August 2023
Importance of the Coombs test in diagnosing the Brucella
Orhan Turan, Tekin Karslıgil
Department of Medical Microbiology, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey
DOI: 10.4328/ACAM.21388 Received: 2022-09-11 Accepted: 2023-05-30 Published Online: 2023-06-10 Printed: 2023-08-01 Ann Clin Anal Med 2023;14(8):668-671
Corresponding Author: Orhan Turan, Department of Medical Microbiology, Faculty of Medicine, Gaziantep University, 27310, Gaziantep, Turkey. E-mail: orhan_turan7@hotmail.com P: +90 538 356 91 27 Corresponding Author ORCID ID: https://orcid.org/0000-0002-6453-1930
This study was approved by the Clinical Research Ethics Committee of Gaziantep University (Date: 2016-03-21, No: 2016/86)
Aim: In Turkey and in many areas of the world, Brucellosis, which is a common zoonotic disease has been widely seen as the cause of serious economic loss. Serum samples from 100 patients, which were sent to the laboratory with a pre-diagnosis of Brucella, were examined at Gaziantep University Medicine Faculty Sahinbey Research Application Hospital. Wright and Coombs agglutination tests were performed on the serum samples.
Material and Methods: Patients were divided into three groups: Wright (+), Wright (-) & Coombs (+), and Wright (-) & Coombs (-). Biochemical parameters were evaluated to elucidate the correlation between the groups. Dilutions were examined with the Wright test and started at 1/20 titer to 1/2560 titer and the Coombs test was started at 1/80 titer to 1/640 titer.
Results: Our study showed that Wright test and Coombs test were found negative in 46 patients among 100, 11 patients among 100 exhibited a Wright (+) result, and 43 patients among 100 presented a Wright (-) and Coombs (+) result together. In biochemical analyzes, WBC was found to be significantly different (p=0.019) in Coombs (+) and Coombs (-) patients. There was a significant difference between the Wright (-) & Coombs (+) and Wright (+) groups in the GGT measurements (p=0.038). Based on the obtained data, the rate of the Wright (-) and Wright (-) & Coombs (+) patients were significantly higher (48.3%). In the serology assay, Brucella also appears to have a high frequency of blocking antibodies that cause false negative results with STA.
Discussion: Due to this high proportion of STA results, it is recommended to seek confirmation using other serological methods such as Coombs or ELISA. Therefore, patients who are admitted with a pre-diagnosis of Brucella should be examined by using the Coombs test or examination only with the Brucella Coombs test would be appropriate in order to avoid economic loss.
Keywords: Brucella, Coombs, Wright, Blocking Antibodies
Introduction
Brucellosis is a common zoonotic disease around the world. It is commonly reported in humans and animals, especially in Mediterranean countries, the Arabian Peninsula, India, Africa and North America. Although it is controlled in developed countries, it remains a significant public health concern in developing countries [available at: http://cmuir.cmu.ac.th/handle/6653943832/35815]. According to data from the World Health Organization, 500.000 new cases are reported worldwide every year [1]. The disease occurs in people through consumption of unpasteurized milk and dairy products, inhalation of infected aerosols or direct contact with disintegrated tissues from animal secretions [2, 3]. Seroepidemiological studies have reported 9-25% and 3% seropositivity in occupational groups such as butchers, breeders, and slaughterhouse and dairy workers who were at risk of brucellosis and those who were not in the risk group, respectively [4, 5]. Showing intracellular settlement in humans and animals, the Brucella species are small, gram-negative, aerobic bacilli that cause infections [6]. In the serological diagnosis of brucellosis, IgG and IgM antibodies are studied with the Wright test, a Standard Tube Agglutination (SAT) test. However, while agglutinating antibodies in the structure of IgG, IgM and IgA occur in some individuals, blocking (non-agglutinating) or incomplete antibodies in the structure of IgG and IgA might occur in some other individuals [7-10]. The mechanism of this occurrence is not clearly understood. Blocking antibodies bind to antigens, however, agglutination does not occur. In the diagnosis of these incomplete antibodies, the Coombs test using anti-human immunoglobulin is applied [11].
No studies have been conducted on the prevalence of the formation of blocking antibodies in the regions of Turkey where brucellosis is particularly common. This study investigated the amount of blocking antibodies formed in these infections and potential differences that could occur between those developing blocking antibodies and those non-developing blocking antibodies in terms of biochemical parameters.
Material and Methods
Ethical approval for the present study was obtained from the local Clinical Research Ethics Committee (Date: 21.03.2016, Decision no: 2016/86). Serum from 100 patients who were referred to our laboratory with a pre-diagnosis of Brucella from various clinics at Gaziantep University Faculty of Medicine Sahinbey Research and Application Hospital were examined. Based on these criteria, 100 samples collected between April-December 2016 were studied as soon as they arrived, and the relevant results were recorded. Patients’ age, gender and biochemical parameters were also recorded. Wright (Vircell, Spain) and Coombs (Vircell, Spain) agglutination tests were studied in the serum samples in line with the recommendations of the manufacturer [13]. In the patients who were Wright-negative, blocking antibodies were examined with the Coombs test. The Wright tube agglutination test was initiated at 1/20 titer and diluted up to titers of 1/2560. The Coombs test was initiated at 1/80 titer and diluted up to the titers of 1/640. Titers at and greater than 1/160 were considered positive in the Wright and Coombs agglutination tests.
Statistical analysis
The SPSS for Windows version 22.0 software package was used for statistical analysis and P<0.05 was considered statistically significant.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
Of the 100 patients evaluated in the study, 77 (77%) were female and 23 (23%) were male. According to the data obtained, there was no significant difference between the groups in terms of gender and mean age (Table 1).
In the study, positivity was detected via both methods in 54 (54%) of patients who were referred with a pre-diagnosis of Brucella. Only the Coombs test was found to be only positive in 43 (43%) patients. The Wright test and the Coombs test were negative, the Wright test was negative and the Coombs test was positive, and the Wright test was positive in 46 (46%) patients in group 1, 43 (43%) patients in group 2 and 11 (11%) patients in group 3 (Table 1).
When the biochemical parameters of the patients were examined, a significant difference was seen between Group1 and Group 2 only in WBC measurements (p=0.027). There is a significant difference between Group 3 and Group 1 (p=0.629). In GGT measurement, there was a significant difference between Group 2 and Group 3 (p=0.038). No significant difference in terms of biochemical parameters was found between the groups, which were negative in both parameters, i.e. Group 1, and the patients who were Wright- or Coombs-positive (Groups 2 and 3) (Table 2).
When the biochemical parameters were examined in the positive (Wright and/or Coombs) and negative groups, no significant difference was found.
Although no significant relationship was observed between the groups in terms of sedimentation, a biochemical parameter, the p-value obtained is notable.
Discussion
Brucellosis is a zoonotic disease caused by Brucella bacteria. According to statistics from the Turkish Public Health Association, the number of reported cases in Turkey in 2015 was 4.173. Its morbidity rate is 5.3/100.000 [available at: https://hsgmdestek.saglik.gov.tr/tr/zoonotikvektorel-bruselloz/istatistik]. Since its symptoms and findings are non-specific, it might imitate many other diseases. The definitive diagnosis method is by examination of the culture. However, bacteria can be cultured in approximately five days in blood culture and in seven days in bone marrow culture with automated systems. Serological methods are significant tests that are ancillary to the diagnosis of brucellosis. Among them, the Standard Tube Agglutination (STA) method is a test that is frequently used in Turkey. However, the presence of blocking antibodies complicates the diagnosis and reveals the need for the Coombs test. In this study, the extent of this need was sought to be determined. The difference in terms of biochemical parameters between the control group (Group 1) and other Brucella patients who developed blocking antibodies was also investigated.
Among the studies in Turkey, Gultekin [available at: https://tez.yok.gov.tr/UlusalTezMerkezi/tezDetay.jsp?id=UwQxrV_-pBJY700iGu1y9A&no=YCdDQaGPUa1wck3DQckHUQ] used four different methods in the postgraduate thesis that aimed to identify Brucella antibodies and covered 117 individuals with a pre-diagnosis of brucellosis. Of 85 patients with positivity in at least one of these tests, 57 (67.1%) and 28 (32.9%) were male and female, respectively. The age range of these patients was 5-75 (mean age 34.0) years. The RBT (Rose Bengal Test), STA, Coombs test and ELISA were used within the context of the study. The RBT, STA, CT and ELISA were positive in 81 (95.3%), 73 (85.9%), 64 (75.3%) and 67 (78.8%) of the serum samples, respectively. The study suggested that the RBT and STA were not always adequate in endemic regions to detect clinical features of the disease and to prevent cases that would adversely affect the diagnosis, such as, cross-reaction, the presence of blocking antibodies and a pre-existing presence, as well as preeclampsia follow up for low titers of STA. It has been suggested that laboratory diagnosis should be supported by tests such as Coombs and ELISA. In this study, 85 individuals were evaluated, and although the CT was 75%, blocking antibodies were not directly examined.
Age, gender, clinical symptoms and findings, routine laboratory results and the results of the Rose Bengal test, STA test and Coombs test of 50 patients who were diagnosed with brucellosis in 2011 were evaluated in a study by Altun et al. [12]. According to the results obtained, the mean age of the patients was 38.2 years, of which 62% and 38%, respectively were males and females (16±78), 50 of them were Rose Bengal-positive, the STA result was at and above 1/160 in 48 of them and 2 cases were Coombs-positive. No significant difference was found between age or gender and Brucella positivity. The study highlighted the importance of using Coombs serum while studying serums of patients suspected of having brucellosis and not agglutinating due to blocking antibodies. In this study, it was seen that Brucella positivity was not correlated with age and gender. However, there are studies asserting a correlation between Brucellosis and age and gender [13-15].
In the dissertation study from Canakkale, Ersoy [available at: https://acikbilim.yok.gov.tr/handle/20.500.12812/109207] found that 14 individuals who were negative in the STA test were Coombs-positive. Again in their study, Alıskan et al. demonstrated that the percentage of patients who were found to be positive using the STA test increased from 40% to 92% with the Coombs test.
Although there are studies showing that the amount of blocking antibodies can be very high in brucellosis, there are no studies investigating the seroprevalence of blocking antibodies in our region. This is why, our present study has important impact in related fields. One of the objectives of this study was to determine whether the presence of blocking antibodies was associated with biochemical parameters or not. However, no significant difference was found in the studies, except for GGT and WBC. GGT (gamma-glutamyl transferase) is an enzyme that is highly concentrated in the liver. The GGT value gives an indication about the health of the liver. The normal GGT value is accepted as 8-38 U/L. WBC (White Blood Cells) are produced in the bone marrow, lymph nodes, spleen and thymus gland. Their normal value interval is 3.98-10.04. A significant difference was found between Group 1 and Group 2 (p=0.019) in WBC measurements. However, this elevation is in favor of patients who were negative in both tests and may be associated with another disease rather than Brucellosis. While GGT values were normal in the Coombs-positive patients in the study, they were higher in the Wright-positive cases producing normal antibodies. A more extensive series of studies should investigate the reason why WBC and GGT are within normal limits in brucellosis cases with blocking antibodies. Sediment is a test that reveals acute phase reactants. In this study, although there was no significant relationship between Group 1 and Group 2 or Group 3 in terms of sedimentation, the results obtained are close to the significant difference value. Therefore, it is recommended to study the relationship between brucellosis patients and sedimentation as a biochemical parameter.
In our study, the Wright test was primarily applied to 100 serums of patients with a pre-diagnosis of brucellosis and the Coombs test was run on 89 negative samples. The Coombs test was positive in 43 Wright-positive samples (48.3%). This situation is an important indicator of the extent to which patients, who present with a pre-diagnosis of Brucella and undergo only STA testing, cannot be diagnosed.
Conclusion
Present study shows that in the serology of Brucella, the frequency of blocking antibodies that cause false negative STA results is too high to be ignored (48.3%). Many studies recommend confirmation of STA results with other serological methods such as Coombs or ELISA. We are of the opinion that, due to this high rate, the Coombs test must also be studied in patients presenting with a pre-diagnosis of Brucella, or only the Brucella Coombs test should be studied to avoid economic loss.
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. Franco MP, Mulder M, Gilman RH, Smits HL. Human brucellosis. J Lancet Infect Dis. 2007;7(12):775-86.
2. Lülleci H. EvaluatIon of Seven Cases WIth Brucella Epididymo-orchitis. J Selcuk Medical Journal. 2019;35(4):259-63.
3. van Dijk MA, Engelsma MY, Visser VX, Keur I, Holtslag ME, Willems N, et al. Transboundary Spread of Brucella canis through Import of Infected Dogs, the Netherlands, November 2016–December 2018. J Emerg Infect Dis. 2021;27(7):1783.
4. Altindis M. Afyon bölgesi besicilerinde, kasaplarda, süt ürünleri toplayıcısı ve imalathanelerinde çalışanlarda bruselloz seropozitifliği (Brucellosis seropositivity in the workers in the breeders, butchers, dairy product collectors and workshops in the Afyon region). İnfeksiyon Dergisi/ Journal of Infection. 2001;15(1):11-5.
5. Buke AÇ, Ciceklioglu M, Erdem İ, Ozacar T, Oztufekci H, Arda B, et al. Süt ürünleri işleyicilerinde bruselloz prevalansı ve brusellozu bilme durumu (Brucellosis prevalence and knowledge of brucellosis in dairy processors). İnfeksiyon dergisi/Journal of Infection. 2000;14(3):321-5.
6. Pappas G, Akritidis N, Bosilkovski M, Tsianos E. Brucellosis. N Engl J Med. 2005;352(22):2325-36. DOI: 10.1056/NEJMra050570.
7. Avijgan M, Rostamnezhad M, Jahanbani-Ardakani H. Clinical and serological approach to patients with brucellosis: A common diagnostic dilemma and a worldwide perspective. Microb Pathog. 2019;129:125-30. DOI: 10.1016/j.micpath.2019.02.011.
8. Xu N, Dong X, Yao Y, Guan Y, Chen F, Zheng F, et al. Improved Early Detection of Focal Brucellosis Complications with Anti-Brucella IgG. J Clin Microbiol. 2020;58(10). DOI: 10.1128/jcm.00903-20.
9. Nielsen K, Yu WL. Serological diagnosis of brucellosis. Prilozi. 2010;31(1):65-89.
10. Al Dahouk S, Nöckler K. Implications of laboratory diagnosis on brucellosis therapy. Expert Rev Anti Infect Ther. 2011;9(7):833-45. DOI: 10.1586/eri.11.55.
11. Young EJ. Serologic diagnosis of human brucellosis: analysis of 214 cases by agglutination tests and review of the literature. Rev Infect Dis. 1991;13(3):359-72. DOI: 10.1093/clinids/13.3.359.
12. Hatice AU, Yakup O, Filiz. Y. Ikinci Basamak Bir Hastanedeki Bruselloz Olgularının Değerlendirilmesi (Evaluation of Brucellosis Cases in a Second Line Hospital). Yeni Tıp Dergisi/ New Medical Journal. 2013(30):187-90.
13. El-Ansary EH, Mohammed BA, Hamad AR, Karom AG. Brucellosis among animals and human contacts in eastern Sudan. Saudi Medical Journal. 2001;22(7):577-9.
14. Luna-Martínez JE, Mejía-Terán C. Brucellosis in Mexico: current status and trends. Vet Microbiol. 2002;90(1-4):19-30. DOI: 10.1016/s0378-1135(02)00241-9.
15. Cetinkaya F, Naçar M, Aydin T, Koç N, Gökahmetoğlu S. Prevalence of brucellosis in the rural area of Kayseri, Central Anatolia, Turkey. Int J Infect Dis. 2006;10(2):179-81. DOI: 10.1016/j.ijid.2004.10.009.
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Orhan Turan, Tekin Karslıgıl. Importance of the Coombs test in diagnosing the Brucella. Ann Clin Anal Med 2023;14(8):668-671
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The effect of coronavirus infection (COVID19) on fetomaternal blood flow at term
Berna Asır 1, Berrin Göktug Kadıoglu 1, Eda Bingül 1, Selvihan Tapanoglu Karaca 1, Sibel Tekgündüz 1, Ayse Nur Aksoy 1, Hava Ozkan 2
1 Department of Obstetrics and Gynecology, University of Health Sciences, Erzurum Regional Training and Research Hospital, 2 Department of Midwifery , Faculty of Health Science, Ataturk University, Erzurum, Turkey
DOI: 10.4328/ACAM.21420 Received: 2022-09-28 Accepted: 2023-04-29 Published Online: 2023-06-11 Printed: 2023-08-01 Ann Clin Anal Med 2023;14(8):672-675
Corresponding Author: Hava Ozkan, Department of Midwifery, Faculty of Health Science, Ataturk University, Erzurum, Turkey. E-mail: havaoran@atauni.edu.tr P: +90 532 330 00 36 Corresponding Author ORCID ID: https://orcid.org/0000-0001-7314-0934
This study was approved by the Ethics Committee of University of Health Sciences, Erzurum Regional Training and Research Hospital (Date: 2021-03-01, No: 2021/05-115)
Aim: The aim of this study is to evaluate maternal and fetal blood flow parameters of term pregnant women who had recovered from COVID-19 during pregnancy.
Material and Methods: The study was conducted on 100 term pregnant women followed at the Department of Obstetrics and Gynecology, University of Health Sciences, Erzurum Regional Training and Research Hospital, Erzurum, Turkey. All of these pregnant women agreed to participate in the study. Two groups were formed. Patients with a term pregnancy who had a positive reverse transcription-polymerase chain reaction for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection at any week of pregnancy, who later recovered, were included in the study group (Group 1). The control group (Group 2) consisted of 50 healthy term pregnant women. Smokers, alcohol users, multiple pregnancies, complicated pregnancies (such as preeclampsia, fetal malformation, gestational diabetes, placenta previa), and those with a pregnancy below 37 weeks were not included. First, a routine ultrasound examination was performed on all pregnant women. Then, the umbilical artery, uterine artery, and middle cerebral artery pulsatility index (PI), resistance index (RI), and systole/diastole ratios (S/D) were recorded using Doppler ultrasonography. Obtained data and results were compared between groups using the independent T-test.
Results: Demographic characteristics of the groups were similar. There was no difference between the groups in terms of maternal and fetal blood flow parameters.
Discussion: In this current study, fetal and maternal blood flow parameters of term pregnant women who recovered and did not have coronavirus infection during pregnancy were compared. The uterine, umbilical and mid cerebral artery blood flow parameters of the participants were observed to be similar.
Keywords: COVID-19, Doppler Ultrasound, Middle Cerebral Artery, Pregnancy, Umbilical Artery, Uterine Artery
Introduction
After the World Health Organization declared COVID-19 a pandemic, various studies were carried out, especially its effect on pregnant women and fetuses [1-4]. The virus, which infected more than 529 million people all over the world, caused the death of more than 6 million people [2]. Naturally, it also affected pregnant women [3]. Although frequency of vertical transmission the disease to the fetus has not been determined, it has been determined to cause severe acute respiratory failure and adversely affect fetal perfusion [4], Although there were high concerns about the effect on the fetus at the beginning of the pandemic, it has been determined that fetal side effects were not so much with increasing clinical experience [5].
Doppler ultrasound detects changes in circulating blood flow patterns. Risky conditions for the fetus may be detected via fetal Doppler ultrasound and it has been reported to be effective to evaluate high-risk pregnancies [6]. Umbilical artery (UA) Doppler is accepted as an important surveillance tool in fetal growth retardation [7]. In chronic hypoxia, cerebral vasodilation occurs; cerebral diastolic flow increases, and Doppler indexes of the Middle cerebral artery (MCA) decrease to protect the brain [8]. Researchers reported that the MCA Doppler may be a good tool for detecting risky fetuses [9]. Uterine artery (UtA) Doppler velocimetry evaluation is a non-invasive approach that reflects the degree of placental perfusion. It reflects the remodeling of the incomplete spiral arteries, which is responsible for preeclampsia [10]. UtA Doppler parameters have been reported to be associated with maternal cardiovascular function [11].
One of the most important purposes of prenatal Doppler ultrasonography is to detect fetuses with a high risk for perinatal morbidity and mortality. The aim of the study is to evaluate the maternal and fetal blood flow parameters of term pregnant women who recovered from COVID-19 during pregnancy, to investigate the effects of COVID-19 infection during pregnancy on these parameters and to reveal the negative effects if any.
Material and Methods
For this prospective case-control study, permission was obtained from the Ethics Committee of the University of Health Sciences, Erzurum Regional Training and Research Hospital (No: 2021/05-115). The study was carried out with 100 pregnant women aged 20-40 years who were followed up at the Obstetrics and Gynecology Clinic, University of Health Sciences, Erzurum Regional Training and Research Hospital, Erzurum, Turkey. All pregnant women agreed to participate in the study and signed informed consent was obtained from all participants. Two groups were formed (n=50 in each group). Patients with a term pregnancy who had a positive reverse transcription-polymerase chain reaction in nasopharyngeal and oropharyngeal samples for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in any week of pregnancy, who later recovered, were included in the study group (Group 1). The control group (Group 2) consisted of 50 healthy term pregnant women. Smokers, alcohol users, multiple pregnancies, complicated pregnancies (such as preeclampsia, fetal malformation, gestational diabetes, placenta previa), and those with a pregnancy below 37 weeks were not included in the study. Age, weight, height, gravida, parity, vital signs, biochemical analysis results, gestational week, and pregnancy week of the participants who recovered from COVID-19 were recorded. Fetal ultrasound examination was performed by two obstetricians (A.N.A and B.A.) transabdominally using the LOGIQ F8 expert GE Healthcare ultrasound system (with a 3.5 M-Hz convex probe). Measurements were made when the fetus was immobile and there were no uterine contractions. Routine ultrasonography examination was performed on all pregnant women using Hadlock formula [12]. The amniotic fluid index value and biometric measurements, including biparietal diameter, abdominal circumference, and femur length were recorded. Then, the pulsatility index (PI), resistance index (RI), and systole/diastole ratios (S/D) of the umbilical, uterine, and middle cerebral arteries were recorded with Doppler Ultrasonography. The UtA was visualized distal to the area where the iliac artery is on both sides. The UA was examined over the free loop of the umbilical cord and MCA was visualized in the transverse axial position of the fetal head. All flow measures were made according to color Doppler Ultrasonography standard protocol [13,14].
Statistical analysis
Statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS.22; IBM SPSS Statistics for Windows, Version 22.0). Data were shown as means ± error standards or numbers. The normality of variables was tested with the Kolmogorov-Smirnov test. Flow parameters between groups were compared using the Independent T-test. Pearson’s correlation analysis was performed to investigate the correlation between the gestational week of coronavirus infection and Doppler parameters. P-value <0.05 was considered statistically significant.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
During the study period, 80 pregnant women were diagnosed with COVID-19 and completed the quarantine process. Twenty patients had comorbidities such as diabetes, chronic hypertension, and high body mass index, and 60 patients met inclusion criteria. Fifty pregnant women agreed to participate in the study. Eventually, the data of 50 participants for the study group were analyzed. Fifty term pregnant women with similar demographic characteristics, who did not have COVID-19 during pregnancy, were matched as the control group. The demographic characteristics of the groups were similar (Table 1).
The ages of the pregnant women were between 20-40 years. Among women who were positive for SARS CoV-2, 10 (20%) were asymptomatic and 40 (80%) were symptomatic, all of whom had mild clinical manifestations, including cough, anosmia, fever, diarrhea, runny nose, nasal congestion, and fatigue. None of the patients required intensive care and steroid treatment. There was no difference between the groups in terms of maternal and fetal blood flow parameters (Table 2). No correlation was observed between study parameters.
Discussion
Fetal Doppler ultrasonography is a very common tool to detect fetal well-being in the last trimester. Doppler measurements are used in case of fetal growth restriction and the follow-up of high-risk pregnancies [15]. Differences between peak systolic and end-diastolic flow rates in each cardiac cycle indicate reverse flow caused by vascular resistance [16]. Researchers suggested that maternal COVID-19 may affect the oxygen supply of the fetus, leading to placental insufficiency, IUGR, fetal distress, and fetal death [17]. In the current study, fetal and maternal blood flow parameters of term pregnant women who recovered and did not have coronavirus infection during pregnancy were compared. The uterine, umbilical and mid cerebral artery blood flow parameters of the participants were observed to be similar.
The UtA Doppler is more valuable in the third trimester. Recent findings show that third-trimester UtA Doppler is important in determining the risk of stillbirth and perinatal death [18]. Fetal MCA Doppler PI is used to evaluate fetal oxygenation. Reduction in MCA impedance has been shown to be associated with fetal hypoxemia and acidemia [19]. Mok et al. [20] reported abnormal neonatal outcomes in pregnant women infected with Zika viruses. They observed low peak systolic velocity measurements of MCA in these patients and they concluded that the MCA blood flow parameter may provide clinical benefit in the surveillance of pregnant women affected by Zika viruses. In the study by Karlsen et al. [21] they evaluated the PI value of MCA to prevent poor perinatal outcomes, and reported a significant correlation between MCA PI and adverse perinatal outcomes in high-risk populations. In the current study, no significant differences were found in terms of PI and RI values of MCA between term pregnant women who had COVID-19 during pregnancy and those who did not [22].
During the COVID-19 pandemic, clinicians investigated the relationship between the SARS-CoV-2 infection during pregnancy and adverse maternal and perinatal outcomes. In a recent Canadian surveillance study, 6012 pregnant individuals with SARS-CoV-2 were analyzed [23]. This exploratory surveillance study reported a significant association between SARS-CoV-2 infection during pregnancy and adverse maternal outcomes and preterm birth. In another study, five cases of fetal death, which occurred in patients with relatively mild forms of COVID-19 were reported [23]. In all five cases, placental histology had acute chorioamnionitis. In the current study, intrauterine fetal death was not detected in any of the continuing pregnancies that have recovered from maternal SARS-CoV-2 infection. Also, fetomaternal blood flow parameters in these patients were similar to the patients who have not had COVID-19. Consistent with our results, Soto- Torres et al. [24] found no significant differences in fetal ultrasound and Doppler findings between pregnant women who were positive for SARS-CoV-2 and those who were negative. But unlike our results, they reported more frequent deliveries ≤ 35 weeks among SARS-CoV-2- positive women compared to controls. Unlike their study, patients with comorbidities were not included in this current study. They included all SARS-CoV-2- positive women in their retrospective case-control study. In another study, Anuk et al. [25] compared maternal-fetal Doppler patterns in pregnant women who were diagnosed with COVID-19 and completed the quarantine period with healthy pregnant women. They reported higher pulsatility and resistance indices of UA and UtA in pregnant women who recovered from COVID-19 compared to the control group. Inconsistent with their results, we observed no significant differences between term pregnant women who recovered from COVID-19 and controls in terms of fetomaternal Doppler flow parameters. The reason for these different results may be related to the methodological differences in the studies. Anuk et al. [25] performed Doppler measurements during the week of pregnancy who had COVID-19 disease and completed the quarantine period. Whereas, we performed all Doppler ultrasound evaluations at term. We recorded the pregnant women who were diagnosed with COVID-19, followed up, and performed Doppler ultrasound and fetal biometry measurements when they reached 37 and above gestational weeks. This is the first study to investigate fetomaternal Doppler parameters in term pregnant women with recovered from COVID-19 infection. We reported that fetomaternal blood flow parameters similar in pregnant women who recovered from COVID-19 infection to healthy pregnant women.
Limitations
The limitation of this study was the lack of information about the long-term follow-up of the participants such as mode of delivery, and APGAR scores of the baby. However, the aim of this current study was to evaluate the effect of COVID-19 infection during pregnancy on fetomaternal blood flow parameters at term.
Conclusion
In conclusion, this present study reported no significant differences in fetomaternal blood flow parameters in term pregnant women who recovered from COVID-19 during pregnancy compared to those who have not had the disease. Further studies are required to investigate the association between the gestational age at the time of diagnosis of COVID-19 and placental perfusion at term.
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. Dashraath P, Wong JLJ, Lim MXK, Lim LM, Li S, Biswas A, et al. Coronavirus disease 2019 (COVID-19) pandemic and pregnancy. Am J Obstet Gynecol. 2020; 222(6): 521-31.
2. Yan J, Guo J, Fan C, Juan J, Yu X, Li J, et al. Coronavirus disease 2019 in pregnant women: a report based on 116 cases. Am J Obstet Gynecol. 2020; 223(1): 111.e1-14.
3. Moore KM, Suthar MS. Comprehensive analysis of COVID-19 during pregnancy. Biochem Biophys Res Commun. 2021; 29;538: 180-6.
4. Diriba K, Awulachew E, Getu E. The effect of coronavirus infection (SARS-CoV-2, MERS-CoV, and SARS-CoV) during pregnancy and the possibility of vertical maternal-fetal transmission: a systematic review and meta-analysis. Eur J Med Res. 2020; 25(4): 1-14.
5. Guan W, Ni Z, Hu Y, Liang W-H, Ou C-Q, He J-X, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020; 382(18): 1708-20.
6. Alfirevic Z, Stampalija T, Dowswell T. Fetal and umbilical Doppler ultrasound in high-risk pregnancies. Cochrane Database Syst Rev. 2017; 13(6): CD007529.
7. American College of Obstetricians and Gynecoclogists. ACOG Practice bulletin no. 134: fetal growth restriction. Obstet Gynecol. 2013; 121(5): 1122-33.
8. Wladimiroff JW, van den Wijngaard J, Degani S, Noordam M, van Eyck J, Tonge H. Cerebral and umbilical blood flow velocity waveforms in normal and growth retarded pregnancies. Obstet Gynecol. 1987; 69(5): 705-9.
9. Ebrashy A, Azmy O, Ibrahim M, Waly M, Edris A. Middle cerebral/umbilical artery resistance index ratio as sensitive parameter for fetal well-being and neonatal outcome in patients with preeclampsia: case-control study. Croat Med J. 2005; 46(5): 821-5.
10. Prefumo F, Campbell S, Jauniaux E. Maternal blood flow to the placenta. BJOG. 2019; 126(8): 972.
11. Tay J, Masini G, McEniery CM, Giussani DA, Shaw CJ, Wilkinson IB, et al. Uterine and fetal placental Doppler indices are associated with maternal cardiovascular function. Am J Obstet Gynecol. 2019; 220(1): 96.e1-8.
12. Hadlock FP, Harrist RB, Sharman RS, Deter RL, Park SK. Estimation of fetal weight with the use of head, body, and femur measurements–a prospective study. Am J Obstet Gynecol. 1985; 1;151(3): 333-7.
13. Gomez O, Figueras F, Fernadez S, Bennasar M, Martínez JM, Puerto B, et al. Reference ranges for uterine artery mean pulsatility index at 11-41 weeks of gestation. Ultrasound Obstet Gynaecol. 2008; 32(2): 128-32.
