of assessing coronary artery flow. Circulation. 1996;93(5):879–88.
22- Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Feigenbaum H, et al. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. J Am Soc Echocardiogr. 1989;2(5):358–67.
23- Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, et al. American Society of Echocardiography’s Nomenclature and Standards Committee; Task Force on Chamber Quantification; American College of Cardiology Echocardiography Committee; American Heart Association; European Association of Echocardiography, European Society of Cardiology. Recommendations for chamber quantification. Eur J Echocardiogr. 2006;7(2):79-108.
24- Ridker PM, Libby P. Risk Markers for Atherothrombotic Disease. In: Robert O. Bonow, Douglas L. Mann, Douglas P. Zipes, Peter Libby, editors. Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine, 9th ed. Philadelphia: Elsevier Saunders; 2012. p. 914-34.
25- Zornoff LA, Duarte DR, Minicucci MF, Azevedo PS, Matsubara BB, Matsubara LS, et al. Effects of beta-carotene and smoking on heart remodeling after myocardial infarction. Arq Bras Cardiol. 2007;89(3):135-41.
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Analysis and demographic characteristics of maxillofacial trauma patients
Murat Doğan 1, Ali Duman 2
1 Department of Otorhinolaryngology, Adnan Menderes University Medical School, 2 Department of Emergency Medicine, Adnan Menderes University Medical School, Aydın, Turkey
DOI: 10.4328/ACAM.20156 Received: 2020-03-10 Accepted: 2020-04-07 Published Online: 2020-04-19 Printed: 2020-09-01 Ann Clin Anal Med 2020;11(5):485-487
Corresponding Author: Ali Duman, Department of Emergency Medicine, Adnan Menderes University Medical School, Aydın, Turkey. E-mail: aliduman3489@gmail.com GSM: +90 505 688 1900 Corresponding Author ORCID ID: https://orcid.org/0000 0001 9461 5812
Aim: Maxillofacial fractures are common in trauma patients. In our study, we aimed to analyze the demographic and clinical characteristics of maxillofacial fracture patients admitted to our tertiary care hospital.
Material and Methods: Among the trauma patients admitted to our tertiary care emergency setting from January 2014 to December 2019, 177 patients with maxillofacial trauma were included in the study.
Results: Of the patients, the mean age was 27.11 ± 20.24 years and 75.7% were male. Mandibular fractures were the most common type (26%). Corpus and symphyseal fractures were the most common in the mandible fractures. Two of our patients (1.1%) died and 70 patients (39.5%) underwent surgical interven- tion.
Discussion: Mandibular fractures and soft tissue injuries are the most common findings observed in maxillofacial traumas. Of these patients, 37.3% were hospitalized and 39.5% underwent surgical interventions.
Keywords: Maxillofacial trauma; Emergency department; Mandible
Introduction
Maxillofacial fractures are common in trauma patients. The incidence of maxillofacial fractures is variable based on the location. These fractures may be isolated or combined with other fractures [1]. Being the most visible area in the human body, the face is significantly important for an aesthetic outlook. Maxillofacial fractures may cause aesthetic and functional deficits which may have substantially untoward consequences on social activities [2]. The epidemiology of facial fractures may vary depending on the type, severity, and cause of injury. Understanding these factors can help achieve effective treatment outcomes and clinical studies may contribute to preventing these types of injuries [3]. In this retrospective study, we aimed to analyze the demographic and clinical characteristics of maxillofacial trauma patients admitted to our tertiary care hospital.
Material and Methods
Our study was performed as a retrospective cross-sectional clinical study. This study included maxillofacial trauma patients among the individuals admitted to our tertiary care emergency department due to trauma from January 1, 2014 to December 31, 2019. The patient information was accessed via the hospital information processing database system and the patients with complete information in their records were included in the study. The demographic data of the patients such as identity information, age, gender, complaints, type of trauma, and the fracture location were recorded in the data form. For statistical analysis, the software package SPSS version 18.0 was used. Continuous variables were presented as mean ± standard deviation. The descriptive statistics of the categorical variables were shown as percentages (%).
Results
The mean age of the 177 patients included in the study was 27.11 ± 20.24 years (1-83 years). Of the study patients, 134 (75.7%) were male and 43 (24.3%) were female. When the mechanisms of trauma found in the patients were examined, it was found out that falls (49.2%) were the most common type. Other reasons for trauma are summarized in Figure 1.
There were no maxillofacial fractures in 63 (35.6%) patients. The most common type was mandibular fractures in 46 patients (26%), followed by zygomatic and nasal fractures with frequencies of 11.3% and 7.3%, respectively (Table 1).When the mandibular fractures were examined in subcategories, corpus and symphyseal-parasymphyseal fractures were the most common (Figure 2). Accompanying soft tissue trauma was found in 109 (61.6%) patients as edema and ecchymosis and in 25 (14.1%) patients as incisions and lacerations. Other fractures in other regions of the body were identified in 20 (11.2%) patients.
Eighty-five patients (48%) were discharged from the emergency department. Sixty-six patients (37.3%) were hospitalized. Twenty-four patients (13.6%) were admitted to the intensive care unit and 2 patients (1.1%) died. While 107 patients (60.5%) did not require surgery, 70 patients (39.5%) underwent surgical intervention.
Discussion
Trauma is the leading cause of death in the first 40 years of life. Although studies conducted in different geographical regions report a wide age distribution, maxillofacial trauma is most commonly seen in the third decade. In our study, the mean age of the patients was 27.11 ± 20.24 years; however, the age distribution ranged from one year to 83 years of age. Maxillofacial trauma is usually seen in men [1-5]. The male gender was predominant in our study, too, in alignment with the literature.
A review of the literature about the causes of maxillofacial trauma demonstrated that they vary depending on regional and sociocultural differences. The most common causes of trauma were reported to be daily life accidents and game and sports injuries by Gassner et al., traffic accidents (43.39 %) and blows (23.45 %) by Manodh et al., motor vehicle accidents by Boonkasem et al., and falls (32.5%) by Park et al [1-4]. In our study, falls and traffic accidents were the most common causes of trauma. We suggest that the underlying reason for this finding is the location of our country in an agricultural and tourism region at the crossroads of transportation.
A literature review about the types of maxillofacial fractures revealed that the most common types of fractures were reported to be mandibular fractures (59.2%) by Manodh et al., zygomatic fractures (37.2%) by Boonkasem et al., nasal fractures (61.7%) by Park et al., and midfacial fractures (71.5%) by Gassner et al [1-4]. In our study, the most common type was the mandibular fractures (26%). This diversity in the literature can be explained by the different causes of trauma.
The location of the fractures in the mandible was reported to be most common in the mandibular angle (22.6%) in the Park et al.’s study; however, Pungrasmi et al. reported symphyseal- parasymphyseal fractures and Manodh et al. reported parasymphyseal fractures as the most common locations for fractures [1]. In our study, the symphyseal-parasymphyseal fractures (30.4%) and mandibular corpus fractures (30.4%) were the most common. In the study by Manodh et al., accompanying soft tissue injuries were present in 41.2% of the patients; however, they were found in 75.3% of the patients in our study. In our study, 39.5% of the patients underwent open and closed surgical interventions and 37.3% of the patients were hospitalized in various specialty services. Manodh et al. reported that 26.44% of the patients were treated with closed reduction and 73.56% were treated with open reduction methods [1]. In a 312-patient study by Boonkasem et al., it was reported that 210 patients underwent open surgical interventions [1]. Pungrasmi et al. conducted a 1,275-patient study, reporting that 58.6% of the patients underwent surgery [1]. Al-Qamachi et al.’s study reported that 38% of the patients underwent medical and surgical treatment and 23% of the patients were hospitalized [1].
Since the most important limitation of our study was its retrospective design, we could not find patient data about the length of hospital stay, follow-up periods or the surgical methods used in treating the patients. In conclusion, mandibular fractures accompanied by soft tissue injuries are the most common lesions in maxillofacial trauma. Of our study patients, 37.3% were hospitalized and 39.5% underwent surgical intervention. To gain a better insight into maxillofacial trauma, well-designed and well-conducted prospective studies are needed.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
1. Gassner R, Tuli T, Hachl, Rudisch A, Ulmer H. Cranio-maxillofacial trauma: a 10 year review of 9543 cases with 21 067 injuries. J Craniomaxillofac Surg. 2003; 31(1): 51–61.
2. Park KP, Lim SU, Kim JH, Chun WB, Shin DW, Kim JY, et al. Fracture patterns in the maxillofacial region: a four-year retrospective study. J Korean Assoc Oral Maxillofac Surg. 2015; 41(6): 306-16.
3. Manodh P, Shankar DP, Pradeep D, Santhosh R, Murugan A. Incidence and patterns of maxillofacial trauma—a retrospective analysis of 3611 patients—an update. Oral Maxillofac Surg.2016; 20(4): 377–83.
4. Boonkasem S, Rojanaworarit C, Kansorn S, Punkabut S. Incidence and etiology of maxillofacial trauma: A retrospective analysis of patients attending a provincial hospital in northern Thailand. J Pub Health Dev. 2015;13(2): 57-71.
5. Pungrasmi P, Haetanurak S. Incidence and etiology of maxillofacial trauma: a retrospective analysis of King Chulalongkorn Memorial Hospital in the past decade. Asian Biomed (Res Rev News). 2017; 11(4): 353–8.
6. Al-Qamachi LH, Laverick S, D.C. Jones. A. Clinico-demographic analysis of maxillofacial trauma in the elderly. Gerodontology. 2012; 29(2): e147–e9.
7. Tuckett JW, Lynham A, Lee GA, Perry M, Harrington U. Maxillofacial trauma in the emergency department: A review. Surgeon. 2014; 12(2): 106-14.
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Murat Doğan, Ali Duman. Analysis and demographic characteristics of maxillofacial trauma patients. Ann Clin Anal Med 2020;11(5):485-487
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Pre-hospital airway management preferences of paramedics
İnan Beydilli 1, İlhan Korkmaz 2, Fevzi Yılmaz 1, Faruk Güngör 3, Vedat Kırpat 1, Nalan Kozacı 1, Mustafa Avcı 1, İsmail Atik 1
1 Department of Emergency Medicine, Antalya Education and Research Hospital, Antalya, 2 Department of Emergency Medicine, Sivas Cumhuriyet University, Medicine Faculty, Sivas, 3 Private Yaşam Hospital, Antalya, Turkey
DOI: 10.4328/ACAM.20166 Received: 2020-03-17 Accepted: 2020-04-17 Published Online: 2020-05-06 Printed: 2020-09-01 Ann Clin Anal Med 2020;11(5):443-447
Corresponding Author: İnan Beydilli, Antalya Training and Research Hospital, Department of Emergency Medicine, Kazım Karabekir Caddesi, Soğuksu, 07100, Antalya/Turkey. E-mail: inan_beydilli@hotmail.com GSM: +90 5449071976 Corresponding Author ORCID ID: https://orcid.org/0000-0002-1639-3254
Aim: The success of paramedics in the pre-hospital airway management in traumatic and non-traumatic critically ill patients, especially in cardiac arrest, is very important in terms of mortality and morbidity.
Materials and Methods: Patients who were admitted to the Emergency Department by pre-hospital emergency ambulance service were included in the study. The standard data registration form was created for the study. Demographic data, pre-hospital and in-hospital vital signs, GCS scores, cardiac rhythms, applied airway method, transport time and 48-hour mortality rates were recorded in the study form.
Results: While the initial approach to airway management was a bag-valve mask in 80 patients (82%), advanced airway management was performed in 18 (18%) patients. The mean time period for the ambulance arriving at the patient was 6.52±3.06 min and the mean time period of transport to the hospital was 11.42±9.53 min in all patients. Although there was no difference between patients managed with BVM and patients managed with advanced airway interven- tions in terms of a time period needed to access patient (p=0.957), there were significant differences in terms of a time period needed to access emergency service (p=0.001) and total time period (p=0.001) Among patients with CPA, there was a significant difference between patients managed with and without advanced airway interventions in terms of 48-hour mortality (p=0.035).
Discussion: Although the pre-hospital airway management still remains its mystery, we think that providing ventilation with BVM without losing time and transportation to the hospital would be more appropriate for patients in short distances and for patients with less risk of aspiration in terms of mortality and transportation time.
Keywords: Supraglottic airways; Heart arrest; Airway management
Introduction
The success of paramedics in the pre-hospital airway management in traumatic and non-traumatic critically ill patients, especially in cardiac arrest, is very important in terms of mortality and morbidity [1]. Endotracheal intubation (ETI) is regarded as the gold standard for advanced airway management. Misplaced intubation, iatrogenic hypoxia, and disruption of cardiac resuscitation are the disadvantages in patients with cardiac arrest. Also, the success of ETI depends on the experience and skill of the practitioner. The pre-hospital ETI success rates of paramedics were found to be between 33- 100% [2]. Therefore, alternative airway management methods such as esophageal-tracheal combitube (ETC), laryngeal mask airway (LMA), LMA FastrachTM and laryngeal tube (LT) were developed.
While pre-hospital emergency ambulance services in the United States are provided by paramedics, in Europe these services are provided mainly by physicians [2]. Although these services were previously provided only by physicians in our country, the majority of these services are provided by paramedics today [3, 4].
In this study, we investigated the pre-hospital airway management methods preferred by paramedics, the factors that influence these choices and the effect of these methods on mortality.
Material and Methods
This is a prospective analytical cross-sectional study performed in Antalya Training and Research Hospital. According to our power analyses we aimed to include 98 patients consecutively in the study and an approximately 2 year period (January 3, 2013- January 1, 2015) was estimated by us to consider the aimed number of the patients. Informed consent was obtained from the paramedics and patient relatives for the study. Our study was approved by the ethics committee (approval number 15/5). The patients who were admitted to the Emergency Department of Antalya Education and Research Hospital by 112 emergency ambulance services were included in the study. Patient who were ≥16 years with the following criteria: a) emergency ambulance service provided by paramedics, b) patients with a Glasgow Coma Scale (GCS) ≤8, c) traumatic and non-traumatic patients with an advanced airway management necessity d) patients undergoing proper cardiopulmonary resuscitation were included in the study. The exclusion criteria were as follows: a) transports from hospitals to hospitals, b) emergency ambulance service provided by physicians and patients with malignancies. The number of patients excluded was not recorded. The standard data registration form was created for the study. Demographic data, pre-hospital and in- hospital vital signs, GCS scores, cardiac rhythms, applied airway method, ambulance arrival time period to the patient and the transport period time to the hospital were recorded.
These data were obtained from patient transport form or provided by an on-duty paramedic. In-hospital SPO2 values were measured and recorded. Forty-eight-hour mortality rates of the hospitalized patients were recorded in the study form. In addition, period of professional work experience, training history, ETI and supraglottic airway experiences in the last 1 year, preferred advanced airway management method and the reason for this preference of a total of 28 paramedics were also recorded.
Statistical analysis
Data were evaluated using SPSS 22 (Statistical Package for the Social Sciences), IBM, USA, licensed by Sivas Cumhuriyet University. Frequency, average value, and percentages were calculated in statistical analysis. Power analyses were made with NCSS PASS-2008 home power analysis and sample size. The sample size and power were calculated according to the previous similar studies by taking mean values, standard deviation, α=0.05, and β=0.20 (1-β)=0.80. As a result, the power was determined as 0,802. According to these results we included 98 patients in this study and then they were classified according to the airway management. The Chi-square is used for the non-parametric values, the Mann-Whitney U test is used to compare differences between two independent groups when the dependent variable is either ordinal or continuous, but not normally distributed. A p- value <0.05 was considered statistically significant.
Results
The study included 98 patients, 35 (36%) women, and 63 (64%) men. While the admission cause was traumatic in 22 (22.5%) patients, 76 (77.5%) admitted due to non-traumatic diseases. While the first cardiac rhythm detected in CPA (+) patients was following: asystole 22 (69%), Pulseless electrical activity (PEA) 6 (19%), Ventricular fibrillation (VF)/pulseless ventricular tachycardia (VT) 4 (12%), the first rhythm among patients without CPA was as follows: normal sinus rhythm (NSR) 63 (95%), Sinus bradycardia 3 (5%). Twelve (54.5%) traumatic patients and 47(61.8%) non-traumatic patients admitted with a 3 point GCS.
Generally, the initial approach to airway management was bag- valve-mask (BVM) in 80 patients (81.6%); advanced airway management was performed only in 18(18.4%) patients. The correct placement of the tube in all patients with advanced airway interventions was confirmed with a capnograph in the emergency room.
None of the patients had vomiting and aspiration. ETI was preferred as the first option in all patients with performed advanced airway management. LMA was applied only in two patients due to a failed ETI attempt. Due to the failure of ETI in 4 patients with cardiopulmonary arrest, BVM was used as the second choice. There was a significant difference in the preferred airway methods between the patient groups according to cardiac arrest (p=0.003) (Table 1). CPA was present in 12 (67%) patients with performed advanced airway management. The mean arrival time for the ambulance to the patient was 6.52±3.06 min and the mean transport time period to the hospital was 11.42±9.53 min in all patients. The patients’ arrival time to the emergency services was longer for the cardiac arrest patients (p=0.025) (Table 2). Although there was no difference between patients managed with BVM and advanced airway in terms of time period needed to access patient (p=0.957), there were significant differences in terms of emergency service arrival time period (p=0.001) and total time period (p=0.001) (Table 3).
Among patients with CPA, the time period needed to access emergency service for patients who were managed with BVM (8.85±5.78min) was significantly shorter than the patients with advanced airway interventions (20.58±15.93min) (p<0.005). While the admission sPO2 value was 75.72±22.79 among patients managed with advanced airway, mean sPO2 result was 77.88±20.69 in the patients managed with BVM among the patients without cardiac arrest, and there was no significant difference between two groups (p=0.696). Likewise, the admission SPO2 value was 63.30±22.21 in patients managed with advanced airway interventions and 67.67±22.55 in patients managed with BVM among patients with CPA, and there was no significant difference between two groups (p=0.644). At the end of the 48-hour follow-up, 49 patients survived and 49 patients died. There was no difference between these patients in terms of transport time periods.
Among patients with CPA, there was a significant difference between patients managed with and without advanced airway management in terms of 48-hour mortality (p=0.035). All patients who underwent advanced airway management (n=12) died within 48 hours. While 6 of 20 patients without advanced airway management survived, the remaining 14 patients died. The mean period of professional work experience of paramedics was 5±3 years. They were found to be trained for ETI, supraglottic airway and BVM on patients, cadavers, and models. Twenty-five (89%) paramedics had not received advanced airway training except ETI on cadavers and patients. It was found that they practiced an average of 10-12 ETIs and 2 supraglottic interventions in the last year and that 22 (79%) of them preferred ETI, 3 (10.7%) preferred supraglottic airway and 3 (10.7%) preferred BVM as the first choice. The stated reasons for preference were ease of applicability and high rate of success.