14. Bahlmann F, Reinhard I, Krummenauer F, Neubert S, Macchiella D, Wellek S. Blood flow velocity waveforms of the fetal middle cerebral artery in a normal population: reference values from 18 weeks to 42 weeks of gestation. J Perinat Med. 2002; 30(6): 490-501.
15. Alfirevic Z, Stampalija T, Gyte GM. Fetal and umbilical Doppler ultrasound in normal pregnancy. Cochrane Database Syst Rev. 2010; (8): CD001450.
16. Seymen CM. Being pregnant in the COVID-19 pandemic: effects on the placenta in all aspects. J Med Virol. 2021; 93(5): 2769-73.
17. Melchiorre K, Leslie K, Prefumo F, Bhide A, Thilaganathan B. First-trimester uterine artery Doppler indices in the prediction of small-for-gestational age pregnancy and intrauterine growth restriction. Ultrasound Obstet Gynecol. 2009; 33(5): 524-9.
18. Khalil A, Morales-Roselló J, Townsend R, Morlando M, Papageorghiou A, Bhide A, et al. Value of third-trimester cerebroplacental ratio and uterine artery Doppler indices as predictors of stillbirth and perinatal loss. Ultrasound Obstet Gynecol. 2016; 47(1): 74-80.
19. Vyas S, Nicolaides KH, Bower S, Campbell S. Middle cerebral artery flow velocity waveforms in fetal hypoxaemia. Br J Obstet Gynaecol. 1990; 97(9): 797-803.
20. Mok T, Pereira Jr JP, Sobhani NC, Cardozo RF, Valle HA, Ribeiro Torres Dutra B, et al. Middle cerebral artery dopplers and abnormal neonatal outcomes among pregnant women with zika virus infection. Am J Perinatol. 2022; 39(6): 577-83.
21. Karlsen HO, Ebbing C, Rasmussen S, Kiserud T, Johnsen SL. Use of conditional centiles of middle cerebral artery pulsatility index and cerebroplacental ratio in the prediction of adverse perinatal outcomes. Acta Obstet Gynecol Scand. 2016; 95(6): 690-6.
22. McClymont E, Albert AY, Alton GD, Boucoiran I, Castillo E, Fell DB, et al. Association of SARS-CoV-2 infection during pregnancy with maternal and perinatal outcomes. JAMA. 2022;327(20):1983-91.
23. Richtmann R, Torloni MR, Oyamada Otani AR, Levi JE, Crema Tobara M, de Almeida Silva C, et al. Fetal deaths in pregnancies with SARS-CoV-2 infection in Brazil: A case series. Case Reports in Women’s Health. 2020;27:e00243.
24. Soto-Torres E, E Hernandez A, Huntley E, Mendez-Figueroa H, Blackwell SC. Ultrasound and doppler findings in pregnant women with SARS-CoV-2 infection. Ultrasound Obstet Gynecol. 2021;58 (1):111-20.
25. Anuk AT, Tanacan A, Yetiskin FDY, Buyuk GN, Senel SA, Keskin HL, et al. Doppler assessment of the fetus in pregnant women recovered from COVID-19. J Obstet Gynaecol Res. 2021;47(5):1757-62.
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Berna Asır, Berrin Göktug Kadıoglu, Eda Bingül, Selvihan Tapanoglu Karaca, Sibel Tekgündüz, Ayse Nur Aksoy, Hava Ozkan. The effect of coronavirus infection (COVID19) on fetomaternal blood flow at term. Ann Clin Anal Med 2023;14(8):672-675
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Morphological examination and clinical significance of the tibialis posterior:
A cadaver study
Berin Tugtag Demir 1, Murat Uzel 2, Ummuhan Yagmurkaya 3, Dilara Patat 1, Burak Bilecenoglu 1
1 Department of Anatomy, Faculty of Medicine, Ankara Medipol University, Ankara, 2 Department of Orthopaedics and Traumatology, Faculty of Medicine, Kocaeli University, Kocaeli, 3 Department of Physiotherapy, Ankara Medipol University, Ankara, Turkey
DOI: 10.4328/ACAM.21521 Received: 2022-12-01 Accepted: 2023-05-30 Published Online: 2023-06-09 Printed: 2023-08-01 Ann Clin Anal Med 2023;14(8):676-680
Corresponding Author: Berin Tuğtağ Demir, Department of Anatomy, Faculty of Medicine, Ankara Medipol University, 06050, Altındağ, Ankara, Turkey. E-mail: berintugdemir@gmail.com P: +90 553 470 65 96 Corresponding Author ORCID ID: https://orcid.org/0000-0001-8301-9257
This study was approved by the Ethics Committee of Kahramanmaraş Sütçü İmam University (Date: 2013-06-25, No: 2013/12-5)
Aim: The purpose of the study was to characterize the morphology of the tibialis posterior muscle, and to determine the relationship of the muscle with the flexor digitorum longus tendon when planning surgical procedures in the region.
Material and Methods: The study was carried out by performing tibialis posterior muscle dissection in 30 lower (40-65 age range, 18 males/12 females) extremities. In the study, muscle and tendon sizes, tendon diameter, distances to reference points, origin and insertion regions were measured for length, and morphological description of the attachment area.
Results: It was found that the tendon diameter was 13×5 mm at the insertion, 9×4 mm at the end of muscle fibers, and 10.4×4.4 mm at the medial malleolus level. As a result of the dissections, it was determined that the tibialis posterior tendon crossed with the flexor digitorum longus tendon approximately 75.0±21.0 mm proximal to the lower end of the medial malleolus.
Discussion: We hold the belief that our cadaver study will guide clinicians.
Keywords: Tibialis Posterior, Flexor Digitorum Longus, Cadaver, Tendon Transfer
Introduction
The tibialis posterior (TP) muscle, located in the posterior-deep compartment of the leg, Designer from the fibula and interosseous membrane, 1/3 proximal to the tibia (below the soleal line). When the tendon of the TP descends 1/4 distal in the posterior compartment, it runs anterior to the flexor digitorum longus muscle (FDL) and enters the fibrous tunnel behind the medial malleolus (MM). The TP tendon is larger and more anterior than FDL’s tendon when it passes behind the MM. Whilst the TP attaches mainly to the navicular and medial cuneiform, it can also partially insert into the intermediate/lateral cuneiform and the cuboid bone [1,2].
The chief task of TP is to perform the varus movement of the foot and to protect the longitudinal medial arch of the foot thanks to the multiple connections of the TP and its tendon on the plantar surface of the foot [3,4]. It is evident that the TP gains clinical importance due to its role in walking and protecting the medial longitudinal arch. In the literature, there have not been enough studies focusing on the morphometric properties of the TP muscle and tendon so far [2-5]. Additionally, a few studies were found to examine the relationship between TP and FDL in the literature. Thereupon, it is thought that dwelling upon the morphological features of the muscle and tendon of the TP will cast light on the adoption of clinical approaches in orthopedic surgery (tibia lower-end deformities, isolated medial malleolar approach, medial incision).
Material and Methods
Permission was obtained from Kahramanmaraş Sütçü İmam University Ethics Committee for Non-Pharmaceutical Practices. (date: 25.06.2013/No: 2013/12-5). TP muscles in 30 lower extremities (40-65 age range, 18 males / 12 females, since 2 out of 32 lower extremities had TP deformation, the study was carried out with total 30 samples without side) which were supracondylar amputated for medical reasons were dissected. It is worth noting here that lower extremities previously operated below the level of the knee joint or impaired muscle/tendon structure were excluded from the study.
Lower extremity dissection was performed according to the predetermined protocol [5]. The dissection was started by removing the skin and the superficial fascia, which runs from the posterior part of the leg to the gastrocnemius. Afterwards, the foot was held in inversion in order to document the course of the TP tendon attaching at the medial and plantar aspects of the foot. After making visible the superficial muscles in the posterior and anterior of the leg, most of the deep-posterior compartment fascia and the TP and FDL muscles’ bellies were dissected, starting from the proximal of leg. The tendon courses of both muscles and around the medial malleolus were dissected in an extremely meticulous fashion. Subsequently, the TP tendon was removed at the osseous insertions.
Following the dissection, the following morphological features of TP were evaluated (Figure 1):
• Diameters of the TP tendon in the origin (myotendinous junction), inferior tip of MM, tibiotalar joint (TTJ) and insertion regions, and the distance between these points and the insertion point of the tendon
• Diameters of TP muscle fibers in TTJ and MM and distance of muscle fibers from insertion
• Morphological features of the TP-FDL intersection (Figure 2).
Statistical analysis
Statistical analysis was performed using SPSS for Windows 21 software. Results are presented as mean and standard deviation unless otherwise stated. The Shapiro-Wilk test was applied to control the normality of the data distribution. As the data were not normally distributed, the Mann-Whitney test was used to compare the TP parameters and anthropometric measurements between the genders, respectively. P<0.05 was accepted as statistical significance.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
In all dissections, it was determined that the TP was attached to the navicular (82%) and medial cuneiform (18%). The presence of addition/accessory tendons extending from the TP to other structures was not witnessed. As the TP tendon passed just below the MM tubercle, there was a thin septum between it and the FDL tendon (Figure 3).
Between the medial malleolus and the sustentaculum tali calcanei, the tendon sheath of the TP tendon can be identified [a, a1]. The first TP tendon insertion is located at the plantar aspect of the navicular bone [b, b1]. (TP: Tibialis posterior, FDL: Flexor digitorum longus, FHL: Flexor hallucis longus, NB: navicular bone, MCB: Medial cuneiform bone, MM: medial malleolus)
It was found out that the diameter of the TP at the TTJ level was 10×4 mm, the diameter at the end of the muscle fibers was 9×4 mm, and the diameter at the insertion was 13×5 mm. Another finding was pertinent to the fact that the width of the insertion of the TP tendon in men (13±4 mm) was higher than in women (10±1), and this difference was statistically significant (p=.04). In addition, the width of the tendon at the end of the muscle fibers was wider in men (p=.03).
To this end, these results were evident (Table 1):
• Mean distance between the initiation of the TP tendon and the MM,
• Distance between the end of the tendon and the TTJ,
• The distance between the origin points of the tendon and insertion. Eighty-two percent of navicular TP insertions were located on the plantar aspect. The TP tendon usually showed oval and o-shaped attachments at its attachment to the navicular bone.
There was no statistically significant difference in gender between the distance of muscle fibers from MM to TTJ and insertion (p>0.05) (Table 2).
It was figured out that the total length of TP in men was higher than in women (p<0.05) (Table 3).
The cross between the TP and the FDL occurred at the posteromedial edge of the tibia almost 45.1-85.8 mm proximal to the MM. Thus, a distance of about 40-50 mm TP was proximal to the FDL. A statistical difference was detected in the TP-FDL cross according to gender (p<0.05) (Table 3).
Discussion
The course of TP tendon lies posterior to the axis of the tibiotalar joint and medial to the axis of the subtalar joint, allowing the muscle to act as a plantar flexor and invertor of the foot. During normal gait, the TP acts to invert the hindfoot, causing the midtarsal joints to lock [4-7]. According to this theory and applying tendon transfer principles, it has been postulated that the FDL tendon, should be placed as far as possible from the subtalar joint axis (at the medial aspect of the navicular bone) in order to maximize leverage in FDL tendon transfer. Nevertheless, following the anatomical course of the TPT, the first fulcrum of the TP tendon is the medial malleolar groove, and the second fulcrum is the navicular tuberosity. Our study showed that the TP tendon is primary attached to the plantar aspect of the navicular bone insertions. With this anatomical knowledge, we claim that the navicular tuberosity acts as an additional pivot point of the TPT to ease the inversion of the foot.
Willegger et al., in their study on 41 cadavers, highlighted that the TP was attached to the navicular in all samples (100%); in addition, they reported the involvement of the lateral cuneiform, medial cuneiform, metatarsal I-V, cuboid, middle cuneiform, calcaneus [8]. Park et al. suggested that a wider adhesion occurred in the insertion of the navicular bone in males than in females [2]. Eighty-two percent of navicular TP insertions were located at the plantar aspect in our study. The TP tendon usually showed oval and o-shaped attachments at its attachment to the navicular bone. The muscle’s tendon ended at the insertion point in the form of a thick bundle. Our research then announced that the males have insertion points wider than females as the research of Park et al. [2] (Table 1). We are of the opinion that this particular situation may be due to the greater muscle strength in men.
Tendon transfer, with dissimilar dorsal attachment sites above the foot (tendon-bone, tendon-tendon), is one of the most frequently applied procedures, at the same time, it is also considered the gold standard for successful surgery [5,9]. Furthermore, tendon transfer is also recommended in cases where direct surgical repair is not possible in nerve lesions and when nerve surgeries prove unsuccessful. As a result of restoring the foot dorsiflexion with tendon transfer, functional gains close to normal are observed in patients [7,10]. Considering the ankle extensors and evertors, the TP tendon will provide the ideal strength to gain dorsiflexion by eliminating the dominant inversion force. In a study, it was propounded that the TP tendon is stronger than the tendons of other muscles in the leg region [4,11]. This functionality of the TP tendon allows for a versatile treatment through minimizing morbidity. If a person both needs more power than TP’s support and the pes planus deformity that may develop as a consequence of removal or loss of the TP tendon, FDL can help with this [4,5,7,12]. Therefore, in our viewpoint, perceiving not only the TP but also the TP-FDL relationship and the distance of the cross point to the land marker points in tendon transfer is extremely valuable in terms of surgical data.
The TP tendon transfer from the interosseus membrane of the leg is among the commonly performed methods. Deciding on the dimension of the space to be opened in the membrane is extremely important for preventing muscle and tendon compression [13]. One of the factors that will determine the incision dimension in the membrane is the tendon diameter. Wagner et al. declared that the tendon diameter was 19.47 mm at 15 cm proximal to the MM tip [13]. They suggested that it would be better to open a membrane space 5 cm or 2.5 times the tendon diameter, to reduce possible complications. Xu et al, in their study on 25 cadavers, shared that a 10 cm space to be opened starting from 5 cm above the distal end of the MM would be sufficient for subcutaneous TP transfer [14]. In our study, tendon width at the end of the muscle fibers was measured larger in men than in women (Table 1). In this context, we believe that gender should be taken into account while performing the tendon transfer, and that men should act more proximal than women and open a larger space. Besides, it is deemed necessary to choose a distant place to gain a mechanical advantage, and at this point, the TP tendon length gains a particular importance [6]. Whereas the tendon’s function determines the position related to the joint, the distance to the joint determines the lever part of the force that can apply across the joint [4]. The mean TP muscle and tendon length meant that the total TP length in males was longer than in females.
TP tendon lesions usually occur at the level of the MM and 2-3 cm proximal to the insertion point in the navicular bone [15]. It has been italicized that TP tendon dysfunction is one of the most significant problems observed nominally in amateur athletes, and even the distal regions of young athletic individuals are very usual regions where the TP tendon injury is seen [15]. One of the significant parameters in tendon transfer is tendon length. The second incision should be as proximal as possible to ensure maximum tendon length. At the same time, muscle-related injuries should be avoided [6]. Thamphongsri et al. suggested that the anterior transfer of the TP tendon should occur with an incision above 7.1 cm from the MM in men and 6.4 cm in women in their study on 45 cadavers [6]. They concluded that with this incision, the root would not be damaged, and the longest movable tendon could be obtained. In our study, there was no statistically significant difference between the distance of muscle fibers from MM and insertion and gender.
The FDL is one of the long flexor muscles in the leg and foot. The muscle starts from the posterior surface of the tibia, just below the baseline of the femur, medial to the TP, and the fascia covering the TP. It inserts into a separate fascial compartment with a tendon that curves behind the MM with the TP [16,17]. There was a thin septum between the FDL tendon when the TP tendon passed just under the MM tubercle as in our study (Figure 1). In this study, the TP crossed the FDL at the lower end of the medial malleolus at a minimum of 30-77 mm proximal. This cross ended after moving below the FDL at a maximum of 70-110 mm proximal to the MM.
FDL tendon transfer is frequently used to reconstruct the TP in TP dysfunction. The location of the FDL and its contiguity to the TP has also directed surgeons to the FDL respecting accessibility [3]. Knowing the level of the TP-FDL cross will basically eliminate possible TP-FDL confusion during the surgical intervention and will provide guidance toward preventing probable damage. In our study, TP’s cross differed between the sexes. In summary, it has been found that this difference in TP-FDL cross distance should be known in surgical interventions to be performed on men and women.
TP thickness is known to increase in degenerative processes. It is important to know the normal thickness of the tendon and normal appearance for monitoring pathological conditions and processes. It is necessary to take into account the size of the muscle tendon unit and the tendon dimensions that we specifically evaluate and to take into account the variables such as height, lengths of the lower extremity, leg and foot, weight, side, age, gender, or activity level that can be effective in determining its dimensions and its 3-dimensional placement. During the surgical planning of the TP tendon transfer, the varying dimensions and placement of the tendon at different points are considered in three dimensions. This information is very valuable in determining the location and size of skin incisions, tenotomies and tunnel to be made at interosseous membrane for tendon transfer.
Conclusion
We tried to provide detailed information on the structure of the TP in a limited number of cadavers. Normal function is better understood from the detailed three-dimensional structure of the TP muscle and tendon. Knowing this allows comparison with the structure and functions of other tendons. This enables the recognition of structural changes and the understanding of their results. It orients the skin and other soft and bone tissue applications for the purpose of the operation in treatment planning. For this purpose, larger and more comprehensive cadavers, diagnostic imaging and clinical studies are needed.
Acknowledgment
We sincerely thank those who donated their amputated lower extremities to science so that anatomical research and teaching could be performed. Results from such research can potentially increase scientific knowledge and can improve patient care. Therefore, these donors and their families deserve our highest respect.
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. Otis JC, Gage T. Function of the posterior tibial tendon muscle. Foot Ankle Clin 2001;6(1):1-14.
2. Park JH, Kim D, Kwon HW, Lee M, Choi YJ, Park KR. A New Anatomical Classification for Tibialis Posterior Tendon Insertion and Its Clinical Implications: A Cadaveric Study. Diagnostics (Basel). 2021;11(9):1619-23.
3. Aronow MS. Tendon transfer options in managing the adult flexible flatfoot. Foot Ankle Clin. 2012;17(3):205–26.
4. Amber S, Christopher R, Jordan C, Ryan V. Posterior Tibial Tendon Transfers. Clin Podiatr Med Surg. 2016; 33(1):29-40.
5. Willegger M, Seyidova N, Schuh R, Windhager R, Hirtler L. The tibialis posterior tendon footprint: an anatomical dissection study. J Foot Ankle Res. 2020;13(5):25.
6. Thamphongsri K, Harnroongroj T, Jarusriwanna A, Chuckpaiwong B. How to harvest the greatest length of tibialis posterior tendon for tendon transfer: A cadaveric study. Clin Anat. 2017;30(8):1083-86.
7. Agarwal P, Gupta M, Kukrele R, Sharma D. Tibialis posterior (TP) tendon transfer for foot drop: A single center experience. J Clin Orthop Trauma. 2020;11(2):457-61.
8. Vigasio A, Marcoccio I, Patelli A, Mattiuzzo V, Prestini G. New tendon transfer for correction of drop-foot in common peroneal nerve palsy. Clin Orthop Relat Res. 2008;466(6):1454-66.
9. Khan MI, Ahmed O, Yasmeen S, Saadıque R, Beg MSA. Tibialis Posterior Transfer for Foot Drop: The Difference in Outcome for Two Different Attachment Sites. Cureus. 2021;13(10).184-61.
10. Jeng C, Myerson M. The uses of tendon transfers to correct paralytic deformity of the foot and ankle. Foot Ankle Clin. 2004;9(5):319-37.
11. Palmer JE, Russell JP, Grıeshober J, Iacangelo A, Ellıson BA, Lease TD, et al. A biomechanical comparison of allograft tendons for ligament reconstruction. Am J Sports Med. 2016;45(1):701-7.
12. Kim J, Kim JB, Lee WC. Dynamic medial column stabilization using flexor hallucis longus tendon transfer in the surgical reconstruction of flatfoot deformity in adults. Foot Ankle Surg. 2020;27(8):920-7.
13. Wagner P, Ortiz C, Vela O, Arıas P, Zanolli D, Wagner E. Interosseous membrane window size for tibialis posterior tendon transfer—Geometrical and MRI analysis. Foot Ankle Surg. 2016;22(3):196-9.
14. Xu J, Geng X, Muhammad H, Ma X, Wang X, Huang J, et al. Posterior tibialis tendon transfer via the circumtibial route: a cadaveric limb analysis. J Orthop Surg Res. 2014;30(9):121.
15. Mengiardi B, Pfirrmann CWA, Zanetti M. MR Imaging of Tendons and Ligaments of the Midfoot. Semin Musculoskelet Radiol. 2005;9(3):187–98.
16. Panchbhavi VK, Yang J, Vallurupalli S. Minimally invasive method of harvesting the flexor digitorum longus tendon: a cadaver study. Foot Ankle Int. 2008;29(1):42–48.
17. Vasudha TK, Vani PC, Sankaranarayanan G, Rajasekhar SSSN, Dinesh Kumar V. Communications between the tendons of flexor hallucis longus and flexor digitorum longus: a cadaveric study. Surg Radiol Anat. 2019;41(6):1411–19.
Download attachments: 10.4328.ACAM.21521
Berin Tugtag Demir, Murat Uzel, Ummuhan Yagmurkaya, Dilara Patat, Burak Bilecenoglu. Morphological examination and clinical significance of the tibialis posterior: A cadaver study. Ann Clin Anal Med 2023;14(8):676-680
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Test-retest reliability of ınspiratory muscle endurance testing in healthy adults
Selda Gokcen, Ozgen Aras
Department of Physiotherapy and Rehabilitation, Faculty of Health Sciences, Kutahya Health Sciences University, Kutahya, Turkey
DOI: 10.4328/ACAM.21604 Received: 2023-01-19 Accepted: 2023-04-29 Published Online: 2023-06-09 Printed: 2023-08-01 Ann Clin Anal Med 2023;14(8):681-685
Corresponding Author: Selda Gokcen, Department of Physiotherapy and Rehabilitation, Faculty of Health Sciences, Kutahya Health Sciences University, 43020, Kutahya, Turkey. E-mail: seldagokcen@gmail.com P: +90 274 260 00 43 F: +90 274 265 21 91 Corresponding Author ORCID ID: https://orcid.org/0000-0003-2017-7148
This study was approved by the Non-Interventional Clinical Research Ethics Committee of Kutahya Health Sciences University (Date: 2020-02-25, No: 2020/04-11)
Aim: The optimal test for inspiratory muscle endurance has not been determined. The aim of this study was to investigate the repeatability of the incremental load test, which is frequently used in the clinic.
Materials and Methods: Thirty healthy adults aged 18-35 years were included in the study. The anthropometric characteristics of the subjects were recorded. Physical activity levels were evaluated with the International Physical Activity Questionnaire. They performed spirometry testing, maximal inspiratory pressure assessment and incremental load test. The incremental load test was started with 30% of the maximal inspiratory pressure and the pressure was increased at one-minute intervals. The test was repeated after two weeks.
Results: Test retest reliability of the incremental load test was found excellent (ICC: 0.979; p< 0.001). There was no significant difference between the breathing parameters, rate of perceived exertion and duty cycle of the test and retest (p> 0.05).
Discussion: The incremental load test is repeatable to evaluate inspiratory muscle endurance in healthy adults. Studies investigating repeatability in the clinical setting and considering multiple repeat tests are required.
Keywords: Respiratory Muscles, Respiratory Muscle Endurance, Test-–Retest Reliability, Work Of Breathing, Maximal Inspiratory Pressure, Maximal Respiratory Pressures
Introduction
Inspiratory muscle function is characterized by strength and endurance. Inspiratory muscle strength is defined as the capacity to generate maximum force, while inspiratory muscle endurance is described as the ability to carry out a task for a specified period of time. Maximal inspiratory pressure (MIP), which is an inspiratory muscle strength measurement method frequently used in the clinic, is accepted as an indicator of respiratory muscle function. However, since inspiratory muscles are used at a submaximal level in daily life, the evaluation of their endurance is more functional than strength measurement. Unlike the measurement of inspiratory muscle strength, there is not yet a generally accepted measurement method for the evaluation of inspiratory muscle endurance [1].
External loading, ventilatory endurance and time trials are methods that are generally used to evaluate inspiratory muscle endurance. Maximal voluntary ventilation (MVV) and maximal sustainable ventilation (MSV) are time trials that aim to provide maximum ventilation within a certain period of time. The 10-15 second MVV test is too short and insufficient to assess respiratory muscle endurance. It is no longer recommended for respiratory muscle endurance testing in patients with respiratory muscle weakness. The MSV test, which measures ventilation that can be sustained over a long period of time (e.g. 12-15 minutes), is a more significant measure of respiratory muscle endurance than MVV. The MSV test, which measures ventilation that can be sustained over a long period of time (e.g. 12-15 minutes), is a more significant measure of respiratory muscle endurance than MVV. However, there is no consensus on which MSV protocol to use [2, 3].
Isocapnic hyperpnea is an endurance test that includes both inspiratory and expiratory muscle loading. Loads are determined as a percentage of MVV. The need for costly special equipment limits the use of the test in the clinic [2, 4].
External load tests, which consist of constant load test and incremental load test, have been used more frequently in recent years because they allow the use of portable and low-cost devices. A constant load test is an external load test in which threshold load (a percentage of the MIP) is maintained until task failure (Tlim) [5, 6]. In an incremental load test, the inspiratory load is increased as a percentage of the MIP at a specified time or breath intervals. Peak pressure is the maximum inspiratory mouth pressure maintained in the last step [7, 8].
Many authors recommend the use of incremental load test instead of constant load test, as they are less affected by participant motivation, tolerated more easily, reflect the response to treatment more accurately, and have higher reproducibility in the pediatric group and patient population [1, 3, 4, 9].
Since external load tests are affected by breathing patterns, it is recommended to control respiratory characteristics such as mouth pressure, flow and inspiratory volume during testing. However, the control of these parameters causes the test procedure to be complicated. For this reason, some authors state that it is necessary to measure with devices that can record respiratory characteristics in order to overcome this problem [3].
The aim of this study was to evaluate the repeatability of the incremental load test in a healthy adult population with a portable device (PowerBreathe KH2) that measures mouth pressure, flow and inspiratory volume during testing. Our hypothesis was that the incremental load test would be repeatable in healthy adult subjects who did not have factors affecting the respiratory muscle.
Material and Methods
Subjects were recruited from an ongoing observational study investigating respiratory muscle endurance in healthy adults (clinicaltrials.gov identifier: NCT05237427). The study was approved by the Non-Interventional Clinical Research Ethics Committee of Kutahya Health Sciences University (2020/04-11).
We included at least 20 % of the total number of participants planned to be included in the ongoing study (120 subjects) in the test-retest analysis [10]. Thirty (11 males, 19 females) healthy non-smoker adult subjects aged 18-35 years were included in the study. Adults with respiratory tract disease, heart disease, neuromuscular disease, scoliosis, previous thoracic surgery, and previously experienced respiratory muscle endurance protocol were not included in the study [9, 11].
Anthropometric Assesment
Body weight was assessed with a digital scale in the orthostatic position, without shoes, with minimal clothing (Tanita BC 730, Tokyo, Japan) [12]. Height was measured with the feet parallel and adjacent to each other, the arms extended by the body, and the head in a neutral position (Seca 213, Hamburg, Germany) [13]. Body mass index (BMI) was calculated by dividing body weight by the square of height (kg/m²).
Pulmonary Function Test (PFT)
Pulmonary function test measurements were made to confirm that the respiratory function parameters of the subjects were within the normal range. Forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) were measured with a portable spirometer (Cosmed Pony FX, Inc, Italy). The test was carried out in a sitting position. The highest of the three maneuvers with 95% agreement with each other was selected for analysis. PFT parameters were expressed as a percentage of expected values for age, height, body weight, and gender [14].
Maximal Voluntary Ventilation (MVV)
MVV measurements were made with a portable spirometer (Cosmed Pony Fx, Inc, Italy). The participant was asked to breathe as deeply and rapidly as possible (90-110 breaths/min) for 12 seconds. The highest value of the three measurements was used for value analysis [15].
Respiratory Muscle Strength
An electronic mouth pressure measuring device (POWERbreathe KH2, POWERbreathe International Ltd, UK) was used for respiratory muscle strength. The participant was asked to do the maximum expiration up to the residual volume, and to make a maximum inspiration for 1-3 seconds after the nose was closed with the help of a clip. The maximum inspiratory pressure (MIP) formed at the mouth was measured. The measurements were repeated nine times, one minute apart, with no difference of 10 cmH2O or 10% between results. Equations of Black and Hyatt were taken as references in the interpretation of the measurements [3, 16].
Respiratory Muscle Endurance
Respiratory muscle endurance test was evaluated with an incremental load test. After the device (POWERbreathe KH2, POWERbreathe International Ltd, UK) was placed in the mouth, the nose was closed with a clamp, and the participant was asked to breathe through the mouth. The test started with 30% of the maximal inspiratory pressure, and the pressure was increased by 10% at one-minute intervals. Breathing frequency was fixed at 15 breaths/minute by a metronome. In the last 10 seconds of each load level, subjects were requested to rate of perceived exertion (RPE) through the Modified Borg Scale. The test was terminated when the participant was too tired to continue or was unable to open the valve three consecutive times. The outcome measure, called sustained maximal inspiratory pressure (SMIP), was defined as the highest load, in percentage of MIP sustained for full one minute. The measurement was repeated at least two weeks later to evaluate the reproducibility reproducibility [3, 6, 17].
Physical Activity
Physical activity level was assessed with International Physical Activity Questionnaire-Short Form (IPAQ-SF). It is used to determine the physical activity level and sedentary life styles of individuals between the ages of 15 and 69. The physical activity score is calculated by converting the questionnaire score to Metabolic Equivalent of Task (MET- min/week, 1 MET=3.5 ml/kg/min). Moderate and intense physical activity and durations of walking and sitting in the previous seven days were evaluated with the IPAQ-SF. Physical activity level was classified as ‘inactive’ for values lower than 600 MET-min/week, ‘minimally active’ for values of 600–3000 MET-min/week, and ‘active’ for values over 3000 MET-min/week [18].
Statistical analyzes
Statistical analyzes were performed using the statistical package program SPSS 15.0. The conformity of the variables to the normal distribution was evaluated with the Shapiro-Wilk test. The repeatability of the test was determined by the intraclass correlation coefficient (ICC). The difference in respiratory parameters was evaluated with the Wilcoxon Test. Statistical significance level was accepted as 0.05.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
Thirty subjects were evaluated. Physical and demographic characteristics of the subjects are given in Table 1. According to the pulmonary function testing, the subjects’ FEV1 and FVC values are in the normal range. There was no respiratory muscle weakness based on MIP results. The subjects had a moderate level of physical activity.
Test-–retest reliability of the incremental load test was found excellent (ICC: 0.979; p< 0.001) (Figure 1).
Reliability parameters obtained for SMIP are summarized in Table 2. There was no significant difference between the breathing parameters, RPE and the duty cycle of the test and retest (Table 3).
Discussion
To the best of our knowledge, this is the first study to examine the repeatability of incremental load test by recording continuously flow, volume, pressure and WOB responses during the test. The incremental load test was repeatable with excellent test retest reliability in healthy non-smoker adults with moderate levels of physical activity.
The pressure reached (SMIP) was on average 7% higher in the second test. This value is considered acceptable as the learning factor may have an effect on the result. In the literature, different opinions on this subject have been reported. Sturdy et al. who performed an incremental endurance test in 10 COPD patients with moderate severe obstruction, stated that not accounting the learning effect would result in underestimating test [19]. Conversely, Martyn and colleagues reported in their study with healthy subjects that the subjects were able to tolerate gradually increasing load in the incremental test, and therefore the test result would not be influenced by the learning effect [6]. Subjects’ age, health status, and motivation may lead to divergence of findings.
In this study we standardized respiratory frequency to 1:2 with a metronome, establishing a frequency of 15 breaths per minute, according to the resting respiratory rate. Subjects had no difficulty in complying with this respiratory rate. Some researchers stated that IME was not affected by respiratory frequency and subjects did not need to be restricted about respiratory rate [20]. In some studies, the respiratory rate was not predetermined, but only recorded during the test [1, 4, 19]. But small changes in the duty cycle may affect the endurance measurement results such as pressure reached and time [17, 21]. Eastwood et al. emphasized that respiratory parameters and RPE were affected by the change of respiratory frequency in repeated tests, in their studies in which they did not control the respiratory frequency. They also stated that differences in breathing pattern in consecutive tests may affect the maximal threshold pressure reached in the test [22]. Moreover, to accurately interpret the change in test results as a change in respiratory muscle endurance, measurements in which the breathing pattern is controlled should be preferred [1]. For this reason, many authors state that respiratory frequency should be fixed during inspiratory muscle endurance testing [1, 3].
Monitoring more specific measures of the respiratory cycle may better characterize the test [4]. Since breathing pattern affects muscle performance, respiratory characteristics should be checked during the test. However, since the control of these parameters leads to the complexity of the method, it is recommended to at least record them to ensure standardization. The device we used for testing stored the data of breathing caharacteristics like mouth pressure, inspiratory volume, flow, power and WOB continuously. Recording these parameters may be important for interpreting adaptive changes such as reaching high inspiratory rates in a shorter time, increasing inspiratory volume after educational interventions, or detecting external load, inspiratory flow and volume differences in different patient populations [3].
Maximal voluntary ventilation is a ventilatory endurance test that is highly dependent on the subject’s cooperation, motivation and respiratory system mechanics (obstructive or restrictive) [23]. Since the test measurement is simple and short, it is used as a measurement of respiratory muscle endurance in different populations. However, from a physiological point of view, it is no longer recommended to evaluate respiratory muscle endurance, considering that a 12-15 second test would be insufficient to evaluate endurance [3]. It has already been stated that MVV is not sensitive to changes in respiratory endurance that occur with training [24]. Also, not only inspiratory muscles but also expiratory muscles are recruited in MVV measurement [25]. In our study, there was a moderate relationship between MVV and SMIP. The moderate correlation between MVV and IME in our study, confirms this recommendation and comments.
The study also presents some limitations. The sample size may constitute a limitation of the study. The present study only incorporated test-retest sessions. Therefore, future studies should consider multiple repeat tests to confirm our findings. Further studies are also required to evaluate reproducibility in clinical settings.
Conclusion
In conclusion, incremental load test using the POWERbreathe KH2 device is repeatable to evaluate inspiratory muscle endurance in healthy adults. Generation of reference equations can contribute to a better assessment of individuals.
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 supported by Kutahya Health Sciences University, Scientific Research Projects Coordination Unit (TDK-2020-41).
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. Hill K, Jenkins SC, Philippe DL, Shepherd KL, Hillman DR, Eastwood PR. Comparison of incremental and constant load tests of inspiratory muscle endurance in COPD. Eur Respir J. 2007;30(3): 479-486.
2. Larribaut J, Gruet M, McNarry MA, Mackintosh KA, Verges S. Methodology and reliability of respiratory muscle assessment. Respir Physiol Neurobiol. 2020; 273:e103321.
3. Laveneziana P, Albuquerque A, Aliverti A, Babb T, Barreiro E, Dres M, et al. ERS statement on respiratory muscle testing at rest and during exercise. Eur Respir J. 2019; 53(6). DOI: 10.1183/13993003.01214-2018.
4. Basso-Vanelli RP, Di Lorenzo VA, Ramalho M, Labadessa IG, Regueiro EM, Jamami M, et al. Reproducibility of inspiratory muscle endurance testing using PowerBreathe for COPD patients. Physiother Res Int. 2018; 23(1):e1687.
5. Reiter M, Totzauer A, Werner I, Koessler W, Zwick H, Wanke T. Evaluation of inspiratory muscle function in a healthy Austrian population–practical aspects. Respir. 2006; 73(5): 590-6.
6. Troosters T, Gosselink R, Decramer M. Respiratory muscle assessment. Eur Respir Monogr. 2005; 31: 57-71.
7. Illi SK, Held U, Frank I, Spengler CM. Effect of respiratory muscle training on exercise performance in healthy individuals. Sports Med. 2012; 42(8): 707-24.
8. Eastwood PR, Hillman DR, Finucane KE. Inspiratory muscle performance in endurance athletes and sedentary subjects. Respirology. 2001; 6(2):95-104.
9. Woszezenki CT, Heinzmann-Filho JP, Vendrusculo FM, Piva TC, Levices I, Donadio MVF. Reference values for inspiratory muscle endurance in healthy children and adolescents. PLoS One. 2017; 12(1):e0170696.
10. Cankaya O, Kerem Gunel M, Ozdemir P. Construct-concurrent validity and reliability of the European Child Environment Questionnaire (ECEQ) in a sample of Turkish children with cerebral palsy. Disabil Rehabil. 2022; 44(10): 2104-12.
11. Silva PE, de Carvalho KL, Frazão M, Maldaner V, Daniel CR, Gomes-Neto M. Assessment of maximum dynamic inspiratory pressure. Respir Care. 2018; 63(10):1231-8.
12. Alazzam MF, Darwazeh AMG, Hassona YM, Khader YS. Diabetes mellitus risk among Jordanians in a dental setting: A cross-sectional study. Int Dent J. 2020; 70(6):482-8.
13. Baharudin A, Ahmad MH, Naidu BM, Hamzah NR, Zaki NAM, Zainuddin AA, et al. Reliability, technical error of measurement and validity of height measurement using portable stadiometer. Pertanika J Sci Technol. 2017; 25(3): 675-85.
14. Ruppel GL, Enright PL. Pulmonary function testing. Respir Care. 2012; 57(1): 165-75.
15. Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, et al. Standardisation of spirometry. Eur Respir J. 2005; 26(2):319-38.
16. Black LF, Hyatt RE. Maximal respiratory pressures: normal values and relationship to age and sex. Am Rev Respir Dis. 1969; 99(5):696-702.
17. American Thoracic Society/European Respiratory Society. ATS/ERS Statement on respiratory muscle testing. Am J Respir Crit Care Med. 2002; 166(4):518-624.
18. 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.
19. Sturdy GA, Hillman DR, Green DJ, Jenkins SC, Cecins NM, Eastwood PR. The effect of learning on ventilatory responses to inspiratory threshold loading in COPD. Respir Med. 2004; 98(1):1-8.
20. Hill K, Jenkins SC, Philippe DL, Cecins N, Shepherd KL, Green DJ, et al. High-intensity inspiratory muscle training in COPD. Eur Respir J. 2006; 27(6):1119-28.
21. Langer D, Charususin N, Jácome C, Hoffman M, McConnell A, Decramer M, et al. Efficacy of a novel method for inspiratory muscle training in people with chronic obstructive pulmonary disease. Phys Ther. 2015; 95(9):1264-73.
22. Eastwood PR, Hillman DR, Morton AR, Finucane KE. The effects of learning on the ventilatory responses to inspiratory threshold loading. Am J Respir Crit Care Med. 1998; 158(4):1190-6.
23. Neufeld EV, Dolezal BA, Speier W, Cooper CB. Effect of altering breathing frequency on maximum voluntary ventilation in healthy adults. BMC Pulm Med. 2018; 18(1):1-7.
24. Sales AT, Fregonezi GA, Ramsook AH, Guenette JA, Lima IN, Reid WD. Respiratory muscle endurance after training in athletes and non-athletes: A systematic review and meta- analysis. Phys Ther Sport. 2016; 17:76-86.
25. Khosravi M, Tayebi SM, Safari H. Single and concurrent effects of endurance and resistance training on pulmonary function. Iran J Basic Med Sci. 2013; 16(4):628.
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Selda Gokcen, Ozgen Aras. Test-retest reliability of ınspiratory muscle endurance testing in healthy adults. Ann Clin Anal Med 2023;14(8):681-685
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What is the best treatment for adult distal 1/3 humerus fractures?
Mehmet Yilmaz 1, Ibrahim Ulusoy 2, Murat Gurger 3, Numan Atilgan 4
1 Department of Orthopedic Surgery, 25 Aralik State Hospital, Gaziantep, 2 Department of Orthopedic Surgery, Selahhadin Eyyubi State Hospital, Diyarbakır, 3 Department of Orthopedic Surgery, Fırat University, Elazığ, 4 Department of Hand Surgery, Şanlıurfa Mehmet Akif İnan Training and Research Hospital, Sanliurfa, Turkey
DOI: 10.4328/ACAM.21605 Received: 2023-01-20 Accepted: 2023-04-29 Published Online: 2023-06-20 Printed: 2023-08-01 Ann Clin Anal Med 2023;14(8):686-690
Corresponding Author: Mehmet Yılmaz, Department of Orthopedic Surgery, 25 Aralik State Hospital, Gaziantep, Turkey. E-mail: doctor_yilmaz@hotmail.com P: +90 532 577 23 76 Corresponding Author ORCID ID: https://orcid.org/0000-0002-1366-9163
This study was approved by the Clinical Research Ethics Committee of Firat University (Date: 2015-02-09, No: 29798557/903.99)
Aim: Adult humeral fractures that do not extend to the elbow joint can be seen in low-energy trauma in the elderly and high-energy trauma in the young. Fractures of the distal 1/3 of the humerus are treated with surgical and non-surgical methods. Our study aimed to evaluate the functional and radiological results of the distal 1/3 humerus fractures, which do not involve the joint, by comparing the conservative and surgical treatments and the surgical techniques used.
Material and Methods: Thirty-five patients with adult distal 1/3 humeral fractures that did not extend to the joint between January 2010 and October 2014 were included in the study. The cases were evaluated retrospectively.
Results: Nine of the cases were female and 26 were male. The mean age of the patients was 33,6. The articular range of motion (ROM) of cases was measured at an average of 118,8˚, and extension loss was measured at an average of 7,14˚. The average Mayo score of cases was measured at 87. Mono plaque osteosynthesis was applied to 20 of all cases (Group I), double plate osteosynthesis was applied to 11 (Group II), and conservative treatment was applied to 4 (Group III). A statistically significant difference between Group I and Group II was not been determined regarding union time, complication, Mayo Score, Cassebaum’s rating, ROM, and extension loss. According to surgical approaches applied to patients (lateral-posterior), while no statistical difference was determined regarding complications, union time, and ROM, a significant difference was determined regarding Mayo Score and extension loss. According to different determination methods, a statistical difference was not been determined regarding complications, ROM, extension loss, Mayo Score and union time.
Discussion: We recommend surgery with a lateral approach to preserve the extensor mechanism in fractures of the distal 1/3 of the humerus.
Keywords: Humerus Distal Fractures, Surgical Treatment, Conservative Treatment, Mayo Score
Introduction
The elbow joint is a structure that has an important role in the fulfillment of daily life activities. The elbow joint plays a role in the wrist and hand functions through the radius and ulna. If fractures of the radius, ulna and distal humerus are not treated appropriately, serious loss of function is observed in the upper extremity [1].
Today, methods used in the treatment of humeral diaphyseal and distal region fractures can be grouped into two main groups as conservative and surgical. In addition to the fracture location and type, its anatomical proximity to neurovascular structures forced the surgeon to consider different treatment plans for each fracture [2]. Due to its tight neighborhood, radial nerve and vessel injury pose a potential risk. Immobilization of the joint for a long time can lead to limitation of movement and union disorders in the shoulder and elbow [3]. When the advantages and disadvantages of both surgical and conservative treatment methods are evaluated, one of the most discussed bone fractures about the treatment method to be applied is humeral fractures. There is still no consensus between conservative treatment and surgical treatment in distal humeral fractures that do not involve the joint, and there is no consensus in terms of fixation with a single plate or double plate even in surgical treatment.
In this study, we aimed to evaluate the functional and radiological results of conservative treatment and surgical treatments (Single Plate? / Double Plate?) preferred in the treatment of distal 1/3 humeral fractures that do not involve the joint.
Material and Methods
Ethical Statement
The study received ethical approval from Firat University Clinical Research Ethics Committee (Approval No: 29798557/903.99. Date: 2015-02-09). This study was carried out in accordance with the Declaration of Helsinki.
Study Design
Patients with a follow-up period of at least 24 months, treated for adult distal 1/3 humeral fractures, according to the AO (Arbeitsgemeinschaft für Osteosynthesefragen) classification types 12-A/B/C and 13-A, not extending to the elbow joint, between January 2010 and October 2014, in a single center were included in the study.
In our retrospective study, patients who were treated by another clinic and then underwent revision surgery by our clinic, patients who were treated by our clinic but were not followed up, patients with missing and/or suspicious information in the hospital information management system or patient files, and pediatric patients were excluded from the study. Considering the inclusion and exclusion criteria, 35 patients out of 41 were included in the study.
By examining patient files retrospectively, age, gender, type and date of trauma, type of fracture according to the AO classification, additional pathologies, if any, type according to Gustillo-Anderson fracture classification, the time elapsed before surgery, surgical approach and technique used, duration of follow-up, the month of fracture union, complications, and the difference in the carrying angle between the elbows of the cases were evaluated. Anteroposterior and lateral radiographs and radiological evaluations, goniometric elbow joint range of motion (ROM) and extension loss were measured in the last outpatient clinic controls of the cases. The Mayo Elbow Performance Score and Cassebaum rating system were used to evaluate the functional outcomes of the cases.
Statistical analysis
Statistical Package for Social Sciences (SPSS) for Windows 16.0 program was used for statistical analysis. Chi-Square, Student-t, Annova and Correlation tests were used for statistical analysis. The results were evaluated at 95% confidence interval and the significance level of p<0.05.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
Group I consisted of 20 patients (57%) with single plate osteosynthesis, 11 (31.4%) patients with double plate osteosynthesis, and Group III with 4 patients (11.6%) treated with conservative treatment.
Among patients of Group I, 12 (60%) were male and 8 (40%) were female. There were fractures in the right humerus in 10 cases and in the left humerus in 10 cases. The mean age was 36.15 (±16.5). Seven (35%) of the cases were open fractures and 13 (65%) were closed fractures. Of the open fractures, 3 were Type 1, 1 was Type 2, and 3 were Type 3. According to the AO/ASIF classification, 6 (30%) of the cases in Group I were 12-A1.3, 3 (15%) 12-A3.3, 2 (10%) 12 B1.3, 4 (20%) ) 12-B2.3, 1 (5%) 12-B3.3, 2 (10%) 13-A2.1, 2 (10%) 13-A3.3 type fractures. The mean follow-up period was 43.9 (±17.4) months.
Among cases in Group II, 10 (90.9%) were male and 1 (9.1%) was female. Six of them had right humerus fractures and 5 of them had left humerus fractures. The mean age was 33.6 (±14.8) years. 1 (9.1%) of the cases were open fractures and 10 (90.9%) were closed fractures. The open fracture was Type 2. According to the AO/ASIF classification, 4 (36%) of the cases in Group II were 12-A1.3, 3 (27%) 12-B1.3, 1 (9%) 12-C1.1, 1 ( 9%) 12-C3.2, 1 (9%) 13-A2.3, 1 (9%) 13-A3.2 type fracture. The mean follow-up period was 36.36 (±14.53) months.
The cases were compared according to the applied surgical technique. Group I consisted of 20 (65%) patients with a single plate and Group II of 11 patients (35%) with a double plate. The groups were statistically similar in terms of gender, age, side, fracture type according to Gustilo-Andersona classification, fracture type according to AO classification, duration of follow-up, trauma mechanism and time to surgery. Although the follow-up period of Group I was longer, it was not statistically significant. Group I and Group II were statistically different in terms of the surgical opening method (p<0.05). While more lateral incisions were made in the single-plated group, it was seen that both lateral and posterior incisions were used in the double plated group. The mean operation time of the cases in Group I was 97 minutes, while the mean operation time of the cases in Group II was 153.6 minutes. It was observed that 6 (30%) of the cases in Group I received blood transfusion, while 2 (18%) of the cases in Group II received blood transfusion (Table 1).
All of the cases in Group III were male. The mean age was 20.75 (±2.21). Three of the fractures were right and one was left. All of them were closed fractures. According to the AO/ASIF classification, 1 (25%) case in Group III had 12-B1.3 type fracture, 1 (25%) had 12-B2.3, 1 (25%) had 12-C1.1, 1 (25%) had 12-C2.1 type fracture. The mean follow-up period was 36 (±6.97) months.
When the cases that underwent surgery (Group I-Group II) and the cases that were treated conservatively were compared, there was no significant difference in terms of gender (p:0.28), side (p:0.37), mean age (p:0.79), fracture type according to Gustilo- Anderson classification (p:0.72) and follow-up time (p:0, 54). However, a statistically significant difference was found in terms of fracture type (p:0.034) according to the AO classification.
When the cases that underwent surgery (Group I-Group II) and the cases that were treated conservatively were compared, no significant difference was detected in the type of trauma (p:0.14), mean follow-up time (p:0.54), mean time to union (p:0.55), complication (p:0.63), mean ROM (p:0.46), loss of extension (p:0.39), Mayo Score evaluation (p:0.23), Cassebaum rating (p:0.14), and time to union of fractures according to Gustilo-Anderson fracture typing (p:0.21). In addition, a significant difference was found in terms of the mean mayo score (p:0.045) (Table 1).
According to the duration of surgery of the cases, there was no statistically significant difference in terms of ROM (p:0.409) and loss of extension (p:0.249). However, a statistically significant difference was found in terms of Mayo Elbow Scoring (p:0.008) (Table 2). A statistically significant relationship was found between the two groups according to surgical approaches (p:0,02) (Table 2).
According to the applied surgical approaches (lateral-posterior), no statistically significant difference was found in terms of complications (p:0.968), union time (0.736), ROM (p:0.131). However, a significant difference was found in Mayo Score (p:0.039) and loss of extension (p:0.048) (Table 3).
While there was a statistically significant relationship between implant failure and Y-Plate between the groups (p:0.048), there was no relationship between plating and implant failure in general (p:0.456). No significant correlation was observed between the plating technique and complication (p:0.279). When we examined it according to the Mayo Elbow Performance Scoring, no significant correlation was observed between plating technique and complication (p:0.678).
Discussion
The elbow joint is a structure that has an important role in the fulfillment of daily life activities. If fractures involving the elbow joint are not treated appropriately, serious loss of function is observed in the upper extremity [1].
Humerus fractures show a bimodal distribution considering age and gender. According to the energy level, injuries can be divided into two groups as high-energy traumas and low-energy traumas. Especially in the young population, open fractures and other system injuries are more likely to occur because they occur as a result of high-energy traumas [4, 5]. In our study, in accordance with the literature, we mostly see it after high-energy traumas in young patients, and mostly after low-energy traumas such as simple falls in elderly patients.
Treatment recommendations for 1/3 distal diaphysis and distal end extra-articular fractures of the humerus are largely based on studies evaluating non-surgical treatments such as functional braces [6,7], and some surgeons advocate surgical treatment for these fractures. Advocates of conservative treatment state that surgery is unnecessary for these patients because of the risks of complications such as infection and neurovascular injury [7-12].
According to O’Driscoll [13], the ideal approach should provide sufficient view, it can be extended when necessary, it should be in the form of a soft tissue dissection without osteotomy, dissection should be in the plane of the nerves and should not cross the nerves, all alternative surgical procedures can be applied with the same opening, allowing early rehabilitation, and possible revisions should be made with the same incision.
In our study, the lateral incision was preferred more frequently. Compared with patients who had posterior and double incisions, it was observed that the Mayo score was better and the loss of extension was less in patients with lateral incisions. We believe that the single incision causes less loss of extension, faster rehabilitation of the patients and better elbow functions (Mayo Score) by causing less damage to the extensor mechanism, especially when compared to the double incision.
Although there is ample evidence that bicolumnar support is advantageous for intra-articular fractures, uncertainty remains as to whether double-plating is necessary for extra-articular supracondylar humeral fractures [14].
The disadvantages of using double plate fixation with a posterior exposure are the wide surgical exposure required to the posterior and medial aspects of the elbow. Ulnar nerve injury, postoperative wound problems, and elbow stiffness are frequently reported complications associated with double plate fixation [15, 16, 7]. It is mentioned in the literature that a single plate was used as a reduction tool before [17]. The lateral plate is not only a means of reduction, but also functions as a structural support. One of the methods used to reduce the surgical risk is the application of a single plate with only lateral exposure. Some authors [7, 18] recommend fixation with a single posterolateral plate to avoid excessive stripping of large soft tissue and reduce surgical time. Some studies [18, 19] showed that a single plate is sufficient for the fixation of extra-articular humeral distal fractures. Yet another study [14] found that posterolateral locking single-plate and orthogonal anatomical double-plate were biomechanically equivalent in distal humerus extraarticular supracondylar fractures.
In our study, no statistically significant difference was found between the two groups in terms of complication, union time and functional outcome in single plate or double plate fixation method. Since there is only one case in which the Y plate was made, it is not correct to comment on the Y plate in a statistical sense.
The normal range of motion of the elbowis 0°-150° flexion, 85° supination, 85° pronation [20]. The most commonly used range of motion in daily life is 30°-130° flexion, 50° supination, 50° pronation [20]. In our study, the mean range of motion was 118.8˚ and the mean extension loss was 7.14˚. We assessed that the mean range of motion of the joint supported the recovery of elbow joint functions. While no significant difference was found between surgical techniques (Group I and Group II) in terms of ROM, when the patients who underwent surgery (Group I-Group II) were compared with the patients who were treated conservatively, the range of motion of the patients who were treated conservatively was significantly better.
In our study, we encountered 16% of complications. Of these, 13% were delayed union and 3% were nonunion. Our patients with non-union problem were re-operated, the implant used for fixation was changed (we revised the single plate with a double plate), and union was achieved by resuscitating the fracture line.
Ulnar neuropathy may occur during initial injury or iatrogenically during surgical fixation. While ulnar nerve lesion due to humeral distal end fractures or treatment is observed between 3-8%, the incidence of ulnar neuropathy during surgical fixation has been reported to be 0-12% [21,22,12]. The anterior transfer of the ulnar nerve is controversial. The ulnar nerve was not transposed anteriorly in the patients included in our study. No iatrogenic nerve damage was observed in our patients.
There are some limitations of our study. The low number of patient groups and the presence of many variable factors prevented us from obtaining statistically significant results. Prospective, randomized, multicenter studies with large numbers of patients are needed.
Conclusion
In these fractures, which are seen after high-energy trauma in young patients and after low-energy trauma in elderly patients, post-traumatic neurovascular structures, especially ulnar nerve examination, should be careful. The Association for Osteosynthesis (AO) classification alone cannot help predict prognosis. The type of fracture (according to AO and Gustilo-Anderson), together with the treatment protocols applied to the patient, affects the patient’s compliance in post-surgical rehabilitation. Early initiation of joint range of motion exercises is of great importance for the success of treatment methods. We recommend surgery with a lateral approach to preserve the extensor mechanism in fractures of the distal 1/3 of the humerus.
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. Ohl X, Siboni R. Surgical treatment of terrible triad of the elbow. Orthop Traumatol Surg Res. 2021; 107(1):102784.
2. Paavolainen P, Bjorkenheim JM, Slatis P, Paukku P. Operative treatment of severe proksimal humeral fractures. Acta Orthop Scand. 1983; 54(3):374-9.
3. Panagopoulos A, Solou K, Tatani I, Triantafyllopoulos IK, Lakoumentas J, Kouzelis A, et al. What is the optimal surgical treatment for Neer type IIB (IIC) distal clavicle fractures. J Orthop Surg Res. 2022; 17(1):215-29.
4. Elmadag M, Erdil M, Bilsel K, Acar MA, Tuncer N, Tuncay I. The olecranon osteotomy provides better outcome than the triceps-lifting approach for the treatment of distal humerus fractures. Eur J Orthop Surg Traumatol. 2014; 24(1):43-50.
5. Amis AA, Hughes S, Miller JH, Wright V, Dowson D. Elbow joint forces in patients with rheumatoid arthritis. Rheumatol Rehabil. 1979; 18(4):230-4.
6. Sarmiento A, Horowitch A, Aboulafia A. Functional bracing of comminuted, extra-articular fractures of the distal third of the humerus. J Bone Joint Surg Br. 1990; 72(2):283-7.
7. Jawa A, McCarty P, Doornberg J. Extra-articular distal-third diaphyseal fractures of the humerus. A comparison of functional bracing and plate fixation. J Bone Joint Surg Am. 2006; 88(11):2343-7.
8. Aitken GK, Rorabeck CH. Distal humeral fractures in the adult. Cun Orthop Relat Res. 1986; 207:191-7.
9. Tinstad EM, Wolinsky PR, Shyr Y. Effect of immediate weightbearing on plated fractures of the humeral shaft. J Trauma. 2000; 49(2):278-80.
10. Capitani P, Chiodini F, Di Mento L, Cavanna M, Bove F, Capitani D. Locking compression plate fixation in humeral shaft fractures: A comparative study to literature conservative treatment. Injury. 2023;54:2-8.
11. Kessler SB, Nast-Kolb D, Brunner U, Wischhofer E. Intramedullary Nailing of The Humerus as an Alternative to Conservative Therapy and to Plate Osteosynthesis. Orthpade. 1996; 25(3):216-22.
12. Gerwin M, Hotchkiss RN, Weiland AJ. Alternative operative exposures of the posterior aspect of the humeral diaphysis with reference to the radial nerve. J Bone Joint Surg Am. 1996; 78(11):1690-5.
13. O’Driscoll S. The triceps-reflecting anconeus pedicle (TRAP) approach for distal humeral fractures and nonunions. Orthop Clin North Am. 2000; 31(1):91-101.
14. Lerman D, O’toole RV, Eglseder WA, Murthi M. Are two plates necessary for extraarticular fractures of the distal humerus? Current Orthopaedic Practice. 2014; 25:5.
15. O’Driscoll SW. Optimizing stability in distal humeral fracture fixation. J Shoulder Elbow Surg. 2005; 14(Suppl.1):S186-94.
16. Athwal GS, Hoxie SC, Rispoli DM. Precontoured parallel plate fixation of AO/OTA type C distal humerus fractures. J Orthop Trauma. 2009; 23(8):575-80.
17. Archdeacon MT, Wyrick JD. Reduction plating for provisional fracture fixation. J Orthop Trauma. 2006; 20(3):206-11.
18. Levy JC, Kalandiak SP, Hutson JJ. An alternative method of osteosynthesis for distal humeral shaft fractures. J Orthop Trauma. 2005; 19(1):43-7.
19. Waddell JP, Hatch J, Richards R. Supracondylar fractures of the humerus-results of surgical treatment. J Trauma. 1988; 28(12):1615-21.
20. Atalar A, Demirhan M, Salduz A, Kilicoglu O, Seyahi A. Functional results of the parallel-plate technique for complex distal humerus fractures. Acta Orthop Traumatol Turc. 2009; 43(1):21-7.
21. Doornberg JN, van Duijn PJ, Linzel D. Surgical treatment of intra-articular fractures of the distal part of the humerus: Functional outcome after twelve to thirty years. J Bone Joint Surg Am. 2007; 89(7):1524-32.
22. Atilgan N, Duman N, Colak TS, Korucu I H, Demiryurek M, Yilmaz M. Comparison of the results of percutaneous and open screw fixation in the treatment of scaphoid nonunion fractures. Eur Rev Med Pharmacol Sci. 2022; 26(24): 9204-11.
23. Atilgan N, Duman N, Colak TS, Korucu IH, Demiryurek M. Multidisciplinary treatment and functional outcome evaluation of combined injuries of nerves, vessels, and flexor tendons: spaghetti wrist. Eur Rev Med Pharmacol Sci. 2022; 26(23):8808-15.
24. Bilge O, Kekeç AF, Atılgan N, Yaka H, Dundar ZD, Karagüven D, et al. The initial analysis of pediatric fractures according to the AO/OTA fracture classification and mechanisms of injuries. Ulusal Travma ve Acil Cerrahi Dergisi. 2022; 28(10): 1500-7.
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Mehmet Yilmaz, Ibrahim Ulusoy, Murat Gurger, Numan Atilgan. What is the best treatment for adult distal 1/3 humerus fractures? Ann Clin Anal Med 2023;14(8):686-690
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Determination of somatotypes of children with adolescent idiopathic scoliosis and its relationship with scoliosis
Adnan Apti 1, Tuğba Kuru Çolak 2, Burçin Akçay 3, İlker Çolak 4
1 Department of Physiotherapy and Rehabilitation, Faculty of Health Sciences, Istanbul Kültür University, Istanbul, 2 Department of Physiotherapy and Rehabilitation, Faculty of Health Sciences, Marmara University, Istanbul, 3 Department of Physiotherapy and Rehabilitation, Faculty of Health Sciences, Bandırma Onyedi Eylül University, Balıkesir, 4 Department of Orthopedi and Traumatology, VM Medical Park Maltepe Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.21629 Received: 2023-01-31 Accepted: 2023-03-12 Published Online: 2023-05-05 Printed: 2023-08-01 Ann Clin Anal Med 2023;14(8):691-695
Corresponding Author: Adnan Apti, Department of Physiotherapy and Rehabilitation, Faculty of Health Sciences, Istanbul Kültür University, 34158, Bakırköy, Istanbul, Turkey. E-mail: adnanapti@yahoo.com P: +90 539 568 71 11 F: +90 212 498 40 86 Corresponding Author ORCID ID: https://orcid.org/0000-0001-9794-9367
This study was approved by the Ethics Committee of Istanbul Kultur University (Date: 2022-04-25, No: 2022/86)
Aim: Adolescent idiopathic scoliosis (AIS) is a three-dimensional deformity of the spine. In adolescence, body morphology can change for various reasons such as genetics, nutrition, and level of physical activity. It has been reported that there are differences in the normal physical growth pattern in children with AIS, which may be due to hormonal changes. The relationship between body morphology and scoliosis is questionable because of the differences that scoliosis creates in the spinal structure. The aim of this study was to define the somatotype characteristics of children with AIS and compare the somatotypes with healthy, age and sex-matched controls.