Discussion
Appropriate airway management in order to provide effective pre-hospital ventilation in patients is important in terms of mortality and neurological outcome [5]. Although the optimal airway management strategy for patients with CPA is still unclear, it is recommended that best airway management should be determined by the environmental conditions and practitioner’s knowledge and skills and that supraglottic airway methods should be used as an alternative to gold standard ETI in the airway management in the pre-hospital setting [6,7]. Supraglottic airway methods provided rapid and effective ventilation during cardiopulmonary resuscitation (CPR) and were suggested as an alternative to ETI as they minimized the duration of chest compression interruption [8]. In a study by Bahathiq et al. paramedics in difficult and easy airway scenarios, they achieved 68% success by direct laryngoscopy, 97% by LMA and 97% by video laryngoscopy on the first attempt in easy airway scenario. The success rates were 60%, 90%, and 94% respectively in difficult airway scenario. In the same study, the time period for the provision of airway in case of easy and difficult airway scenarios were 31.5 vs. 40 seconds by direct laryngoscopy, 20 vs. 19 seconds by LMA and 22 vs. 21 seconds by video laryngoscopy, respectively [9].
In a study, paramedics achieved successful crash ETI in 29 (64%) patients out of 45 patients, including 27 patients with CPA. They also had a success rate of 92% for crash supraglottic airway attempt [10]. Timmerman et al. found that the success rate of inexperienced practitioners was 90% on the first attempt and 100% on the second attempt for LMA, and the application period was found to be as short as 10-30 seconds [11]. Likewise, Reutzler et al. found that paramedics had a success rate of 78% and duration of 24.43 sec. for ETI on models, and a success rate of 100% and duration of 10.8 sec. for LMA [12]. Besides having higher success rates, short application period of supraglottic airway methods is another advantage. In our study, ETI was attempted in patients with CPA, but only 69% of them were successful, so 1 patient had undergone LMA and 4 patients had undergone BVM. As in other studies, ETI success rate was found to be lower in our study. Although supraglottic airway devices were present in the ambulance and supraglottic airway interventions are a part of the training of paramedics, supraglottic airway interventions had been used only in 2 patients. Although ETI was the preferred method in terms of applicability and success rate, we believe that one of the main reasons of disfavor of supraglottic airway interventions by paramedics is basically the lack of experience, possibly due to inadequate supraglottic airway applications in the last year, application of supraglottic airway training only on models, and inadequacy of training on cadavers or patients. Ventilation with BVM is the most basic positive pressure ventilation technique.
But it may be inadequate to provide effective ventilation. Some portion of the air that was aimed to be sent to the lungs during ventilation with BVM continuously flows to the stomach and distends the stomach. Regurgitation and aspiration due to stomach distension are the most serious complications. These complications hinder the effectiveness of CPR. The success rate of effective ventilation with BVM is 43-51%. While the incidence of aspiration was 12% with BVM, it was 3% with LM [13]. In another study performed in non-hospital cardiac arrest patients, the success rate of effective ventilation with LM was found to be 85% [14]. In our study, 80 patients (82%) had been transported with BVM and aspiration was not detected in any of our patients. We linked the absence of aspiration to a short time period (9.48±6.87 minutes) needed to access emergency service and the inability of BM to cause gastric distension and regurgitation in such a short time. No significant difference was detected between patients managed with BVM and patients managed with advanced airway interventions among patients with cardiac arrest in terms of admission sPO2 values. This situation was interpreted as the similarity of ventilation efficiency of BVM to advanced airway interventions in short ranges. This finding supports the idea that BVM may be used for transportation of patients for short distances.
There is no evidence that advanced airway placement increases survival rates in CPA in the pre-hospital setting. During a CPR with rescuers with good knowledge of supraglottic airway, supraglottic airway interventions are good alternatives to BVM (Class IIa, Level of Evidence B) and ETI (Class IIa, Level of Evidence A) [15]. In a study in patients with pre-hospital CPA in Japan, patients managed with advanced airway methods were found to have worse neurological outcomes compared to patients managed with BVM [16]. In their systematic review, Jensen et al. compared ETI with alternative airway methods and found no difference in any study in terms of mortality rates [17]. Likewise, compared with BVM, advanced airway interventions were found to increase mortality especially in CPA cases in a number of other studies [18, 19].
Consistent with the literature, 48-hour mortality was also found to be increased in CPA patients with advanced airway management compared to patients with BVM in our study. Regarding transportation durations, while there was no difference between patients with and without CPA in terms of a time period needed to access patient, a time period of access to emergency service significantly increased in patients with CPA. Likewise, a time period of access to emergency service was significantly higher in patients with advanced airway management compared to patients managed with BVM among CPA patients. Among all patients, a time period of access to emergency service was significantly increased in patients with advanced airway management compared to patients managed with BVM. Especially in CPA and ETI patients, arrival time period to emergency service has been increased due to lack of paramedics’ experience, unsuitable ETI conditions of the ambulance and unsuccessful trials of ETI during transport. Lack of significant difference in effective ventilation in patients managed with BVM and the presence of significantly reduced mortality support the use of BVM in patients with particularly short transport duration and less risk of aspiration.
The most common cardiac rhythms in patients with pre- hospital CPA were VF and pulseless VT, followed by pulseless electrical activity (PEA) and asystole. The return of spontaneous circulation possibility of VF decreases by time, and rhythm turns into asystole or pulseless electrical activity [20-22]. In our study, emergency service admission rhythm was asystole in 69% of the patients. The increased rate of asystole was thought to be associated with delayed activation of the ambulance system. Limitations
Conditions associated with increased mortality, such as multisystem injuries in trauma patients and concomitant diseases in non-traumatic patients, were not evaluated. The absence of alternative airway methods, except for 2 patients, highlighted the comparison of ETI method and BVM. As there are no clear studies in terms of the transportation durations of patients in the literature, we introduced the short distance as a predicted period of time. Also, we did not know the consistency of capabilities of participant paramedics. We believe that our results on transportation duration and airway method preference will become stronger and clearer with future studies in multicenter studies with larger patient populations. Conclusion
Although pre-hospital airway management still keeps its mystery, effective ventilation should be ensured as soon as possible and the patient should be transported. As is the case in our study, we think that providing ventilation with BVM without losing time and transport to the hospital for patients in short distances and for patients with less risk of aspiration would be more appropriate in terms of mortality and transport time.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
1. Nasim S, Maharaj CH, Butt I, Malik MA, O’ Donnell J, Higgins BD, et al. Comparison of the Airtraq® and Truview® laryngoscopes to the Macintosh laryngoscope for use by advanced paramedics in easy and simulated difficult intubation in manikins. BMC Emerg Med. 2009; 9(1): 1. DOI: 10.1186/1471-227X- 9-2
2. Wang HE, Mann NC, Mears G, Jacobson K, Yealy DM. Out-of hospital airway managment in the United States. Resuscitaiton. 2011; 82(4): 378-85.
3. Soysal S, Karcioglu O, Topacoglu H, Yenal S, Koparan H, Yaman O. Evaluation of Prehospital Emergency Care in the Field and During the Ambulance Drive to Hospital. Adv Ther. 2005; 22(1): 44-48.
4. Kuvaki B. Use of Supraglottic Airway Devices in the Prehospital Setting and During CPR.. Anestezi Dergisi/ Journal of Anesthesia. 2011; 19 (2):79 – 89.
5. Paksu MS, Tasdemir HA. Çocuklarda Akut Bilinc Degisikligine Yaklasım. Gücel Pediatri/ The Journal of Current Pediatrics. 2006;3: 80-87.
6. Deakin CD, Nolan JP, Soar J, Sunde K, Koster RW, Smith GB, et al. European Resuscitation Council Guidelines for Resuscitation 2010 Section 4. Adult advanced life support. Resuscitation. 2010; 81(10): 1305-52.
7. Soar J, Nolan JP, Bottiger BW, Perkins GD, Lott C, Carli P, et al. European Resuscitation Council Guidelines for Resuscitation 2015 Section 3. Adult advanced life support. Resuscitation. 2015;95:100–47.
8. Muller JU, Semmel T, Stepan R, Seyfried TF, Popov AF, Graf BM, et al. . The use of the laryngeal tube disposable by paramedics during out-of-hospital cardiac arrest: a prospectively observational study (2008–2012). Emerg Med J. 2013; 30(12):1012-16.
9. Bahathiq AO, Abdelmontaleb TH, Newigy MK. Learning and performance of endotracheal intubation by paramedical students: Comparison of GlideScope® and intubating laryngeal mask airway with direct laryngoscopy in manikins. Indian J Anaesth. 2016; 60(5): 337. DOI: 10.4103/0019-5049.181595.
10. Lockey DJ, Healey B, Crewdson K, Chalk G, Weaver AE, Davies GE. Advanced airway management is necessary in prehospital trauma patients. Br J Anaesth. 2015; 114 (4): 657–62.
11. Timmermann PA, Cremer S, Heuer J, Braun U, Graf BM, Russo SG. Laryngeal mask LMA SupremeTM Application by medical personnel inexperienced in airway management. Anaesthesist. 2008; 57(10): 970-5.
12. Ruetzler K, Roessler B, Potura L, Priemayr A, Robak O, Schuster E, et al. Performance and skill retention of intubation by paramedics using seven different devices, a manikin study. Resuscitation. 2011; 82(5): 593-7.
13. Paal P, Gruber E, Beikircher W, Herff H, Brugger H. Sunset of bag-valve mask and rise of supra-glottic airway ventilation devices during basic life support. Resuscitation. 2010; 81(11): 1594-5.
14. Heuer JF, Barwing J, Eich C, Quintel M, Crozier TA, Roessler M. Initial ventilation through laryngeal tube instead of face mask in out-of-hospital cardiopulmonary arrest is effective and safe. Eur J Emerg Med. 2010; 17(1):10-15.
15. Neumar RW, Otto CW, Link MS, Kronick SL, Shuster M, Callaway CW, et al. Part 8: Adult advanced cardiovascular life support 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2010; 122(18 Suppl 3): S729-67.
16. Hasegawa K, Hiraide A, Chang Y, Brown DF. Association of prehospital advanced airway management with neurologic outcome and survival in patients with out-of-hospital cardiac arrest. JAMA. 2013; 309(3): 257-66.
17. Jensen JL, Cheung KW, Tallon JM, Travers AH. Comparison of tracheal intubation and alternative airway techniques performed in the prehospital setting by paramedics: a systematic review. 2010; 12(2): 135-40.
18. Hanif MA, Kaji AH, Niemann JT. Advanced airway management does not improve outcome of out-of-hospital cardiac arrest. Acad Emerg Med. 2010; 17(9): 926-31.
19. Shin SD, Ahn KO, Song KJ, Park CB, Lee EJ. Out-of-hospital airway management and cardiac arrest outcomes: a propensity score matched analysis. Resuscitation. 2012; 83(3): 313-19.
20. Ilkhanoff L, Goldberger JJ. Out-of-hospital cardiac arrest: getting beyond the tip of the iceberg. Circulation. 2012; 126(7): 793-6.
21. Larsen MP, Eisenberg MS, Cummins RO, HallstromAP. Predicting survival from out-of hospital cardiac arrest: a graphic model. Ann Emerg Med. 1993; 22(11): 1652-8.
22. Chan PS, Krumholz HM, Nichol G, Nallamothu BK, American Heart Association National Registry of Cardiopulmonary Resuscitation Investigators. Delayed time to defibrillation after in-hospital cardiac arrest. N Engl J Med. 2008; 358(1): 9-17.
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İnan Beydilli, İlhanKorkmaz, Fevzi Yılmaz, Faruk Güngör, Vedat Kırpat, Nalan Kozacı, Mustafa Avcı, İsmail Atik. Pre-hospital airway management preferences of paramedics. Ann Clin Anal Med 2020;11(5):443-447
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The effect of short-term electromagnetic fields caused by mobile phones on the electrical activity of alpha and beta brain waves
Mehmet Cihan Yavaş
Department of Biophysics, Faculty of Medicine, Kırşehir Ahi Evran University, Kırşehir, Turkey
DOI: 10.4328/ACAM.20220 Received: 2020-05-25 Accepted: 2020-06-24 Published Online: 2020-07-03 Printed: 2020-09-01 Ann Clin Anal Med 2020;11(5):474-478
Corresponding Author: Mehmet Cihan Yavaş, Department of Biophysics, Faculty of Medicine, Kırşehir Ahi Evran University, 40200, Kırşehir, Turkey. E-mail: mcihanyavas@ahievran.edu.tr P: +90 386 280 25 04 F: +90 386 280 39 17 Corresponding Author ORCID ID: https://orcid.org/0000-0002-2923-050X
Aim: The widespread use of mobile phones by people is increasing in society. The effect of these areas on neurophysiological and EEG is intriguing. In this study, we aimed to investigate the effect of short-term cell phone-induced electromagnetic field on the electrical activity of the EEG alpha and beta bands in the human brain.
Materials and Methods: The study was carried on twenty males divided into four groups such as Group 1: eyes closed (10 sec), Group 2: eyes open (10 sec), Group 3: phone exposure (3 min) and Group 4: control group (no phone, 3 min).
Results: In our study, no significant change was observed in the EEG electrical activity of the alpha waves between mobile phone use and non-use (p>0.05). As a result of the analysis made for the beta waves, in the comparison between the group exposed to the mobile phone and the non-exposed group, there was a significant difference between the FFT max F and PSD max power parameters (p<0.05), and an insignificant difference between the FFT max value and PSD max F parameters was found (p>0.05).
Discussion: The use of mobile phones can lead to some changes in the electrical activity of some bands of the brain.
Keywords: Mobile phone; Radiofrequency; Electromagnetic field; Alpha wave; Beta wave; Brain electrical activity
Introduction
The spread of new electronic devices is the effect of technology so that it is impossible for people to avoid the electromagnetic exposure caused by the use of these tools. The most widely used of these tools are mobile phones. According to 2017 data, there are approximately 8 billion mobile phone users worldwide [1]. Mobile communication technologies are based on radiofrequency electromagnetic field. Studies are carried out in different areas related to the possible biological effects of these areas. These are in vivo, in vitro, experimental human studies, and epidemiological studies. After all the evidence has been reviewed, radiofrequency electromagnetic fields are classified as possible carcinogens for humans by the IARC (the International Agency for Research on Cancer) [2].
Possible changes in electroencephalography were investigated with the use of mobile phones by medical students. In empirically researched studies, it was emphasized that mobile phones can cause some EEG changes and some bad effects on the well- being of the users [3]. When brain cells are active, it causes local currents to form in the environment. EEG measures the electrical potential changes flowing. There are 10-20 reference points which are determined internationally for registration, and recording is done with electro cap and AG/AgCI electrodes [4]. Electroencephalography (EEG) detects electrical activities that occur in the brain itself, recorded with multiple electrodes placed on the scalp [5].
In healthy adults, the amplitudes and frequencies of the electrical signals that occur in the brain can vary from one human condition, such as wakefulness and sleep. The characteristics of the waves can also change with age. Five major brain waves with different frequency ranges are observed in EEG. From low to high frequencies, these frequency bands consist of delta (δ), theta (θ), alpha (α), beta (β) and gamma (γ), respectively [6]. Electromagnetic radiation is reported to affect the EEG frequency bands in the power spectrum of alpha, theta, delta, beta and gamma bands [7]. As a result of short-term (approximately 3.5 minutes) exposure of 900 MHz electromagnetic field, it is reported that it does not cause any change in spectral power intensity in awake EEGs [8]. In the research carried out by the researchers on brain electroencephalography of the cell phone- induced electromagnetic field, it was reported that visible and measurable changes were observed in all five brain waves with short-term exposure time [9].
In light of the above-mentioned discussions, the aim of our study is to investigate whether healthy young people exposed to radiofrequency electromagnetic fields published on mobile phones are at any risk. Thus, in our study, we hypothesized whether short-term cell phone exposure changes in the electrical activity of frequency and power spectral densities for alpha and beta waves that occur during the rhythmic activity of the brain.
Material and Methods
Subjects
This study was conducted on 20 healthy male subjects aged 18- 28 years (mean±SD: 21.15±2.10). All subjects included in the study were healthy and did not have any disease or neurological history. Subjects were kept away from drugs, caffeine, and alcohol before the study and they were asked to take regular sleep. The subjects were informed about the study and voluntary consent forms were filled and their consents were obtained before starting the study. They stated that the subjects used their cell phones less than 20 minutes per day. The approval of the Clinical Research Ethics Committee of the Kırsehir Ahi Evran University Faculty of Medicine was taken (2019-07/85). The experiment was carried out according to the Declaration of Helsinki.
Exposure system and grouping
A standard commercial mobile phone was used (HTC Cor., Desire 610n, Taoyuan, Taiwan); 900 MHz, the SAR value of head for 10 g tissue: 0.346 W/kg, the SAR value for the body of 10 g tissue: 0.336 W/kg. The subjects used their right hands and held mobile phones to their right ears for conversation. Four groups were formed for alpha and beta waves as follows: Group 1: eyes closed, Group 2: eyes open, Group 3: three minutes talking by cell phone and Group 4: control group (no phone). Electromagnetic field measurement was performed with PCE EM-29 electromogmeter. The electric field was 49.02 V/m, the magnetic field was 243.1 mA/m, and the energy density was 11.80 mW/m2 [3, 8, 9].
Experimental procedure and EEG data acquisition
This study was carried out in the Biophysics research laboratory of Faculty of Medicine, Kırşehir Ahi Evran University. Biopac MP36 Student Lab instrument (BIOPAC System Inc., Goleta, CA, USA) and AcqKnowledge 4.1 software were used in the study. The Biopac electrode set (SS2L) was connected to CH1 of the MP36. The Biopac disposable vinyl electrodes (EL 503) were placed on the T3 and T5 region in the 10-20 International electrode system. During the recording, the subjects were seated in the chair and remained motionless. Electrode conductivity was measured as 5.38 kohms. Domain measurements, FFT, and power spectral densities of EEG signals were measured. The measured raw EEG signals were subdivided. Time- domain characteristics and FFT and PSD measurements were performed for alpha and beta waves. FIR, High pass filters, hand movements and other noises were removed. For domain measurements, 2048 point of FFT, cell phone 65560 point of FFT, pad with zeros, magnitude, linear, window: hamming, PSD, Windows: Hamming operations were applied. Figure 1 shows the experiment protocol. While recording, the mobile phone was kept open and being held to the subject’s ear. The subjects remained silent to prevent muscle activity and parasites from forming.