Material and Methods: A retrospective evaluation was performed on 38 children with AIS and 27 age-matched healthy control subjects. Cobb angles and angle of trunk rotation (ATR) values were used to determine scoliosis and trunk gibbosity. Cobb angles were measured on standing anterior-posterior radiographs and the ATR using Adam’s forward bending test with a scoliometer. Somatotypes were defined according to the Heath-Carter method and body morphology was categorized into three different components: endomorphy, mesomorphy, and ectomorphy.
Results: Ectomorphy was the dominant type in the AIS group, and endomorphy was the dominant type in the control group. The endomorphic somatotype in individuals with scoliosis was determined at a statistically significantly lower rate than in the control group (p=0.048). There was a moderate negative correlation (p=0.001, r=-0.466) between the Cobb angle and the values of the endomorphy component, and between the ATR and the endomorphy values (p=0.010, r=-0.318).
Discussion: The lower rate of endomorphic somatotype was an evident difference in children with scoliosis. These differences may cause problems in the growth and development of the spine and the skeletal structures attached to the spine during adolescence when rapid growth and development occur. Whether this difference is related to nutrition, genetic and hormonal factors, or psychosocial factors remains to be determined.
Keywords: Somatotype, Scoliosis, Adolescents, Human Body Morphology
Introduction
Adolescent Idiopathic Scoliosis (AIS) is a structural deformity that affects the spine and trunk during the growth period. According to the Cobb method, lateral curvatures of 10 degrees or more in the spine are defined as scoliosis. Curvatures measured below 10 degrees are considered physiological spinal asymmetry [1,2]. Although the magnitude of scoliosis is defined only according to the Cobb angle and the type of curvature in the frontal plane, it is a three-dimensional deformity characterized by sagittal plane changes and rotation in the transverse plane [1,2]. Some neurological diseases and musculoskeletal problems are known to have a role in the etiology, but in 80% of cases, it is defined as idiopathic [3]. AIS and scoliosis caused by underlying neuro-musculoskeletal diseases are orthopedic disorders of the developmental period usually seen during growth and development [4]. Adolescence is a period of rapid growth and development, and the physical maturation of the body. During this period, somatotype changes may occur depending on various factors such as genetic characteristics, nutrition, physical activity habits, and sporting activities [5,6].
Somatotype is a classification system that morphologically categorizes the human body into three different components: endomorphy (relative obesity), mesomorphy (relative musculoskeletal development) and ectomorphy (relative linearity) [6,7]. Endomorphy is characterized by the predominance of the digestive organs, and soft and rounded body contours. Low endomorphy indicates a weak physique with minimal subcutaneous fat, whereas high endomorphy values are indicative of obesity. Mesomorphy is characterized by the dominance of muscle, bone and connective tissue and sharply delineated muscles. Low mesomorphy is an indication of narrow bone diameter and low muscle weight compared to physical structure. High mesomorphy is indicative of large bone diameter and high muscle weight. An example of this body structure is an elite bodybuilder. Ectomorphy is characterized by a linear and fragile structure with limited muscle development. While low ectomorphy means more weight compared to the structure, high ectomorphy values are indicative of low weight relative to the build and relatively long limbs. Ectomorphy values correlate with endomorphy and mesomorphy values. For example, low ectomorphy values are associated with increased endomorphy and/or mesomorphy values [8, 9].
The relationship between body morphology and scoliosis is questioned because of the differences that scoliosis creates in the spinal structure. Since the 1990s, the relationship between scoliosis and body morphology has been studied in different societies and it has been suggested that children with AIS may have some anthropometric differences compared to healthy children [10,11]. It has been reported that there are differences in the normal physical growth pattern in children with AIS, which may be due to hormonal changes [12-14]. Some studies have reported that eating disorders are related to low body weight and BMI in adolescents due to the stress caused by deformity [12,14]. The results of studies examining the somatotypes of individuals with AIS are contradictory. Some studies have reported that individuals with AIS are taller than healthy control subjects [15,16], while others have reported that they are shorter in stature [14,17]. In a study with 905 participants, it was reported that girls with AIS were significantly shorter than healthy control subjects before puberty began, and taller than healthy control subjects after puberty [13].
To the best of our knowledge, there is no study in the Turkish population examining the body morphology of children diagnosed with AIS. The identification of structural differences associated with growth and development in individuals with scoliosis may lead to new targets and strategies for the treatment of AIS to be able to prevent progression or reduce the risks of this growth and developmental problem.
The aim of this study was to define the somatotype characteristics of children with AIS and to compare these with the somatotypes of healthy control subjects with similar age and gender characteristics.
Material and Methods
This retrospective controlled cohort study included data obtained from the evaluation of healthy adolescents with idiopathic scoliosis who presented at Silivri Municipality, Disabled and Elderly Coordination Center between 2011 and 2021. All identifying information was removed so that all the data included in the study were analyzed anonymously using computer software. The research was carried out in accordance with the Declaration of Helsinki, and with the approval of the Ethics Committee of Istanbul Kultur University (Date: 2022-04-25, No: 2022/86).
The study inclusion criteria were defined as being a healthy adolescent between the ages of 10-19 years, and diagnosed with AIS by a specialist physician. Exclusion criteria were defined as any mental, neurological, rheumatological, or orthopedic problem, the presence of a congenital or acquired orthopedic problem other than scoliosis in individuals diagnosed with AIS, any diagnosis that may cause growth and developmental retardation, receiving growth hormone treatment, having undergone surgical treatment for AIS, or a history of injury that would affect posture.
Demographic characteristics such as age, gender, weight, height, anthropometric measurement results, and Cobb angles and ATR (Angle of Trunk Rotation) angles of the adolescents diagnosed with AIS were obtained from the evaluation records recorded for each patient. Height was measured using a wall-mounted Mesilife, Q100 height meter, and body weight using scales sensitive to 0.1 kg (Charder®).
Cobb angles were measured on standing anterior-posterior whole spine X-ray images of adolescents diagnosed with idiopathic scoliosis by a specialist physician, and in patients with more than one curvature, the highest measured Cobb angle value was included for analysis. The trunk rotation angles of all the participants were measured with the Bunnell scoliometer in Adam’s forward bending test, and the largest trunk rotation angle values were included for analysis.
The somatotypes of the adolescents were determined according to the Heath-Carter method, with the dominant shoulder at 90° flexion, 45° elbow flexion, and the fist clenched. Using a flexible tape measure from the widest part of the arm, arm circumference and dominant side, leg circumference were measured. Triceps, subscapular, supraspinal subcutaneous fat from the widest part of the calf, and medial calf subcutaneous fat measurements were taken with knees flexed at approximately 90° while sitting, with a Holtain skinfold caliper. The elbow joint diameter at 90° flexion while standing, and knee joint diameter at 90° flexion while sitting were measured with a Holtain bicondylar caliper. All these recorded anthropometric parameters were imported into calculator program for the calculation of somatotypes using the Heath-Carter method [21].
The data obtained in the study were analyzed statistically using the SPSS vn. 16 software (Statistical Package for Social Sciences Inc., Chicago, IL, USA). The normality of the data was assessed with the Kolmogrov-Smirnov test. The distribution of gender and body somatotype classifications of the groups was analyzed with the Chi-square test. The Independent Samples t-test was used to compare the height, weight and BMI average values of the groups, and mesomorphy and ectomorph body somatotype measurement values. The Mann-Whitney U-test was used to compare the age and endomorphy somatotype values. The distribution of somatotype classifications according to Cobb angle and age was analyzed with the Chi-square test. The relationship between related parameters was also analyzed using Pearson’s correlation coefficient test. A value of p<0.05 was accepted as statistically significant in all the analyses. Power analysis showed that the number of participants (43) included was above the minimum sample size required to ensure a power of 95% confidence level and to detect statistical significance at a two-sided significance level of 0.05.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
The study included a total of 65 participants, including 38 children diagnosed with AIS and 27 healthy control subjects in a similar age group without scoliosis.
The study included 60 (92.3%) females and 5 (7.7%) males. The gender distribution, age, height, weight and body mass index values of the participants in both groups were similar (Table 1).
When the somatotype data were compared, it was determined that ectomorphy was the dominant type and mesomorphy was the predominant type in the AIS group (respectively: Endomorphy; 2.3 – Mesomorphy; 2.8 – Ectomorphy; 3), while endomorphy was the dominant type in the control group, and ectomorphy was the predominant type (Table 1). The endomorphy value in the AIS group was found to be statistically significantly lower than in the control group (p<0.001).
When the dominant somatotypes of the groups were evaluated with the Chi-square test, there were determined to be significantly fewer endomorphic types in the group with scoliosis. The endomorphic somatotype in individuals with scoliosis was statistically significantly lower than in the control group (p= 0.048). The somatotypes of the groups are shown in Figure 1.
The AIS group was separated into two sub-groups: mild scoliosis (Cobb angle 10°-19°) and moderate scoliosis (Cobb angle >20°) according to the intensity of the curvature, and the somatotypes were then analyzed. The mild scoliosis group included 10 patients (mean Cobb: 12.8 ± 2.6), and the moderate and high grade (30 ± 10.1) scoliosis group included 28 patients. The curvature pattern was determined as right thoracic, left lumbar in 27 patients, thoracolumbar in 6, lumbar in 4, and left thoracic, right lumbar in 1. A Cobb angle of ≥ 40° was determined in 5 patients and these were included in the moderately severe scoliosis group. When the somatotype values were compared between the mild and moderate scoliosis groups according to the severity of the scoliosis angle, there was no significant difference between the groups (p= 0.101), however, the number of participants with endomorphic body type was lower in both groups. There was a moderate negative correlation between the Cobb angle and the values of the endomorphy component (p= 0.001, r= -0.466) and a moderate negative correlation between the trunk rotation angle and the endomorphy values (p= 0.010, r= -0.318).
The participants in both groups were aged 10-16 years. Two sub-groups were formed as <14 years and ≥14 years, and the dominant somatotype distributions of the children were compared with the Chi-square test (Table 2). A statistically significant difference was determined between the groups (p= 0.019). When the dominant somatotypes of children aged ≥14 years were compared, a statistically significant difference was observed between the AIS and control groups (p= 0.014). There were no children <14 years of age with somatotype-dominant ectomorphic features in the AIS group, while endomorphy-dominant children aged ≥14 years were present in the control group.
Discussion
The results of this study demonstrated a significantly lower endomorphic somatotype of adolescents with idiopathic scoliosis compared to healthy control subjects. The endomorphy values associated with the body fat ratio were determined to be lower in the AIS group. The ectomorphic somatotype was more dominant in scoliosis patients with a Cobb angle of >20°, and the mesomorphic somatotype was dominant in children with a Cobb angle of ≤19°.
Throughout history, researchers have investigated the physical structure of the body in different ways. Hippocrates was the first to introduce concepts related to body structure [8]. The three-component body configuration classification method defined by William Sheldon as endomorphy, mesomorphy and ectomorphy, is still widely used today for the evaluation of body structure [8, 9]. It is accepted that this theoretical approach is based on the hypothesis that there is a continuous change in body structure distribution and that this change is associated with different contributions of three specific components that characterize body configuration.
During growth and development, there are significant changes in the size, structure, proportion and composition of the body. It has been shown that somatotype changes occur depending on age and cultural characteristics [19-22]. Girls are more endomorphic and less ectomorphic than boys. The mesomorphic component tends to decrease in girls during adolescence, whereas in boys, the mesomorphic component continues to be more dominant. Both males and females tend to have higher endomorphism with increasing age, although this trend occurs earlier in adolescent girls [19,22]. It has been reported that individuals with endomorphic somatotypes mature early and ecto-mesomorphic individuals have delayed maturation [23]. In a more recent study, it was revealed that the susceptibility to the endomorphic component increased in both genders for all age groups over the years [24].
Although there are studies investigating the relationship between adolescent idiopathic scoliosis and somatotype, these are limited in number. The first studies investigating somatotype in adolescent idiopathic scoliosis were conducted with the hypothesis that body type has an effect on determining the risk of progression [10,11]. LeBlanc (1997,1998) suggested that it may be possible to distinguish healthy adolescents, adolescents with non-progressive scoliosis, and adolescents with progressive scoliosis by somatotype classification [10,11]. The same researchers also thought that early diagnosis of AIS would be possible with somatotype assessment [10,11] and reported that girls with AIS had problems in the development of bone and muscle structure and were less mesomorphic [10].
Unlike the work of LeBlanc (1997, 1998), Barrios (2017) reported that girls with scoliosis were higher ectomorphic and lower mesomorphic than healthy control subjects. It was stated that the most important difference in the somatotype of girls with scoliosis was not the predominant endomorphic component associated with the fat ratio [14].
Cheung (2003) reported that abnormal growth and development in girls with scoliosis are usually observed at the age of 12-15 years and older [13]. Girls diagnosed with AIS were found to be shorter before puberty than the control group, and taller after the onset of puberty, with lower weight and BMI values compared to the control group during the peri-pubertal growth period [13]. Smith (2002) reported that children diagnosed with AIS with a mean age of 16 years had a lower body weight and BMI, which could indicate an eating disorder, compared to a control group [12]. The results of the current study, in parallel with the literature, showed that the endomorphy component was lower in children with AIS.
LeBlanc (1997) reported that children diagnosed with AIS with a mean age of 14 years and a Cobb angle of 10°-19° have more pronounced muscle and bone development than children with a Cobb angle of ≥20° [10]. In another study (Smith 2002), it was reported that BMI, which is an indicator of body adiposity during the rapid pubertal growth period, was significantly lower in children with AIS [12]. Those authors also reported a weak correlation between the severity of the Cobb angle and body weight and BMI values. [12] In the current study, a weak to moderate correlation was found between the severity of the Cobb angle and ATR and the endomorphic component.
Normalli (1985) reported that girls with idiopathic scoliosis had a later menarche than the control group and were taller during menarche [17]. Similarly, in another study (Weiss HR et al. 2015), it was determined that girls with AIS had a later menarche, were shorter at the age of 12 years, but reached the height of the control group at age 14 – 16 years. Around the age of 14 years, girls usually reach the Risser 3 stage, and the growth potential and the risk of curvature progression decrease [4]. In the current study, when the somatotype characteristics of the children were examined in the age groups of <14 years and ≥ 14 years, it was determined that the predominance of endomorphy was significantly less in children diagnosed with AIS aged over 14 years. In the children included in this study, the age of menarche and bone development levels such as Risser or Sanders were not evaluated. Due to the insufficient number of cases, somatotype characteristics could not be examined according to curvature patterns. It can be suggested that in future studies a more detailed somatotype evaluation should be made by evaluating physical activity characteristics in children with different curvature patterns and curvature severity. It would also be beneficial to examine whether different treatment methods influence the body somatotype of children with AIS.
Conclusion
The number of studies examining body morphology in individuals with adolescent idiopathic scoliosis is quite limited. When compared with healthy individuals in the same age group, it can be seen that there is a difference in the somatotypes of adolescents with idiopathic scoliosis. These differences may cause problems in the growth and development of the spine and the skeletal structures attached to the spine during adolescence, when rapid growth and development occur. Endomorphy values were seen to be low in children with AIS, indicating that the body fat ratio is low. There is a need for further studies with longer follow-up periods to determine whether this situation is caused by nutrition, genetic and hormonal factors, or psychosocial factors as a result of the scoliosis treatment.
Acknowledgment
We thank the Silivri Municipality Presidency for providing the retrospective data used in 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. Lonstein JE, Winter RB, Bradford DS, Ogilvie JW, editors. Moe’s Textbook of Scoliosis and other Spinal Deformities. 3rd ed. Philadelphia: WB Saunders; 1995. p.219-56.
2. Goldberg CJ, Moore DP, Fogarty EE, Dowling FE. Adolescent idiopathic scoliosis: natural history and prognosis. In: Research into Spinal Deformities. London: IOS Press; 2002. p.59-63.
3. Asher M, Burton D. Adolescent idiopathic scoliosis: natural history and long-term treatment effects. Scoliosis. 2006;1(1):1-10.
4. Weiss HR, Lehnert-Schroth C, Moramarco M, Moramarco K, editors. Advancements in conservative scoliosis treatment. Saarbruecken: Lambert Academic Publishing; 2015. p.159-84.
5. Subramanian SK, Vivek KS, Vinayathan A, Krishnakumar R, Rajendran R. Somatotyping in adolescents: stratified by sex and physical activity. Int J Anat Appl Physiol. 2016; 2:32-38.
6. Silventoinen K, Maia J, Jelenkovic A, Perriere S, Gouveia E, Antunes A, et al. . Genetics of somatotype and physical fitness in children and adolescents. Am J Hum Biol. 2021; 33(3):e23470.
7. Carter JEL. Somatotyping. In: Norton K, Olds T, editors. Anthropometrica. Sydney: University of New South Wales Press; 1996. p.147-70.
8. Carter JEL, Heath BH. Somatotyping Development and Applications. New York: Cambridge University Press; 1990. p.30-72.
9. Duquet W, Carter JEL. Somatotyping. In: Eston R, Reilly T, editors. Kinanthropometry and Exercise Physiology Labaratory Manual. 3rd ed. NY: Routledge; 2009. p.54-72.
10. LeBlanc R, Labelle H, Rivard CH, Poitras B. Relation between adolescent idiopathic scoliosis and morphologic somatotypes. Spine. 1997; 22(21):2532- 36.
11. LeBlanc R, Labelle H, Forest F, Poitras B. Morphologic discrimination among healthy subjects and patients with progressive and nonprogressive adolescent idiopathic scoliosis. Spine. 1998; 23(10):1109-15.
12. Smith FM, Latchford G, Hall RM, Milliner PA, Dickson DA. Indications of disordered eating behaviour in adolescent patients with idiopathic scoliosis. J Bone Joint Surg Br. 2002; 84(3):392-4.
13. Cheung CSK, Lee WTK, Tse YK, Tang SP, Lee KM, Guo X, et al. Abnormal Peri-pubertal Anthropometric Measurements and Growth Pattern in Adolescent Idiopathic Scoliosis: A Study of 598 Patients. Spine. 2003;28(18):2152-7.
14. Barrios C, Cortés S, Pérez-Encinas C, Escrivá MD, Benet I, Burgos J, et al. Anthropometry and body composition profile of girls with nonsurgically treated adolescent idiopathic scoliosis. Spine 2011; 36(18):1470-7.
15. Carr AJ, Jefferson RJ, Weisz I. Correction of body height in scoliosis patients using ISIS scanning. Spine. 1989;14(2):220-2.
16. Willner S. The proportion of legs to trunk in girls with idiopathic structural scoliosis. Acta Orthop Scand. 1975; 46:84-89.
17. Normelli H, Sevastik J, Ljung G, Aaro S, Jönsson-Sönderström AM. Anthropometric data relating to normal and scoliotic Scandinavian girls. Spine. 1985; 10(2):123-6.
18. Amendt LE, Ause-Ellias KL, Eybers JL, Wadsworth CT, Nielsen DH, Weinstein SL. Validity and reliability testing of the scoliometer®. Phys Ther. 1990; 70(2):108–17.
19. Kalichman L, Kobyliansky E. Sex- and age-related variations of the somatotype in a Chuvasha population. Homo. 2006; 57:151-62.
20. Widiyani T, Suryobroto B, Budiarti S, Hartana A. The growth of body size and somatotype of Javanese children age 4 to 20 years. HAYATI Journal of Biosciences. 2011; 18:182-92.
21. Carter JEL, Mirwald RL, Heath-Roll BH, Bailey DA. Somatotypes of 7-to 16-year-old boys in Saskatchewan, Canada. Am J Hum Biol. 1997; 9(2):257-72.
22. Ji CY, Ohsawa S. Changes in somatotype during growth in Chinese youth 7–18 years of age. Am J Hum Biol. 1996; 8(3):347-59.
23. Zuk GH. The plasticity of the physique from early adolescence through adulthood. J Genet Psychol. 1958; 92:205-14.
24. Lizana PA, Olivares R, Berral FJ. Somatotype tendency in Chilean adolescents from Valparaíso: review from 1979 to 2011. Nutr Hosp. 2014; 31(3):1034-43.
25. Yim AP, Yeung HY, Hung VW, Lee KM, Lam TP, Ng BK, et al. Abnormal skeletal growth patterns in adolescent idiopathic scoliosis-a longitudinal study until skeletal maturity. Spine. 2012; 37(18):1148-54.
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Adnan Apti, Tuğba Kuru Çolak, Burçin Akçay, İlker Çolak. Determination of somatotypes of children with adolescent idiopathic scoliosis and its relationship with scoliosis. Ann Clin Anal Med 2023;14(8):691-695
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CTLA4+rs231775 gene polymorphism increases PCOS, regardless of the levels of interleukin-6 and tumor necrosis factor-α in the serum
Fatma Beyazit 1, Meliha Merve Cicekliyurt 2, Hakan Turkon 3, Mesut Abdulkerim Unsal 1, Eren Pek 1
1 Department of Obstetrics and Gynecology, Faculty of Medicine, Canakkale Onsekiz Mart University, Canakkale, 2 Department of Medical Biology, Faculty of Medicine, Canakkale Onsekiz Mart University, Canakkale, 3 Department of Biochemistry, Meddem Hospital, Isparta, Turkey
DOI: 10.4328/ACAM.21638 Received: 2023-02-06 Accepted: 2023-03-27 Published Online: 2023-06-04 Printed: 2023-08-01 Ann Clin Anal Med 2023;14(8):696-701
Corresponding Author: Meliha Merve Cicekliyurt, Department of Medical Biology, Faculty of Medicine, Canakkale Onsekiz Mart University, 17100, Canakkale, Turkey. E-mail: mervemeliha@comu.edu.tr P: +90 286 218 00 18 F: +90 +90 286 218 37 38 Corresponding Author ORCID ID: https://orcid.org/0000-0003-4303-9717
This study was approved by the Ethics Committee of Çanakkale Onsekiz Mart University (Date: 2016-05-11, No: 2017/09)
Aim: Polycystic ovarian syndrome (PCOS) is a long-standing inflammation-related disease with increased levels of circulating pro-inflammatory markers. By affecting inflammatory cytokine production, cytotoxic T lymphocyte-associated antigen (CTLA-4) polymorphism can alter the immune system and trigger distinct disease states. The aim of the study was to investigate if CTLA4 polymorphism is associated with PCOS, and if so, (2) whether this situation influences serum interleukin-6 (IL-6) and TNF-alpha in PCOS.
Material and Methods: CTLA4+rs231775 gene polymorphism with IL-6 and TNF-α levels were determined in 92 PCOS women and 88 healthy controls. Study groups were further subdivided according to body mass index (BMI) and the degree of insulin resistance (IR), and comparisons were made within each study group.
Results: The prevalence of the A allele of single nucleotide polymorphism (SNP) rs231775 was more frequent in PCOS women compared with healthy controls [OR: 1.99, 95% CI:1.273-3.107, p =0.0023]. The heterozygous genotype was also shown to be strongly associated with PCOS development [OR: 3.041, 95%CI:1.604-5.766, p=0.0005]. Although TNF-α levels of PCOS patients were detected to be elevated, no difference was found in the study groups with respect to serum IL-6 levels. In addition, no association was observed between CTLA4+rs231775 polymorphism and serum pro-inflammatory cytokine levels.
Discussion: The present study demonstrates for the first time that CTLA4+rs231775 gene polymorphism increases susceptibility to PCOS 2 times more in the case of A allele carriage and 3 times more in heterozygous individuals, independent from the long-standing low-grade inflammatory disease state encountered in patients with PCOS.
Keywords: Polycystic Ovary Syndrome, CTLA4, TNF-α, IL-6, Polymorphism
Introduction
Polycystic ovary syndrome (PCOS) is a primary reason for infertility in females and is estimated to affect 5-15% of women of reproductive age. Although PCOS is considered a hormonal disorder characterized by insulin resistance and a hyperandrogenic state, growing evidence in recent years suggests that genetic abnormalities play an influential role in PCOS development by altering immune and autoimmune responses [1].
It is well established that various cytokines are critically important for the basic phases of reproduction, such as ovarian follicular development (follicle formation and activation), ovulation, fertilization, implantation of the fertilized ovum, and normal pregnancy [2]. Furthermore, it is commonly recognized that cytokines likely take part in the pathophysiology of endometriosis, PCOS, and unexplained infertility [1, 3-4]. In this
sense, it has been demonstrated that the inflammatory state is important in PCOS.
Cytotoxic T lymphocyte antigen-4 (CTLA-4) controls the activation of primary and secondary peptide-specific CD4(+) T cells and is considered a strong candidate susceptibility gene for distinct types of autoimmune and tumoral diseases [5].
The CTLA-4–ligand interplay negatively alters interleukin-2 (IL-2) production, T-cell proliferation, and cell cycle progression [5]. Furthermore, antibody-mediated CTLA-4 blockade prevents tolerance development, enhances antitumor responses, and exacerbates autoimmune diseases [6]. Accumulating evidence in recent years has demonstrated a particular CTLA-4 genetic polymorphism conferring susceptibility to numerous disease states [7].
Since PCOS is a highly complex and heterogeneous disorder with a significant influence from environmental and genetic factors, no satisfactory theory still explains the clinical and biochemical diversity of the disease. Furthermore, despite having similar biochemical and hormonal similarities, some PCOS patients experience insulin resistance, accompanying autoimmune disease, and low oocyte fertilization to the implant, while others do not. Genetic differences among alleles at different genetic loci contributing to IR and autoimmunity are numerous possible explanations for this observation [8]. In this context, genetic aberrations that include microsatellites, single nucleotide polymorphisms (SNPs), and cell adhesion molecules can produce susceptibility to distinct disease states, including PCOS. Therefore, to investigate the processes linked with IR, inflammation, and genetic aberrations in PCOS, we designed the current study to ascertain the frequency of CTLA4+rs231775 polymorphism in Turkish PCOS women and its influence on clinical, biochemical, and hormonal phenotype.
Material and Methods
Study design
Ethical approval granted from Çanakkale Onsekiz Mart University local ethics committee (Ethical approval no: 2017/09). This cross-sectional study was performed in the Gynecology and Obstetrics department of Çanakkale Onsekiz Mart University Training and Research Hospital. Informed consent was obtained from all individuals who volunteered to participate in this study.
Subjects
PCOS diagnosis was made depending on the existence of predetermined criteria suggested by the Rotterdam ESHRE/ASRM-sponsored PCOS consensus workshop group [9]. Exclusion criteria were defined as patients without any previous systemic, metabolic, or endocrine diseases. Furthermore, a history of oral contraceptive agent use, severe dyslipidemia, prescription of corticosteroids, or glucose-lowering drugs within the previous 90 days was also excluded. The healthy control group comprised 88 age and BMI-matched women with no systemic or endocrine diseases.
Laboratory analyses
An 8-ml fasting serum for hormonal and biochemical evaluation and 2 ml blood for genotyping were taken from each study participant after 8-12 hours of fasting during the early follicular phase of menstruation. The samples for biochemical analysis were further centrifuged at a speed of 6,000 rpm for 12 minutes at 4°C to obtain serum and saved for final analysis at -60 °C. Routine laboratory work-up and hormone tests, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), fasting glucose and insulin level, serum estradiol, total testosterone, prolactin, and thyroid-stimulating hormone (TSH) were measured for each subject. Biochemical tests were analyzed spectrophotometrically, and hormone tests were measured by the electrochemiluminescence immunoassay method. HOMA-IR estimated IR by using serum glucose and insulin levels.
Genotyping
The genomic DNA purification from mononuclear cells was performed using a commercial kit (Thermo Fisher Scientific, USA). Real-time polymerase chain reaction (PCR) was performed for each sample in a total volume of 10 µL PCR reaction mixture that consisted of 50 ng of genomic DNA, 5 μL of SYBR® Green Realtime PCR Master Mix (Analytic-Jena, Germany), and 0.4 μL of each primer (10 pmol/μL) filled with PCR-grade water. The PCR cycling protocol included initial activation at 95°C for 3 minutes, 40 cycles of denaturation at 95°C for 5 seconds, annealing at 60°C for 20 seconds, and extension at 72°C for 15 seconds. Melting curve analyses following PCR were performed to determine mutant, heterozygous, and wild-type genotypes.
TNF-α and IL-6 measurement
TNF-α and IL-6 levels were determined with an enzyme-linked immunosorbent assay (ELISA) kit (TNF-α, Cat. No: KAP1751; IL-6 Cat KAP1261, DIAsource, Belgium). Results were shown as picograms per milliliter (pg/ml) of serum. The intra-assay and inter-assay coefficients of variations were < 6.6 and < 4.5, and < 4.3% and < 5.4 for TNF-alpha and IL-6, respectively.
Statistical analyses
Statistical Package for Social Sciences (SPSS) v20.0 (SPSS for Windows, SPSS, Chicago) was used for statistical analysis. Laboratory and hormonal parameters are demonstrated as mean ± SD for normally distributed variables, whereas non-normally distributed variables are presented as median (minimum-maximum). One-way analysis of variance (ANOVA) was used to compare normally distributed variables, whereas the Kruskal-Wallis test was used to compare non-normally distributed variables. Spearman’s test was used for correlation analysis. A p-value below 0.05 was considered statistically significant. The gene-counting method was used to measure allele and genotype frequencies, and comparisons within each subgroup were made with the chi-square test and Fisher’s exact test. Genotype associations and relative risks were assessed via odds ratio by performing the Armitage trend test.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
A total of 92 PCOS women (mean age ± SD: 26.4 ± 6.1 years, range 17-46 years) and 88 healthy women (mean age ± SD: 28.9 ± 7.3 years, range 19-48 years) were studied in this trial. Overall, the mean BMI levels of PCOS patients and controls were 25.8 ± 5.2 and 24.0 ± 4.3, respectively. The detailed clinical features of the patients and control group are shown in Table 1. Although the demographic and clinical characteristics of PCOS women and healthy control group at the baseline with respect to age and BMI were found to be similar in both study groups, mean BMI levels of women with IR PCOS were statistically higher than those of non-IR PCOS patients and controls, as displayed in Table 1.
A statistically significant elevation was detected in body weight and insulin levels in PCOS women with HOMA-IR ≥ 2.5 compared to women with HOMA-IR below 2.5. Furthermore, patients with PCOS had a significant increase in respect to TNF-α, LH, and total testosterone levels (Figure 1) compared to controls. IL-6 levels were detected to be similar in PCOS women with HOMA-IR < 2.5, HOMA-IR ≥ 2.5, and controls (27.1 ± 10.5, 29.9 ± 19.4, and 27.7 ± 10.5 respectively) (Figure 2).
To analyze the further effect of obesity on HOMA-IR, TNF-α, IL-6, and other metabolic and hormonal parameters, we divided PCOS patients and controls into two groups according to BMI levels. As expected, HOMA-IR levels were shown to be elevated in PCOS women compared with healthy controls with respect to BMI levels (< 25 vs. ≥ 25 kg/m2). Although TNF-α levels were found to be elevated (p = 0.001) in PCOS women with BMI ≥ 25 kg/m2 compared to healthy controls with BMI ≥ 25 kg/m2, no difference was found between PCOS women and healthy controls with BMI < 25 kg/m2. Although increased BMI levels in PCOS women were found to be associated with an increasing trend in IL-6 levels, this was not statistically significant (Table 1).
When we investigated potential associations between TNF-α and IL-6 with respect to other demographic and clinical characteristics, we found that in the non-IR PCOS group, TNF-α levels were positively correlated with BMI (r=0.365, p=0.010) and HOMA-IR (r=0.335, p=0.019). However, in the IR PCOS group, TNF-α levels were correlated with only BMI levels (r=0.402, p=0.008).
The genotype distributions and carriage rate of CTLA4 promoter region polymorphisms in PCOS patients and controls are presented in Table 2. Genotype distribution of PCOS patients was as follows: out of 92 cases, 26 had wild (AA) genotype, 56 had heterozygous (AG), and 10 had mutant genotype (GG). The variant allele frequency (G allele) for CTLA4 + rs231775 polymorphism was calculated as 0.41 among PCOS patients, and the PCOS population was found to deviate from the Hardy-Weinberg equilibrium (HWE) (χ²:5.99; p-value:0.0143). In contrast, the variant allele frequency (G allele) for CTLA4 + rs231775 polymorphism was calculated as 0.26, and none of the variants were found to deviate from the HWE in the control group (χ²:3.93; p-value:0.994).
The distribution of genotypes in the healthy controls was as follows: out of 88 controls, 48 had wild (AA), 34 had heterozygous (AG), and 6 had mutant genotype (GG). The frequency of the G-allele carriers on rs231775 was significantly elevated in patients with PCOS compared to control subjects (41% vs. 26% respectively). The present data indicate that the conversion of an A allele to a G in PCOS cases (allele frequency differences) increases PCOS risk 1.99 times compared to the general population (OR:1.989; CI=[1.273-3.107]; χ²=9.24, p=0.0024) (Table 2).
The AA genotype was related to a significantly elevated risk of PCOS development compared with the AG genotype (OR, 3.041; 95%CI, 1.60-5.77; χ²:11.92, p:0.0005). In this study, PCOS risk increases approximately three times compared to homozygous wild and mutant genotype [OR, 3.077; 95% CI, 1.005-9.421; χ²:4.10, p:0.043]. Allele positivity was found to significantly affect the increased risk of PCOS, namely three times greater than in counterparts with the AA wild genotype (OR:3.046; 95%CI = [1.642-5.652], χ²:12.84; p=0.0003). A strong allelic (with G as the risk allele) or genotypic (GG or AG) association was found for CTLA4+rs231775 polymorphism in the PCOS group.
The same genotypic analysis was also executed after PCOS women were divided into two subgroups according to HOMA-IR status (Table 3). No significant relation was found between CTLA-4+rs231775 polymorphism and HOMA-IR status among the PCOS group.
In patients with PCOS, there was no significant difference in the TNF-α and IL-6 levels in carriers of the genotypes AA, AG, and GG of CTLA-4+rs231775 polymorphism. In the healthy control group, the TNF-α and IL-6 levels in carriers of genotypes AA, AG, and GG of CTLA-4+rs231775 polymorphism were also not significantly different. We also explored the genotypic differences in PCOS patients concerning IR status. In patients with HOMA-IR<2.5, the TNF-α and IL-6 levels did not differ significantly in carriers of AA, AG, and GG genotypes of CTLA-4+rs231775 polymorphism. In PCOS patients with HOMA-IR ≥2.5, there were only two individuals with the GG genotype. Neither of these individuals was included in the final analysis. Again, no significant difference was found in this subgroup between carriers of the AA and AG genotypes of CTLA-4+rs231775 polymorphism.
Discussion
Overstimulation of the immune system in PCOS usually alters the production and secretion of inflammatory cytokines and leads to various clinical and metabolic manifestations [10, 11]. The present study’s findings demonstrate that serum TNF-α levels in PCOS women (either with the presence or absence of IR) are elevated compared with controls. On the other hand, IL-6 levels were comparable in PCOS women and controls, independent of IR status. One interesting finding of the present study is the correlation between TNF-α levels with BMI. We demonstrated that only in obese (BMI≥25 kg/m2) PCOS patients serum TNF-α levels were elevated compared with controls. In this context, our findings are consistent with previous research studies applied in obese and non-obese PCOS women except for the unaltered IL-6 levels [11, 12].
The polymorphic sites in the CTLA4 gene, including C>T polymorphism in the promoter -318 (rs5742909) and A>G polymorphism in exon 1 +49A/G (rs231775), are demonstrated to be linked with a variety of autoimmune diseases [13-15]. Among these, rs231775 is the most extensively investigated immune disorder marker [16, 17]. Based on the altered immune system in PCOS pathophysiology, we hypothesized that CTLA4 rs231775 polymorphism might be associated with PCOS development.
In the present study, we also demonstrated a significant alteration in the distribution of CTLA4+rs231775 A/G mutant allele frequency between patients and controls. The genotype-phenotype association revealed that the G allele of SNP rs231775 was more frequent in PCOS women than in healthy controls (OR:1.99, 95%CI:1.273-3.107, p=0.0023). The heterozygous genotype was also shown to be strongly associated with PCOS development (OR:3.041, 95% CI:1.604-5.766, p=0.00056). The excess of heterozygous (AG) mutant variants and G alleles observed in our patients may indicate a susceptibility to developing PCOS regardless of IR in PCOS.
The association between PCOS and IL-6 and TNF-α is well known, but the relation between CTLA4+rs231775 gene polymorphism with these parameters has not been studied. Therefore, we determined whether IL-6 and TNF-α levels were altered in PCOS women and healthy volunteers genotyped with CTLA4+rs231775 gene polymorphism. Although no data in the literature provide evidence for a possible immunologic mechanism underlying CTLA4 gene polymorphism, TNF-α, and IL-6 in PCOS patients, various reports are exploring the intimate relationship between these parameters in distinct disease states. Han et al. [18] demonstrated that the CTLA4+49 GG genotype was related to TNF-α and IFN-gamma levels in HBV-infected patients, and this association was found to be decreased by haplotype formation with -318C/T alleles.
Conclusion
In conclusion, our results suggest strong evidence of the relationship between circulating TNF-α and PCOS. BMI and IR were the parameters most strongly associated with TNF-α levels. Enhanced levels of TNF-α in PCOS (particularly in women with PCOS-IR and obese PCOS women) may represent a significant underlying factor in the diverse clinical manifestations seen in patients with PCOS. Moreover, we also demonstrated for the first time that CTLA4+rs231775 gene polymorphism is strongly associated with PCOS development, providing advances in understanding the molecular basis of PCOS development independent from BMI, HOMA-IR, TNF-alpha, and IL-6 levels in the clinic. Although, CTLA4+ rs231775 polymorphism is a potential genetic risk factor for PCOS and is not affected by insulin resistance or increased body weight. As this is the first report on the relation between CTLA4+rs231775 polymorphism and PCOS, further trials will be required to outline the role of genetic polymorphism on the expression and functional properties of CTLA4.
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 research is supported by The Scientific Research Projects Coordination Unit of Canakkale Onsekiz Mart University (Project ID: THD-2017-1208).
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. Luan YY, Zhang L, Peng YQ, Li YY, Liu RX, Yin CH. Immune regulation in polycystic ovary syndrome. Clin Chim Acta. 2022;531:265-72.
2. Adamczak R, Ukleja-Sokołowska N, Lis K, Dubiel M. Function of Follicular Cytokines: Roles Played during Maturation, Development, and Implantation of Embryo. Medicina (Kaunas). 2021;57(11):1251.
3. Kokot I, Piwowar A, Jędryka M, Sołkiewicz K, Kratz EM. Diagnostic Significance of Selected Serum Inflammatory Markers in Women with Advanced Endometriosis. Int J Mol Sci. 2021;22(5):2295.
4. Velez LM, Seldin M, Motta AB. Inflammation and reproductive function in women with polycystic ovary syndrome. Biol Reprod. 2021;104(6):1205-17.
5. Irfan M, Iqbal T, Hashmi S, Ghani U, Bhatti A. Insilico prediction and functional analysis of nonsynonymous SNPs in human CTLA4 gene. Sci Rep. 2022;12(1):20441.
6. Hosseini A, Gharibi T, Marofi F, Babaloo Z, Baradaran B. CTLA-4: From mechanism to autoimmune therapy. Int Immunopharmacol. 2020;80:106221.
7. Ohkura N, Sakaguchi S. Transcriptional and epigenetic basis of Treg cell development and function: its genetic anomalies or variations in autoimmune diseases. Cell Res. 2020;30(6):465-74.
8. Alanbay I, Ercan CM, Sakinci M, Coksuer H, Ozturk M, Tapan S. A macrophage activation marker chitotriosidase in women with PCOS: does low-grade chronic inflammation in PCOS relate to PCOS itself or obesity? Arch Gynecol Obstet. 2012;286(4):1065-71.
9. Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 2004;81(1):19-25.
10. Luan YY, Zhang L, Peng YQ, Li YY, Liu RX, Yin CH. Immune regulation in polycystic ovary syndrome. Clin Chim Acta. 2022;531:265-272.
11. Rudnicka E, Suchta K, Grymowicz M, Calik-Ksepka A, Smolarczyk K, Duszewska AM, et al. Chronic Low Grade Inflammation in Pathogenesis of PCOS. Int J Mol Sci. 2021;22(7):3789.
12. Abraham Gnanadass S, Divakar Prabhu Y, Valsala Gopalakrishnan A. Association of metabolic and inflammatory markers with polycystic ovarian syndrome (PCOS): an update. Arch Gynecol Obstet. 2021;303(3):631-43.
13. Schneider H, Downey J, Smith A, Zinselmeyer BH, Rush C, Brewer JM, et al. Reversal of the TCR stop signal by CTLA-4. Science. 2006;313(5795):1972-5.
14. Ueda H, Howson JM, Esposito L, Heward J, Snook H, Chamberlain G, et al. Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease. Nature. 2003;423(6939):506-11.
15. Furugaki K, Shirasawa S, Ishikawa N, Ito K, Ito K, Kubota S, et al. Association of the T-cell regulatory gene CTLA4 with Graves’ disease and autoimmune thyroid disease in the Japanese. J Hum Genet. 2004; 49(3):166-8.
16. Ting WH, Chien MN, Lo FS, Wang CH, Huang CY, Lin CL, et al. Association of Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA4) Gene Polymorphisms with Autoimmune Thyroid Disease in Children and Adults: Case-Control Study. PLoS One. 2016;11(4):e0154394.
17. Vaidya B, Pearce S. The emerging role of the CTLA-4 gene in autoimmune endocrinopathies. Eur J Endocrinol. 2004;150(5):619-26.
18. Han Q, Duan S, Zhang G, Li Z, Li N, Zhu Q, et al. Associations between cytotoxic T lymphocyte-associated antigen-4 polymorphisms and serum tumor necrosis factor-α and interferon-γ levels in patients with chronic hepatitis B virus infection. Inflamm Res 2011;60(11):1071-8.
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Fatma Beyazit, Meliha Merve Cicekliyurt, Hakan Turkon, Mesut Abdulkerim Unsal, Eren Pek. CTLA4+rs231775 gene polymorphism increases PCOS, regardless of the levels of interleukin-6 and tumor necrosis factor-α in the serum. Ann Clin Anal Med 2023;14(8):696-701
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Comparison of trauma patients with typical – atypical rib fractures
Muharrem Cakmak
Department of Thoracic Surgery, Faculty of Medicine, Fırat University, Elazig, Turkey
DOI: 10.4328/ACAM.21671 Received: 2023-03-01 Accepted: 2023-04-05 Published Online: 2023-04-30 Printed: 2023-08-01 Ann Clin Anal Med 2023;14(8):702-706
Corresponding Author: Muharrem Cakmak, Department of Thoracic Surgery, Faculty of Medicine, Fırat University, Elazig, Turkey. E-mail: drmhrm23@outlook.com P: +90 537 330 52 12 F: +90 424 233 35 55 Corresponding Author ORCID ID: https://orcid.org/0000-0002-9504-2689
This study was approved by the Ethics Committee of Firat University (Date: 2021-09-23, No: 10-14)
Aim: Morphologically, ribs are classified as typical or atypical. While typical ribs are the 3-9th ribs, atypical ribs are the 1st, 2nd, and 10-12th ribs. There are several studies on rib fractures. However, no specific studies and comparisons have been reported on rib fractures according to the calcifications of the ribs. In our study, we aimed to share the results of trauma patients with typical-atypical rib fractures.
Material and Methods: According to the morphological features of the broken ribs, the patients were divided into two groups: Group 1 (patients with typical rib fractures; 322) and Group 2 (patients with atypical rib fractures; 160). The results were evaluated. p<0.05 was considered significant.
Results: According to the demographic distribution of the patients, the male gender was more significant in Group 1 compared to Group 2 (p<0.05). However, there was no significant difference between the groups in terms of the number of patients who died and localization (p>0.05). In terms of concomitant pathologies, pneumomediastinum, contusion, and flail chest development were statistically significant in Group 1 patients compared to Group 2 (p<0.05). The mean CWIS of Group 1 was found to be significant compared to Group 2 (p<0.05).
Discussion: According to our study, in terms of concomitant pathologies, pneumomediastinum, contusion, and flail chest development in typical rib fractures were more common in patients with atypical rib fractures. Although trauma scores were generally higher in Group 2 than in Group 1, they were not significant in patients with typical-atypical rib fractures except for CWIS. Especially in patients with a high CWIS, surgical treatment can be performed depending on the condition of the concomitant organ injuries.
Keywords: Ribs, Fractures, Thorax, Trauma
Introduction
A rib consists of a caput, collum, tubercle, and corpus. The first 7 ribs are called true ribs and fuse with both the vertebrae and the sternum, while the 8-9-10-11-12th ribs are called false ribs. The cartilage parts of the 8-9-10th ribs combine with each other and adhere to the cartilage of the 7th rib anteriorly, whereas they fuse with the vertebrae posteriorly. The 11th and 12th ribs are called the vertebral or floating ribs [1]. Morphologically, ribs are classified as typical or atypical. While typical ribs are the 3-9th ribs, atypical ribs are the 1st, 2nd, and 10-12th ribs [2]. Rib fractures are seen in 35-40% of thoracic traumas [3]. Fractures are common between the 4-9th ribs. The 1st and 2nd rib fractures are traumas that require high energy. Subclavian vascular injuries are seen with 1st and 2nd rib fractures. Intrathoracic injuries are more common in fractures between the 3-7th ribs, while intra-abdominal and spinal injuries as well as intrathoracic injuries are seen in fractures between the 8-12th ribs [4, 5, 6].
There are several studies on rib fractures. These studies reported factors affecting mortality and morbidity. However, no specific studies and comparisons have been reported on rib fractures according to the calcifications of the ribs. In our study, we aimed to share the results of trauma patients with typical-atypical rib fractures.
Material and Methods
Patients
Ethics committee approval was received for the study (approval date and number: 23.09.2021/10-14). A total of 482 patients who were followed up and treated for post-traumatic typical or atypical rib fractures between 2015 and 2021 were included in the study.
Procedures
According to the morphological features of the broken ribs, the patients were divided into two groups: Group 1 (patients with typical rib fractures; 322) and Group 2 (patients with atypical rib fractures; 160). Age, gender, symptoms, localization of fractures, radiological findings, diagnosis and treatment methods, complications, concomitant pathology and organ injuries, mean number of fractures, rib fractures score (RFS), chest wall injury score (CWIS), chest trauma score (CTS), thoracic trauma severity score (TTSS), injury severity score (ISS), and mortality and morbidity rates were recorded.
Statistics
IBM SPSS Statistics Base 22.0 program (IBM Corporation, Armonk, NY, USA) was used for data analysis. Continuous variables were expressed as mean ± standard deviation, while categorical variables were explained as number-ratio. Homogeneity analysis of variances was conducted with Levene’s test (p>0.05). The Shapiro-Wilk test was used to evaluate the normal distribution (p>0.05). Results were evaluated with the Kruskal-Wallis, analysis of variance, and Mann-Whitney-U tests. p<0.05 was considered significant.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
The most common complaints of the patients were chest pain and shortness of breath. The main diagnostic methods were physical examination findings, chest X-ray, and mostly computed tomography of the thorax (Figure 1). According to the demographic distribution of the patients, male gender was more significant in Group 1 compared to Group 2 (p<0.05). However, there was no significant difference between the groups in terms of the number of patients who died and localization (p>0.05) (Table 1).
In terms of concomitant pathologies, pneumomediastinum, contusion, and flail chest development were statistically significant in Group 1 patients compared to Group 2 (p<0.05). There was no statistically significant difference between the groups in terms of concomitant organ injuries (p>0.05) (Table 2).
The mean CWIS of Group 1 was found to be significant compared to Group 2 (p<0.05) when the groups were evaluated in terms of the mean number of fractures, RFS, CWIS, CTS, TTSS, and ISS (p<0.05) (Table 3).
In treatment, it was observed that 60 (12%) patients underwent tube thoracostomy, 10 (2%) patients underwent thoracotomy (7 bleeding control + hematoma evacuation, 3 primary diaphragmatic repair), and 2 (0.41%) underwent chest wall reconstruction. In addition, it was determined that 10 (2%) of the flail chest patients were followed in the intensive care unit, 3 (1%) had fixation + intensive care follow-up, and all of the patients with pneumomediastinum got fiberoptic bronchoscopy + esophageal passage graphy and endoscopy.
The most common morbidities in patients were wound infection (n: 103, 21%), pneumonia (n: 42, 9%), and atelectasis (n: 52, 11%). The mean hospital stay was 7 ± 5.2 days.
Discussion
The most common condition following blunt thoracic trauma is rib fractures with a rate of 50% [7]. Morphologically, ribs are classified as typical or atypical. Typical ribs (ribs 3-9) consist of a head, neck, tubercle, and body. The head parts articulate with the lower part of the corresponding vertebral body and the upper part of the next vertebra, forming two separate articular surfaces. The tubercle, on the other hand, is the junction of the neck and body and combines with the transverse process of the numerically corresponding vertebra to form the costotransverse joint. The body part is curved and contains a groove in the inferomedial region, through which intercostal vessels and nerves pass. They articulate anteriorly with the sternum [8]. The 1st, 2nd, 10th, 11th, and 12th ribs are atypical. At the head of the first rib, there is a single face that articulates with the Th1 vertebral body. Its upper surface has two grooves for the subclavian vessels. The main atypical feature of the second rib is the superiorly located tuberosity, from which the serratus anterior muscle partially originates. The 10th, 11th, and 12th ribs have only one articular surface in their heads. In addition, the 11th and 12th ribs lack neck and tubercles [2]. In our study, we aimed to evaluate the outcomes of trauma patients with these rib fractures with different morphological features.
In a study conducted with 214 patients with rib fractures, the mean age was reported to be 51.50 years, and a correlation was found between the increasing number of broken ribs with mortality and morbidity independent of concomitant injuries [9]. In our study, we found the mean age as 56.55 ± 18.17 (group 1; 56.30 ± 18.30, group 2; 57.06 ± 17.96) and mortality rate as 16% (group 1; 43, 13%, group 2; 21, 13%). There was no significant difference in terms of mortality between the groups (p>0.05).
In another study, rib fractures were reported to be 69% in men and 53% in women, and the male gender was significant. In the same study, it was also stated that fractures occur more frequently in the 5-8th ribs, less frequently in the upper ribs, and least in the anterior parts [10]. In our study, while the male gender was significant in Group 1 patients compared to Group 2, localization was not significant between groups.
The main diagnostic methods in rib fractures are physical examination, posteroanterior chest X-ray, and, rarely, computed tomography of the thorax. Pleurotic chest pain and local tenderness guide the examination. The pain increases with coughing and breathing. Due to severe pain, patients cannot secrete. Atelectasis occurs and patients face the danger of hypoxia and metabolic acidosis due to pulmonary shunts. Rib fractures may not be seen up to 50% in chest X-ray, lateral rib fractures may be hidden by rib lines when there is no obvious separation. Lower rib fractures can be observed on thoracolumbar radiographs. Intra-abdominal hemorrhage should be evaluated in lower rib fractures [11]. The main diagnostic methods in our patients were chest X-ray and computed tomography of the thorax. This is due to the need for tomography for the evaluation of other systems in multi-trauma patients.
Early complications are contusion, pneumothorax, and hemothorax, while late complications are atelectasis and pneumonia in patients with thoracic trauma with rib fractures. The average blood loss from a broken rib is 100-150 milliliters. Broken rib ends may lacerate the intercostal muscles and develop massive hemothorax. The prognosis depends on the age of the patient, the number of broken ribs, and the condition of concomitant injuries. Fractures of the first and second ribs require high energy, and subclavian vascular injuries may occur in these fractures. There may be minor aorta and innominate artery injuries and tracheobronchial injuries. Intra-abdominal organs and spinal injuries should not be ignored in intercostal fractures between 9-12. Liver and spleen injuries may occur, especially in fractures of the 10th and 11th ribs [11, 12, 13]. In our study, the number of fractures in typical ribs was higher than in atypical ribs. In terms of concomitant pathologies, pneumomediastinum, contusion, and flail chest development were statistically significant in Group 1 patients compared to Group 2 (p<0.05). There was no statistically significant difference between the groups in terms of concomitant organ injuries (p>0.05). No serious intracranial injuries were observed in any of the patients, except for major vessel injuries and simple facial injuries. We think that this is due to the fact that patients with intracranial injuries are followed up by the relevant clinics or directly to the intensive care unit.
The Rib fractures score (RFS) is used to determine the risk ratio of complications that may develop in rib fractures. With this method it is possible to decide whether the patient needs care or not. Moreover, it has been reported that optimal analgesic treatment for mobilization, deep breathing exercises, coughing, and respiratory physiotherapy can be provided, and patients with an RFS above 7 points should be referred to pain relief units (algology or anesthesia) [14]. In our study, the RFS values were below 7, and there was no statistically significant difference between the groups (p>0.05).
Chest Wall Injury Scale (CWIS) is a scoring system that helps to determine the treatment method according to the condition of the injury in the chest wall. Taylor et al. reported that this scale system is a guide for the decision of surgical intervention and that mortality and morbidity increase with the elevation in scoring [15]. In our study, the mean CWIS value in Group 1 was statistically significant compared to Group 2 (p<0.05). As it is especially high in patients undergoing reconstruction and fixation, the elevation of CWIS may guide surgical treatment. However, despite surgery, the mortality rate varies according to concomitant pathology and organ injuries.
Chest trauma score (CTS) is a scoring method based on the patient’s age, number of broken ribs, location of the fracture, and lung contusion. Chen et al. reported increased morbidity and mortality in patients with thoracic trauma with a CTS greater than 5 [16]. In our study, although CTS values were higher in Group 2 patients than in Group 1, there was no statistically significant difference between the groups (p>0.05).
The Thoracic Trauma Severity Score (TTSS) is a scoring system with a score between 0-25, covering patient age and findings such as PaO2/FIO2 ratio, pulmonary contusion, pleural pathology, and rib fracture. This system is closely associated with mortality and morbidity. It has been reported that TTSS is a very significant scoring system for mortality and morbidity [17, 18]. In our study, although TTSS values in Group 2 patients were higher than in Group 1, there was no statistically significant difference between the groups (p>0.05).
The Injury severity score (ISS) provides numerical calculation and identification of the total severity of injuries in persons with multiple body injuries. It is associated with mortality, morbidity, and length of hospital stay. If the ISS is greater than 16, major trauma is present. All injuries should be identified when calculating [19]. In our study, although ISS values were higher in Group 2 patients compared to Group 1, no statistically significant difference was found between the groups (p>0.05).
The main approach in the treatment of rib fractures is pain control and breathing exercise. Hypoventilation due to pain predisposes to secretion retention, atelectasis, and infection. Therefore, pain should be prevented and respiratory physiotherapy should be performed. Young cases and patients without complications can be followed up on an outpatient basis. However, it is essential that elderly patients be observed in the hospital and have good pain treatment. Although the treatment of rib fractures is conservative, complications caused by broken ends may require surgical intervention. In these cases, the platinum application is an important method that facilitates stabilization [20]. In our study, 60 (12%) patients underwent tube thoracostomy, 10 (2%) patients underwent thoracotomy (7 bleeding control+hematoma evacuation, 3 primary diaphragmatic repair), and 2 (0.41%) patients underwent chest wall reconstruction. In addition, it was determined that 10 (2%) of the flail chest patients were followed in the intensive care unit, 3 (1%) of them had fixation+intensive care follow-up, and all of the patients with pneumomediastinum underwent fiberoptic bronchoscopy+esophageal passage graphy and endoscopy.
Conclusion
According to our study, there was no difference between the two groups in terms of mortality in trauma patients with typical or atypical rib fractures. However, in terms of concomitant pathologies, pneumomediastinum, contusion, and flail chest development in typical rib fractures were more common in patients with atypical rib fractures. Although trauma scores were generally higher in Group 2 than in Group 1, they were not significant in patients with typical-atypical rib fractures except for CWIS. In treatment, patients should be monitored, and oxygen saturation, arterial blood pressure, cardiac rhythm, and arterial blood gas should be monitored. In addition, pain control and respiratory physiotherapy should be provided. While the primary treatment method in patients with intrathoracic complications is simple tube thoracostomy, larger surgical interventions can be performed when necessary, despite high mortality. Especially in patients with high CWIS, surgical treatment can be performed depending on the condition of the concomitant organ injuries.
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. Paydar S, Akbarzadeh A, Jahanabadi S. Anatomy of the Ribs and Management of their Fractures as Viewed by Avicenna. Acta Med Hist Adriat. 2019;17(2):305-12.
2. Graeber GM, Nazim M. The Anatomy of the Ribs and the Sternum and Their Relationship to Chest Wall Structure and Function. Thoracic Surgery Clinics. 2007;17(4):443-666.
3. Kim M, Moore JE. Chest Trauma: Current Recommendations for Rib Fractures, Pneumothorax and Other Injuries. Curr Anesthesiol Rep. 2020;10(1): 61-8.
4. Dehghan N, Mestral C, McKee MD, Schemitsch EH, Nathens A. Flail chest injuries: a review of outcomes and treatment practices from the National Trauma Data Bank. J Trauma Acute Care Surg. 2014;76(2):462-8.
5. Shi HH, Esquivel M, Staudenmayer KL, Spain DA. Effects of mechanism of injury and patient age on outcomes in geriatric rib fracture patients. Trauma Surg Acute Care Open. 2017; 2(1): e000074. DOI: 10.1136/tsaco-2016-000074.
6. Tsai PL, Huang CY, Chuang JF, Chou SE, Su WT, Hsu SY, et al. Factors affecting mortality in trauma patients with more than three rib fractures. Formosan Journal of Surgery. 2020;53(5):184-90.
7. Kaewlai R, Avery LL, Asrani AV, Novelline RA, Multidetector CT of blunt thoracic trauma. Radiographics. 2008;28(6):1555-70.
8. O’Brien SD, Bui-Mansfield LT. Costovertebral fracture dislocations: important radiographically difficult diagnosis. J Comput Assist Tomogr. 2009;33(5):748-51.
9. Karadayi S, Nadir A, Sahin E, Celik B, Arslan S, Kaptanoglu M. An analysis of 214 cases of rib fractures. Clinics. 2011;66(3):449-51.
10. Gungor F, Akyol KC, Kilic T, Kesapli M, Ari A, Sayrac AV. Blunt Minor Thoracic Trauma: A Prostective Analysis of 186 Patients in the Emergency Department. Kafkas J Med Sci 2017;7(3):203-208.
11. Russell RJ, Hodgetts TJ, McLeod J, Starkey K, Mahoney P, Harrison K, at al. The role of trauma scoring in developing trauma clinical governance in the Defence Medical Services. Philos Trans R Soc Lond B Biol Sci. 2011;366(1562):171-91.
12. Brown SD, Walters MR. Patients With Rib Fractures. Clınıcal Care. 2012;19(2):89-91.
13. Maxwell C, Mion L, Dietrich M. Hospitalised injured older adults; clinical utility of a rib fracture scoring system. J Trauma Nurs. 2012;19(3):168-74.
14. May L, Hillermann C, Patil S. Rib fracture management. BJA Education. 2016;16(1):26-32.
15. Taylor BC, Fowler TT, French BG, Dominguez N. Clinical Outcomes of Surgical Stabilization of Flail Chest Injury. J Am Acad Orthop Surg. 2016;24(8):575-80.
16. Chen J, Jeremitsky E, Philp F, Fry W, Smith RS. A chest trauma scoring system to predict outcomes. Surgery. 2014;156(4):988‑94.
17. Pape H, Remmers D, Rice J, Ebisch M, Tscherne H. Appraisal of early evaluation of blunt chest trauma: development of a standardized scoring system for initial clinical decision making. J Trauma. 2000; 49(3):496–504.
18. Elbaih A, Elshaboury I, Kalil N, El-Aouty H. Evaluation of thoracic trauma severity score in predictıng the outcome of isolated blunt chest trauma patients. International Journal of Surgery and Medicine. 2016;2(3):100-6.
19. Grimal Q, Salah Naili S, Watzky A. A high-frequency lung injury mechanism in blunt thoracic impact. J Biomech. 2005; 38(6):1247-54.