Data analysis
Statistical analysis of the study was performed using Statistical Package for Social Sciences version 21.0 software for Windows (IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp., USA). The normality assumption was tested by the Kolmogorov-Smirnov and the Shapiro-Wilk tests. Descriptive statistics of the variables are given as mean error standard deviation. Paired t test and Wilcoxon matched-pair test were used for univariate analysis of dependent variables.
Results
In our study, 20 healthy men were included. They used mobile phones adhered to the right ears of the subjects. The effects of mobile cell phones on EEG alpha and beta waves were investigated. Average, min, max, std, skew, kurtosis, FFT (Max F, Max value), PSD (Max F and Max power) parameters were examined, and recording was done in four stages (eye closed and open, mobile phone exposure and no exposure recording). In the study, the frequency range of the Alpha waves was found in the normal range (8-12 Hz). In our study, we found 10.55 Hz with eyes closed, 11.04 Hz with eyes open, GSM-EMF group 10.86 Hz, control group (no phone) 9.91 Hz. No significant change in power spectral densities was observed. The frequency range of the beta wave was in the normal range (13-30 Hz). In our study, eyes were closed 15.33 Hz, eyes were open 19.11 Hz, GSM-EMF group 18.13 Hz, control group (no phone) 20.72 Hz. A significant increase in power spectral density was observed in the group using mobile phones.
The results of the alpha waves are given in Table 1. According to these results, there is a statistically significant difference in terms of FFT max value and PSD max power variables with eyes open and eyes closed (p<0.05). In terms of FFT max F and PSD max F variable, there was no significant difference between eyes open or eyes closed (p>0.05). There is no difference between mobile phone speech and 3 minutes fixed recording in terms of all variables of alpha waves (p>0.05).
The analysis results obtained for the beta waves are summarized in Table 2. In our study, there was no significant difference between eyes closed or eyes open in terms of FFT max and PSD Max power variables (p>0.05). The FFT max F value in eyes open group was found to be lower than the FFT max F value when the eyes were closed (p<0.05). In terms of PSD max F variable, the values measured when the eyes are open are lower than the values measured when the eyes are closed, and the difference was statistically significant (p<0.05). A statistically significant difference was detected between FFT max F and PSD max power parameters of a mobile phone (phone exposure) and non-mobile groups (no phone) (p<0.05). There was no significant change between the other parameters of these groups (p>0.05).
Discussion
In an experimental study on rats, cell phone exposure at different frequencies (900, 1800 and 2100 MHz) was created, and as a result of the study, an increase in oxidative DNA damage in rat brain tissues after the radiation emitted by the cell phones was reported [20]. Fourteen published studies on the effect of GSM mobile phone exposure on brain electrical activity and sleep change have been compiled. When the findings of the study are analyzed, it is reported that there are no changes in three studies and eleven studies have caused changes in brain activities [10]. When another similar study was examined, it was reported that 20% of mobile phones had no effect on brain activity, 3% were reported to affect only beta and gamma bands, 30% had an effect on alpha and other frequency bands, and 47% had only one alpha band change [1]. A 5-minute exposure (before, during, and after) was established using a commercial mobile phone on 30 healthy subjects. The result of the study provides evidence that mobile phone use affects brain waves (alpha and beta) [11]. In our study, it is seen that both alpha and beta waves can cause activity change in the brain when the minimum, maximum, skew and kurtosis parameters are examined.
In humans, 15 minutes of electromagnetic field exposure from a mobile phone was made. It has been reported that exposure at the T3 position does not cause a statistically significant change in the bioelectric activity occurring in the human brain [12]. The effect of GSM-EMF fields on young and old people was investigated. In the study, it was reported that there was a significant increase in alpha rhythms in the frontal region in the elderly. It shows that mobile phone-induced EMF affects interhemispheric synchronization [13]. As a result of the research, they stated that electromagnetic fields originating from mobile phones affect the human brain and that GSM- powered mobile phones may have a higher effect on brain activity than CDMA-powered mobile phones [5]. A decrease in the EEG alpha power band was detected in eyes-closed position during and after 900 MHz GSM-EMA exposure on 26 healthy volunteers [14]. The effect of ELF-MF field (100 μT) on EEG parameters was investigated in 19 men. In the study, a decrease in the strength of the beta band and an increase in the alpha band were observed in eyes closed exposure. A reduction in the power spectrum of the alpha band was observed with eyes open exposure [15]. In our study, compared to the group not using the mobile phone, an increase in maximum data of alpha rhythms, and a significant change in FFT and PSD parameters were not observed. A statistically significant difference was found in the FFT max F value and PSD max power values of the beta waves. They stated that the 20-minute RF-electromagnetic field created using a commercial mobile phone caused a reduction in the alpha frequency band [16]. Another 20-minute study reported that exposure to 3G and 4G mobile cell phones on 60 healthy volunteers may have some local biophysical effects [17]. In our study, there was no correlation with long-term exposures because there was a short-term exposure. However, there was no significant statistical difference in the alpha band.
The high strength of the increased beta waves causes stress, anxiety, and some physical and mental discomfort [7]. The effect of heavy and medium cell phone use on brain EEG was investigated. Researchers have not observed a slowdown in brain activity and a significant effect on the beta waves [18]. Croft et al. reported that acute cell phone exposure could alter rest EEG, and also reported no EMF effect in theta, beta or gamma bands in the study [19]. In our study, PSD max power value in the group using mobile phones increased compared to the group not using phones and was found statistically significant.
Conclusion
In the literature, different reports on the effect of mobile phone use on brain electrical activity are published. In our study, the short-term effects of cell phone-induced electromagnetic field on brain waves were examined and no statistically significant change was observed in the parameters of the electrical activity of the alpha waves as a result of this short exposure, but as a result of Fast Fourier transform and power spectral density analysis of the electrical activity of the beta waves, there was a statistical difference. The source of possible changes due to mobile phones mentioned in the literature data is uncertain. It is therefore a matter of debate whether these changes are due to movement of people during EEG recording, whether they are due to the recording device, environmental noise, or people’s current thinking activity. Therefore, studies on short and long term detailed EEG activity of electromagnetic fields originating from mobile phones are needed.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
1. Wallace J, Selmaoui B. Effect of mobile phone radiofrequency signal on the alpha of human waking EEG: A review. Environ Res.2019; 175: 274-86.
2. Danker-Hopfe H, Eggert T, Dorn H, Sauter C. Effects of RF-EMF on the human resting-state EEG-the inconsistencies in the consistency. Part 1: Non-exposure- related limitations of comparability between studies. Bioelectromagnetics. 2019; 40(5): 291-318.
3. Parmar K, Tandon R, Kumar N, Garg K. Variations in electroencephalography with mobile phone usage in medical students. Neurol India. 2019; 67(1): 235-41.
4. Teplan M. Fundamentals of EEG measurement. Meas Sci Rev. 2002; 2(2): 1-11.
5. Tyagi A, Duhan M, Bhatia D. Effect of mobile phone radiation on brain activity GSM vs CDMA. IJSTM. 2011;2(2): 1-5.
6. Singla R, Chambayil B, Khosla A, Santosh J. Comparison of SVM and ANN for classification of eye events in EEG. J Biomed Sci Eng. 2011; 4(1): 62-9.
7. Singh G. The effects of mobile phone usage on human brain using EEG. Int J Comput Appl. 2014; 105(13): 16-20.
8. Röschke J, Mann K. No short-term effects of digital mobile radio telephone on the awake human electroencephalogram. Bioelectromagnetics. 1997; 18(2): 172-6.
9. Pattnaik S, BS Dhaliwal, Pattnaik SS. Impact analysis of mobile phone electromagnetic radiations on human electroencephalogram. Sādhanā. 2019; 44(6): 134.
10. Hamblin DL, Wood AW. Effects of mobile phone emissions on human brain activity and sleep variables. Int J Radiat Biol. 2002; 78(8): 659-69.
11. Murat ZH, Kadir R, Isa RM, Jahidin AH, Taib MN, Sulaiman N. Observation of human brainwave signals due to mobile phone usage. Int J Simul Syst Sci Technol. 2011; 12: 22-8.
12. Kaneta LA, Watson AL. The effect of mobile telephone electromagnetic field on human brain bioelectric activity and information processing speed. Psychol Cogn Sci Open J. 2017; 3(4): 105-9.
13. Vecchio F, Babiloni C, Ferreri F, Buffo P, Cibelli G, Curcio G, et al. Mobile phone emission modulates inter-hemispheric functional coupling of EEG alpha rhythms in elderly compared to young subjects. Clin Neurophysiol. 2010; 121(2): 163-71.
14. Ghosn R, Yahia-Cherif L, Hugueville L, Ducorps A, Lemaréchal JD, Thuróczy G, et al. Radiofrequency signal affects alpha band in resting electroencephalogram. J Neurophysiol. 2015; 113(7): 2753-59.
15. Shafiei SA, Firoozabadi SM, Tabatabaie KR. Ghabaee M. Study of the frequency parameters of EEG influenced by zone-dependent local ELFMF exposure on the human head. Electromagn Biol Med. 2012; 31(2): 112-21.
16. Perentos N, Croft RJ, McKenzie RJ, Cvetkovic D, Cosic I. The effect of GSM-like ELF radiation on the alpha band of the human resting EEG. Conf Proc IEEE Eng Med Biol Soc. 2008; 2008: 5680-83.
17. Vecsei Z, Knakker B, Juhász P, Thuróczy G, Trunk A, Hernádi I. Short-term radiofrequency exposure from new generation mobile phones reduces EEG alpha power with no effects on cognitive performance. Sci Rep. 2018; 8(1): 1-12.
18. Arns M, Van Luijtelaar G, Sumich A, Hamilton R, Gordon E. Electroencephalographic, personality, and executive function measures associated with frequent mobile phone use. Intern J Neuroscience. 2007; 117(9): 1341-60.
19. Croft RJ, Chandler JS, Burgess AP, Barry RJ, Williams JD, Clarke AR. Acute mobile phone operation affects neural function in humans. Clin Neurophysiol. 2002; 113(10): 1623-1632.
20. Alkis ME, Bilgin HM, Akpolat V, Dasdag S, Yegin K, Yavas MC, et al. Effect of 900-, 1800-, and 2100-MHz radiofrequency radiation on DNA and oxidative stress in brain. Electromagn Biol Med. 2019; 38(1): 32-47.
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Mehmet Cihan Yavaş. The effect of short-term electromagnetic fields caused by mobile phones on the electrical activity of alpha and beta brain waves. Ann Clin Anal Med 2020;11(5):474-478
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Assessment of nutritional status and malnutrition risk with different methods in surgical patients
Hakan Mustafa Köksal 1, Demet Güler Yılmazer 2, Mustafa Fevzi Celayir 1
1 Department of General Surgery, Sisli Hamidiye Etfal Research and Training Hospital, İstanbul, 2 Department of Family Medicine, Sinop Erfelek Family Health Center, Sinop, Turkey
DOI: 10.4328/ACAM.20241 Received: 2020-06-10 Accepted: 2020-07-21 Published Online: 2020-07-27 Printed: 2020-09-01 Ann Clin Anal Med 2020;11(5):462-466
Corresponding Author: Mustafa Fevzi Celayir, Department of General Surgery, Sisli Hamidiye Etfal Research and Training Hospital, İstanbul, Turkey. E-mail: fcelayir@gmail.com GSM: +90 532 241 8245 F: +90 212 224 0772 Corresponding Author ORCID ID: https://orcid.org/0000000193538261
Aim: Malnourished surgical patient morbidity and mortality are increased. In this study, we aimed to evaluate and improve the malnutrition status of these patients in the preoperative period.
Material and Methods: Age, gender, height, weight, body mass index (BMI), nutritional risk index (NRI) degrees, albumin, and total protein levels were deter- mined in the first 24 hours of admission of all cases. Mini nutritional assessment (MNA) was performed for the malnutrition situation assessment.
Results: One hundred twenty patients were examined. The BMI scores were as follows: 5.8% of the cases were in the ≤ 18.5 group, 36.7% of the cases were in the 18.6-24.9 group, 45% of them were in 25-29.9 group, and 12.5% of them were in the ≥ 30 group. Albumin levels showed a significant difference ac- cording to the BMI levels (p<0.05). Total protein levels showed significant difference according to the NRI levels (p <0.05) and, total protein levels in patients with normal levels of NRI were much higher compared to the NRI severe cases (p = 0,022, p <0.05). Albumin levels were significantly different according to the NRI levels (p <0.05) and, the albumin levels at patients with normal levels of NRI were higher against the dangerous levels of NRI cases (p = 0,045, p <0.05).
Discussion: If malnourished patients could be well planned, their recovery time would be shorter. By simple measures, we were able to obtain precious results about the patient’s health status.
Keywords: Malnutrition; Body mass index; Nutritional risk index
Introduction
Malnutrition is affecting nearly 20% of hospitalized patients. It causes depression of the immune system, impaired wound healing, and muscle wasting. Prolonged hospital stays are associated with higher treatment costs and increased mortality [1].
Malnutrition prevalence is reported to be 39% in cancer patients. The rate is 67% for pancreatic cancer, 60% for esophageal cancer, and 39% for colon cancer [2]. It could be noted that this rate is higher in Turkey. Malnutrition is usually undiagnosed and untreated. One of the most essential factors behind it is inadequate nutritional training and knowledge of staff members. Furthermore, there is a lack of adequate screening and assessment protocols [3].
There is no standardization of the methods adopted for the assessment of the nutritional status. The fact that the weight loss and a decrease in visceral and somatic proteins are actually accompanied by surgical diseases can at some point be considered “natural”. Causes of malnutrition include cancer, obstruction, or fistula surgery, loss of appetite, nausea, vomiting, dysphagia, and commonly-unnoticed cases of preoperative fasting prescribed to perform various tests [4]. Since surgical patients are exposed to stress for several reasons, the main components of metabolism manifest themselves. Preoperative fasting, wounds, wound healing, and infections are the most critical factors causing stress [5]. Protein and energy malnutrition is reported in nearly 40% of patients in intensive care units [6]. We aim to show that it is easy to learn about the nutritional state of our patients through a nutritional assessment based on various easy-to-analyze parameters, such as albumin and total protein concentration, height and weight measurement, MNA and NRI.
Material and Methods
This study was planned at the General Surgery Clinic of the Sisli Hamidiye Etfal Hospital in March 2009. The permission for the study was obtained from the Ministry of Health Ethics Committee No.4 on clinical trials in Istanbul. All informed consent was received.
The study was conducted with 120 cases in total. All the patients were evaluated within the first 24 hours of their hospitalization. Age, gender, height, weight, BMI, albumin, and total protein concentrations of the hospitalized patients were recorded. The BMI was calculated based on kg/m2. This assessment revealed malnutrition for <18, the risk for malnutrition for 18 to 20, healthy nutrition for 20 to 25, and obesity for more than 30 patients. The NRI of the patients was calculated based on NRI = 1.519 × alb (gr/dl) + 41.7 × present weight/usual weight. The patients with an NRI score of > 97.5 were considered to have limited malnutrition, from 83.5 to 97.5 mild malnutrition, and < 83.5 severe malnutrition. An MNA was performed for the purpose of malnutrition assessment in patients. The patients with an MNA score of ≤ 11 were considered to suffer from malnutrition.
Mini Nutritional Assessment (MNA): The short-form MNA meets some of the aforementioned expectations. It comprises six items derived from the original MNA and correlates well with the conventional nutritional assessment. These parameters are a decrease in food intake, weight loss, mobility, psychological distress, or acute illness in the past three months, neuropsychological problems, and BMI. Should the score be 11 or below, patients are considered to have a malnutrition risk, and the long-form MNA should be performed. The sensitivity of the short form was successfully tested. The short-form MNA is intended to assess non-hospitalized patients in particular. The full-length MNA should be performed given the high prevalence of malnutrition in patients staying in nursing homes and hospitals.
As a result of the assessment, patients are classified as well-nourished, at risk, or clinically apparent malnutrition. Many studies have reported that MNA correlates well with nutritional intake, anthropometry, laboratory data, functional state, morbidity, mortality, and length of hospital stay. Based on the literature, MNA should be considered the most crucial instrument for geriatric nutrition. MNA results may vary according to the conditions. It is considered to be the best option to screen and assess elderly people living on their own in society. These people are expected to be cooperative to a nearly optimal extent. One may face challenges in nursing homes and hospitals that prevent MNA from being successfully performed. Full cooperation cannot be achieved with such patients, and testing will lead to a loss of much more time. It may not be possible to get any responses to questions about the self- assessment of patients with dementia in particular. The rate of failure to perform MNA in nursing homes or hospitals can go up to 40% [7]. The length of stay is higher for patients at risk or with malnutrition than those with a healthy MNA score [8]. Statistical analysis: NCSS Statistical Software (Utah, USA) was used for the statistical analysis of the results. Oneway Anova test was performed for the inter-group comparison of parameters with normal distribution and of quantitative data in addition to descriptive statistical methods (mean, standard deviation), and Tukey HDS test was performed to determine what group caused the difference. The Chi-square test was performed for the comparison of qualitative data. P < 0.05 was considered statistically significant.
Results
The study was conducted with 120 cases in total, including 40.8% (n=49) females and 59.2% (n=71) males at our clinic from March to September 2009. The age of the cases was in the range of 15-93 years, and their mean age was 50.80±18.89 years.
Among all cases, 30.8 % (n=37) were diagnosed with malignant malnutrition while 69.2 % (n=83) were diagnosed with benign. Total protein concentrations ranged from 4.55 to 8.24, and the mean concentration was 6.91±0.91. Albumin concentrations ranged from 1.97 to 4.94, and the mean concentration was 3.66 ± 0.67.The BMI scores in 5.8% of the cases (n=7) were ≤18.5, in 36.7% of the cases (n=44) ranging from 18.6 to 24.9, in 45% of the cases (n=54) from 25 to 29.9, and in 12.5% of the cases (n=15) ≥ 30 (Table 1).
Diagnoses reported a statistically significant difference in malnutrition state (p<0.01). The prevalence of the benign disease in cases without risk for malnutrition was significantly higher than that of malignant disease (Table 2). Malnutrition was reported in 5% (n=6) of the cases, with 30.8% (n=37) at risk, and 64.2% (n=77) at no risk. The NRI scores in 9.2% of the cases (n=11) were below 83.5, with 36.7% of the cases (n=44) ranging from 83.5 to 97.5, and 54.2% of the cases (n=65) ≥97.5 (Table 1).
Age was not statistically significant for malnutrition state (p>0.05). Total protein and albumin concentrations reported no statistically significant difference for malnutrition state (p>0.05). BMI scores reported a statistically significant difference in malnutrition state (p<0.05). The cases with a BMI score of ≤18.5 were at a higher risk for malnutrition while the prevalence of no risk was higher in other BMI scores. The proportion of benign cases with no chance for malnutrition was significantly higher than in malignant cases. Malnutrition state reported a statistically significant difference in NRI scores (p<0.01). The prevalence of malnutrition was high in cases with an NRI score below 83.5, and the risk for malnutrition was high in cases with an NRI score ranging from 83.5 to 97.5, and no risk for malnutrition was high in cases with an NRI score of ≥97.5. (Table 2).
Post-Hoc Tukey HSD test reported that the albumin concentrations of cases with an NRI score of 25 to 29.9 were statistically higher than that of cases with an NRI score of ≤18.5 (p:0.040; p<0.05). There was no statistically significant difference among other BMI scores (p>0.05). Gender reported no statistically significant difference in BMI scores (p>0.05), diagnoses said no statistically significant difference in BMI scores (p>0.05), NRI scores reported no statistically significant difference in BMI scores, either (p>0.05) (Table 3).
Total protein concentrations reported a statistically significant difference in NRI scores (p<0.05). Total protein concentrations of cases with good NRI score were higher than that of cases with severe NRI score (p:0.022; p<0.05). Albumin concentrations reported a statistically significant difference in NRI scores (p<0.05). The albumin concentrations of cases with a good NRI score were higher than that of cases with a severe NRI score (p: 0.045; p<0.05). Gender reported no statistically significant difference. Diagnoses reported a statistically significant difference in NRI scores (p<0.01). The prevalence of malignancy was high in cases with a severe NRI score.
Discussion
Nutrition is a significant factor affecting the state of health. Malnutrition is usually undiagnosed and untreated, especially in hospitalized patients [9]. The risk of malnutrition ranges from 30 to 65% among hospitalized elderly [10]. Cereceda FC. et al. reported 20% mild and 18% severe protein-energy malnutrition in 620 patients hospitalized for non-surgical purposes [11]. Malnutrition is reported in 39% of cancer patients. The rate amounts to 67% for pancreatic cancer, 60% for esophageal cancer, and 39% for colon cancer [12]. The risk of mortality is four times higher for malnourished patients [13].
The lack of nutritional assessment of hospitalized patients results from the lack of importance attached and time spared for this, and of the globally-acknowledged system for the nutritional evaluation [14]. The incidence of malnutrition rises unless strict attention is paid to the nutritional state of patients during their hospital stay [15]. We found that the prevalence of a benign disorder in cases with no risk of malnutrition was significantly higher than the prevalence of a malign disease (p<0.01). Cohendy R et al. have suggested a routine nutritional assessment for people aged 60 and above with ASA 3 or 4, as morbidity and mortality rate are higher in this age group [16]. All of the elderly patients are at risk of malnutrition [17]. The risk is even higher when it is accompanied by a chronic mental or physical disorder.
Guigoz et al. compiled the data of 21 studies (14.149 patients) in a meta-analysis of the prevalence of malnutrition in the elderly population and reported that the prevalence of malnutrition was 2%±0.1 for the elderly with no reliance on a nursing home or a medical center, and the risk for malnutrition was 24% ±0.4 [18]. Another similar study conducted based on MNA reported that 1 to 5% of the older people suffer from malnutrition or are at risk of malnutrition. However, our study indicated that age was not statistically significant for malnutrition state (p>0.05) [19]. The age of our cases ranged from 15 to 93, and their mean age was 50. We think that no difference was reported between malnutrition and age as the selected sample for our study was a population of rather young people. According to the results of our research, those admitted with a malignant disorder are at higher risk for malnutrition than those with benign disease. Therefore it would not be wrong to expect malnutrition in cancer patients who look healthy.
Kelly et al. used the BMI for nutritional assessment as a part of their study. They assessed 337 cases admitted to a university hospital for internal and surgical procedures. Those with a BMI score of < 18.5 kg/m2 were considered to present with malnutrition, and 13% of the patients reported malnutrition. The rate rises to 18% as those with a BMI score of 18.5 to 20 kg/m2 and loss of weight for more than 3 kilograms over the past three months were considered to present with malnutrition [20].
Whirter and Pennington included a total of 500 hospitalized cases from five departments, with age ranging from 16 to 64. They considered those with a BMI score of < 20 slight, < 18 mild and < 16 severe malnutrition as a part of their assessment; 27% of general surgery cases and 39% of orthopedic cases presented with malnutrition. [21] Our malnutrition rates are lower. We think that this result has to do with the fact that most of our patients did not need to stay in the hospital for more than 48 hours and were ambulant and their overall state of health was good. Among the cases in our study, 54.2% reported borderline malnutrition, with 36.7% mild, and 9.2% severe malnutrition based on the NRI; 5.8% of the cases were slim, with 36.7% of healthy weight, and 45% overweight and 12% obese based on their BMI scores.
The risk of malnutrition was higher in cases considered slim, with a BMI score of ≤ 18.5, while it was lower for any other BMI score. NRI scores reported no statistically significant difference than BMI scores in our study (p>0.05). However, one must keep in mind that BMI and NRI do not always give the same results. The fact that three assessments (BMI, NRI, MNA) give different results may due to using different parameters. BMI is based on height and weight, while NRI relies on albumin concentration and the ratio of actual to usual body weight. MNA, on the other hand, is performed based on responses given by a patient. The measurement of weight for BMI can be misleading in nutritional assessment. BMI score and weight of overweight people may be within normal limits despite a short-term loss of weight that amounts to more than 10% of their normal weight [22]. NRI is considered to be sensitive and specific for the estimation of complication risks followed by laparotomy or non-cardiac thoracotomy [23].
We compared albumin concentrations, MNA scores, and nutritional risk index of our patients. Both assessments revealed that the worse the nutritional state of patients was, the lower their albumin concentrations. The serum albumin concentration is a test performed to assess chronic malnutrition. Because of its long half-life, albumin concentration is an insensitive indicator to determine acute changes. It is reported that low albumin concentrations are associated with morbidity and mortality [23]. However, albumin concentration is affected by factors such as non-malnutrition inhibition and catabolism of albumin synthesis, loss of albumin in the body, and variations in the infused volume in albumin concentration. Nevertheless, low serum albumin concentration is currently a standard parameter to determine malnutrition state as it is easy and cost-effective to measure, and it is strongly associated with mortality. In our study, total protein concentrations did not report any statistically significant difference for BMI scores, whereas albumin concentrations in the cases with a BMI score of 25 to 29.9 were significantly higher than that of the cases with a BMI score of ≤18.5.
In our series, 5% of the patients presented with malnutrition. The risk becomes higher, especially in patients with malignancy. BMI, NRI, and MNA may not give similar results for nutritional assessment. Even if BMI is within normal limits, a patient may still suffer from malnutrition.
We are of the opinion that it would be better to adopt multiple methods that are cost-effective, easy, and reliable for patients to be operated. In our study, we merely determined the malnutrition prevalence of cases at the time of admission into the general surgery clinic. Therefore, our results do not indicate the malnutrition prevalence of all the surgical cases admitted to the hospital. Even though we have determined the malnutrition prevalence in the cases, we think that further studies are required to demonstrate the effects of malnutrition on anesthesia. The preoperative and postoperative nutritional supplements can be scheduled for patients. Early oral nutrition has always been preferable in surgical patients [24,25]. Conclusion:
We are of the opinion that the assessment of the nutritional state of patients to be operated would be beneficial for patients and us in many aspects. We have concluded that it is highly convenient to adopt the aforementioned methods of assessment within the bounds of available capabilities and that one can get valuable results through simple measurements, and professionals from any discipline can perform them. Improving the nutritional status of malnourished surgical patients accelerates hospital recovery and reduces readmission. This means a severe cost reduction and satisfaction for the doctor and patient. In the end, simple evaluations will bring significant benefits to all partners.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
1. Barker LA, Gout BS, Crowe TC. Hospital Malnutrition: Prevalence, Identification and Impact on Patients and the Healthcare System. Int J Environ Res Public Health. 2011; 8(2): 514–27.
2. Şahinoğlu, AH. Yoğun Bakım Sorunları ve Tedavileri (Intensive Care Problems and Treatments). 2nd ed. Ankara: Türkiye Klinikleri;2003. p.251-80.
3. Reber E, Gomes F, Vasiloglou MF, Schuetz P, Stanga Z. Nutritional Risk Screening and Assessment. J Clin Med. 2019; 8(7): 1065.
4. Stratton, RJ, Elia, M. Who benefits from nutritional support: what is the evidence? Eur J Gastroenterol Hepatol.2007;19:353-8.
5. Guo S, Di Pietro LA. Factors Affecting Wound Healing. Dent Res. 2010; 89(3): 219–29.
6. Elia M. Energy expenditure in the whole body. In: Kinney JM, Tucker HN, editors. Energy Metabolism: Tissue determinants and Cellular Corollaries. New York: Raven Press. 1992.
7. Bauer JM, Vogl T, Wicklein S, Trögner J, Mühlberg W, Sieber CC. Comparison of Mini Nutritional Assessment, Subjective Global Assessment and Nutritional Risk Screening (NRS 2002) for Nutritional Screening and Assessment in Geriatric Hospital Patients. Z Gerontol Geriatr. 2005;38(5):322-7.
8. Cohendy R, Rubenstein LZ, Eledjam JJ. The Mini Nutritional Assessment-short- form for preoperative nutritional evaluation of elderly patients. Aging (Milano). 2001;13(4):293-7.
9. Atalay BG, Yagmur C, Nursal TZ, Atalay H, Noyan T. Use of Subjective Global Assessment and Clinical Outcomes in Critically III Geriatric Patients Receiving Nutrition Support. J Parenter Enteral Nutr. 2008; 32(4):454-9.
10. Jeejeebhoy KN, Keller H, Gramlich L, Allard JP, Laporte M, Duerksen DR, et al. Nutritional assessment: comparison of clinical assessment and objective variables for the prediction of length of hospital stay and readmission. Am J ClinNutr. 2015; 101(5): 956–65.
11. Cereceda FC, Gonzalez I, Antolin JFM, Garcia FP, Tarrazo ER, Cuesta BS, et al. Detection of malnutrition on admission to hospital. Nutr Hosp. 2003;18(2):95- 100.
12. Correia MI, Caiaffa WT, da Silva AL, Waitzberg DL. Risk Factors for Malnutrition in Patients Undergoing Gastroenterological and Hernia Surgery: An Analysis of 374 Patients. Nutr Hosp. 2001;16(2):59-64.
13. Curtis LJ, Bernier P, Jeejeebhoy K, Allard J, Duerksen D, Gramlich L, et al. Costs of hospital malnutrition. Clin Nutr. 2017; 36(5): 1391–6.
14. Bonnefoy M, Jauffret M, Kostka T, Jusot JF. Usefulness of calf circumference measurement in assessing the nutritional state of hospitalizad elderly people. Gerontology. 2002;48(3):162-9.
15. McClave S, Snider H, Spain D. Preoperative issues in clinical nutrition. Chest. 1999;115( Suppl. 5): S64-70.
16. Cohendy R, Gros T, Arnaud-Battandier F, Tran G, Plaze JM, Eledjam J. Preoperative Nutritional Evaluation of Elderly Patients: The Mini Nutritional Assessment as a Practical Tool Clin Nutr. 1999;18(6):345-8.
17. Visvanathan R. Under-nutrition in older people: a serious and growing global problem. J Postgrad Med. 2003; 49(4): 352-60.
18. Guigoz Y, Lauque S, Vellas BJ. Identifying the elderly at risk for malnutrition: The Mini Nutritional Assessment. Clin Geriatr Med. 2002; 18:737-57.
19. Başıbüyük G, Ayremlou P, Saeidlou SN, Çınar Z, Ay F, Bektaş Y, et al. Evaluation of Malnutrition among Elderly People Living in Nursing Homes by Mini Nutritional Assessment Short Form (MNA-SF) in Turkey. Maedica (Buchar). 2019; 14(1): 38– 44.
20. Saka B, Özturk GB, Uzun S, Erten N, Genç S, Karan MA, et al. Nutritional risk in hospitalized patients: impact of nutritional status on serum prealbumin. Rev Nutr Campinas. 2011;24(1):89-98.
21. Mc Whirter JP, Pennington CR. Incidence and Recognition of Malnutrition in Hospital. BMJ. 1994;308(6934):945-8.
22. Nuttall FQ. Body Mass Index: Obesity, BMI, and Health: A Critical Review. Nutr Today. 2015; 50(3): 117–28.
23. Bharadwaj S, Ginoya S, Tandon P, Gohel TD, Guirguis J, Vallabh H, et al. Malnutrition: laboratory markers vs nutritional assessment. Gastroenterol Rep (Oxford). 2016; 4(4): 272–80.
24. Sungurtekin H, Sungurtekin U, Hanci V, Erdem E. Comparison of Two Nutrition Assessment Techniques in Hospitalized Patients. Nutrition. 2004; 20(5):428-32.
25. Weimann A, Braga M, Carli F, Higashiguchi T, Hübner M, Klek, et al. ESPEN guideline: clinical nutrition in surgery. Clini Nutr. 2017; 36(3): 623– 50.
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Hakan Mustafa Köksal, Demet Güler Yılmazer, Mustafa Fevzi Celayir. Assessment of nutritional status and malnutrition risk with different methods in surgical patients. Ann Clin Anal Med 2020;11(5):462-466
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Pediatric firearm injuries: A 5 year single-center experience
Güleser Akpınar, Mehmet Cihat Demir
Department of Emergency Medicine, Düzce University, School of Medicine, Düzce, Turkey
DOI: 10.4328/ACAM.20249 Received: 2020-07-01 Accepted: 2020-07-03 Published Online: 2020-07-06 Printed: 2020-09-01 Ann Clin Anal Med 2020;11(5):453-456
Corresponding Author: Güleser Akpınar, Department of Emergency Medicine, Düzce University, School of Medicine, Konuralp campus, 81620, Düzce, Turkey. E-mail: guleserakpinarduman@gmail.com GSM: +90 505 2655516 Corresponding Author ORCID ID: https://orcid.org/0000-0001-8559-5098
Aim: Firearm-related injuries are causes of severe morbidity and mortality among pediatric injuries. An average number of pediatric firearm violence incidents for the USA is about 20 000 annually. In this study, we aimed to evaluate firearm injuries in the pediatric population. We aimed to contribute to national data on firearm violence characteristics.
Material and Method: In total, eleven patients admitted to the emergency department during a 5-year period with firearm injury were evaluated. The Glasgow Coma Scale (GCS), Injury Severity Score (ISS), injured body part, consulting knowledge, hospital stay duration, and the healing and mortality rates of the patients were described.
Results: The majority of the victims were male (n=8, 72.7%), the average age was 12.7 years, the average GC and IS scores at the presentation were 14.6 and 27.45, respectively. The cause of rime was not reported in a significant number of the cases (n8, 72.7%), and extremities were the most wounded area. No mortality was reported in the study.
Discussion: Firearm injuries are one of the common medicolegal issues. Because of violence in society, children may frequently be subjected to firearm injuries during incidents of crossfire, peer violence, and family conflicts. To date, there is limited information on short-term clinical outcomes and resource utilization in pediatric patients who sustain a firearm injury.
Firearm-related injury is a life-threatening emergency that contributes to 0.3% of the total pediatric mortality in childhood for our country. Evaluation of firearm violence characteristics will lead to a better understanding of the incidences and will aid in establishing preventive policies.
Keywords: Emergency; Firearm injury; Violence; Childhood
Introduction
Firearm injuries are an important public health problem, contributing substantially to premature death and disability of children. Understanding their nature and impact is the first step toward prevention [1].
Homicides, suicides, and accidental deaths that involve firearms are more common in the United States of America (USA) than in other high-income countries. The incidence of firearm mortality in children continues to increase in the USA [2-3].
Pediatric firearm injuries provide information about children and their environment, access to weapons, neglect, or exposure to violence [4-5].
Firearm injury is also one of the severe causes of death in children and adolescents in our country. In Turkey, 0.3% of the deaths have occurred due to firearms; this rate is similar to the rates in other countries and is a significant public health problem for our country [6].
We aimed to identify the reasons and the frequency of pediatric firearm injuries in our region, since firearm injuries have preventable factors such as access to weapons, seeing or presenting them as toys and family recklessness.
Material and Methods
The study data were obtained with a retrospective scan of data collected from the hospital information processing system and archive records of pediatric patients. The patients involved in the study had presented to the Emergency Medicine Clinic of the tertiary hospital of Düzce University between 01/01/2015- 31/01/2019 with a firearm injury.
Patients under the age of 18 with firearm injuries were included in the study, and adult patients and patients with missing data were excluded from the study. In the patient files, age, gender, injured body area, the department consulted, the department hospitalized in, the length of hospital stay, the ISS scores, permanent sequelae, and the mortality were recorded. Information regarding the patients’ consultation, hospitalization, and referral were also evaluated.
When defining the firearm entry zone, the patient’s body was divided into six regions as the head, neck, thorax, abdomen, upper extremity, and the lower extremity.
Ethics committee approval was obtained from the Düzce University Ethics Committee on 2.3.2020 with the number 202038.
Statistical data analysis:
Data analysis was carried out using the Statistical Package for Social Sciences (SPSS, version 24.0) software. The data were expressed as percentages, mean ± standard deviation (SD), and median values. Descriptive statistics were used.
Results
A total of 11 cases were evaluated in the study. The number of male patients with a firearm injury was higher than the number of girls: 8/3 patients, respectively. The average age of the patients was identified as 12.73 + 3.2 years. The demographic characteristics and the initial presentation of clinical scores (GCS, ISS) of the patients who had presented with firearm injuries have been presented in detail in Table 1. The length of hospital stay was evaluated in hours.
Cases with a firearm injury were evaluated according to the reason for the incident. Patients were also grouped according to the region of the major injury for evaluation. Detailed information related to the patients’ injury sites and the reason for the incident have been presented in Table 2.