20. Cohen SP, Christo PJ, Moroz L. Pain management in trauma patients. Am J Phys Med Rehabil. 2004;83(2):142-61.
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Muharrem Cakmak. Comparison of trauma patients with typical – atypical rib fractures. Ann Clin Anal Med 2023;14(8):702-706
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Determination of preoperative hypertension prevalence and awareness in patients before elective surgery
Eyüp Aydoğan 1, Munise Yıldız 2, Betül Kozanhan 2, Nuran Akıncı Ekinci 2
1 Department of Anesthesiology and Reanimation, Alanya Alaaddin Keykubat University, Alanya Training and Research Hospital, Antalya, 2 Department of Anesthesiology and Reanimation, Health Sciences University, Konya City Hospital, Konya, Turkey
DOI: 10.4328/ACAM.21686 Received: 2023-03-13 Accepted: 2023-05-05 Published Online: 2023-06-09 Printed: 2023-08-01 Ann Clin Anal Med 2023;14(8):707-710
Corresponding Author: Eyüp Aydoğan, Department of Anesthesiology and Reanimation, Alanya Alaaddin Keykubat University, Alanya Training and Research Hospital, Antalya, Turkey. E-mail: eypaydogan@hotmail.com P: +90 555 710 79 83 Corresponding Author ORCID ID: https://orcid.org/0000-0003-3432-4946
This study was approved by the Ethics Committee of University of Health Sciences (Date: 2021-01-29, No: E-46418926-050.01.04-5425)
Aim: This study was conducted to reduce target organ damage and perioperative morbidity by early diagnosis of uncontrolled hypertension, considering the morbidities associated with hypertension.
Material and Methods: The data of 400 volunteer patients who met the sample eligibility criteria and applied to the anesthesiology outpatient clinic before elective surgery in Konya City Hospital were analyzed. The socio-demographic characteristics, anthropometric data, and the average of two blood pressure measurements of the patients were recorded. Hypertension (HT) was defined as systolic blood pressure (SBP) ≥ 130 mmHg and/or diastolic blood pressure (DBP) ≥ 80 mmHg. Body Mass Index (BMI) and Body Roundness Index (BMI) were calculated with the formula. They were categorized as average weight (BMI <25 kg m-2), overweight (25 ≤ BMI <30 kg m-2), and obese (BMI ≥ 30 kg m-2) according to their BMI.
Results: Seven out of ten adult patients admitted to the anesthesiology outpatient clinic before elective surgery were hypertensive. While 60% of these were unaware of having HT, only 22% of those diagnosed had blood pressure under control.
Discussion: As a result of our study, the high prevalence and low awareness of blood pressure indicate that hypertension is a common problem in our country. Furthermore, since HT remains a significant risk factor for morbidity and mortality, preoperative evaluation of patients provides a unique opportunity to diagnose and initiate treatment.
Keywords: Hypertension, Body Mass Index, Preoperative, Blood Pressure, Awareness
Introduction
Hypertension (HT) is the most common medical diagnosis. It is predicted that more than 1 billion people worldwide suffer from HT, and with increasing age and sedentary living conditions, HT prevalence will rise to 1.5 billion in 2025 [1]. High blood pressure is associated with life-threatening comorbidities such as ischemic heart disease, heart failure, renal failure, and cerebrovascular disease [2]. Although effective blood pressure management can reduce the incidence of complications in patients with hypertension, in general, poorly controlled blood pressure prevalence is quite high. Moreover, in a significant part of the population, non-diagnosed hypertension is common in both developed and developing countries [3, 4].
The relationship between uncontrolled HT and negative perioperative results has been known since the 1950s. HT has a high prevalence in patients presenting for surgery. Therefore, it is very important for anesthetists to determine blood pressure to evaluate the patient’s condition before and during surgery. Considering the morbidity associated with HT, which is not noticed, even though it has been diagnosed at all, is not treated or untreated at the optimal level, the diagnosis of preoperative hypertension provides a unique opportunity to initiate or optimize the treatment. This study aimed to determine the prevalence of HT and awareness in patients who applied to the anesthesia polyclinic for surgery preparation and to determine the relationship between HT and demographic and anthropometric measurements.
Material and Methods
For this prospective, observational, and descriptive research, the University of Health Sciences (SBU) scientific studies Ethics Committee (No: E-46418926-050.01.04-5425) and Konya City Hospital TUEK (Issue No: 34028083-799) were obtained from the Ethics Committee (NO: E-46418926-050.01.04-5425- 15.01.2021 Ethics ethical approval date). The sample of this study consists of patients aged 18 years and older who applied to the anesthesiology outpatient clinic before electrical surgical procedures other than Cardiovascular Surgery and Obstetric Surgery between April 2021 and June 2021 at Konya City Hospital. Oral and written consent was obtained from all patients evaluated to comply with the sample criteria and to be included in the research. Patients’ detailed medical history, demographic characteristics, comorbid diseases, existing drug use, smoking, and alcohol use data were recorded.
Blood pressure measurement; The patients did not smoke and did not drink tea, coffee, and caffeine 30 minutes before the blood pressure measurement, and they were allowed to rest for at least 10 minutes. Using the appropriate size blood pressure cuff (Microlife Exact BP, Microlife Ag, Widnau, Switzerland), two measurements were made from the right arm with a 5-minute interval. The average of two measurements was evaluated. According to the definition of the 2017 ACC/AHA guide; Patients with systolic (SBP) and/or diastolic (DBP) blood pressure ≥130/80 mmHg and/or those using antihypertensive medication were recorded as hypertensive patients (Table 1) [5].
HT Disease Duration: The time since the diagnosis was defined as Month(s). HT awareness ; It has been described as a health worker telling the presence of hypertension to individuals with hypertension. HT treatment; was defined as the use of antihypertensive treatment in for patients who applied to the anesthesia polyclinic before surgery. Controlled HT:; Taking medication for hypertension was defined as the fact that blood pressure measurements are SBP <130 mmHg and DBP <80 mmHg.
Body Mass Index (BMI) was calculated using the following formula: BMI = Weight (kg) /height (m)2.
Patients According to the Global Classification WHO (World Patients were classified According to WHO (World Health Organization) Classification; BMI <25 kg m-2: Normal weight, 25 ≤ BMI <30 kg m-2): overweight, and BMI ≥ 30 kg m-2: obese [6].
Waist circumference (cm) was measured along thein horizontal circumference between the costal margins and the iliac crest at the end of expiration using a non-stretchable tape measure.
Body roundness index (BRI); has been developed as an alternative to the measurement of BMI and waist circumference calculated based on size (m) and waist circumference (m) [7]. The BRI values calculated by the formula below were evaluated between 1 and 16.
BRI=364,2-(365,5*√(1-((waist circumference )⁄2π)^2/((0,5 height)^2 )))
Statistical analysis
In When analyzing the data obtained in the study, the IBM-Statistic Package for Social Sciences (IBM-SPSS INC., Chicago, IL, USA) was used. The suitability of the data to normal distribution was examined with the ‘Kolmogorov-Smirnov test. Continuous variables were expressed as average and standard deviation depending on the distribution status, and categorical variables were expressed as numbers and percentages. In cases where parametric test assumptions were provided in the analysis of continuous variables, T-Test was applied in independent groups ; otherwise, the ‘The Mann-Whitney U test’ was applied. ‘Pearson’s ChKi- Square tTest’ was used to compare categorical variables. Logistics regression analysis was used in patients to determine possible independent risk factors associated with hypertension. The statistical significance level was considered at p <0.05.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
In this study, the data of 400 patients who met the requirements of inclusion were analyzed. In the study, 49.5 % (198) female and 50.5 % (202) male participants included. While the average age of the patients was 51 ± 15.47 years, the mean age of men and women was 51,53 ± 14.37 and 51.61 ± 16.51 years, respectively. The demographic data of the patients are shown in Table 2.
HT prevalence was found to be 67.75 % (271 people). While 61.3 % (166 people) were not aware of the height of blood pressure, 38.7 % were diagnosed with HT. 77.14 % (81 patients) of patients diagnosed with HT used antihypertensive drugs (Figure 1). 23.4 % of these patients had blood pressure values within the normal range.
There was a statistically significant difference between age and HT (p <0.01) (Table 2). In logistics regression analysis, BMI and age were independent hypertension risk factors. High BMI (21.4% increase) and advanced age (6%) significantly increased the risk of hypertension (Table 2). A statistically significant relationship was found between HT and cigarette consumption, diabetes, and ASA score (each p <0.01). Patients were divided into two groups: non-obese (BMI <30) and obese (BMI≥30) according to BMI values. The relationship analysis between obesity and BRI is shown in Figure 1. The average BRI average of obese patients was 6.74 ± 1.48 and the average of non-obese patients was 4,18 ± 1.21. This difference between the groups was found statistically significant.
Discussion
The most important results we reached as a result of this research were; Seven out of ten adult patients admitted to the anesthesiology outpatient clinic before elective surgery were hypertensive. While approximately 60 % were HT, the blood pressure of only one-fifth of the diagnostic areas were under control.
HT is a global public health problem. According to the first comprehensive global analysis report of tendencies in the detection, treatment, and control of HT prevalence, the number of adults with hypertension between the ages of 30-79 years has doubled in the last thirty years around the world [8]. HT is also a very common problem in our country and 1 out of every 3 people has HT [9]. We found preoperative HT prevalence as 67.75 %. The fact that this rate is higher than in previous research may be associated with the average age of our patient population. Age is an important risk factor for HT. Therefore, a more detailed research is required in terms of HT presence in the preoperative period, especially in the geriatric patient population. Another possible reason for this high prevalence may be that in clinical guidelines that were valid in previous years, may have adopted lower blood pressure for the diagnosis of HT [1, 10, 11].
A recent study reported that approximately half of the individuals with high blood pressure measurements are unaware of this and that more than half of them cannot receive the necessary [8]. Similar to the literature, we have found that two-thirds of patients with high preoperative blood pressure are unaware of the presence of HT. Since hypertension cannot be realized, the risk of fatal complications in individuals such as cardiovascular diseases and stroke increases. Since it is a major risk factor for HT morbidity and mortality, every opportunity should be evaluated to start diagnosis and treatment. For many patients, the most intense contact with the healthcare system usually occurs in the perioperative process, which they encounter for the first time. Thus, anesthetists can significantly contribute to the long-term prognosis of hypertensive patients who have not been identified or have been insufficiently treated.
General recommendations of all guidelines for the effective control of hypertension include lifestyle changes such as descending to an appropriate weight, limiting sodium intake, avoiding processed food consumption, and avoiding smoking and alcohol. However, the most serious problem the treatment of HT is that patients cannot adapt to clinical recommendations [12]. Our study determined that only one-fifth of patients who use regular medication were under the control of blood pressure. Despite the use of drugs, it suggests that poor blood pressure control may be related to the lack of life changes.
There are several limitations to this study. First, HT prevalence in this cohort may be more predicted. Although the HT was assessed in patients undergoing electrical surgery, the day before the surgery, some of the patients were worried. Thus, incorrectly high measurements may have been obtained. In addition, since emergency cases and cardiac and obstetric cases were excluded, it was impossible to determine the real hypertension prevalence in patients who applied for all surgeries. However, since they are likely to have more comorbid diseases than the electrical population, hypertension prevalence in patients presenting for emergency surgery is different and could not be determined in our research. Finally, more comprehensive studies are needed because the study sample is relatively small.
Conclusions
In this study, blood pressure was high in 7 of every ten patients evaluated in the anesthesiology outpatient clinic before the surgical procedure, while awareness was approximately 40 %. HT is one of the common diseases that often occur in the preoperative period and should be regulated before surgery. Preoperative assessment has a significant potential impact on the patient results with the opportunity to identify undiagnosed hypertension and improve management of known hypertensive patients. As a result of our study, the high prevalence of blood pressure and low awareness shows that hypertension is a common problem in our country. Since HT continues to be a major risk factor for morbidity and mortality, it provides a unique opportunity to evaluate patients in the preoperative period to start diagnosis and 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: 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. Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH). Eur Heart J. 2018; 39(33): 3021-104.
2. Braunwald E. Diabetes, heart failure, and renal dysfunction: the vicious circles. Prog Cardiovasc Dis. 2019; 62(4):298-302.
3. Joffres M, Falaschetti E, Gillespie C, Robitaille C, Loustalot F, Poulter N, et al. Hypertension prevalence, awareness, treatment and control in national surveys from England, the USA and Canada, and correlation with stroke and ischaemic heart disease mortality: a cross-sectional study. BMJ. 2013; 3(8): 003423.
4. Johnson HM, Thorpe CT, Bartels CM, Schumacher JR, Palta M, Pandhi N, et al. Undiagnosed hypertension among young adults with regular primary care use. J Hypertens. 2014; 32(1):65-74.
5. Whelton PK, Whelton PK. Guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice. Guidelines.Hypertension 2018;71(6):1269-324. DOI: 10.1161/HYP.0000000000000066.
6. Liu Z, Xu HM, Wen LM, Peng YZ, Lin LZ, Zho S, et al. A systematic review and meta-analysis of the overall effects of school-based obesity prevention interventions and effect differences by intervention components. International Journal of Behavioral Nutrition and Physical Activity. 2019; 16(1):1-12.
7. Rico-Martín S, Calderón-García JF, Sánchez-Rey P, Franco-Antonio C, Alvarez MM, Muñoz-Torrero JFS. Effectiveness of body roundness index in predicting metabolic syndrome: A systematic review and meta-analysis. Obes Rev. 2020. 21(7):13023.
8. Zhou B, Carrillo-Larco RM, Danaei G, Riley LM, Paciorek CJ, Stevens GA, et. al. Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants. Lancet. 2021; 398(10304): 957-80.
9. Pamukcu B. Profile of hypertension in Turkey: from prevalence to patient awareness and compliance with therapy, and a focus on reasons of increase in hypertension among youths. J Hum Hypertens. 2022; 36(5): 437-44.
10. Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Böhm M, et. al. 2013 ESH/ESC Guidelines for the management of arterial hypertension. Arterial Hypertension. 2013; 17(2): 69-168.
11. Bakris G, Ali W, Parati G. ACC/AHA versus ESC/ESH on hypertension guidelines: JACC guideline comparison. J Am Coll Cardiol. 2019; 73(23): 3018-26.
12. Palacholla RS, Fischer N, Coleman A, Agboola S, Kirley K, Felsted J, et. al. Provider and patient-related barriers to and facilitators of digital health technology adoption for hypertension management: scoping review. JMIR Cardio. 3(1):e11951. DOI:10.2196/11951.
Download attachments: 10.4328.ACAM.21686
Eyüp Aydoğan, Munise Yıldız, Betül Kozanhan, Nuran Akıncı Ekinci. Determination of preoperative hypertension prevalence and awareness in patients before elective surgery. Ann Clin Anal Med 2023;14(8):707-710
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Radiological tips on pulmonary sarcoidosis imaging: The invisible side of iceberg’s
Ensar Turko 1, Mesut Ozgokce 1, Fatma Durmaz 1, Enes Ozel 1, Selvi Asker 2, Cemil Goya 1, Ilyas Dundar 1, Sercan Ozkacmaz 1
1 Department of Radiology, 2 Department of Pulmonology, Faculty of Medicine, Van Yuzuncu Yil University, Van, Turkey
DOI: 10.4328/ACAM.21707 Received: 2023-03-30 Accepted: 2023-05-17 Published Online: 2023-05-30 Printed: 2023-08-01 Ann Clin Anal Med 2023;14(8):711-715
Corresponding Author: Ensar Turko, Department of Radiology, Faculty of Medicine, Van Yuzuncu Yil University, 65080, Tusba, Van, Turkey. E-mail: ensarturko@hotmail.com P: +90 432 444 50 65 F:+90 432 225 13 68 Corresponding Author ORCID ID: https://orcid.org/0000-0001-7989-5668
This study was approved by the Ethics Committee of Van Yuzuncu Yil University (Date: 2021-09-10, No: 12)
Aim: In our study, we aimed to investigate computed tomography (CT) findings in lung sarcoidosis in the light of different studies in the literature.
Material and Methods: Between January 2018 and September 2021, all thorax computed tomography reports were retrospectively scanned in our clinic. The imaging characteristics of 60 patients were examined, whose sarcoidosis findings were defined and diagnosed as sarcoidosis.
Results: In the staging of sarcoidosis, 15 (25%) patients were stage I, 42 (70%) patients were stage II, 2 (3.3%) patients were stage III, and 1 (1.7%) patient were stage IV. All our patients with lymph nodes (57 (Stage I and II)) were observed symmetrically. Calcification was present in 5 (8.7%) patients with lymph nodes, and 52 (91.3%) did not have calcification or necrosis. In 6 patients, lymph nodes other than the mediastinum were detected in the axilla and abdomen. When the lymph nodes seen in the axilla and abdomen other than the mediastinum were examined, it was found that the lymph nodes in the mediastinum were larger. In addition, it was determined that the fatty hilus of these lymph nodes, which were detected outside of the mediastinum, could not be distinguished. No accompanying cavitary lesion was observed in any of the lung parenchymal findings. In addition, in 16 (26.6%) patients with parenchymal results, scattered nodules smaller than 1 cm were observed without any other parenchymal conclusion. An increase in peribronchovascular cuffing and peribronchovascular nodular appearances were observed in 20 (33.3%) patients.
Discussion: Sarcoidosis is a disease that should always be considered in the differential diagnosis of atypical parenchymal findings in the lung or mediastinal lymph nodes.
Keywords: Sarcoidosis, Lung, Tomography, Lymph Nodes
Introduction
Sarcoidosis is a systemic disease of unknown etiology characterized by histologically non-caseating granulomas that occur in any organ, with more involvement in the intrathoracic lymph nodes and lung [1]. When the disease occurs, mediastinal lymph nodes and lungs are frequently affected. Therefore, a biopsy of the mediastinal lymph nodes is recommended in the definitive diagnosis and treatment management of the disease [2]. Sarcoidosis is more common between the ages of 25-45 and can appear in younger or older generations. The condition is slightly more common in women [3,4].
Mediastinal lymphadenopathy in sarcoidosis is symmetrical, and the resulting lymphadenopathies do not show a mass effect on adjacent vascular structures. In lung parenchymal findings, micronodules, macro nodules, ground glass opacities, reticulations, and fibrosis can be seen [5]. The lungs, the most frequently affected organ in pulmonary sarcoidosis, can be classified into four stages according to the state of the disease. There is lymphadenopathy in stage I, lymphadenopathy and parenchymal findings in stage II, parenchymal findings in stage III, and parenchymal fibrosis in stage IV [6]. Although the optimal treatment method for sarcoidosis has not been specified, corticosteroid therapy has been used for a long time in patients with severe symptoms or patients with severe extrapulmonary findings. Spontaneous remission was detected in two-thirds of patients, even if they did not receive treatment [7].
Sarcoidosis can be indistinguishable from many diseases clinically and radiologically. However, since sarcoidosis can progress with atypical findings such as mediastinal asymmetric and peripheral lymphadenopathy, differential diagnosis with lung cancer, lymphoma, tuberculosis, and other granulomatous diseases becomes difficult. Furthermore, atypical lung parenchymal findings can be indistinguishable from bronchiolitis, lymphangitic carcinomatosis, and some interstitial pneumonia [4]. Therefore, in our study, we aimed to investigate a wide range of computed tomography (CT) findings in pulmonary sarcoidosis, which is overlooked in the differential diagnosis, in light of different studies in the literature.
Material and Methods
Patients: This single-center retrospective observational study was initiated with the approval of the medical faculty’s clinical research ethics committee with ethical approval number 2021/10-12. All thorax computed tomography (CT) reports in our clinic between January 2018 and September 2021 were scanned retrospectively. PACS (picture archiving and communication system) examined two hundred ten patients with sarcoidosis findings. Among these patients, patients with a histopathological diagnosis or typical tomography findings who responded to treatment and whose clinical-radiological follow-ups were performed in our center were included in the study. In addition, 89 patients with suspicious sarcoidosis, 27 patients who were not followed up in our hospital, 32 patients without histopathological diagnosis or questionable response to treatment, and two patients with apparent artifacts were excluded from the study. The study was performed with 60 patients who met the inclusion criteria.
Acquisition and evaluation of images: All tomography examinations were performed using a 16-slice (Siemens Medical Systems, Germany) CT device, according to the routine thorax CT protocol, with the patients lying in the supine position and holding the breath after deep inspiration with or without intravenous contrast material, thorax CT scans were performed from the lung apex to the lowest level of the hemidiaphragm. In contrast-enhanced examinations, patients were injected with 1-1.5 mL/kg non-ionizing intravenous contrast agent iohexol (Amersham Health, Ireland) or iopromide (Schering, Germany) at a rate of 2-3 mL/second through the forearm vein via an automatic injector. Images were obtained with an average of 120 kV, 200 practical mA, 16×1.5 mm collimation, 3 mm section thickness, and 512×512 matrix parameters. The images were evaluated in standard mediastinal and parenchymal window settings by two radiologists with 14 and 7 years of experience in thoracic radiology, with consensus. Regardless of the clinical data of the patients, the images were examined. The stage of sarcoidosis, symmetric/asymmetric lymph nodes involved, presence of necrosis or calcification in lymph nodes, presence of accompanying cavitary mass in the lung, presence of accompanying pneumonia, isolated nodular involvement in parenchymal findings, peribronchovascular nodular appearance, and lower-middle-upper zone intensity parenchymal involvement were noted. In addition, the presence of accompanying organomegaly and extrathoracic participation in the upper abdominal images were examined. Then, the age, gender, biopsy result, and concomitant solid-hematological malignancy were noted. Patients with histopathological examination were accepted as sarcoidosis according to the pathology result. Also, patients with typical radiological findings who responded to treatment and whose other differential diagnoses were excluded were taken as sarcoidosis. The characteristic radiological findings of sarcoidosis were accepted as bilateral symmetric hilar lymphadenopathy, accompanied by parenchymal findings [4]. Patients with pulmonary sarcoidosis involvement and radiological extrathoracic findings were considered to have sarcoidosis involvement.
Statistical analysis and examination of findings: The features determined in the tomography were recorded in an Excel file, and the relevant results were evaluated in the statistics program if necessary. Descriptive statistics for the variables studied were presented as mean, standard deviation, minimum and maximum values. The SPSS (ver: 20) statistical program was used for all statistical calculations.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
A total of 60 patients, 43 females (71.6%) and 17 males (28.4) with a mean age of 49.26 ± 11.30 (20-70 years), were included in the study.
The diagnosis of sarcoidosis was made by biopsy in 37 patients and by having typical radiological findings in 23 patients or responding to treatment.
In the staging of sarcoidosis, 15 (25%) patients were stage I (Figure 1), 42 (70%) patients were stage II (Figure 2), 2 (3.3%) patients were stage III, and 1 (1.7%) was stage IV. In all our patients with lymph nodes, 57 (Stage I and Stage II) lymph nodes were observed symmetrically. Calcification was present in 5 (8.7%) patients with lymph nodes, and 52 (91.3%) did not have calcification or necrosis (Table 1). Axillary and abdominal lymph nodes were detected in 6 patients, except for the mediastinum. When the lymph nodes seen in the axilla and abdomen other than the mediastinum were examined, it was found that the lymph nodes in the mediastinum were larger. In addition, it was determined that the fatty hilus of these lymph nodes, which were detected outside of the mediastinum, could not be distinguished.
No accompanying cavitary lesion was observed in any of the lung parenchymal findings. In addition, in 16 (26.6%) patients with parenchymal results, scattered nodules smaller than 1 cm were observed without any other parenchymal conclusion. An increase in peribronchovascular cuffing and peribronchovascular nodular appearances were observed in 20 (33.3%) patients. Other findings (consolidation, ground glass, atelectasis) were present in 9 patients (Table 2).
The involvement was classified as an upper, middle, and lower zone in 45 patients with parenchymal involvement. In in 22 (48.8%) patients, in all zones, in 12 (26.6%) patients, upper and middle zone involvements, and in 11 (24.6%) patients, middle and lower zone involvements were detected. The dominant findings were in patients with all-zone involvement in the upper zone.
When accompanying organomegaly was examined, only hepatomegaly was found in 6 patients, and hepatomegaly and splenomegaly were found in 6 patients. Only 1 of 6 patients with hepatomegaly had sarcoidosis involvement in the liver. Sarcoidosis involvement in the spleen or liver was detected in 5 of 6 patients with hepatomegaly and splenomegaly (Figure 3).
When extrathoracic involvement was examined, six patients had spleen or liver, 3 had cutaneous, and 1 had pituitary involvement.
When examined regarding solid or hematologic malignancies that may accompany sarcoidosis, two patients had breast cancer, and no hematological malignancy was detected in any of our patients.
Discussion
In this study, we retrospectively analyzed the radiological findings and demographic data of patients with sarcoidosis. A total of 60 patients, 43 females (71.6%) and 17 males (28.4) with a mean age of 49.26 ± 11.30 (20-70) years were included in the study. Most of the patients were stage II (70%) and later stage I (25%).
Although there is no significant epidemiological difference between men and women with sarcoidosis in the literature, 71.6% of the female patients in our study indicate that the disease is more common in women in our region [8]. Furthermore, considering the age range, it is observed that it is compatible with the literature, with an average age of 49 years [8].
Although there are different methods of diagnosing sarcoidosis, the diagnosis was made in our clinic with endoscopic biopsy, typical radiological findings, and evaluation of response to treatment [9]. When the stage of the diagnosed patients was examined, although results were found parallel to the literature, especially Stage II patients were detected more frequently in our clinic [9]. We think this is because patients apply to us later or prefer our hospital for their follow-up because we are an advanced center.
Although asymmetrical lymph nodes are not typical for sarcoidosis lymph nodes in the literature, it has been determined that they are rarely seen [10]. In our study, the lymph nodes were symmetrical in all of our patients, and we did not observe asymmetric lymph nodes in any of our patients. Studies of calcification in sarcoidosis lymph nodes have reported that it can be kept at 11%. In our research, calcification was observed in the lymph nodes in 8.7% of our patients, consistent with the literature [11]. Although rare, necrosis in the lymph nodes has been reported, and no necrosis was detected in our study patients [11].
In parenchymal lesions, mainly increased peribronchovascular cuffing and peribronchovascular nodular were observed. In addition, when we examined the parenchymal lesions, 26.6% of our patients had scattered nodules smaller than 1 cm in the parenchyma without any other finding. When the tomographies of the patients recorded in our system were examined, it was determined that they were previously diagnosed with sarcoidosis and that their lung parenchymal findings regressed. Nevertheless, sequelae in the form of nodules remained in their follow-up. In studies in the literature, it has been determined that there are only patients with accompanying nodules in the parenchyma [11].
Our patients had no solitary or cavitary mass regarding differential diagnosis in parenchymal findings regarding lung cancer that may accompany sarcoidosis. Lung cancer that may accompany sarcoidosis has been reported in the literature [12].
When the zonal distribution was examined, it was found that there was no significant difference in the involvement of the upper and lower zones, where diffuse involvement was predominant. The dominant findings were located in the upper zone in patients with all-zone participation. When the parenchymal involvement was examined, the upper zone involvement was slightly higher than the lower zones, but we did not observe a significant difference. Studies in the literature have reported that the upper zone can be involved two times more than the lower zone [11]. In addition, earlier literature studies have reported that the upper zone predominates [13].
The liver is the most frequently involved organ in abdominal sarcoidosis, although all abdominal organs can be affected. Liver involvement is sometimes not detected by tomography, and only hepatomegaly can be seen. Radiologically, it is observed as non-enhancing hypodense lesions varying from 1-3 mm to a few cm in the liver [5,14]. Isolated liver involvement in abdominal sarcoidosis is rare and is often accompanied by splenomegaly and spleen involvement. Folz et al. reported that in 75% of patients with liver involvement, spleen, and abdominal lymph nodes were involved. In our study, isolated hepatomegaly was observed in 6 patients, and only 1 (16.6%) of these patients had radiological involvement in the liver [15]. There was radiological sarcoidosis involvement in the spleen or liver in 5 (83.3%) of 6 patients with accompanying hepatomegaly and splenomegaly, and the findings were consistent with the detection of Folz et al. [15].
In studies on extrathoracic sarcoidosis in the literature, involvement rarely occurs and may present different clinical findings [4]. In our study, out of 60 patients, 6 (10%) patients had liver and spleen involvement, 3 (5%) patients had cutaneous involvement, and 1 (1.6%) had pituitary involvement.
Many studies indicate that hematological and solitary organ cancers may develop more in sarcoidosis patients [16,17]. Our analysis detected no hematological malignancy in any of our patients, but we saw breast cancer in 2 (3%) patients. When breast cancer was detected in one of the patients, sarcoidosis was not diagnosed. The other patient had advanced age and a family history of breast cancer.
Among the limitations of our study, it can be mentioned that study was retrospective; not all cases had a histopathological diagnosis, and some patients were not initially diagnosed in our hospital.
Conclusion
Sarcoidosis is a systemic disease that most commonly affects the lungs and can affect many other organs. In particular, the central and symmetrical distribution of lymph nodes, consideration of lung parenchymal findings and accompanying lymph nodes, and evaluation of attending extrathoracic results and pulmonary findings are essential in the differential diagnosis of thoracic sarcoidosis. Therefore, Sarcoidosis is a disease that should always be considered in the differential diagnosis of atypical parenchymal results in the lung or mediastinal lymph nodes.
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. Soto Gomez N, Peters JI, Nambiar AM. Diagnosis and management of sarcoidosis. Am Fam Physician. 2016;93(10):840-8.
2. Gupta S, Seaberg K, Wallace MJ, Madoff DC, Morello FA Jr, Ahrar K, et al. Imaging-guided percutaneous biopsy of mediastinal lesions: different approaches and anatomic considerations. Radiographics. 2005;25(3):763-88.
3. Baughman RP, Teirstein AS, Judson MA, Rossman MD, Barnard J, Frederick M, et al. Clinical characteristics of patients in a case-control study of sarcoidosis. Am J Respir Crit Care Med. 2001;164(10 Pt 1):1885-9.
4. Ganeshan D, Menias CO, Lubner MG, Pickhardt PJ, Sandrasegaran K, Bhalla S. Sarcoidosis from head to toe: what the radiologist needs to know. Radiographics. 2018;38(4):1180-200.
5. Tana C, Donatiello I, Coppola MG, Ricci F, Maccarone MT, Ciarambino T, et al. CT findings in pulmonary and abdominal sarcoidosis. Implications for diagnosis and classification. J Clin Med. 2020;9(9):3028.
6. Srinivasan M, Thangaraj SR, Arzoun H, Kulandaisamy LBG, Mohammed L. The Association of Lung Cancer and Sarcoidosis: A Systematic Review. Cureus. 2022;14(1). DOI: 10.7759/cureus.21169.
7. Kim JJ, Park JK, Wang YP, Choi SH, Jo KH. Lung cancer associated with sarcoidosis – a case report. Korean J Thorac Cardiovasc Surg. 2011;44(4):301-3.
8. Arkema EV, Cozier YC. Epidemiology of sarcoidosis: current findings and future directions. Ther Adv Chronic Dis. 2018;9(11):227-40.
9. Zhang Y, Du SS, Zhao MM, Li QH, Zhou Y, Song JC, et al. Chest high-resolution computed tomography can make higher accurate stages for thoracic sarcoidosis than X-ray. BMC Pulm Med. 2022;22(1):1-8.