All patients who had presented with a firearm injury had undergone consultative evaluation. At least one discipline had been required for consultation of the patients (for one patient: ear, nose, and throat diseases), and most commonly, the pediatric surgery department had been consulted (for five patients). Four patients had multiple traumas, one patient had pneumothorax + hematoma, two patients had abdominal trauma + hemothorax, and one patient had nasal trauma + abdominal trauma.
Detailed information about the patients’ hospitalization or discharge after the diagnosis and evaluation in the emergency department and post-discharge follow-ups and diseases are presented in Table 3.
Discussion
Firearm injuries are one of the common medicolegal issues. Because of violence in society, children may frequently be subjected to firearm injuries during incidents of crossfire, peer violence, and family conflicts.
For years, firearms have been an essential factor in attacks, crimes, and murders involving young men [7]. In the study conducted by Ashley E. Wolf et al., it was identified that firearm injuries were inflicted by adolescent males between the ages of 15-17 (74.8%) [8]. In our study, the average age of the cases was determined as 12.7 years, and our male to female ratio was 3:1. The results of our study support the literature.
In case of firearm injuries, thoracic and abdominal injuries are observed in 6-42% of cases [9]. In general, many thoracic injuries may be observed and can be treated non-operatively by placing the chest tube [10].
In our study, 27.2% (n=3) of the cases had a thoracic injury, and 27.2% had an abdominal injury. In one patient, the foreign body (bullet) was detected between the lower edge of the thoracic vertebra and the aorta on the tomography scan (Figure 1). In this patient, aortic injury, mediastinal hematoma, and subsequent hemothorax were considered. The patient was deemed suitable for referral by an air ambulance due to the need for endovascular surgery. In such injuries, the benefit of air transport for survival cannot be overlooked, and it should be considered at the moment when it becomes apparent that the institution’s facilities are not sufficient. A chest tube was placed in one patient. Since extremity injuries were the most common, the most frequently consulted department was the orthopedics department (36.4%).
Several scoring systems have been developed over the past few decades to assess the severity of trauma and predict patient mortality and morbidity. ISS is one of the most frequently used scoring systems [11]. It has been reported that the morbidity and mortality rates of firearm injuries range between 3-31.4% and 7-46%, respectively [12]. Although there is no particular value for the ISS score, it has been reported that the predictability of mortality and morbidity increases as the value increases. It has been found that an ISS score of over 25 is directly related to mortality [13]. The most critical factors for mortality are an accompanying picture of shock, multiple injured organs, multiple blood transfusions, accompanying thoracic trauma, and the time needed to reach the hospital. In our study, despite the high ISS score value, we had no fatal cases. The reason for our low mortality rates may be the small number of cases in the study and the transfer of patients to the hospital in a short time. Further studies are needed to develop the approach and care of trauma cases and to predict the probable outcomes. Our permanent sequelae rate was determined as 36.4%.
Pediatric firearm injuries and deaths due to the injuries are a significant public health problem and cause early death, illness, and disability in children every year. Understanding the nature of firearm violence against children is an essential step. Finding ways to prevent such injuries and providing safe environment for all children will continue to be one of our top priorities.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with
the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
1. Katherine AF, Linda LD, Tadesse H, Carmen G, Sarah B. Childhood Firearm Injuries in the United States. Pediatrics.2017; 140(1):e20163486
2. Down MD, Sege RD. Injury, Violence and Poison Prevention Council Executive Committee, American Academy of Pediatrics. Firearm-related injuries affecting the pediatric population. Pediatrics. 2012:130(5):e1416-23.
3. Cunningham RM, Walton MA, Carter PM. The Major Causes of Death in Children and Adolescents in the United States. N Engl J Med. 2018;379(25):2468.
4. James SD, Diego MC, Carl IS, Perez EA, Neville HL, Sola JE. Twenty years of pediatric gunshot wounds: an urban trauma center’s experience. J Surg Res.2013;184(1):556-60.
5. Demir ÖF, Aydin K, Turan F, Yurtseven A, Erbil B, Gülalp B. Analysis of pediatric forensic cases presented to emergency department. Turk Pediatri Ars. 2013;48(3):235-40.
6. Kır MZ, Ketenci HC, Basbulut AZ, Ozsoy S. Evaluation of firearm-related deaths in Erzurum. J For Med. 2012;1:27-37.
7. Kalesan B, Vyliparambil MA, Bogue E, Villarreal DM, Vasan S, Fagan J C, et al. Firearm Injury Research Group. Race and ethnicity, neighborhood poverty and pediatric firearm hospitalizations in the United States. Ann Epidemiol. 2016;26(1):1–6.
8. Ashley EW, Michelle MG, Brianna M, Titus C, Ali RR. Evaluation of Injury Severity and Resource Utilization in Pediatric Firearm and Sharp Force Injuries. JAMA Network Open. 2019;2(10):e1912850. DOI: 10.1001/ jamanetworkopen.2019.12850.
9. Powell BS, Magnotti LJ, Schroeppel TJ, Finnell CW, Savage SA, Fischer PE, et al. Diagnostic laparoscopy for the evaluation of occult diaphragmatic injury following penetrating thoracoabdominal trauma. Injury. 2008;39(5):530-4.
10. Lichte P, Oberbeck R, Binnebösel M, Wildenauer R, Pape H-C, Kobbe P. A civilian perspective on ballistic trauma and gunshot injuries. Scandinavian journal of trauma, resuscitation and emergency medicine. 2010;18(1):35.
11. Koksal O, Ozdemir F, Bulut M, Aydın S, Almacıoglu ML, Ozguc H. Comparison of trauma scoring systems for predicting mortality in firearm injuries. Ulus Travma Acil Cerrahi Derg. 2009; 15(6): 559-64.
12. Tas H, Mesci A, Eryılmaz M, Zeybek N, Peker Y. The affecting factors on the complication ratio in abdominal gunshot wounds. Ulus Travma Acil Cerrahi Derg. 2011; 17(5): 450-4.
13. Iflazoglu N, Ureyen O, Oner OZ, Tusat M, Akcal MA. Complication and risk factors fo rmortality in penetrating abdominal firearm injuries: Analiysis of 120 cases. Int J Clin Exp Med. 2015; 8(4): 6154–62.
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Güleser Akpınar, Mehmet Cihat Demir. Pediatric firearm injuries: A 5 year single- center experience. Ann Clin Anal Med 2020;11(5):453-456
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Comparison of two different surgical treatments of forearm double diaphysis fractures in adolescents
Duran Topak 1, Fatih Doğar 1, Muhammet Yıldız 1, Ökkeş Bilal 1, Özhan Şakı 2, Ersin Ekici 2
1 Department of Orthopaedic and Traumatology, Kahramanmaras Sutcu Imam University Faculty of Medicine, 2 Department of Orthopaedic and Traumatology, Kahramanmaras Necip Fazıl City Hospital, Kahramanmaras, Turkey
DOI: 10.4328/ACAM.20253 Received: 2020-06-18 Accepted: 2020-06-29 Published Online: 2020-07-04 Printed: 2020-09-01 Ann Clin Anal Med 2020;11(5):457-461
Corresponding Author: Duran Topak, Department of Orthopaedic and Traumatology, Kahramanmaras Sutcu Imam University Faculty of Medicine, Kahramanmaras, Turkey. E-mail: drdtopak@gmail.com P: +90 344 300 3331 F: +90 344 300 4045 Corresponding Author ORCID ID: https://orcid.org/0000-0002-1442-3392
Aim: In this study, it was aimed to compare the clinical and radiological results of the two different surgical methods for the treatment of forearm double bone diaphysis fractures in children at early and mid-adolescence (ages 10–16).
Material and Methods: Children aged between 10 and 16 years who underwent surgical treatment for a forearm double bone fracture between the years 2015–2019 were evaluated retrospectively after the approval of the local ethics committee. The patients were separated into two groups: TEN group included 34 patients for whom both bones were fixated with TEN following closed reduction; plate-screw osteosynthesis (PO) group included 18 patients who had fixa- tion with PO following open reduction.
Results: A total of 52 children with forearm double bone diaphysis fracture with the mean age of 12.40±1.79 (10–16) years, 86.5% (n=45) of whom were males and 53.8% (n=28) had left side fracture were followed up for 30.40±14.03 (12–64) months. When the data of both groups were compared, it was observed that average union time was shorter compared with the PO group and the difference was statistically significant (p=0.007). When the functional results and complication rates of the two groups were compared, there was no statistically significant difference found between the two groups (p=0.756 and p=0.052, respectively).
When the number of radiographs of both groups was compared, it was observed that the number of radiographs during the operation, during implant extrac- tion, and total radiography was higher in the TEN group compared with the PO group and that the difference was statistically significant (p=0.000, p=0.002, p=0.000, respectively).
Discussion: TEN after closed reduction can be safely preferred for pre-adolescent period children with adequate remodeling capacity and incomplete skeletal maturity because of its positive outcomes including less operation and hospital stay duration, fast union, better cosmetic results. However, plate-screw fol- lowing open reduction can be preferred for mid-adolescent period children with complete or near-complete skeletal maturity and limited remodeling capacity because of its positive aspects such as rigid fixation, anatomic reduction, and less radiation exposure.
Keywords: Adolescent; Forearm double; Diaphysis fractures
Introduction
Double bone fractures of the forearm constitute 5.4% of all fractures and 30% of upper limb fractures in pediatrics [1, 2]. They are the 2nd most common type of fractures in the adolescent age group [3]. The incidence rate of forearm double bone fractures among children has been increasing in recent years [2].
Approximately 85% of pediatric forearm double bone fractures are treated perfectly by conservative methods, but some children may develop limitations in forearm rotation [4, 5]. However, surgical treatment is needed for patients with fragmented, unstable, irreducible fractures or fractures with an unacceptable angling after reduction, open fractures, and fractures along with soft tissue damage [6-9]. In recent years, despite the lack of evidence guiding optimal surgical methods, there is a tendency toward surgical treatment in pediatric and adolescent forearm double bone fractures [10].
However, the ideal method of fixation in children aged 10–16 years with a double fracture of the forearm is still controversial [2]. Elastic intramedullary nailing technique was first described in the late 1970s and has been successfully applied with little change since then to the present day [10]. TEN is considered to be the ideal treatment for children with incomplete skeletal development due to its many positive aspects, such as less damage to the soft tissue, short operation duration, and fast union duration [11-13]. Perfect results are achieved in pediatric forearm double bone fractures by providing rigid internal fixation after anatomical reduction with plate-screw osteosynthesis (PO) after traditional open reduction [14].
The objective of this study was to compare the clinical and radiological outcomes of treatment of forearm double bone diaphysis fractures via two different types of surgical techniques among early and mid-adolescence children aged 10–16 years.
Material and Methods
Children aged 10-16 years who underwent surgical treatment for a double bone forearm fractures between the years 2015– 2019 at our clinic were evaluated retrospectively after the approval of the local ethics committee (Session: 2020/07, Date: April 15, 2020, Decision no: 11).
Patients aged 10–16 years who had surgical treatment performed due to forearm double bone fracture, who had type 1 open fracture, fractures that were 5 cm or farther from both joints (wrist and elbow), for whom both fractures were fixed with TEN or plate-screw, who had arterial injury without nerve injury, who had a primary repair performed, and who had at least 12 months of the follow-up period were included in the study. Fracture of the upper extremities on the same side, open fractures of type 2 or type 3, compartments opened due to fasciotomy, pathological fractures, nerve injuries, concomitant vital organ injury, complex special fractures (such as Galeazzi and Monteggia fractures), fractures closer than 5 cm to the joint, fractures in which radius and ulna were each fixed with different implants were excluded from the study.
Fifty-two patients meeting the criteria were included in the study and their files were examined retrospectively. Patients were separated into two groups as follows: TEN group with 34 patients in whom both bones were fixed with TEN after closed reduction; PO group with 18 patients in whom the bones were fixed with PO after closed reduction.
Later, age, gender, direction, fracture etiology, surgery indication, operation indication, operation durations, number of radioscopy scans (fracture operation, implant extraction operation, and total operation), time of implant removal, complications, hospitalization durations, and follow-up durations were evaluated from the patient files. Union time and angling amount on the fracture line were recorded from the radiographic examinations of the patients. In the final follow- up of the patients, functional and cosmetic evaluations were carried out according to the criteria defined by Price et al. [15]. To determine the time of union, anteroposterior and side radiographs were used, three cortex continuity and absence of pain in the fracture line were evaluated as a union (Figures 1, 2). The determination of the number of radiographs was determined as the total number (per unit) of imaging during the operation.
Statistical Analysis
IBM SPSS 20.0 (IBM, Armonk, NY, USA) package program was used to analyze the data obtained from patient files. Categorical variables were defined as frequency (n, %), whereas quantitative data were defined as (mean±SD). The Kolmogorov–Smirnov and the Shapiro–Wilk tests showed that the two groups did not match the normal distribution. The chi-squared (x2) test was used in the comparison of the categorical variables of two independent groups and the Mann–Whitney U test from non- parametric tests was used to evaluate the quantitative data. P<0.05 was considered statistically significant.
Results
A total of 52 children with forearm double bone diaphysis fracture with the mean age of 12.40±1.79 (10–16) years, 86.5% (n=45) of whom were males and 53.8% (n=28) had left side fracture, were followed up for 30.40±14.03 (12–64) months. When the etiological factors of the cases were evaluated, it was observed that the fractures occurred most commonly as a result of falling in the house (n=15), sports injuries (n=15), and playgrounds accidents (n=15). Most common surgery indications were irreducible fracture (n=15), loss of reduction (n=15), and unacceptable post-reduction position (n=14), respectively. The demographic data of the cases by groups are shown in Table 1. When the data of both groups were compared, it was observed that the average union time was shorter compared to the PO group, and the difference was statistically significant (TEN: 8.14±2.74, PO: 11.22±4.41, p=0.007). When the functional results and complication rates of the two groups were compared, no statistically significant difference was observed between the groups (p=0.756 and p=0.052, respectively). The duration of hospital stay in the TEN group was shorter compared with the other group (p=0.000).
Fracture reduction, implant extraction, and total operation durations were shorter in the TEN group and the difference was found to be statistically significant (p=0.000, p=0.000, and p=0.000, respectively). When the number of radiographs of both groups was compared, it was observed that the number during the operation, during implant extraction and total radiography images was higher in the TEN group compared with the PO group and that the difference was statistically significant (p=0.000, p=0.002, and p=0.000, respectively). A comparison of groups is shown in Table 2.
Discussion
The aim of this study was to compare the treatment results of 10–16 years old patients who had PO performed after TEN and open reduction in forearm diaphyseal double bone fractures. When the functional outcomes and complication rates were compared, it could be observed that both treatment options can be successfully performed in this age group. But the preferred method depends on the experience and preference of the surgeon because of the lack of scientific evidence.
Surgeons often prefer fixation with titanium elastic nails after closed reduction for young children with incomplete skeletal maturity and adequate remodeling capacity, whereas they prefer PO after open reduction for older children with complete or almost complete skeletal maturity and decreased remodeling capacity. This is the cause of the age difference between the two groups in our study.
TEN is defined as a simple and easy-to-apply technique that does not disrupt fracture biology as it is applied with mini lacerations, without periosteal stripping, by causing less soft tissue damage and frequently applied closed. Therefore, better cosmetic results, rapid union, short operation time, fewer complications, and shorter hospitalization duration are its main advantages [6, 7, 9, 10, 15]. In our study, hospital stay duration was found to be significantly shorter in the TEN group. This may be because when it is applied without the need for soft tissue dissection, post-op pain management becomes easy.
PO after open reduction is a surgical technique that allows early and unprotected movement, as it provides rigid fixation after anatomical reduction. As it is performed with larger incisions and by periosteal stripping, it forms longer incision scars and more soft tissue damage. In addition to the good functional result, long operation duration has been reported [4, 11, 14, 16]. As most of the comparative studies include all pediatric ages, a clear evaluation is not possible. However, a few studies compare children aged 10 years and older.
When TEN application and PO due to forearm double fractures were compared among children in the 10–16 age group, it was reported that although the surgical techniques and fixation options are different, functional results and complication rates are similar [16-21]. In our study, functional results in both groups were similar, and although the complications observed were different, complication rates were the same.
In children aged 10–16 years with double bone forearm fractures, the union time in the TEN group was observed to be longer than in the children undergoing open reduction [21, 22]. However, most studies reported that there was no difference between the two groups in terms of union times [19, 23, 24]. In our study, union time was found to be shorter in the group in which TEN was applied. This could be due to the fact that all patients who were applied TEN also had intramedullary fixation following closed reduction or that they had a lower average age.
In comparative studies, it was noted that the duration of the operation was significantly shorter in the TEN group [19-24]. In patients who were performed TEN, fracture reduction, implant removal and total operation times were found to be significantly shorter compared with the PO group. This is because of the ease of application of the implant.
In their comparative study, Zheng et al. reported that the number of radiography scans in the TEN group was higher than in the PO group [21]. In this study, it can be observed that the number of fracture reduction, implant extraction, and total radiography scans was higher in the TEN group. A large number of radiography scans were the result of insisting on closed reduction and the need for radiography because of the nature of the surgical technique.
In our study, the difference in the average age of the two groups and the retrospective planning of our study were considered the most important limitations. The surgery and the follow-up of the patients conducted by three different surgeons can affect the outcome.
Conclusion
In conclusion, there is no complete consensus among surgeons for the surgical treatment of double bone diaphyseal forearm fractures in adolescence. The applied technique depends on the experience of the surgeon because of the lack of scientific evidence.
TEN after closed reduction can be safely preferred for pre- adolescent children with adequate remodeling capacity and incomplete skeletal maturity because of its positive outcomes such as less operation and hospital stay duration, fast union, and better cosmetic results. However, plate-screw following open reduction can be preferred for mid-adolescent children with complete or near-complete skeletal maturity and limited remodeling capacity because of its positive aspects such as rigid fixation, anatomic reduction, and less radiation exposure. It should be noted that there is a need for randomized prospective studies with a sufficiently large scale to allow the separate comparison of pre-adolescent and mid-adolescent age groups for definitive results.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
1. Rennie L, Court-Brown CM, Mok JY, Beattie TF. The epidemiology of fracture in children. Injury. 2007;38(8):913-22.
2. Sinikumpu JJ, Lautamo A, Pokka T, Serlo W. The increasing incidence of paediatric diaphyseal both-bone forearm fractures and their internal fixation during the last decade. Injury. 2012;43(3):362-6.
3. Cheng JC, Ng BK, Ying SY, Lam PK. A 10-year study of the changes in the pattern and treatment of 6,493 fractures. J Pediatr Orthop. 1999;19(3):344-50.