10. Ma J, Wang YC, Sun XW, Sun CY. Atypical computed tomography manifestations of thoracic sarcoidosis. Zhonghua Jie He He Hu Xi Za Zhi. 2017;40(12):925-30.
11. Ayçiçek O, Bülbül Y, Öztuna F, Özlu T, Akkaya S. Diagnostic Value of Radiographic Characteristics of Mediastinal and Hilar Lymph Nodes in Sarcoidosis. Turk Thorac J. 2022;23(4):284.
12. Kobak S, Yildiz F, Semiz H, Orman M. Malignancy in patients with sarcoidosis. Rheumatol Clin. 2021;17(1):49-51.
13. Koyama T, Ueda H, Togashi K, Umeoka S, Kataoka M, Nagai S. Radiologic manifestations of sarcoidosis in various organs. Radiographics. 2004;24(1):87-104.
14. Palmucci S, Torrisi SE, Caltabiano DC, Puglisi S, Lentini V, Grassedonio E, et al. Clinical and radiological features of extrapulmonary sarcoidosis: a pictorial essay. Insights Imaging. 2016;7(4):571-87.
15. Folz SJ, Johnson CD, Swensen SJ. Abdominal manifestations of sarcoidosis in CT studies. J Comput Assist Tomogr. 1995;19(4):573-9.
16. Chopra A, Judson MA. How are cancer and connective tissue diseases related to sarcoidosis? Curr Opin Pulm Med. 2015;21(5):517-24.
17. Haddadi S, Adkinson BC, Holt GE, Mirsaeidi M. Sarcoidosis or cancer? That is the question. Respir Med Case Rep. 2021;33:101426.
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Does COVID-19-related viral sepsis stimulate angiotensin II levels more than bacterial sepsis?
Selcuk Demircan 1, Nilüfer Bulut 2, Serkan Kalkan 1, Deccane Duzenci 1, Murat Bicakcioglu 1, Mehmet Ozden 3, Zafer Dogan 1, Ayse Belin Ozer 1
1 Department of Anesthesia and Reanimation, Intensive Care Unit, 2 Department of Biochemistry, 3 Department of Infectious Diseases, Inonu University, Malatya, Turkey
DOI: 10.4328/ACAM.21713 Received: 2023-04-05 Accepted: 2023-05-17 Published Online: 2023-06-04 Printed: 2023-08-01 Ann Clin Anal Med 2023;14(8):716-720
Corresponding Author: Ayse Belin Ozer, Department of Anesthesiology and Reanimation, Inonu University, Turgut Ozal Medical Center, Malatya, Turkey. E-mail: abelinozer@gmail.com P: +90 533 447 89 24 F: +90 850 297 90 03 Corresponding Author ORCID ID: https://orcid.org/0000-0002-0113-6466
This study was approved by the Ethics Committee of Inonu University (Date: 2021-04-28, No: 2021/89)
Aim: Angiotensin II and its receptors play a role in both COVID and bacterial sepsis. The aim of this study was to compare the levels of serum angiotensin II and its receptors in viral sepsis due to COVID-19 with the levels in bacterial sepsis.
Material and Methods: The study included 62 sepsis patients (n=31 COVID and n=31 non-COVID) with similar disease severity in the tertiary ICU. The serum angiotensin II, angiotensin II receptors 1 and 2 (ATR1, ATR2) and other inflammatory parameters were measured. Demographic data and 28-day mortality were recorded.
Results: Angiotensin II level was significantly higher in COVID patients than in non-COVID patients (p<0.05). ATR1 and ATR2 did not differ between the two groups. There was a negative correlation between angiotensin II and procalcitonin levels in all patients, and a positive correlation between ATR1 and procalcitonin, APACHE II score, and SOFA score in COVID patients (p<0.05).
Discussion: Observation showed that angiotensin II levels were higher in patients with COVID-19 compared to those with bacterial sepsis, and ATR1 level was higher in COVID-19 patients who died. It was thought that the renin-angiotensin cascade could be stimulated differently in bacterial sepsis compared to viral sepsis due to COVID.
Keywords: Angiotensin II, Bacterial Infection, COVID-19, Sepsis
Introduction
Sepsis is a public health problem with high morbidity and mortality. Bacterial, fungal, viral, and parasitic microorganisms can be causative agents. Many pathways are blamed or take part in its pathogenesis [1-3]. There are many studies showing that the renin-angiotensin-aldosterone system (RAS) and related angiotensin II and its receptors play a role in the pathogenesis of bacterial sepsis and septic shock [4-7]. The demonstration that treatment with RAS component inhibitors (angiotensin converting enzyme inhibitors, angiotensin receptor blockers, etc.) can have positive effects in the treatment of patients with COVID-19 during the COVID-19 pandemic has caused angiotensin II and its receptors to be the focus of attention in patients with COVID-19 [8]. However, there is no clinical study in the literature comparing the mediators of the renin-angiotensin system between bacterial sepsis and viral sepsis due to COVID-19.
The aim of this clinical observational study is to examine the changes in serum angiotensin II and its receptors in patients with viral sepsis associated with COVID-19 who are followed up and treated in the intensive care unit, and in patients with bacterial sepsis, which we frequently see in intensive care units.
Material and Methods
This study was carried out in the COVID-19 intensive care and reanimation intensive care units of a university hospital following the approval of the local ethics committee (2021/89). Both intensive care units were followed by the same team, and the same clinical approaches were applied to all patients. From among patients in the two intensive care units, patients with similar disease severity were included in the study. The study included 31 COVID-19 patients whose diagnosis was confirmed by PCR (+) and who were followed up in the COVID-19 intensive care unit due to sepsis, and 31 patients who were hospitalized in the reanimation intensive care unit and were not considered to have COVID-19 according to PCR test, thorax CT findings, and clinical symptoms, did not previously have COVID-19, and where culture confirmed the presence of bacterial sepsis.
The primary outcome of the study was serum angiotensin II, angiotensin II receptor 1 and 2 (ATR1, ATR2) levels. Ten ml of blood was collected from sepsis clinic patients from both intensive care units and centrifuged at 4000 rpm for 10 minutes. Sera separated after centrifugation were placed in polypropylene tubes and stored at -80°C until analysis. The analysis was performed using the ELISA method in accordance with the procedure in the package insert. At the same time, the PaO2/FiO2 ratios, C-reactive protein (CRP), procalcitonin, D-dimer, troponin, ferritin, and IL-6 levels of the patients were measured and recorded. In addition, patients’ age, gender, comorbidities, source of infection, need for vasopressors, Sequential Organ Failure Assessment (SOFA) score, Acute Physiology, Assessment and Chronic Health Evaluation 2 (APACHE II) score, and 28-day mortality were recorded. The oxygen delivery method and whether the patients received steroids, tocilizumab, and other anti-inflammatories were recorded.
When the sample size was determined with effect size 0.7, α error probability 0.05, and power 0.8 with the G Power 3.1.9.4 program, the total sample size was found to be 52. The data of 62 patients were included in the study. With the data obtained at the end of the study, power analysis was evaluated with the biostatapps.inonu.edu.tr/WSSPAS/ program, and the effect size was evaluated as 1.34 and power as 0.99 [9].
IBM SPSS Statistics 22 program was used for statistical analysis. The suitability of the parameters to the normal distribution was evaluated with the Levene test. While evaluating the study data, quantitative data were compared as well as descriptive statistical methods. Student’s t-test was used for the comparison of normally distributed parameters between groups, and the Mann-Whitney U test was used for the comparison of non-normally distributed parameters. The Chi-square test and Fisher’s Exact Chi-square test were used to compare qualitative data. Significance was evaluated at the p<0.05 level.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
There was no significant difference between the patients in terms of demographic data. All patients except two of the patients in the COVID group were using methylprednisolone, and none of the patients in the non-COVID group used steroids. While the rates of invasive mechanical ventilation support were similar, the use of high-flow nasal cannula (HFNC)/noninvasive mechanical ventilation (NIV) was significantly higher in the COVID group. The PaO2/FiO2 ratio was significantly lower in the COVID group than in the non-COVID group (p<0.05) (Table 1).
Angiotensin II level was found to be significantly higher in patients with COVID-19 than in non-COVID patients (p<0.05). There were no significant differences between the groups in terms of ATR1 and ATR2. Procalcitonin, CRP, and IL-6 levels were significantly higher in non-COVID patients than in patients with COVID-19 (p<0.05) (Table 1).
When patients with COVID were divided into surviving and non-surviving, with 11 being survivors and 20 being non-survivors, age, APACHE II and SOFA scores, vasopressor use, and need for invasive mechanical ventilation were significantly higher in non-survivors (p<0.05). An insignificantly lower angiotensin II level was observed in non-survivors compared to survivors (p>0.05). ATR1 receptor, D-dimer, and HS-troponin levels were significantly higher in non-survivors compared to survivors (p<0.05). Fibrinogen levels were significantly lower in non-survivors (p<0.05) (Table 2). There were no significant differences between any of the parameters in the surviving or nonsurviving non-COVID patients (p>0.05).
A negative correlation was observed between angiotensin II levels and procalcitonin in patients with COVID (r= -0.445, p=0.012). A positive correlation was observed between ATR1 and procalcitonin (0.459, p=0.009), APACHE II score (0.421, p=0.018), and SOFA score (0.511, p=0.003). A significant negative correlation was found between angiotensin II level and procalcitonin levels in non-COVID patients (-0.485, p=0.007).
Discussion
RAS is a complex and dynamic biaxial molecular cascade found in almost all organ systems and has an important role in neural, pulmonary, renal, cardiovascular and immune homeostasis [10]. The classical axis, ACE, includes angiotensin II and AT1R, while the counter-regulatory axis ACE2 creates the Ang-(1–7) and Mas receptor (MasR) [10]. Sepsis and SARS-CoV-2 infection are thought to cause changes in RAS. In our study, some mediators, especially angiotensin II levels, were compared in patients with viral sepsis due to COVID-19 and non-COVID patients with bacterial sepsis.
While there was no significant difference between the groups in terms of invasive mechanical ventilation use in our study, it was observed that the PaO2/FiO2 ratio was lower and HFNC/NIV use was higher in patients with COVID. Low PaO2/FiO2 ratio, high HFNC/NIV use, and high steroid use in patients with COVID-19 were thought to be related to respiratory failure and ARDS due to COVID-19. ARDS and the need for mechanical ventilation are the most common reasons for hospitalization in the intensive care unit in patients with COVID-19 [11,12]. In fact, although more invasive mechanical ventilation was expected in the group with COVID-19 compared to the non-COVID group, no difference was found in our study. This can be explained by the inclusion of patients who were previously admitted to the intensive care unit for another reason and who later developed sepsis amongst the non-COVID patient group (bacterial sepsis).
In recent years, the number of studies investigating the relationship between sepsis and the renin-angiotensin-aldosterone system has increased. However, the studies in the literature have mainly included bacterial sepsis or septic shock cases, and reported variable results [4,5,7,13]. In our previous study that we conducted on patients with bacterial sepsis and septic shock, we observed that the angiotensin II level was higher in sepsis patients who did not develop shock compared to those who did develop shock [5]. In our other study, in which we included only patients who developed shock and divided them into two groups as catecholamine-sensitive and -resistant, we observed that angiotensin II levels remained high in catecholamine-resistant patients [6]. With the COVID-19 pandemic that emerged at the end of 2019, the detection of SARS CoV-2 virus entering the cell via the ACE2 enzyme attracted attention to the renin-angiotensin-aldosterone system in patients with COVID-19 [14,15]. It has been shown that there is no significant difference between the angiotensin II levels of patients with and without COVID who sought emergency care with the same complaints [16]. In a study involving hospitalized patients with COVID-19, no significant difference was found between ACE and ACE2 levels between patients with and without COVID. However, it has been shown that the levels of both vasoconstrictor-acting angiotensin II and other vasodilator-acting angiotensin derivatives are decreased [17]. In another study comparing patients with and without COVID, it was shown that while ACE2 protein level and activity increased, angiotensin II and angiotensin 1-7 levels decreased [18]. In a study evaluating angiotensin II levels in patients with severe or mild COVID-19, angiotensin II levels were high in patients with severe COVID-19. It has been shown that the level of angiotensin II decreased over time in both groups, and the level of angiotensin 1-7 increased in the group with COVID-19 [19]. In the study by Xavier et al. in which they compiled studies on the course of angiotensin II in patients with COVID, they reported that the best case scenario was associated with high angiotensin II and AT-1 receptor levels, and the worst case scenario was low/stable angiotensin II and stable AT-1 level [10]. As can be seen, there are different results in the literature regarding both bacterial sepsis and COVID sepsis. However, apart from our study, there is no study yet comparing angiotensin II and its receptors between viral sepsis due to COVID-19 and bacterial sepsis. In summary, in our study, which is the first study in this field, angiotensin II level was found to be higher in patients who developed COVID-19 sepsis compared to non-COVID sepsis.
When surviving and nonsurviving patients were compared, angiotensin II levels were found to be lower in nonsurviving patients with COVID sepsis, while no significant difference was found between surviving and nonsurviving patients without COVID. While studies have shown that angiotensin II levels are low in patients with bacterial sepsis who develop shock or have a mortal course, another study has shown that there is a difference in early angiotensin II levels between surviving and nonsurviving patients but not in the late period [4,5]. Angiotensin II level was found to be lower in patients with COVID who did not survive in congruity with the worst-case scenario of Xavier et al. [10].
It has been found that the level of ATR1 decreases in bacterial sepsis and septic shock compared to non-septic patients and increases in patients who recover in the following days [5]. In addition, it was found that in catecholamine-resistant patients, unlike catecholamine-sensitive patients, ATR1 increased with angiotensin II level and had high specificity and sensitivity in detecting catecholamine-resistant patients [6]. The opinion that ATR1 constitutes a gateway to COVID-related diseases also makes the function or level of ATR1 important [20]. In our study, we determined that there was no significant difference in ATR1 and ATR2 levels between patients with bacterial sepsis and patients with viral sepsis due to COVID-19. When surviving and nonsurviving patients with COVID-19 were compared, high ATR1 receptor levels were accompanied by high D-dimer and HS-troponin levels and low fibrinogen levels in the nonsurviving. In addition, a correlation was observed between ATR1 level and procalcitonin levels and APACHE II and SOFA scores. The same correlation was not observed in patients with non-COVID sepsis.
Studies have shown that there is a relationship between the severity of COVID-19 and procalcitonin levels [21,22]. It has also been reported in studies that the severity of COVID or bacterial sepsis is associated with a decrease in angiotensin II levels [4,5,10]. Therefore, the correlation between procalcitonin and angiotensin II is not surprising. High APACHE and SOFA scores and high procalcitonin levels are expected results in septic patients who die or who develop shock.
Inflammatory mediators such as procalcitonin, CRP, and IL-6 have been used in the differentiation of bacterial and viral infections or in the differentiation of infectious and non-infectious inflammation [23-25]. Consistent with the literature, in our study, CRP, procalcitonin, and IL-6 levels were higher in patients with bacterial sepsis than in patients with COVID.
Conclusion
In conclusion, in our study, which consisted of patients with similar clinical disease severity, it was observed that, unlike in bacterial sepsis, the angiotensin II level was higher in patients with COVID, and ATR1 level was higher in nonsurviving patients with COVID-19. This suggests that the renin-angiotensin cascade may be stimulated by different pathways than bacterial sepsis or the same pathways can be stimulated at different intensities in viral sepsis due to COVID-19. This is an untapped issue that needs to be clarified, and this study is valuable because it is the first study in its field. However, extensive studies are needed to fully elucidate the pathogenesis and to put these mediators into practical application.
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. Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001;29(7):1303-10.
2. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315(8):801-10.
3. Martin GS, Mannino DM, Eaton S, Moss M. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med. 2003;348(16):1546-54.
4. Schmidt C, Höcherl K, Kurt B, Moritz S, Kurtz A, Bucher M. Blockade of multiple but not single cytokines abrogates downregulation of angiotensin IItype-Ireceptors and anticipates septic shock. Cytokine. 2010;49(1):30-8.
5. Ozer AB, Bicakcioglu M, Baykan S, Bulut N, Kalkan S, Demircan S, et al. Angiotensin II and Angiotensin II receptor 2 levels can predict shock and mortality in septic patients. Minerva Anestesiol. 2022;88(12):1021-9.
6. Baykan S, Bicakcioglu M, Bulut N, Yucel N, Ersoy Y, Kibrislioglu Uysal N, et al. Hydrocortisone may act through the angiotensin II receptor-2 level in patients with catecholamine-resistant septic shock. Minerva Anestesiol. 2022; DOI: 10.23736/S0375-9393.22.16766-0.
7. Zhang W, Chen X, Huang L, Lu N, Zhou L, Wu G, et al. Severe sepsis: low expression of the renin-angiotensin system is associated with poor prognosis. Exp Ther Med. 2014;7(5):1342-488.
8. Yang G, Tan Z, Zhou L, Yang M, Peng L, Liu J, et al. Effects of Angiotensin II Receptor Blockers and ACE (Angiotensin-Converting Enzyme) Inhibitors on Virus Infection, Inflammatory Status, and Clinical Outcomes in Patients With COVID-19 and Hypertension: A Single-Center Retrospective Study. Hypertension. 2020;76(1):51-8.
9. Arslan AK, Yasar S, Colak C, Yologlu S. WSSPAS: An Interactive Web Application for Sample Size and Power Analysis with R Using Shiny. Turkiye Klinikleri J Biostat. 2018;10(3): 224-46.
10. Xavier LL, Neves PFR, Paz LV, Neves LT, Bagatini PB, Timmers LFSM, et al. Does Angiotensin II Peak in Response to SARS-CoV-2? Front Immunol. 2021;11:577875.
11. Karakike E, Giamarellos-Bourboulis EJ, Kyprianou M, Fleischmann-Struzek C, Pletz MW, Netea MG, et al. Coronavirus Disease 2019 as Cause of Viral Sepsis: A Systematic Review and Meta-Analysis. Crit Care Med. 2021;49(12):2042-57.
12. Tzotzos SJ, Fischer B, Fischer H, Zeitlinger M. Incidence of ARDS and outcomes in hospitalized patients with COVID-19: a global literature survey. Crit Care. 2020;24(1):516.
13. Bellomo R, Wunderink RG, Szerlip H, English SW, Busse LW, Deane AM, et al. Angiotensin Iand angiotensin II concentrations and their ratio in catecholamine-resistant vasodilatory shock. Crit Care. 2020;24(1):43.
14. Xu H, Zhong L, Deng J, Peng J, Dan H, Zeng X, et al. High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. Int J Oral Sci. 2020; 12(1):8.
15. Bestle D, Heindl MR, Limburg H, Van Lam van T, Pilgram O, Moulton H, et al. TMPRSS2 and furin are both essential for proteolytic activation and spread of SARS-CoV-2 in human airway epithelial cells. Life Sci Alliance. 2020; 3(9):e202000786.
16. Rieder M, Wirth L, Pollmeier L, Jeserich M, Goller I, Baldus N, et al. Serum ACE2, Angiotensin II, and Aldosterone Levels Are Unchanged in Patients With COVID-19. Am J Hypertens. 2021;34(3): 278-81.
17. Kutz A, Conen A, Gregoriano C, Haubitz S, Koch D, Domenig O, et al. Renin-angiotensin-aldosterone system peptide profiles in patients with COVID-19. Eur J Endocrinol. 2021;184(4):543-52.
18. Silva MG, Corradi GR, Pérez Duhalde JI, Nuñez M, Cela EM, Gonzales Maglio DH, et al. Plasmatic renin-angiotensin system in normotensive and hypertensive patients hospitalized with COVID-19. Biomed Pharmacother. 2022;152:113201.
19. Reindl-Schwaighofer R, Hödlmoser S, Eskandary F, Poglitsch M, Bonderman D, Strassl R, et al. ACE2 Elevation in Severe COVID-19. Am J Respir Crit Care Med. 2021;203(9):1191-6.
20. El-Arif G, Khazaal S, Farhat A, Harb J, Annweiler C, Wu Y, et al. Angiotensin II Type I Receptor (AT1R): The Gate towards COVID-19-Associated Diseases. Molecules. 2022; 27(7):2048.
21. Ticinesi A, Nouvenne A, Prati B, Guida L, Parise A, Cerundolo N, et al. The Clinical Significance of Procalcitonin Elevation in Patients over 75 Years Old Admitted for COVID-19 Pneumonia. Mediators Inflamm. 2021;2021:5593806.
22. Hussain A, Singh L, McAlister Iii J, Jo Y, Makaryan TT, Hussain S, et al. Serum Procalcitonin as a Predictive Biomarker in COVID-19: A Retrospective Cohort Analysis. Cureus. 2022;14(8):e27816.
23. Duan S, Gu X, Fan G, Zhou F, Zhu G, Cao B. C-reactive protein or procalcitonin combined with rhinorrhea for discrimination of viral from bacterial infections in hospitalized adults in non-intensive care units with lower respiratory tract infections. BMC Pulm Med. 2021;21(1):308.
24. Gendrel D, Raymond J, Coste J, Moulin F, Lorrot M, Guérin S, et al. Comparison of procalcitonin with C-reactive protein, interleukin 6 and interferon-alpha for differentiation of bacterial vs. viral infections. Pediatr Infect Dis J. 1999;18(10):875-81.
25. Simon L, Gauvin F, Amre DK, Saint-Louis P, Lacroix J. Serum procalcitonin and C-reactive protein levels as markers of bacterial infection: a systematic review and meta-analysis. Clin Infect Dis. 2004;39(2):206-17.
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Selcuk Demircan, Nilüfer Bulut, Serkan Kalkan, Deccane Duzenci, Murat Bicakcioglu, Mehmet Ozden, Zafer Dogan, Ayse Belin Ozer. Does COVID-19-related viral sepsis stimulate angiotensin II levels more than bacterial sepsis? Ann Clin Anal Med 2023;14(8):716-720
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Investigation of the level of PAPP-A and ceruloplasmin in pericardial fluid in patients with open heart surgery
Nur Dilber Aslan 1, Mehmet Salih Aydın 2, Reşat Dikme 3, Mahmut Padak 4
1 Department of Perfusion Technology, 2 Department of Cardiovascular Surgery, Faculty of Medicine, 3 Department of Dialysis Program, Faculty of Health Services, 4 Department of Perfusion Techniques, Faculty of Health Services, Harran University, Şanlıurfa, Turkey
DOI: 10.4328/ACAM.21716 Received: 2023-04-06 Accepted: 2023-05-30 Published Online: 2023-06-09 Printed: 2023-08-01 Ann Clin Anal Med 2023;14(8):721-725
Corresponding Author: Mahmut Padak, Department of Perfusion Techniques, Faculty of Health Services, Harran University, 63300, Haliliye, Şanlıurfa, Turkey. E-mail: mpadak@harran.edu.tr P: +90 543 525 85 63 Corresponding Author ORCID ID: https://orcid.org/0000-0001-6863-1907
This study was approved by the Clinical Research Ethics Committee of Harran University Faculty of Medicine (Date: 2016-04-01, No: 64)
Aim: PAPP-A is a specific activator of insulin-like growth factor I (IGF-I), which plays a role in the development of atherosclerosis by acting on the smooth muscle cells of the vessels. Ceruloplasmin, on the other hand, is an acute-phase protein with 7-8% carbohydrate content and a moderate response to inflammation. In our study, it was aimed to determine the level of PAPP-A, Ceruloplasmin, PON1, Arylesterase, TOS, TAS and OSI values filtered into the pericardial fluid of patients undergoing open heart surgery for cardiovascular diseases.
Material and Methods: Forty patients who were operated on by the cardiopulmonary bypass method were included in this study. Pericardial fluid was taken from these patients and PAPP-A with the ELISA method, Ceruloplasmin with the Erel method, PON1 and Arylesterase were studied with the rel assay kit. In addition, Total Antioxidant Stress (TAS), Total Oxidative Stress (TOS) and Oxidative Stress Index (OSI) measurements were also made.
Results: As a result of the study, no significant correlation was found between PAPP-A and Ceruloplasmin. There was a negative correlation (r=-0.509) between ceruloplasmin and Arylesterase, and a significant correlation was found between them (p=0.022, p<0.05).
Discussion: PAPP-A and ceruloplasmin values have been shown to be important in terms of protection against atherosclerosis during cardiopulmonary bypass. With these parameters, which have been observed to have protective effects against the formation of atherosclerosis and against atherosclerosis, possible cardiac damage can be prevented by therapeutic strategies that reduce myocardial damage.
Keywords: Cardiopulmonary Bypass, PAPP-A, Ceruloplasmin, Paraoxonase, Arylesterase
Introduction
Cardiovascular disease (CVD) is a syndrome characterized by a structural or functional heart abnormality that results in decreased cardiac output or high intracardiac pressures at rest or during stress [1].
Cardiopulmonary bypass (CPB) has clarified one of the most difficult questions in the history of medicine, such as “Can we operate on the human heart without killing the patient?” With the dawning of a new era for cardiac surgery, a bloodless environment has been created that allows surgeons to open and repair the heart efficiently and deliver warm oxygenated blood to the rest of the heart without disrupting the heart’s work [2,3].
Recently, pericardial fluid (PF) has been used in addition to blood and heart tissue in the diagnosis of CVDs. PF analysis provides insight into many pathophysiological mechanisms in a variety of pericardial and CVD. Many studies to compare cardiac biomarkers have had better results from PF studies than from blood plasma [4].
PF is a biologically active part of the heart that communicates with the myocardial interstitium and creates a unique cardiac microenvironment [5]. This fluid contains many bioactive compounds thought to be products of serum ultrafiltration and leakage from the myocardium into the pericardial space [6].
The pregnancy-associated plasma protein-A (PAPP-A) enzyme has been shown to be an important regulator of local insulin-like growth factor (IGF) signaling and exhibits proatherogenic activity [7]. PAPP-A is responsible for the cleavage of IGF-binding protein-4 (IGFBP-4) in many tissues and is effective in increasing the density of IGF. Studies have reported that PAPP-A plays an important role in the formation of atherosclerosis, and circulating PAPP-A concentrations are associated with cardiovascular risk and acute disease [8].
Ceruloplasmin (Cp), also known as copper oxidase, is a blue-looking copper glycoprotein that was first purified from human serum α2-globulin in 1948 by Holmberg and Laurell. SP exists in two molecular isoforms, secreted SP (sSP) and a membrane glycosylphosphatidylinositol (GPI) associated CP (GPI-SP). sSP is mainly produced by the liver [9].
Cp has multiple physiological functions. It plays important roles in transporting 40-70% of Cu in plasma, iron (Fe) regulation, free radical scavenging and antioxidant processes [10].
Paraoxonase, on the other hand, is a glycoprotein enzyme and a calcium-dependent ester hydrolase with both arylesterase (E.C. 3.1.1.2) and paraoxonase (E.C.3.1.8.1) activities. Paraoxonase has three different structures: PON 1, PON 2 and PON 3. This enzyme is encoded in the long arm of chromosome 7q 21.3 22.1. PON 1 is synthesized by the liver and released into the blood [11].
Considering all this information in our study, the aim of this study is to determine the level of PAPPA, Ceruloplasmin, PON1, Arylesterase, TOS, TAS and OSI values filtered into the pericardial fluid of patients who have undergone open heart surgery for various cardiovascular diseases in cardiovascular diseases, to analyze the relationship between these parameters and CVD, and thus to contribute to the understanding of the pathophysiology of the disease.
Material and Methods
Ethics committee approval
This study was approved by the Harran University Faculty of Medicine Clinical Research Ethics Committee, with the decision dated 01.04.2016, session 03 and number 64.
Patients included in the study
This study was conducted in accordance with the Helsinki Declaration, which was revised in 1989. A total of 40 patients who were operated with the cardiopulmonary bypass method were included in this study. The study group was formed by taking pericardial fluid after sternotomy from the patients included in the study.
Obtaining Pericardial Fluid
After median sternotomy was performed with standard cardiopulmonary bypass procedures in patients who underwent open heart surgery, the pericardium was opened and pericardial fluid was aspirated with a sterile syringe. Pericardial fluid was then collected in sterile tubes without anticoagulant. The sterile tube from which the pericardial fluid was taken was immediately transferred into an ice-filled container. Then, the pericardial fluid in the sterile tube was passed through the centrifugation step. Then, the supernatant part was taken into a sterile Eppendorf tube and stored at -80 for analysis.
Study of Pericardial Fluid Samples
Elabscience Human PAPP-A ELISA Kit was used for this study. PAPP-A ELISA kit works according to the Sandwich-ELISA method. Before the study, the pericardial fluid of 40 patients, which was removed from –80 °C, was brought to room temperature and expected to dissolve. It was then centrifuged at 1000 g at +4 degrees for 20 minutes. The study was started by transferring the supernatant part on the Eppendorf tube to another Eppendorf tube.
Ceruloplasmin (Ferroxidase) Level Measurement
The ferro-oxidase enzyme activity of ceruloplasmin was measured according to the Erel method. This method involves the oxidation of ferrous iron ion to ferric iron ion. Results were expressed as U/L [12].
Paraoxonase Enzyme Activity Measurement
Paraoxonase activity, a lipophilic, hydrophobic antioxidant enzyme linked to HDL-Cholesterol, was measured using a commercial Rel Assay kit. The absorbance of the formed product was monitored in the kinetic mode at 412 nm, and the enzyme activity was expressed as U/L [13].
Arylesterase Activity Measurement
Arylesterase activity of paraoxonase enzyme, an antioxidant enzyme, was measured using a commercial Rel Assay kit. Results were expressed in kU/L as the enzyme activity is at very high levels [14].
Measurement of Antioxidant and OS Parameters in PF
Total Antioxidant Status (TAS) Measurement
TAS measurement in PF was performed using the Rel Assay Diagnostics total oxidant capacity measurement kit (Rel Assay Diagnostics, Lot. No: HN20106A, Turkey). Plasma TAS levels were determined using a new automated measurement method developed by Erel [15].
Total Oxidant Status (TOS) Measurement
Rel Assay Diagnostics total oxidant capacity measurement kit (Rel Assay Diagnostics, Lot. No: OK20115O, Turkey) was used for TOS measurement in PF. Plasma TOS levels were determined using a new automated measurement method developed by Erel [16].
Oxidative Stress Index (OSI) Measurement
OSI was calculated by dividing Total Oxidant Level (TOS)/Total Antioxidant and expressed as Arbitrary Unit (AU).
Statistical analysis
Statistical analyzes were performed using the SPSS Version 17 (SPSS Inc. Chicago USA) computer program. The significance of the difference between the means of the groups was compared with the One-Way ANOVA test. The relationship between the parameters was investigated by Pearson’s correlation analysis. Values less than p < 0.05 were considered statistically significant.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
Demographic Data of the Working Group
Of the patients included in the study, 12 were female and 28 were male, and the mean age was 60.97 years. Demographic data of 40 patients included in the study are shown in Table 1.