4. Cai L, Wang J, Du S, Zhu S, Wang T, Lu D, et al. Comparison of hybrid fixation to dual plating for both-bone forearm fractures in older children. Am J Ther. 2016;23(6):e1391-6.
5. Price CT, Scott DS, Kurzner ME, Flynn JC. Malunited forearm fractures in children. J Pediatr Orthop. 1990;10(6):705-12.
6. Garg NK, Ballal MS, Malek IA, Webster RA, Bruce CE. Use of elastic stable intramedullary nailing for treating unstable forearm fractures in children. J Trauma. 2008; 65(1):109-15.
7. Sun YQ, Penna J, Haralabatos SS, Carrion WV. Intramedullary fixation of pediatric forearm diaphyseal fractures. Am J Orthop. 2001; 30(1):67-70.
8. Cullen MC, Roy DR, Giza E, Crawford AH. Complications of intramedullary fixation of pediatric forearm fractures. J Pediatr Orthop. 1998;18(1):14-21.
9. Kelly BA, Shore BJ, Bae DS, Hedequist DJ, Glotzbecker MP. Pediatric forearm fractures with in situ intramedullary implants. J Child Orthop. 2016;10(4):321-7.
10. Parikh SN, Jain VV, Denning J, Tamai J, Mehlman CT, McCarthy JJ, et al. Complications of elastic stable intramedullary nailing in pediatric fracture management: AAOS Exhibit Selection. J Bone Joint Surg Am. 2012;94(24):e184.
11. Flynn JM, Jones KJ, Garner MR, Goebel J. Eleven years’ experience in the operative management of pediatric forearm fractures. J Pediatr Orthop. 2010;30(4):313-19.
12. Altay M, Aktekin CN, Ozkurt B, Birinci B, Ozturk AM, Tabak AY. Intramedullary wire fixation for unstable forearm fractures in children. Injury. 2006;37:966-73.
13. Kang SN, Mangwani J, Ramachandran M, Paterson JM, Barry M. Elastic intramedullary nailing of paediatric fractures of the forearm: a decade of experience in a teaching hospital in the United Kingdom. J Bone Joint Surg Br. 2011;93(2):262-5.
14. Ortega R, Loder RT, Louis DS. Open reduction and internal fixation of forearm fractures in children. J Pediatr Orthop. 1996;16(5):651-4.
15. Baldwin K, Morrison MJ III, Tomlinson LA, Ramirez R, Flynn JM. Both bone forearm fractures in children and adolescents, which fixation strategy is superior – plates or nails? A systematic review and meta-analysis of observational studies. J Orthop Trauma. 2014;28(1):e8-14.
16. Lee Pace J. Pediatric and adolescent forearm fractures: Current controversies and treatment recommendations. J Am Acad Orthop Surg. 2016;24(11):780-8.
17. Smith VA, Goodman HJ, Strongwater AS, Smith B. Treatment of pediatric both-bone forearm fractures-a comparison of operative techniques. J Pediatr Orthop. 2005;25(3):309-13.
18. Van der Reis WL, Otsuka NY, Moroz P, Mah J. Intramedullary nailing versus plate fixation for unstable forearm fractures in children. J Pediatr Orthop. 1998;18(1):9-13.
19. Reinhardt KR, Feldman DS, Green DW, Sala DA, Widmann RF, Scher DM. Comparison of intramedullary nailing to plating for both-bone forearm fractures in older children. J Pediatr Orthop. 2008;28(4):403-9.
20. Fernandez FF, Egenolf M, Carsten C, Holz F, Schneider S, Wentzensen A. Unstable diaphyseal fractures of both bones of the forearm in children: plate fixation versus intramedullary nailing. Injury. 2005;36(10):1210-16.
21. Zheng W, Tao Z, Chen C, Zhang C, Zhang H, Feng Z, et al. Comparison of three surgical fixation methods for dual-bone forearm fractures in older children: A retrospective cohort study. Int J Surg. 2018;51:10-6.
22. Freese KP, Faulk LW, Palmer C, Baschal RM, Sibbel SE. A comparison of fixation methods in adolescent patients with diaphyseal forearm fractures. Injury. 2018;49(11):2053-7.
23. Shah AS, Lesniak BP, Wolter TD, Caird MS, Farley FA, Vander Have KL. Stabilization of adolescent both-bone forearm fractures: a comparison of intramedullary nailing versus open reduction and internal fixation. J Orthop Trauma. 2010;24(7):440-7.
24. Kose O, Deniz G, Yanik S, Gungor M, Islam NC. Open intramedullary Kirschner wire versus screw and plate fixation for unstable forearm fractures in children. J Orthop Surg (Hong Kong). 2008;16(2):165-9.
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Duran Topak, Fatih Doğar, Muhammet Yıldız, Ökkeş Bilal, Özhan Şakı, Ersin Ekici. Comparison of two different surgical treatments of forearm double diaphysis fractures in adolescents. Ann Clin Anal Med 2020;11(5):457-461
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Nighttime eating syndrome and its relationship with impulsivity in major depressive disorder
Oğuzhan Kılınçel 1, Rukiye Ay 2
1 Department of Psychiatry, SakaryaYenikent State Hospital, Sakarya, 2 Department of Psychiatry, Bursa Training and Research Hospital, Bursa, Turkey
DOI: 10.4328/ACAM.20296 Received: 2020-07-28 Accepted: 2020-08-17 Published Online: 2020-08-20 Printed: 2020-09-01 Ann Clin Anal Med 2020;11(5):448-452
Corresponding Author: Oğuzhan Kılınçel, SakaryaYenikent State Hospital, Department of Psychiatry, Sakarya, Turkey. E-mail: okilincel@gmail.com GSM: +90 505 296 24 32 Corresponding Author ORCID ID: https://orcid.org/0000-0003-2988-4631
Aim: This study aims to investigate the frequency, clinical features, and role of Nighttime Eating Syndrome (NES) in patients with major depressive disorder (MDD).
Material and Methods: Patients experiencing depression who applied to the psychiatry outpatient clinic were included in this study. All participants completed structured questionnaires, including socio-demographic data form, Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Night Eating Diagnostic Questionnaire (NEDQ), and Barratt Impulsiveness Scale (BIS).
Results: A total of 142 patients, consisting of 112 (78.9%) women and 30 men (21.1%), between ages 18-64 years were included in the study. Among patients with MDD, NES prevalence was 26.1%. No statistically significant correlation was found between NEDQ score and age, BMI, or disease onset age (p>0.05). There was a statistically significant positive correlation between NEDQ scores and BDI (r: 0.448, p<0.001), BAI (r: 0.351, p<0.001), BIS-total (r: 0.473, p<0.001), BIS-Attention (r: 0.351, p <0.001), BIS-Motor (r: 0.351, p<0.001) and BIS-Nonplanning (r: 0.451, p <0.001) scores. The number of smokers was statistically significantly higher among patients with NEDQ>30 compared to those with NEDQ<30 (p<0.001). BDI (p=0.027), BIS-Total (p<0.001), BIS-Attention (p=0.013), BIS-Motor (p=0.002), and BIS-Nonplanning scores were significantly higher (p<0.001) among patients with NEDQ>30 compared to patients with NEDQ<30.
Discussion: NES is commonly encountered in psychiatric outpatient clinics and is associated with major depression, impulse control disorder, and nicotine ad- diction. In addition, it could be said that impulsivity is more associated with NES than depression.
Keywords: Depressive Disorder; Eating Syndrome; Impulsive Behavior
Introduction
Night Eating Syndrome (NES) is classified under “Other Specified Eating or Feeding Disorders” in DSM-V. NES is an eating disorder characterized by a delayed circadian pattern of food intake [1]. Allison et al. used a verified measurement tool to demonstrate the association between NES and evening hyperphagia, morning anorexia, and mental health and sleep disorders [1]. It is stated that NES may be clinically significant due to its relationship with obesity and its prevalence may increase with bodyweight [2]. It has been shown that obese individuals with NES had significantly more depressive symptoms and significantly lower self-respect compared to other obese individuals [2].
There are a very limited number of studies related to NES in psychiatric outpatients. NES prevalence has been reported as 12.4% among psychiatric outpatients, and 25% among a sampling consisting of overweight or obese patients with schizophrenia, bipolar disorder, and depression [3, 4]. Another study reported NES prevalence as 35.2% among major depressive patients and 19.2% among healthy participants [5]. While studies indicate that NES may be associated with psychiatric illness, especially depression, our knowledge on this subject is rather limited.
Impulsivity, with stable and similar components, is a complex multi-dimensional attribute that can lead to negative real- life consequences such as poor decision-making, suicide, and aggression, and has been shown to be associated with characteristics of major depression patients in varying degrees [6]. Impulsivity has been associated with bipolar disorder (BD) and major depressive disorder (MDD). It was shown to be significantly higher in euthymic BD, both during and between manic attacks and depressive BD, and in unipolar MD patients compared to healthy controls [7-8].
This study aims to investigate the frequency and clinical features of NES in MDD patients. We also aimed to determine whether or not impulsivity plays a mediating role in the development of NES, which is often accompanied by MDD.
Material and Methods
Study Sample
This cross-sectional study was conducted on a sample of patients consisting of MDD patients who applied to the Sakarya Yenikent State Hospital. Minitab 17.0 program was used to determine the sample size. The sample size was calculated according to similar studies (11.0%) based on 5% type I error and 95% working power, and the number of patients to be included in the study was found as 128. The research study was approved by the Sakarya University Non-Interventional Applications Ethics Committee (Approval No. 31.03.2020- 715224473 / 050.01.04 / 166). Written informed consent was obtained from all participants of the study.
The first seven items of the questionnaire were related to sociodemographic characteristics, including age, gender, number of children, place of residence, employment status, age at disease onset, number of hospitalizations, number of relapses, suicide attempts, family history of psychiatric disease, smoking, alcohol, substance abuse, and body mass index (BMI). Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Night Eating Diagnostic Questionnaire (NEDQ), and Barratt Impulsiveness Scale (BIS) were used for the rest of the questionnaire.
Inclusion criteria included diagnosis of MDD, and age between 18 and 65 years. Exclusion criteria included the presence of neurologic disease that may affect cognitive functions, cortisone use, additional eating disorder, additional psychiatric comorbidity, history of substance abuse, and benzodiazepine use.
Beck Depression Inventory (BDI): This self-report scale was developed by Beck et al. in 1961 to measure the changes in severity and level of depressive symptoms in adults [9]. Turkish validity-reliability study was conducted by Hisli et al. in 1988 [10]. The scale consists of 21 items, each item is a self-assessment statement scored from 0-3. Researchers reported that the inventory included two sub-factors, somatic and cognitive.
Beck Anxiety Inventory (BAI): This inventory was developed by Beck et al. in 1988 to measure anxiety symptoms [11]. Individuals are asked to mark the extent to which they have been affected by the anxiety symptoms listed in the inventory over the past week. The inventory is a four-point Likert scale consisting of 21 items (0 indicating “never” and the other three corresponding to severity). Turkish validity-reliability study of the scale was conducted by Ulusoy et al. [12]. The minimum score possible is 0 and the maximum score is 63. Cronbach’s alpha value was found to be 0.89.
Night Eating Diagnostic Questionnaire (NEDQ): This 16-item measurement tool is used to screen NES symptoms related to nighttime eating, evening hyperphagia, morning anorexia, and mental health and sleep disorders [13]. The first nine questions of the questionnaire were completed by all participants. Participants who did not wake up at night or eat at night were instructed not to continue answering the rest of the questions. The total score ranges between 0-52 and ≥25, indicating that the patient has NES. Turkish validity-reliability study of the scale was conducted by Atasoy et al [14]. A higher score indicates increased symptoms of NES, while a score of >30 indicates the presence of NES.
Barratt Impulsiveness Scale-11-Short Form (BIS-11-SF): BIS- 11-SF is a 15-item self-reporting questionnaire designed to measure impulsivity. It is comprised of three main factors: Attention Impulsivity (A), Motor Impulsivity (M), and Nonplanning (NP) [15]. In this study, the Turkish adaptation of BIS-11-SF was used to evaluate impulsivity [16].
Statistical Analysis
SPSS (Statistical Package for Social Sciences) program version 15.0 was used for statistical analysis of the data obtained from the study. Descriptive statistical methods (mean, standard deviation, median, minimum, maximum, frequency, percentage), as well as the Chi-square and Fisher’s Exact test for categorical variables and the Mann Whitney-U test for continuous variables, were applied for comparisons between the two groups. Spearman correlation test was used for correlation analysis. The results were evaluated within a 95% confidence interval with a level of significance set to p<0.05.
Results
A total of 142 patients, including 112 (78.9%) women and 30 men (21.1%), aged between 18-64 years were included in the study. The mean age of the patients was 33.16 ± 10.84 (median 33) years and 57% (n:81) of the patients were married. Education levels were as follows: primary school in 26.1% (n: 37), high school in 29.6% (n: 42), associate degree in 5.6% (n: 8), and undergraduate in 38.7% (n: 55). In total, 40.1% (n: 57) of the participants were unemployed, 16.9% (n: 24) were students, and 43% (n: 61) were employed. Among the patients, 43% (n: 61) were smokers, and 19.7% (n: 28) drank alcohol. Mean BMI was 24.57 ± 4.20 (range: 15-40.2) kg/m2. Age at the time of disease onset ranged between 10 and 61 years of age, and the mean age at onset was 28.56 ± 9.37 (median: 26) years. A history of suicide attempts was present in 7.7% (n: 11) of the patients. The medication was used by 45.1% (n: 64) of the patients, the most common being SSRI (Table 1).
The mean BDI score was 23.26 ± 12.26 (median:23, range:1-58), the mean BAI score was 23.67 ± 15.32 (median: 21, range: 0-58), the mean BIS-Total score was 66 ± 12.78 (median: 65, range: 35-104), the mean BIS-A score was 17.90 ± 4.11 (median: 18, range: 8-27), the mean BIS-M score was 20.93 ± 5.55 (median: 20, range: 10-41), the mean BIS-NP was 27.27 ± 6.99 (median: 27, range: 12-74), and the mean NEDQ score was 21.38 ± 11.58 (median: 18, range: 4-50).
According to NEDQ scores, 73.9% (n: 105) of the patients were NEDQ<30 and 26.1% (n: 37) were classified as NEDQ>30. There was no statistically significant correlation between NEDQ score and age, BMI, and age of onset of a disease (p>0.05). There was a weak statistically significant positive correlation between NEDQ scores and BDI (p<0.001), BAI (p<0.001), BIS- Total (p<0.001), BIS-Attention (p<0.001), BIS-Motor (p<0.001), and BIS-Nonplanning scores (p<0.001) (Table 2).
There was no statistically significant difference between patients with NEDQ<30 and NEDQ>30 in terms of age, gender, marital status, education level, employment, alcohol use, BMI, disease onset age, suicide attempts, drug use, types of drugs used, or mean BAI score (p>0.05). The number of smokers was statistically significantly higher among patients with NEDQ>30 compared to those with NEDQ<30 (p<0.001). BDI (p=0.027), BIS-Total (p<0.001), BIS-Attention (p=0.013), BIS-Motor (p=0.002), and BIS-Nonplanning scores were significantly higher (p<0.001) among patients with NEDQ>30 compared to patients with NEDQ<30 (Table 3).
There were 54 patients who scored 17 and below on the Beck Depression Scale. BIS-Total, BIS-Attention, BIS-Motor and BIS- Nonplanning scores were significantly higher among those with NEDQ>30 than those who had NEDQ<30 (p<0.001, p=0.024, p=0.007, p=0.002, respectively).
Discussion
In our study, the NES prevalence among patients with MDD was 26.1%. Patients with NES had significantly higher BDI, BAI, BIS total and attention, motor, and non-planning subscores. This indicates that NES is associated with depression, anxiety, and impulsivity. In addition, compared to patients with low NES, patients with high NES scores had significantly higher BDI, BIS total scores and attention, motor, and non-planning subscores, indicating that patients with NES have an increased severity of depression and increased impulsivity. Furthermore, impulsivity was significantly higher in NES patients diagnosed with depressive disorder and with high BDI score. Therefore, it could be said that impulsivity is more associated with NES than depression. There was also an increased rate of smoking among patients with NES.
In our study, the NES prevalence was 26.1% among patients with MDD. The prevalence of NES (26.1%) according to NEDQ cutoff score of 30 was higher in our study compared to the results of the study by Cengiz et al., which found a 19.8% prevalence of an NES among a population of psychiatric patients including 51% of patients with MDD [17]. Lundgren et al. reported NES prevalence of 12.3% in a sample of general psychiatric patients [18]. Another study by Lundgren et al. reported a rate of 40% NES among patients who were diagnosed with any Axis I disorder [19]. In a descriptive study on NES, de Zwaan et al found that 56% of patients had a life-long history of major depressive disorder, which was higher than that seen among the healthy control group [20]. Orhan et al. found a higher rate of NES (35.2%) among outpatients compared to healthy participants (19.2%) [5]. These differences in NES prevalence may be attributed to cultural differences or severity of psychiatric diseases among the study samples.
It is important to identify other risk factors which may affect the development of NES. There are limited data on the relationship between gender and NES. Some authors have found that NES prevalence is comparable between genders [21]. On the other hand, three studies reported that the male gender was a risk factor for NES [5, 22]. Despite the higher number of female patients in our study, no significant relationship was found between gender and NES.
The literature has indicated that high BMI is a risk factor for NES. However, there was no significant difference between our study groups according to BMI. The literature has frequently stated that obesity or higher BMI is associated with NES in the general population [23,24]. In studies on psychiatric patient groups, only one study found higher BMI in the NES group [19]. In a study by Lundgren et al., although the study group was overweight on average (mean BMI=29.1 kg/m2), obese psychiatric patients (BMI ≥30 kg/m2) had five times higher likelihood of meeting NES criteria compared to non-obese patients (BMI 18.5–25.9 kg / m2) [19]. Previous studies have not found a significant difference between psychiatric participants with and without NES according to BMI [5,17,19]. This result may be attributed to the fact that the prevalence of high BMI is higher in psychiatry outpatients compared to normal population samples. Future studies are needed to examine possible changes in all weight ranges in psychiatric outpatients with NES.
Nicotine addiction was more prevalent among the NES group (p=0.001). In contrast, Lundgren et al. reported that 30.6% of patients with NES met the criteria for lifetime substance use disorder compared to 8.3% of patients without NES [18]. Considering the rates of impulse control disorder and nicotine use in the NES group, we believe that the presence of another risky behavior in addition to poor eating habits may contribute to the development of NES.
It is important to investigate the effects of drugs on NES. It was reported that the likelihood of being prescribed multiple atypical antipsychotics was higher among NES patients (38.8%) compared to non-NES patients (30.8%) [18]. We did not observe a significant relationship between drug use (antipsychotics, antidepressants, mood regulators) and NES among our study group. We believe that further studies on NES groups that specifically investigate the effect of atypical SSRIs and SNRIs, and that consider the relationship between these drugs and high body mass index are needed.
In our study, impulse control disorders were found among patients with NES. As the NEDQ score increased, the impulsivity total score and subscores were observed to significantly increase. Saraçlı et al. conducted a study on a psychiatric population and found that the rate of impulse control disorders in the NES group was 7.2%, and stated that impulsivity was positively correlated with NES [21]. Tekin et al. investigated the relationship between eating addiction and impulsivity in young adults and stated that impulsivity was a risk factor in patients with NES [25]. The same study found that individuals with NES had higher impulsivity total scores and motor subscores compared to individuals without NES. In our study, NES patients were found to have significantly higher impulsivity total scores, and impulsivity attention, motor, and non-planning subscores. Our study had various limitations. The lack of healthy control subjects was an important limitation. We did not use SCID to validate their MDD diagnoses and exclude other psychiatric comorbidities. Another limitation that the distribution of gender (women ratio is too high), all of the scales are self- reported. This study sample may contain other factors that may contribute to NES prevalence such as daily stress, sleeping disorder, and cultural differences. However, our sample size, as well as the evaluation of the relationship between NES and impulsivity as well as depressive symptoms distinguishes our study from other studies.
In conclusion, future studies with larger populations are needed to support our findings, to understand why this population is at high risk of developing NES, and to determine the effects of NES on the clinical outcomes of psychiatric patients. In addition, further comprehensive studies investigating psychotherapeutic and psychopharmacologic interventions of impulsive control disorder, which may play a role in the development of NES, to prevent its development and facilitate its treatment are needed.
Acknowledgment
The authors would like to thank the patients of Sakarya Yenikent State Hospital for their participation in the study, and Sarah Isaacs for English grammar revision.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
1. Allison KC, Lundgren JD, O’Reardon JP, Geliebter A, Gluck ME, Vinai P, et al. Proposed diagnostic criteria for night eating syndrome. Int J Eat Disord. 2010;43(3):241-7.
2. O’Reardon JP, Peshek A, Allison KC. Night eating syndrome: diagnosis, epidemiology and management. CNS Drugs. 2005;19(12):997-1008.
3. Arslan FC, Tiryaki A, Aykut DS, Özkorumak E, Ilter ZÇ, Günaydin D. Ağır ruhsal bozukluğu olan kilolu veya obez ayaktan hasta grubunda gece yeme sendromu yaygınlığı (Prevalence of night eating syndrome in the overweight or obese outpatient group with severe mental disorders). Türk Psikiyatri Dergisi/ Turkish Journal of Psychiatry. 2015;26(4):242-8.
4. Kucukgoncu S, Bestepe E. Majör Depresyon ve Anksiyete Bozukluğu Hastalarında Gece Yeme Sendromu (Night Eating Syndrome in Patients with Major Depression and Anxiety Disorder). Archives of Neuropsychiatry/ Noropsikiatri Arsivi. 2014;51(4):368-75.
5. Orhan FO, Ozer UG, Ozer A, Altunoren O, Çelik M, Karaaslan MF. Night eating syndrome among patients with depression. Isr J Psychiatry Relat Sci. 2011;48(3):212-7.
6. Congdon E, Canli T. A neurogenetic approach to impulsivity. J Pers. 2008;76(6):1447-84.
7. Kilinçel O, Kilinçel Ş, Gündüz C, Cangür Ş, Akkaya C. Klozapinin Hızlı Döngülü Bipolar Afektif Bozuklukta Duygudurum Düzenleyicisi Olarak Rolü. Turk Psikiyatri Dergisi. 2019;30(4).
8. Kilinçel Ş, Vural AP, Kilinçel O. Theory of mind deficit in adolescents with major depressive disorder. Anadolu Psikiyatri Dergisi. 2020;21(2):158-64.
9. Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J. An inventory for measuring depression. Arch Gen Psychiatry. 1961;4:561-71.
10. Hisli-Sahin N. Beck Depresyon Envanteri’nin gecerligi uzerine bir calisma. Türk Psikoloji Dergisi. 1988;6(22):118-26.
11. Beck AT, Epstein N, Brown G, Steer RA. An inventory for measuring clinical anxiety: psychometric properties. J Consult Clin Psychol. 1988;56(6):893-7.
12. Ulusoy M, Sahin NH, Erkmen H. The Beck anxiety inventory: psychometric properties. J Cogn Psychother. 1998;12(2):163-72.
13. Allison KC, Lundgren JD, O’Reardon JP, Martino NS, Sarwer DB, Wadden TA, et al. The Night Eating Questionnaire (NEQ): psychometric properties of a measure of severity of the Night Eating Syndrome. Eat Behav. 2008;9(1):62-72.
14. Atasoy N, Saraçlı Ö, Konuk N, Ankaralı H, Güriz SO, Akdemir A, et al. The reliability and validity of Turkish version of The Night Eating Questionnaire in psychiatric outpatient population. Anatolian J Psychiatry. 2014;15(3):238-47.
15. Patton JH, Stanford MS, Barratt ES. Factor structure of the Barratt impulsiveness scale. J Clin Psychol. 1995;51(6):768-74.
16. Tamam L, Gulec H, Karatas G. Short form of Barratt Impulsiveness Scale (BIS- 11-SF) Turkish adaptation study/Barratt Durtusellik Olcegi kisa formu (BIS-11- KF) Turkce uyarlama calismasi. Archives of Neuropsychiatry/Noropsikiatri Arsivi. 2013;50(2):130-5.
17. Cengiz Y TS, Karamustafalıoğlu K, Bakım B, Özçelik B. Prevalence of night eating syndrome and comorbidity with other psychiatric disorders in psychiatric outpatient population. New Symposium. 2011;49(2):83-8.
18. Lundgren JD, Allison KC, Crow S, O’Reardon JP, Berg KC, Galbraith J, et al. Prevalence of the night eating syndrome in a psychiatric population. Am J Psychiatry. 2006;163(1):156-8.
19. Lundgren JD, Rempfer MV, Brown CE, Goetz J, Hamera E. The prevalence of night eating syndrome and binge eating disorder among overweight and obese individuals with serious mental illness. Psychiatry Res. 2010;175(3):233-6.
20. de Zwaan M, Roerig DB, Crosby RD, Karaz S, Mitchell JE. Nighttime eating: a descriptive study. Int J Eat Disord. 2006;39(3):224-32.
21. Saraçlı Ö, Atasoy N, Akdemir A, Güriz O, Konuk N, Sevinçer GM, et al. The prevalence and clinical features of the night eating syndrome in psychiatric out- patient population. Comprehensive Psychiatry. 2015;57:79-84.
22. Grilo CM, Masheb RM. Night-time eating in men and women with binge eating disorder. Behav Res Ther. 2004;42(4):397-407.
23. Cerú-Björk C, Andersson I, Rössner S. Night eating and nocturnal eating—two different or similar syndromes among obese patients? Int J Obes Relat Metab Disord. 2001;25(3):365-72.
24. Gluck ME, Geliebter A, Satov T. Night eating syndrome is associated with depression, low self-esteem, reduced daytime hunger, and less weight loss in obese outpatients. Obes Res. 2001;9(4):264-7.
25. Tekin A, Yetkin A, Gürsoy Ç. Genç erişkinlerde yeme bağımlılığı ile dürtüsellik arasındaki ilişkinin incelenmesi (Investigation of the relationship between food addiction and impulsivity in young adults). Online Türk Sağlık Bilimleri Dergisi/ Online Turkish Journal of Health Sciences. 2018;3(4):171-8.
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Oğuzhan Kılınçel, Rukiye Ay. Nighttime eating syndrome and its relationship with impulsivity in major depressive disorder. Ann Clin Anal Med 2020;11(5):448-452
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Risk factors associated with HCV infection among adults in Damietta Governorate, Egypt
Basem M. M. Salama
Department of Community Medicine, Damietta Faculty of Medicine, Al-Azhar University, Egypt
DOI: 10.4328/ACAM.20149 Received: 2020-03-05 Accepted: 2020-04-06 Published Online: 2020-04-13 Printed: 2020-09-01 Ann Clin Anal Med 2020;11(5):519-522
Corresponding Author: Basem M. M. Salama, Department of Community Medicine, Damietta Faculty of Medicine, Al-Azhar University, 34511, New Damietta, Egypt. E-mail: drbasemsalama@yahoo.com T: 00201027383983 Corresponding Author ORCID ID: https://orcid.org/0000-0001-6639-9673
Aim: Hepatitis C virus (HCV) is a major cause of cirrhosis, liver cancer, and mortality worldwide. Egypt has the highest burden of Hepatitis C in the world. HCV prevalence is directly related to the prevalence of persons who routinely share injection equipment and to the prevalence of unsafe parenteral practices in healthcare settings. The study aimed to identify risk factors associated with HCV infection among adults.
Material and Methods: This case control study nested from a household survey that was conducted to screen for hepatitis B virus and hepatitis C virus was conducted in Damietta Governorate, Egypt. One hundred-fifty cases and controls were randomly selected from those showed positive HCV (278) and 300 controls were randomly selected from those showed negative HCV (2699).
Results: Participants were aged between 20 and 67 years (mean 42.0 +10.6 years). The study revealed a significant difference between case and control group regarding age, residence, education level and marital status (P = 0.001). Case-patients were more likely than controls to have exposure to dental procedure, previous stitches, surgical operation schistosomiasis injection treatment, blood transfusion and intravenous(IV) fluid intake were significantly associated with HCV infection (P < 0.05). Also, unsafe community practices (cupping, acupuncture, shared shaving razor, traditional cauterization, needle or sharp stick and tattooing) were significantly different between HCV-infected patients and controls (P < 0.01).
In multivariable analysis, marital status and rural residence and history of stitches, intravenous fluid, dental procedure, renal dialysis, sharing shaving razor, acupuncture, needle or sharp stick and cupping were associated with higher odds of having HCV.
Discussion: The results of this study showed that exposure to unsafe medical procedures and social practices were risk factors for HCV infection. Promotion of infection control programs in healthcare settings and health education campaigns to increase the awareness and empowerment of the community are strongly recommended.
Keywords: Risk factors; Case; Control; HCV; Infection; Egypt
Introduction
Hepatitis C virus (HCV) infection is a major health problem. It is a liver infection caused by a blood-borne hepatitis C virus (HCV). World Health Organization (“Hepatitis C: fact sheet no. 164. (2017)) reported that 1.75 million new hepatitis C virus (HCV) infections occurred worldwide in 2015, with the highest incidence in the European Region and the Eastern Mediterranean Region.
About 55-85% of HVC infected persons develop chronic infection. About 5-20% of those chronically infected will develop cirrhosis within 20-30 years, and 1% to 5% die from consequences of chronic infection (cirrhosis and hepatocellular carcinoma) [1].
Viral hepatitis is the seventh leading cause of mortality globally. A third of this mortality is attributed to hepatitis C virus (HCV). In the Middle East and North Africa, HCV accounts for two-thirds of viral hepatitis mortality and disability-adjusted life years [2, 3].
World Health Organization (“Hepatitis C: fact sheet no. 164. (2017)) reported that approximately 71 million persons were living with chronic HCV infection in the world, accounting for 1% of the population. The prevalence of HCV infection is more heterogeneously distributed, with differences across and within WHO regions and countries. Spread through breaks in infection control practices or injection drug use may explain this pattern. The highest was in the Eastern Mediterranean Region (2.3%) followed by the European Region (1.5%).
Central Asia and Central Africa are estimated to have high prevalence (> 3.5%); East, South and Southeast Asia, West and East Africa, North Africa and the Middle East, Southern and Tropical Latin America, Caribbean, Australasia, and Eastern Europe are estimated to have moderate prevalence (1.5%-3.5%); whereas Southern Africa, North America, Andean and Central Latin America, Pacific Asia and Western and Central Europe have low prevalence (< 1.5%) [4]. Globally, 80% of all HCV infections occur in 31 countries, with six countries (China, Pakistan, Nigeria, Egypt, India, and Russia) accounting for greater than 50% of all infections [5].
The prevalence of Hepatitis C virus in Egypt is about 10 -15%, which is considered the highest in the world. Genotype 4 represents 93 % of Egyptian HCV infections [6-8]. A cross-sectional survey of 21 governorates in Egypt (included 12169 adult persons) showed that overall anti-HCV seroprevalence was 14.8% [9]. High prevalence among Egyptian attributed to previously extensive intramuscular anti-schistosomal treatment campaigns during the second half of the twentieth century [10]. Evidence of ongoing transmission was reported that might be due to infection control or behavioral issues [11].
Hepatitis C virus (HCV) is transmitted through contact with blood of an infected person, unsafe injections or other invasive medical and non-medical practices (such as tattooing or piercing) when the skin is damaged, sharing of personal items such as razors and toothbrushes, and accidental needle-stick exposures among healthcare workers; and, where blood safety measures are suboptimal, via transfusion of unscreened blood and blood products [12].
World Health Organization (Hepatitis C in the WHO European Region Fact sheet, 2019) revealed that Hepatitis C is curable and the new antiviral medicines can cure more than 95% of people, reducing the risk of complications and death but access to diagnosis and treatment is low. There is no vaccine for hepatitis C. Prevention should, therefore, be focused on reducing the risk of exposure to the virus.
The aim of this study was to identify risk factors associated with HCV infection among adults.
Material and Methods
Study design
This case-control study derived from a household survey that was conducted to screen for hepatitis B virus and hepatitis C virus in the period from December 2011 to September 2012 in Damietta Governorate, located in the north Nile Delta area, Egypt, using multistage random sampling, 3 districts out of 5 districts were chosen randomly. Then 1 village or city (as a cluster) was chosen from each district. Thus, the sample consisted of 3 villages and 3 cities representing the 5 districts in these selected areas, one in every three houses was chosen. All residents aged 20 or older years accepted to share in the survey were included. The sample size was determined using Epi info, version 7.1.5, 2015. One hundred fifty cases and controls were randomly selected from those who showed positive HCV (278) and 300 controls were randomly selected from those who showed negative HCV (2699).
The ethical issue was considered and the survey was approved by the institutional review board of Al-Azhar University. All subjects included in the survey gave their consent to participate in the research; they were informed that all collected data will be used for scientific purposes only.
Data collection
The data were collected by an interview questionnaire which included sociodemographic data (age, sex, residence, marital status, education, and occupation); risk factors (history of previous exposure to surgical operations, dental procedures, stitches, intravenous drugs, blood transfusion, schistosomiasis injection treatment, needle stick, endoscopic examination, or renal dialysis); and risky behaviors such as sharing shaving razors, traditional cauterization, acupuncture, cupping (hijama) and tattooing.
Viral serology
Venous sampling (5 ml) was collected and allowed to clot. Serum was separated and kept frozen at –20 °C until assay. ELISA kits (Fortress Diagnostic Ltd) was used to estimate anti-HCV.
Statistical Analysis
Data were analyzed using SPSS software, version 16.0 (SPSS Inc. Chicago, USA) Univariate analysis was used to compare variables for the outcomes of interest. Continuous data (age) were compared using the Student’s t-test. Either χ2 or the Fisher’s exact tests were used to compare categorical variables. A multivariate analysis was also performed using multiple logistic regressions. All p-values lower than 0.05 were considered statistically significant with a 95% confidence interval.
Results
Total of 450 patients aged 20 to 67 years were included in this study, 150 as cases (positive for HCV) and 300 patients as controls (negative for HCV). Regarding socio-demographic characteristics of the study groups, Table 1 reveals a highly significant difference between case and control group regarding age, residence, education level, and marital status (p = 0.001).
Table 2 shows a history of dental procedure, previous stitches, surgical operation schistosomiasis injection treatment, blood transfusion and intravenous (IV) fluid intake were significantly associated with HCV infection (p< 0.001). Also, unsafe community practices (cupping, acupuncture, shared shaving razor, traditional cauterization, needle or sharp stick and tattooing) were significantly different between HCV-infected patients and controls (p < 0.01).
Table 3 shows the multivariable analysis, two socioeconomic factors (marital status and residence) were associated with higher odds of having HCV (OR =2.7, CI = 1.5 -5.0; OR =3.6, CI = 1.9 – 6.5 respectively). Regarding health care practices, patients with history of stitches or minor surgeries, intravenous fluid, dental procedure and renal dialysis were more likely to have HCV infection (OR =5.2, CI = 2.5 – 10.8; OR =3.7, CI = 1.8 -7.4; OR =1.9, CI = 1.1 -3.4; OR =2.6, CI = 1.1 – 6.5 respectively), compared with those without this history. Also four unsafe practices in the community (razor sharing, acupuncture, needle or sharp stick and cupping) were more likely to cause HCV infection (OR =4.8, CI = 2.0-11.5; OR =3.4, CI = 1.6- 7.1; OR =3.2, CI = 1.5-6.8; OR =2.3, CI = 1.1- 4.5 respectively).
Discussion
Hepatitis C virus (HCV) infection is a major cause of cirrhosis, liver cancer, and mortality worldwide. HCV seroprevalence is at up to 40% in some areas of Egypt [13]. Prevalence of HCV infection is directly related to the prevalence of persons who routinely share injection equipment and to the prevalence of unsafe parenteral practices in healthcare settings [1]. Reducing disease prevalence in any country requires not only enhanced rates of diagnosis and treatment but also strategies to prevent new infections.
Regarding sociodemographic factors, age, residence, education level, and marital status were significant risk factors for HCV infection that is similar to the results of different studies [14-16]. On the other hand, a study [17] in Egypt showed no association between age and HCV infection.
In this study, we observed that several unsafe invasive procedures such as dental procedure, previous stitches, surgical operation, schistosomiasis injection treatment, blood transfusion and [IV] fluid intake were significantly associated with a risk of HCV infections that is similar to the results of different studies [18-20].
The risk of HCV infection is significantly associated with unsafe practices in the community such as cupping, acupuncture, traditional cauterization, needle or sharp stick and tattooing and sharing shaving razors at community barbers which is consistent with other studies [21,22].
Residence, marital status, dental procedure, stitches, intravenous fluid, cupping, acupuncture, sharing shaving razor and needle or sharp object stick, were significant predictive risk factors for HCV infection in the multivariate logistic analysis. This results are supported by other studies [23,24].
Limitations
First, the study used a case-control design and data on the exposure were collected retrospectively, so recall bias is unavoidable. Secondly, the sample was not representative of all the Egyptian population as it was conducted in one governorate only
Conclusion
The results of this study showed that exposure to unsafe medical procedures and social practices were risk factors for HCV infection in Egypt.
Recommendations
Due to limited resources, activities to prevent the transmission HCV should focus on:
– Safe practices in the healthcare setting through expansion and promotion of infection control program.
– Health education campaigns, to increase the awareness of the community about the dangers of unsafe medical practices and empowering them to refuse unsafe medical practices.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
1. Heymann DL, editor. Control of Communicable Diseases Manual. 20th ed. Washington, D.C: American Public Health Association; 2015.p.331
2. Stanaway JD, Flaxman AD, Naghavi M, Fitzmaurice C, Vos T, Abubakar I, et al. The global burden of viral hepatitis from 1990 to 2013: findings from the Global Burden of Disease Study 2013. Lancet. 2016; 388 (10049):1081-18.
3. Mohd Hanafiah K, Groeger J, Flaxman AD, Wiersma ST. Global epidemiology of hepatitis C virus infection: new estimates of age-specific antibody to HCV seroprevalence. Hepatology. 2013; 57(4):1333-42.
4. Lavanchy D. Evolving epidemiology of hepatitis C virus. Clin Microbiol Infect. 2011; 17(2):107-15.
5. Petruzziello A, Marigliano S, Loquercio G, Cozzolino A, Cacciapuoti C. Global epidemiology of hepatitis C virus infection: An up-date of the distribution and circulation of hepatitis C virus genotypes. World J Gastroenterol. 2016;22(34):7824-40. DOI: 10.3748/wjg. v22.i34.7824.
6. Polaris Observatory HCV Collaborators. Global prevalence and genotype distribution of hepatitis C virus infection in 2015: a modelling study. Lancet Gastroenterol Hepatol. 2017; 2(3): 161-76.
7. Saleh, LM, Canioni D, Shamaa S, El-Zaafarany M, Emarah Z, Abdel-Aziz S, et al. High prevalence of hepatitis c virus associated b-cell lymphoma in Mansoura region (Egypt), ANRS 12263 study. Mediterr J Hematol Infect Dis. 2019,11(1): e2019011.
8. Mohamoud YA, Mumtaz GR, Riome S, Miller D, Abu-Raddad LJ. The epidemiology of hepatitis C virus in Egypt: a systematic review and data synthesis. BMC Infect Dis. 2013; 13:288.
9. Kouyoumjian SP, Chemaitelly H, Abu-Raddad LJ. Characterizing hepatitis C virus epidemiology in Egypt: systematic reviews, meta-analyses, and meta-regressions. Sci Rep. 2018; 8(1):1661.
10. Frank C, Mohamed MK, Strickland GT, Lavanchy D, Arthur RR, Magder LS, et al. The role of parenteral antischistosomal therapy in the spread of hepatitis C virus in Egypt. Lancet. 2000;355(9207):887–91.
11. El-Ghitany EM, Farghaly AG. Geospatial epidemiology of hepatitis C infection in Egypt 2017 by governorate. Heliyon. 2019; 5(8): e02249.
12. Miller FD, Abu-Raddad LJ. Evidence of intense ongoing endemic transmission of hepatitis C virus in Egypt. Proc Natl Acad Sci USA. 2010;107 (33): 14757–62.
13. Elgharably A, Gomaa AI, Crossey MM, Norsworthy PJ, Waked I, Taylor-Robinson SD. Hepatitis C in Egypt – past, present, and future. Int J Gen Med. 2016; 10:1–6.
14. Sharhani A, Mehrabi Y, Noroozi A, Nasirian M, Higgs P, Hajebi A, et al. Hepatitis C Virus seroprevalence and associated risk factors among male drug injectors in Kermanshah, Iran. Hepat Mon. 2017;17(10). DOI:10.5812/hepatmon.58739
15. Custer B, Kessler D, Vahidnia F, Leparc G, Krysztof DE, Shaz B, et al. Risk factors for retrovirus and hepatitis virus infections in accepted blood donors. Transfusion. 2015;55(5):1098–107.
16. Czerwinski M, Grabarczyk P, Stepien M, Kubicka-Russel D, Tkaczuk K, Brojer E, et al. What weighs more-low compliance with selfdeferral or minor medical procedures? Explaining the high rate of hepatitis C virus window-period donations in Poland. Transfusion. 2017; 57(8): 1998–2006.
17. Dahiya P, Kamal R, Sharma V, Kaur S. “Hepatitis” – Prevention and management in dental practice. J Educ Health Promot. 2015; 4:33.
18. Al-Kubaisy MW, Bobryshev YV, Shamsidah Ni N, Al-Naggar RA, AlKubaisy W. Is dental extraction a risk factor for contracting HCV infection: Abs, RNA and genotype detection. Oral Biol Dentistr. 2014;2(1):7.
19. Carney K1, Dhalla S, Aytaman A, Tenner CT, Francois F. Association of tattooing and hepatitis C virus infection: a multicenter case-control study. Hepatology. 2013;57(6):2117-23.
20. Yepes IJ1, Lince B, Caez C, De Vuono G. Risk factors for hepatitis C virus infection in the Colombian Caribbean coast: A case-control study. Biomédica. 2016;36 (4):564-71.
21. Rezaei N, Amini-Kafiabad S, Maghsudlu M, Abolghasemi H. Risk factor analysis of hepatitis C virus seropositivity in Iranian blood donors: A case-control study. Transfusion. 2016;56 (7):1891–8.
22. Mitrovic N, Delic D, Markovic-Denic L, Jovicic M, Popovic N, Bojovic K, et al. Seroprevalence and risk factors for hepatitis C virus infection among blood donors in Serbia: A multicentre study. Dig Liver Dis. 2015;47(7):572–6.
23. Khodadost M, Maajani K, Arabsalmani M, Mahdavi N, Tabrizi R, Alavian SM, et al. Is tattooing a risk factor for hepatitis c transmission? An updated systematic review and meta-analysis. Hepat Mon. 2017;17(9). DOI:10.5812/hepatmon.14308
24. Mohd Suan MA, Said SM, Lim PY, Azman AZF, Abu Hassan MR. Risk factors for hepatitis C infection among adult patients in Kedah state, Malaysia: A case–control study. PLoS ONE. 2019; 14(10): e0224459.
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A rare case: spinal subdural and spinal subarachnoid hemorrhage due to anticoagulant use
Zeynep Karakaya, Adem Çakır, Gizem Aydınok Akçay, Fatih Esad Topal, Pınar Yeşim Akyol, Umut Payza, Yusuf Şahin
Department of Emergency Medicine, Izmir Katip Çelebi University Atatürk Training and Research Hospital, İzmir, Turkey
DOI: 10.4328/ACAM.20106 Received: 2020-01-06 Accepted: 2020-01-26 Published Online: 2020-01-31 Printed: 2020-09-01 Ann Clin Anal Med 2020;11(5):523-526
Corresponding Author: Adem Çakır, Attending physician, Department of Emergency Medicine, Ataturk Research and Training Hospital, Katip Çelebi University, İzmir, Turkey. E-mail: dr.ademcakir@hotmail.com GSM: +90 (507) 531 77 37 Corresponding Author ORCID ID: https://orcid.org/0000-0002-4966-4882
Spinal Subdural Hematoma (SSDH) and Spinal Subarachnoid Hematoma (SSAH) are the spinal hematoma types that can cause spinal cord and nerve compres- sion. The risk of formation of atraumatic spinal hematoma due to warfarin use is rare. Specifically, the association between SSDH and SSAH is even more rare. Here we present a patient with a history of warfarin use who had paraplegia followed by analgesic complaints of irregular low back pain in our case.
We have tried to emphasize that emergency care physicians should be careful about spontaneous spinal hematomas that may require emergency intervention in the presence of predisposing factors, even in the case of a simple back pain complaint.
Keywords: Anticoagulants; Spinal; Subarachnoid Hemorrhage
Introduction
Warfarin is an anticoagulant commonly used to prevent systemic embolism. Although the increased risk of intracerebral hematoma in patients receiving anticoagulant therapy is a well-known phenomenon, spinal hematoma is rarely reported in the literature [1]. Patients with warfarin-associated intraspinal hematoma may also develop atypical symptoms, depending on the slow development of the bleeding so diagnosis is delayed [1]. Acute SSDH is a rare and potentially life-threatening disease. Spontaneous hemorrhage should be considered in patients receiving anticoagulant treatment, or in patients with bleeding disorders who have evidence of compression on the spinal cord or cauda equina. SSAH is a rare lesion that is difficult to diagnose and has destructive results. It occurs in 0.05-1.5% of all SSAH cases in the literature [2,3]. Patients with intraspinal hematoma are admitted to the Emergency Department with variable symptoms. Early diagnosis of spinal hemorrhage is important for the urgent treatment of patients and maintenance of normal function. Prognosis depends on the severity of the neurological sequelae. Delaying in diagnosis and treatment easily causes irreversible and serious neurological sequelae.
Case Report
A patient with back pain was admitted to the emergency room and her pain started 3 days ago and did not relieve with analgesic medication. The pain of the patient was like a rupture spreading from both sides of the waist toward the two feet, did not change with the position, sometimes regressed and sometimes exacerbated. It was learned that the patient’s pain continued for three days despite oral or IM analgesic and had recurrent applications for different emergency services. When the anamnesis is detailed, it was learned that the patient’s pain started after the patient had done housework by carrying heavy objects three days ago and there was no trauma story. The patient had surgery for the femur ten years ago and she has been using warfarin since mitral valve replacement operation. The neurological and other system examination was completely normal at the first examination of the patient. No motor-sensory deficits were detected in the extremities. When the vital findings were evaluated, pulse rate was 93 beats/ min, Blood Pressure: 135/84mmHg.The patient had pain in a rupture-style manner, starting from the thoracolumbar region and increasing in severity, extending to the feet. Mechanical back pain was considered as a preliminary diagnosis. The patient was treated with intramuscular non-steroidal analgesic and intravenous tramadol. The patient’s pain decreased after analgesic administration. In laboratory tests, the INR value was 7.61 (0.8-1.2), while the other laboratory values were within normal limits. Warfarin treatment was stopped and IV K vitamin was administered. The pain of the patient was re-exacerbated. Toracolumbar angio CT was arranged for differential diagnosis to detect the pain from the aortic dissection and lumbar pathologies. No dislocation or lumbar fracture was detected. Fluid localization at T9-L2 level was observed. The physical examination of the patient was repeated when her pain increased suddenly and violently. Acute urinary incontinence occurred, paraplegia developed with loss of sensation in both lower extremities. On this basis, thoracolumbar MRI was requested considering the preliminary diagnosis of haemorrhage in patient’s spine. MRI detected hemorrhagic material in the thoracolumbar spinal canal locally between T8-9 and L1-3 distances. In addition, central spinal cord dilatation (syringomyelia) appeared in some parts of the spinal cord. There was no evidence of contrast enhancement to suggest a neoplastic lesion in the postcontrast study, and there was no evidence to support vascular malformation within the examination limits (Figure 1-2). Subarachnoid and subdural hemorrhages were considered in the thoracolumbar spinal canal due to the use of anticoagulant in the patient. The patient was hospitalized in the brain surgery clinic. Twenty-four hours after the emergency department visit, the patient’s INR value was corrected and she was taken to the operating room. During the operation, subdural hemorrhage drainage and T9-L2 total laminectomy were performed. No abnormal vascular or mass findings were observed.
Discussion
Spontaneous spinal hematomas were first described more than 60 years ago by Schiller et al. [4]. SSAH is defined as a blood pack with a solid arachnoid membrane which can cause compression and neuropathy in the spinal cord in the subarachnoid space [5]. Intracranial abnormalities occur in the majority of SSHD patients [3]. Less than 1% of patients have a subarachnoid hemorrhage, which includes arteriovenous malformation of the spinal artery or saccular aneurysm of the spinal cord. Sometimes primary spinal cord tumors (eg, ependymoma, hemangioblastoma), nerve plexus tumors or metastases cause subarachnoid hemorrhage. Spinal trauma, coagulopathies, and autoimmune vascular disorders are additional sources of bleeding in the subarachnoid space [6]. SSDH’s are less common than intracranial subdural hematomas and spinal epidural hematomas.
The causes of SSDH’s can be divided into three groups including (a) posttraumatic, (b) iatrogenic (following surgical lumbar puncture), and (c) spontaneous underlying malformations (eg vascular malformation neoplasm) and coagulation failure. One theory is that the hemorrhage originates within the more vascular subarachnoid space, possibly after sudden raised intra- abdominal or intrathoracic pressure [7,8]. If the cerebrospinal fluid (CSF) can not neutralize this force, the spinal cord will pull the veins and cause subarachnoid hemorrhage [8]. Depending on the physical activity, the sudden increase in pressure can break the extra small arachnoid vessels on the inner surface of the dura and the blood can pass through the thin and sensitive arachnoid membrane [9,10]. Conversely, the root of the bleeding may be the subdural space that can pass through the arachnoid membrane and cause subarachnoid hemorrhage. In this case, it may be impossible to determine whether the source of the blood is in the subarachnoid or subdural region. Daily physical activity may induce bleeding in anticoagulated drug users, as in our case [11]. A typical clinical picture is severe back pain with sudden onset with or without radiculopathy. In many cases in the literature, patients complain of frequently back pain (93%), paraplegia/paracentesis (84%) and bladder dysfunction (45%) and variable clinical presentation and prognosis according to the location of the spinal canal [12, 13].
In our case, the patient was admitted to the emergency room with complaints of back pain only, neurological examination was completely normal, and paraplegia and urinary retention were developed at follow-up. In studies conducted by Domeniucci et al., SSAH patients reported that 14% of the bleeds were thoracal, 26% of the thoracolumbar, and 14% of the bleeding were observed in the lumbar region [6]. In Margin et al.’s study of patients with SSDH, they showed a 40% bleeding rate in the thoracic spinal segment and a 23% bleeding rate in the thoracolumbar region [12]. In our case, the hemorrhagic region was in the thoracolumbar region and was compatible with the literature.
Spinal angiography is generally considered to be the gold standard for imaging of spinal arterial aneurysms, arteriovenous malformations, or other pathologies that can cause spinal subarachnoid hemorrhage [13,14]. MR imaging is very effective in defining the degree of spinal hemorrhage and in determining the relationship between bleeding and thecal sac [3]. MRI is the first imaging method to follow up the treatment, showing chronological changes of hemorrhage. Although MR imaging is the most effective method for diagnosing hemorrhage in the spinal canal, it is difficult to distinguish subdural and subarachnoid hemorrhage with MRI. In two cases reported by Komiyama et al., comorbid SSDH and SSAH, which can not be completely separated in MR imaging, have been reported [15]. The exact location of the hematoma is determined by surgical exploration [6,9].
Spontaneous resolution has been shown in many cases with SSAH [14]. But at the same time in our case, the subdural hematoma was also accompanied, and neurological symptoms appeared. Patients with SSAH and SSDH reported the worst outcome in the review by Domenicucci et al. who evaluated SSDH patients [6]. Emergency surgery is needed as a primary treatment for such patients.
Conclusion
It should be kept in mind that SSAH concomitant SSDH is very rare, especially in patients taking anticoagulant therapy and have high INR. In addition, spinal hematomas are preliminary diagnoses that should be kept in mind in patients who come to the emergency service with complaints of back pain. Even before the development of paraplegia, early diagnosis is possible by a proper anamnesis and correct questioning of the drugs used. The first diagnosis should be intraspinal hematoma in patients who are admitted to the hospital with acute cord or caudal compression findings and using anticoagulants.
Acknowledgment
The authors appreciate kind support of Katip Çelebi University Atatürk Research and Training Hospital, Department of Emergency Medicine
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
References
1. Leep Hunderfund AN, Wijdicks EF. Intramedullary spinal cord hemorrhage (hematomyelia). Rev Neurol Dis 2009; 6(2): E54–61.
2. Bruni P, Esposito S, Oddi G, Hernandez R, Martines F, Patricolo A. Subarachnoid hemorrhage from multiple neurofibromas of the cauda equina: case report. Neurosurgery. 1991; 28: 910–913.
3. Luxon LM, Harrison MJ. Subarachnoid hemorrhage and papilledema due to a cervical neurilemmoma. Case report. J Neurosurg. 1978; 48: 1015–18.
4. Schiller F, Neligan G, Budtz-Olsen O. Surgery in haemophilia; a case of spinal subdural haematoma producing paraplegia. Lancet.1948;2(6535):842-5.
5. Gaitzsch J, Berney J. Spinal subarachnoid hematoma of spontaneous origin and complicating anticoagulation. Report of four cases and review of literature. Surg Neurol. 1984; 21:534-8.
6. Domenicucci M, Ramieri A, Paolini S, Russo N, Occhiogrosso G, Di Biasi C, et al. Spinal subarachnoid hematomas: our experience and literature review. Acta Neurochir (Wien). 2005;147(7):741–50.
7. Inamasu J, Ito K, Hattori N, Hirose Y. Warfarin-associated Intraspinal Hematoma. Keio J Med. 2016; 65(4):74-77.
8. Morandi X, Riffaud L, Chabert E, Brassier G. Acute nontraumatic spinal subdural hematomas in three patients. Spine. 2001; 26(23):E547–51.
9. Kakitsubata Y, Theodorou SJ, Theodorou DJ, Miyata Y, Ito Y, Yuki Y, et al. Spontaneous spinal subarachnoid hemorrhage associated with sub¬dural hematoma at different spinal levels. Emerg Radiol. 2010;17(1): 69-72.
10. Liu CL, Cheng CH, Cho DY. Rhabdomyolysis accompanied by spontaneous spinal subdural and subarachnoid hematoma related to amphetamine abuse. Spine. 2010;35(2):E71–73.
11. Kyriakides AE, Lalam RK, El Masry WS. Acute spontaneous spinal subdural hematoma presenting as paraplegia: a rare cause. Spine.2007;32 (21): E619-22.
12. De Beer MH, Eysink Smeets MM, Koppen H. Spontaneous Spinal Subdural Hematoma. Neurologist. 2017;22(1):34-39.
13. Rettenmaier LA, Holland MT, Abel TJ. Acute, Nontraumatic Spontaneous Spinal