ELISA Results in PF
Optical density results read at 450 nm using commercial kits for PAPP-A and Ceruloplasmin level determination in PF by ELISA method and the results of Paraoxonase, Arylesterase, OS Parameters are shown in Table 2.
At the values indicated in Table 2, the lowest value of PAPP-A in the pericardial fluid of the patients was 3.19 ng/mL, the highest value was 10.61 ng/mL, and the mean was 5.83 ng/mL. When the ceruloplasmin values were examined, the lowest value was 432 U/L, the highest value was 763 U/L, and the average was 638 U/L. The paraoxonase value was found to be a minimum of 21 U/L, a maximum of 100 U/L, and an average of 67 U/L. Arelisterase values were found to be a minimum of 321 U/L, a maximum of 399 U/L, and an average of 368 U/L. The OSI average value was 1.11, the minimum value was 0.38, and the maximum value was 1.67 arbitrary units.
When the correlation between PAPP-A and ceruloplasmin was examined, although there was a negative relationship between these two parameters (r=-0.399), there was no significant relationship between them (p=0.081, p>0.05).
When the correlation between ceruloplasmin and Arylesterase was examined, a negative relationship was found between these two parameters (r=-0.509) and a significant relationship between them was revealed (p=0.022, p<0.05).
When the correlation between paraoxonase and arylesterase was examined, although there was a positive correlation between the two (r=0.039), no significant relation was found between them (p=0.871, p>0.05).
Considering the correlation between paraoxonase and OSI value, although there was a negative relationship between the two parameters (r=-0.104), there was no significant relationship between them (p=0.663, p>0.05).
Considering the correlation between Arylesterase and OSI, although there was a positive correlation (r=0.009), no significant correlation was found between these two parameters (p=0.969, p>0.05).
Considering the correlation between PAPP-A and OSI value, although there was a positive relationship between the two parameters (r=-0.359), there was no significant relationship between them (p=0.120, p>0.05).
Considering the correlation between PAPP-A and paraoxonase, although there was a positive correlation (r=0.256), no significant correlation was found between these two parameters (p=0.275, p>0.05).
When the relationship between PAPP-A and arylesterase was examined, although there was a positive relationship between these two parameters (r=-0.242), there was no significant relationship between them (p=0.303, p>0.05).
When the correlation between PAPP-A and ceruloplasmin was examined, although there was a negative relationship between these two parameters (r=-0.399), no significant relationship was found between them (p=0.081, p>0.05).
Discussion
In addition to blood and heart tissue, PF can be used to diagnose CVD. PF analysis may not provide an understanding of many pathophysiological systems in various pericardial and cardiovascular diseases [17].
In this study, we aimed to determine the level of PAPP-A, Ceruloplasmin, Paraoxonase, Arylesterase, TOS, TAS and OSI values in CVD that filtered into the pericardial fluid of patients who had open heart surgery, to analyze the relationship between these parameters and CVD, and thus to contribute to the understanding of the pathophysiology of the disease.
With the emergence of the concept of fragile plaque, studies on the diagnosis and treatment of fragile plaque have increased. However, many studies have indicated that high PAPP-A activity contributes to the formation of an atherogenic environment. In a study in mice, it was stated that transgenic overexpression of PAPP-A accelerated plaque progression, while the absence of PAPP-A caused an 80% reduction in plaque development [7].
In the studies, the function of the IGF system in cardiac dysfunction and CVD has been the subject of much debate, and there are conflicts as to whether the IGF system mainly exerts proatherogenic or atheroprotective functions. Studies have shown that high PAPP-A activity supports the theory that it supports an atherogenic environment. Transgenic overexpression of PAPP-A in mice accelerated plaque progression, while the absence of PAPP-A resulted in an 80% reduction in plaque development. [18].
In a study conducted, total concentration of IGF in the pericardial fluid was found to be 72% ± 10% lower than the plasma concentration, while the PAPP-A concentration was reported to be approximately 15 times more concentrated. They reported that 2 IGFBP-4 produced by PAPP-A and reflecting PAPP-A activity increased approximately more than 25% from the baseline levels. They found that IGF bioactivity was 62 ± 81% higher in pericardial fluid than in plasma [19]. In our study, the lowest value of PAPP-A in the pericardial fluid of the patients was 3.19 ng/mL, the highest value was 10.61 ng/mL, and the mean was 5.83 ng/mL.
In a study with 40 stable coronary patients and 20 normal coronary patients, it was observed that the ceruloplasmin value increased after approximately 48 hours by examining the rise of acute phase reactants immediately after the stent was placed in stable angina pectoris patients. In addition, it was observed that the serum ceruloplasmin level was higher in patients with Pulmonary Artery Disease than in patients without [20]. In our study, when the ceruloplasmin values in the pericardial fluid of our patients who underwent open heart surgery were examined, the lowest value was 432 U/L, the highest value was 763 U/L, and the mean was 638 U/L. When the correlation between PAPP-A and ceruloplasmin was examined, although there was a negative correlation between these two parameters (r=-0.399), no significant correlation was found between them (p=0.081, p>0.05).
In recent years, PON1 has been shown to inhibit LDL oxidation, prevent or slow down atherosclerotic formation by preventing oxidation of HDL particles and other mechanisms, and it has been investigated whether it can be a protective factor for cardiovascular diseases. At the same time, PON1 is also found in the normal arterial wall and its concentrations increase gradually in the atherosclerotic process [21].
In another study, they revealed that PON-1 arylesterase activity was significantly lower in the CAD group compared to the controls (p < 0:0001). They reported that PON-1 arylesterase activity in CAD patients was significantly higher in nondiabetic CAD patients compared to diabetic patients. (p = 0:03). PON-1 activity was found to be significantly lower in CAD patients [22]. In our study, the Arylesterase value was found to be a minimum of 321 U/L, a maximum of 399 U/L, and an average of 368 U/L. OSI average value is 1.11, minimum value is 0.38, and maximum value is 1.67 arbitrary units.
Conclusion
In conclusion, in this study, no significant correlation was found between PAPP-A and Ceruloplasmin. There was a negative correlation (r=-0.509) between ceruloplasmin and Arelisterase, and a significant correlation was found between them (p=0.022, p<0.05). In the literature review, no study was found showing the distribution of these parameters in the pericardial fluids of patients who were taken to cardiopulmonary bypass for various reasons, and the presence of a relationship between them. When these results in our study are compared, we think that studies with larger and specific patient groups are needed to explain the relationship between the parameters and cardiovascular diseases, since the studies do not support each other. We think that statistically significant results can be found when patient groups are formed, the number is increased and new studies with the same and similar parameters are performed.
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. Prasad AS, Bao B. Molecular mechanisms of zinc as a pro-antioxidant mediator: clinical therapeutic implications. Antiox (Basel) 2019;8(6):164-74.
2. Rosinski BF, Idrees JJ, Roselli EE, Germano E, Pasadyn SR, Lowry AM, et al. Cannulation strategies in acute type A dissection repair: A systematic axillary artery approach. J Thorac Cardiovasc Surg. 2019;158(3):647-59.
3. Squiccimarro E, Labriola C, Malvindi PG, Margari V, Guida P, Visicchio G, et al. Prevalence and Clinical Impact of Systemic Inflammatory Reaction After Cardiac Surgery. J Cardiothorac Vasc Anesth. 2019;33(6):1682-90.
4. Göç Ö, Göz M, Dikme R, Padak M. Investigation of oxidative stress and Interleukin 33 (IL33) level in pericardial fluid of patients with coronary artery bypass surgery. Ann Clin Anal Med. 2023;14(1):55-9.
5. Vogiatzidis K, Zarogiannis SG, Aidonidis I, Solenov EI, Molyvdas PA, Gourgoulianis KI, et al. Physiology of pericardial fluid production and drainage. Front Physiol. 2015;6:62.
6. Elie AGIM, Bloksgaard M, Sun WY, Yang K, Man AWC, Xu A, et al. Local enrichment of fatty acid-binding protein 4 in the pericardial cavity of cardiovascular disease patients. PLoS One. 2018; 5;13(11):e0206802.
7. Conover CA, Bale LK, Oxvig C. Targeted inhibition of pregnancy-associated plasma protein-A activity reduces atherosclerotic plaque burden in mice. J Cardiovasc Transl Res. 2016;9(1):77-9.
8. Hjortebjerg R, Berryman DE, Comisford R, List EO, Oxvig C, Bjerre M, et al. Depot-specific and GH-dependent regulation of IGF binding protein-4, pregnancy-associated plasma protein-A, and stanniocalcin-2 in murine adipose tissue. Growth Horm IGF Res. 2018;39:54-61.
9. Linder MC. Ceruloplasmin and other copper binding components of blood plasma and their functions: an update. Metallomics. 2016;8(9):887-905.
10. Chapman AL, Mocatta TJ, Shiva S, Seidel A, Chen B, Khalilova I, et al. Ceruloplasmin is an endogenous inhibitor of myeloperoxidase. J Biol Chem. 2013;288(9):6465–77.
11. Kıratlı K, Gül HC, Artuk C, Kozan S, Oztuna A, Tunca Y, et al. Kronik Hepatit C Enfeksiyonu Olan Hastalarda Paraoksonaz-1 Gen Polimorfizmi ile Tedaviye Yanıt Arasındaki İlişkinin Araştırılması (Investigation of the Relationship Between Paraoxonase-1 Gene Polymorphism and Response to Treatment in Patients with Chronic Hepatitis C Infection). Mikrobiyol Bul 2014; 48(4):596-605.
12. Erel O. Automated measurement of serum ferroxidase activity. Clin Chem. 1998; 44(11):2313-9.
13. Eckerson HW, Wyte CM, La Du BN. The human serum paraoxonase/arylesterase polymorphism. Am J Hum Genet. 1983; 35(6): 1126-38.
14. Haagen L, Brock A. A new automated method for phenotyping arylesterase (EC 3.1.1.2) based upon inhibition of enzymatic hydrolysis of 4-nitrophenyl acetate by phenyl acetate. Eur J Clin Chem Clin Biochem. 1992; 30(7):391-5.
15. Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin Biochem. 2004; 37(4):277-85.
16. Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem. 2005; 38(12):1103-11.
17. Duran A, Ocak T, Üyetürk Ü, Erdem A, Önder H, Maltaş M.Ş. Kardiyak Tamponad Kliniği ile Gelen Primeri Belli Olmayan Malignite: Olgu Sunumu (Malignancy of Undetermined Primary Presenting with Cardiac Tamponad Clinic: A Case Report). Konuralp Tıp Dergisi/ Konuralp Medical Journal. 2014; 6(2):58-60.
18. Hjortebjerg R. IGFBP-4 and PAPP-A in normal physiology and disease. Growth Horm IGF Res. 2018;(41):7-22.
19. Hjortebjerg R, Rasmussen LM, Gude MF, Irmukhamedov A, Riber LP, Frystyk J, et al. Local IGF Bioactivity Associates with High PAPP-A Activity in the Pericardial Cavity of Cardiovascular Disease Patients. J Clin Endocrinol Metab. 2020;105(11):4083-93.
20. Kaya Z, Esmer A, Asoğlu R, Yıldız A, Ulaş T, Sezen H, et al. Pulmoner arter basıncının serum seruloplazmin düzeyi ile ilişkisi (Relationship between pulmonary artery pressure and serum ceruloplasmin level). Journal of Harran University Medical Faculty. 2012; 9(3):104-11.
21. Caner C, Özeç AV, Aydın H, Topalkara A, Arıcı M.K, Erdoğan H, et al. Diyabetik ve Diyabetik Olmayan Katarakt Hastalarında Hümör Aközde ve Serumda Total Oksidatif Stres, Total Antioksidan Kapasite, Paraoksonaz, Arilesteraz ve Lipidperoksidaz Seviyelerinin Karşılaştırılması (Comparison of Total Oxidative Stress, Total Antioxidant Capacity, Paraoxonase, Arylesterase and Lipidperoxidase Levels in Humor Aqueous and Serum in Diabetic and Non-Diabetic Cataract Patients). Turkish Joutnal of Ophthalmology 2012; 42(1):47-52.
22. Zuin M, Trentini A, Marsillach J, D’Amuri A, Bosi C, Roncon L,et al. Paraoxonase-1 (PON-1) Arylesterase Activity Levels in Patients with Coronary Artery Disease: A Meta-Analysis. Dis Markers. 2022;(10):42643148.
Download attachments: 10.4328.ACAM.21716
Nur Dilber Aslan, Mehmet Salih Aydın, Reşat Dikme, Mahmut Padak. Investigation of the level of PAPP-A and ceruloplasmin in pericardial fluid in patients with open heart surgery. Ann Clin Anal Med 2023;14(8):721-725
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Demographic characteristics of 3,182 patients transferred by 112 emergency services in the Bolu province of Türkiye
Burcin Balaban
Department of Emergency Medicine, Gharrafat Al Rayyan Health Center, Qatar
DOI: 10.4328/ACAM.21728 Received: 2023-04-14 Accepted: 2023-05-17 Published Online: 2023-05-31 Printed: 2023-08-01 Ann Clin Anal Med 2023;14(8):726-730
Corresponding Author: Burcin Balaban, Department of Emergency Medicine, Gharrafat Al Rayyan Health Center, Ar-Rayyan, Qatar. E-mail: balabanburcin@gmail.com P: +90 +974 4406 9917 Corresponding Author ORCID ID: https://orcid.org/0000-0002-6215-9100
This study was approved by the Ethics Committee of of Bolu Izzet Baysal University (Date: 2012-12-20, No: 239)
Aim: In this study we aimed to analyze the demographic characteristics including gender and age groups of 3,182 emergency patients transferred by 112 EMS in the Bolu province of Türkiye.
Material and Methods: A total of 3,182 patients who used EMS were included in the study. Demographic characteristics of the patients such as age and gender, and outcomes of the cases were recorded in the forms developed by the researcher in line with the current relevant literature. The data used in our study were obtained by examining the patient transfer forms in 112 command and control centers.
Results: Of all patients, 1,287 (40.4%) were female, 1,658 (51.8%) were male and 247 (7.8%) were unspecified. In the current study, 394 patients were in the 0-18 age group, 1327 in the 19-45 age group, 626 in the 45-65 age group and 723 patients in the >66 years group. The rate of referral to hospital was lower in the 19-45 age group than in other age groups, the rate of death was significantly higher in the ≥ 66 years group.
Discussion: The use of emergency medical services varies according to gender and different age groups. Male patients used EMS more commonly compared to women. The most common EMS usage was found in the 19-45 age group. Further comprehensive multicenter studies are needed to develop strategies and policies for an efficient EMS system management.
Keywords: Emergency Medicine, Emergency Medical Service, Ambulance, Dispatch, Referral
Introduction
The number of emergencies is increasing due to the development in industry, the rapidly increasing population and traffic in the world and in our country [1, 2]. In addition, our country has extraordinary situations such as earthquakes and explosions, terrorist incidents and big fires experienced intensely. Therefore, emergency medical services (EMS) are of great importance in these situations [3, 4].
Emergency health services in our country were established in 1994 by the Ministry of Health as 112 Emergency Aid and Rescue Services, which can be reached by phone number 112, to provide rapid transport of seriously injured and critical patients to emergency services [1]. Since then, a crew consisting of a practitioner, a nurse and a driver have begun working in ambulances. The aim of EMS is to provide emergency healthcare services to patients and injured people and to deliver these persons as soon as possible to the hospital [5]. In our country, this service is provided free of charge by the Ministry of Health.
Patients benefit from the EMS due to acute conditions such as hypoglycemia, septicemia, labor, asthma attack or emergency situations such as myocardial infarction, bleeding and injuries [6, 7]. The provision of EMS in developing countries and ambulance utilization rates in societies vary depending on local, socio-economic and cultural conditions [8]. Emergency patients are those who need to receive the necessary medical attention as quickly as possible. This situation requires quick and immediate decisions in medical interventions, which differentiates emergency patients from other patients. The American College of Emergency Physicians (ACEP) states that every patient who considers himself/herself as an emergency and applies to EMS, for this reason, is an emergency patient [9]. In emergency aid, it is known that the first hour following injury is very valuable for patients in emergency situations, and this period is described as the “golden hour” in which resuscitation and stabilization are performed [10]. Ambulance usage rate varies depending on age, gender, the severity of trauma or illness, geographical factors, time, socioeconomic status and insurance status [3].
In this study, we aimed to analyze the demographic characteristics, including gender and age groups of 3,182 emergency patients transferred by 112 EMS in the Bolu province of Türkiye.
Material and Methods
This study was approved by the Ethics Committee of Bolu Izzet Baysal University (Date: 2012-12-20, No: 239). Informed consent was not needed due to the retrospective nature of the study. This study followed the ethical principles of the Declaration of Helsinki revised in 2013.
A total of 3,182 patients who used EMS were included in the study. The data used in our study were obtained by examining the patient transfer forms in 112 command and control centers. Demographic characteristics of the patients such as age and gender, and the outcome of the cases were recorded in the forms developed by the researcher in line with the current relevant literature. Patients with missing data were excluded from the study.
Social security status of the cases included Social Security Institution (SSI), social security organization for artisans and the self-employed (Bag-Kur), private health insurance and abroad (others), those who do not have any health insurance (insecure), and the green card. The scene was grouped as home, vehicle, closed area and open area. The personnel group accompanying the cases was grouped as follows: those who were doctors in the accompanying group were grouped as ‘team with doctors’, those who were paramedics were grouped as ‘paramedic teams’, and those who were midwives, nurses, health officers and emergency medical technicians in the accompanying group were grouped as ‘team with health personnel’. The places where the cases specified in the forms were grouped as follows: the patients who came to the university outpatient clinics as the patients who came to the ‘Abant Izzet Baysal University Faculty of Medicine polyclinics’, and those who presented to the Izzet Baysal Maternity and Gynecology Hospital, Mental Health and Neurological Diseases Hospital and the State Hospital polyclinics and services as patients presenting to ‘state hospitals services and outpatient clinics’. The patients who came to the university emergency services were grouped as ‘university emergency’, and the patients who applied to the emergency services of public hospitals were grouped as ‘state hospitals emergency’. Referrals made outside the province were grouped as ‘patient referrals between provinces’. After the cases were seen at the scene by the health teams, the type of transport was considered as ‘’transfer rejection’ in cases where the patients did not want to go to the hospital on their own volition, despite they needed to be transferred to the hospital.
Statistical Analysis
Statistical analysis of the article was performed using the SPSS (SPSS Statistical Package for Social Sciences, IBM Inc., Armonk, NY, USA) statistical software. The normality of the data was evaluated using the Kolmogorov-Smirnov test. Since the variables were normally distributed, comparison of the continuous variables was made using the independent t-test. Categorical variables were compared between the groups using the Chi-Square test. Continuous variables were expressed as mean ± standard deviation and categorical variables were given as frequency (n, %). p<0.05 values were considered statistically significant.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
During the study period, a total of 3,182 patients who were transferred by 112 EMS in the Bolu province of Türkiye were included in the study. Of all patients, 1,287 (40.4%) were female, 1,658 (51.8%) were male and 247 (7.8%) were unspecified. In the current study, 394 patients were in the 0-18 age group, 1327 in the 19-45 age group, 626 in the 45-65 age group and 723 patients in the >66 years group. Figure 1 shows the distribution of the patients according to age groups.
There were 191 (51.9%) female and 177 (48.11%) male patients in the 0-18 age range. When the gender distributions by age groups were analyzed, the ratio of women aged 0-18 and over 66 years was found to be higher than the rate of women in other age groups (p<0.001). There were more men in the age ranges 19-45 and 46-65 compared to other age ranges (p<0.001). Three hundred and twenty-eight patients were not included in the evaluation because they did not have data. The distribution of the patients by age and gender is presented in Figure 2.
The distribution of patients’ outcomes is presented in Table 1.
The distribution of the patients’ outcomes according to gender is presented in Table 2.
Considering the distribution of accompanying personnel according to the types of transfer, the rate of referral from the scene to the hospital and the rate of cases that did not require referral as a result of the on-site evaluation were found to be higher in the teams with a physician, while the rate of transfer rejection was higher in teams with a paramedic. It was observed that the highest rate of transfer between hospitals and from hospital to home was in teams with other health personnel.
Discussion
In the present study, we investigate the characteristics of 3,182 patients transferred by the 112 Emergency Medical Services (EMS) in the Bolu province of Türkiye. There are some factors influencing the usage of EMS such as gender, age groups, place of dispatch, scene, social security status, etc.
In addition to fatal injuries, non-fatal injuries and emergency situations are the leading cause of hospital admission using EMS [11, 12]. In a study from Srilanka, Zimmerman et al. reported that patients use commercial, private or non-motor vehicles to get to the hospital [13]. In our country, 112 EMSs are used free of charge and provided by the Ministry of Health. In our study, the rate of EMS usage was 40.4% in female and 51.8% in male patients. Similar to our study, in a study by Rantala et al. from Sweden, the rate of using EMS was reported as 45% in females and 55% in males [14]. In a study by Karakus et al. from our country, 48.6% of the patients using EMS were females and 51.4% were males [15]. In another study by Onge et al., 46.5% of the patients were females and 53.5% were males [1]. We think that this was a result of the fact that men are more actively involved in work or other challenging conditions compared to women. However, the rate of men using EMS has begun to decrease and the rate of women to increase due to women becoming increasingly involved in more social life and increase in the number of female drivers [1].
The EMS usage differs among age groups. In this study, 394 patients (12.83%) were in the 0-18 age group, 1327 (43.22) in the 19-45 age group, 626 (20.39%) in the 45-65 age group and 723 patients (23.55%) in the >66 years group. In a study by Say et al. the rate of EMS usage was the highest among patients ≥65 years old [10]. Whereas, in our study, EMS weas used most commonly by patients in the 19-45 age group, while the >66 age group has a rate of 23.55%. In another study by Serin et al. investigating patients brought to a newly opened EMS in Balikesir province of Türkiye, 17.5% of the patients were in the 18-39 age group, 22.57% in the 40-59 age group and 59.48% in the >60 age group [6]. In another study by Zenginol et al. performed in Gaziantep province, the rate of patients aged >65 using EMS was 17.9% [3]. In a study by Sultan et al. from Ethiopia, the rate of patients in the 56-95 age group had lower EMS usage compared to the 18-39 age group [16]. In another study by Eastwood from Australia, the likelihood of using EMS increased after 80 years of age [17]. In a study by Henricson et al. from Sweden, hospital arrival by EMS was the most common for patients between 65 and 80 years (32%), and those 81 years old and older (52%) [18], suggesting an obvious difference between developed and developing countries due to the age range of patients who use EMS transfer because of prolonged life expectancy in older patients in developed countries. On the other hand, in a study by Reynolds et al. investigating predictors of using EMS among injured patients, patients in the 56-95 age group had a lower possibility of using EMS compared to the 18-39 age group [12]. The authors stated that this result conflicts with previous studies in resource-limited settings.
In our study, the rate of dispatch from the scene to the hospital was lower in patients aged 19-45 years compared to other age groups. In addition, the rate of cases that did not require referral was lower in the 19-45 age group when compared to other age groups. In addition, the rate of transport from the hospital to the home was the highest in patients over the age of 66 similar to other studies [6, 10].
When the outcomes of the patients using EMS were evaluated, it was found that 74.2% of the patients used EMS for transfer to the hospital, 11.2% rejected dispatch, in 2.4% of the patients, on-site intervention was performed and 0.8% of the patients died at the scene. In a study by Mcmanamny et al, 84% of the patients used EMS, 13% were not transferred, and 1% died on arrival or at the scene [19]. In a study by Silanbolatlaz examining patients admitted to a third-level ED through EMS, 0.2% of patients who used EMS died in the hospital [20].
Study Limitation
The main limitation of this study is its retrospective design and being conducted in a single center. In addition, the number of patients is relatively low for such a study. Finally, we could not compare our results with previous studies exactly, because there is no study in the literature focusing on demographic characteristics of patients using emergency medical services. Within this regard, we think that our findings will be a guide for future studies.
Conclusion
The use of emergency medical services varies according to gender and different age groups. Male patients used EMS more commonly compared to women. The most common EMS usage was found in the 19-45 age group. Further comprehensive multicenter studies are needed to develop strategies and policies for the efficient EMS system management.
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. Onge T, Satar S, Kozacı N, Açıkalın A, Köseoğlu Z, Gülen M, et al. 112 ile Acil Tıp Servisine Getirilen Erişkin Hastaların Analizi (Analysis of Patients Admitted to the Emergency Medicine Department by the 112 Emergency Service). Eurasian J Emerg Med. 2013;12(2):150-4.
2. Borowy I. Road traffic injuries: social change and development. Med Hist. 2013;57(1):108-8.
3. Zenginol M, Al B, Genc S, Deveci I, Yarbil P, Ari Yilmaz D, et al. Gaziantep İli 112 Acil Ambulanslarının 3 Yıllık Çalışma Sonuçları (3 Yearly Study Results of 112 Emergency Ambulances in the City of Gaziantep). JAEM. 2011;10(1):27-32.
4. Afzali F, Jahani Y, Bagheri F, Khajouei R. The impact of the emergency medical services (EMS) automation system on patient care process and user workflow. BMC Med Inform Decis Mak. 2021;21(1):292.
5. Yenal S, Gültekin T, Pakdemirli A. Driver Behaviors of 112 Emergency Medical Services Personnel. Eurasian J Emerg Med. 2020;19(2):78-81.
6. Serin S, Caglar B. Yeni açılan acil servise ambulans ile getirilen hastaların analizi (Analysis of Patients Brought to the Newly Opened Emergency Service by Ambulance). Medical Journal of İzmir Hospital. 2020;24(4):289-93.
7. Ma J, Wang J, Zheng W, Zheng J, Wang H, Wang G, et al. Usage of ambulance transport and influencing factors in acute coronary syndrome: a cross-sectional study at a tertiary centre in China. BMJ Open. 2017;7(8):e015809.
8. Ozata M, Toygar SA, Yorulmaz M, Cihangiroglu N. Comparative Analysis of Using 112 Emergency Ambulance Services in Turkey and the Province of Konya. Eur J Gen Med. 2011;8(4):262-7.
9. Say A, Ayar A, Cakir D. The Evaluation of 112 Emergency Ambulance Services Uses in Amasya. IJBiMeS 1-2. 2016;1(2):5-7.
10. Navaratne KV, Fonseka P, Rajapakshe L, Somatunga L, Ameratunga S, Ivers R, et al. Population based estimates of injuries in Sri Lanka. Injury Prevention. 2009;15(3):170-5.
11. Reynolds LM, De Silva V, Clancy S, Joiner A, Staton CA, Østbye T. Predictors of ambulance transport to first health facility among injured patients in southern Sri Lanka. PLoS One. 2021;16(6):e0253410.
12. Zimmerman JR, Bertermann KM, Bollinger PJ, Woodyard DR. Prehospital System Development in Jaffna, Sri Lanka. Prehospital and disaster medicine. 2013;28(5):509-16.
13. Rantala A, Sterner A, Frank C, Heinrich E, Holmberg B. Older patients’ perceptions of the Swedish ambulance service: A qualitative exploratory study. Australas Emerg Care. 2023; DOI: 10.1016/j.auec.2023.01.005.
14. Karakus BY, Cevik E, Dogan H, Sam M, Kutur A. Metropolde 112 Acil Sağlik Hizmeti (112 Emergency Medical Service in the Metropolis). J Ist Faculty Med. 2014;77(3):37-40.
15. Sultan M, Abebe Y, Tsadik AW, Jennings CA, Mould-Millman NK. Epidemiology of ambulance utilized patients in Addis Ababa, Ethiopia. BMC Health Serv Res. 2018;18(1):997.
16. Eastwood K, Nambiar D, Dwyer R, Lowthian JA, Cameron P, Smith K. Ambulance dispatch of older patients following primary and secondary telephone triage in metropolitan Melbourne, Australia: a retrospective cohort study. BMJ Open. 2020;10(11):e042351.
17. Henricson J, Ekelund U, Hartman J, Ziegler B, Kurland L, Björk Wilhelms D. Pathways to the emergency department – a national, cross-sectional study in Sweden. BMC Emerg Med. 2022;22(1):58.
18. McManamny TE, Dwyer R, Cantwell K, Boyd L, Sheen J, Smith K, et al. Emergency ambulance demand by older adults from rural and regional Victoria, Australia. Australas J Ageing. 2022;41(1):e74-e81.
19. Silibolatlaz A, Gulen M, Avci A, Satar S. Üçüncü Basamak Acil Servise 112 Ambulansı ile Getirilen Erişkin Hastaların Analizi (The Analysis of Adult Patients Admitted to Third Level Emergency Department by 112 Ambulance). Boğaziçi Tıp Dergisi. 2018;5(2):51-7.
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Burcin Balaban. Demographic characteristics of 3,182 patients transferred by 112 emergency services in the Bolu province of Türkiye. Ann Clin Anal Med 2023;14(8):726-730
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Maternal mortality in Adiyaman province: A five-year review
Osman Küçükkelepçe 1, Erdoğan Öz 2, Osman Kurt 1
1 Department of Public Health, 2 Department of Family Medicine, Adıyaman Provincial Health Directorate, Adıyaman, Turkey
DOI: 10.4328/ACAM.21730 Received: 2023-04-16 Accepted: 2023-05-30 Published Online: 2023-06-07 Printed: 2023-08-01 Ann Clin Anal Med 2023;14(8):731-735
Corresponding Author: Osman Küçükkelepçe, Department of Public Health, Adıyaman Provincial Health Directorate, 02100, Adıyaman, Turkey. E-mail: osmankkelepce@hotmail.com P: +90 533 510 34 92 Corresponding Author ORCID ID: https://orcid.org/0000-0002-7138-692X
This study was approved by the Non-interventional Clinical Research Ethics Committee of Firat University (Date: 2021-07-05, No: 10293)
Aim: Maternal deaths in Adiyaman between 2017-2021 and the causes and distribution of these deaths were evaluated. It was aimed to find possible solutions to reduce maternal deaths.
Material and Methods: The maternal mortality rate (MMR) was calculated by dividing the number of maternal deaths by 100,000 live births. In the study, variables such as the place of deaths (province/district, home/hospital), time of death (pregnancy/postpartum), preventability status, direct/indirect death decision, maternal age, and educational status, along with the variation of MMR by years were evaluated. In addition to these data, the delays related to service delivery in deaths were also examined.
Results: MMR was calculated as 23 per hundred thousand in 2017, 7.9 per hundred thousand in 2018, 16.8 per hundred thousand in 2019, 45.4 per hundred thousand in 2020, and 54.7 per hundred thousand in 2021. Five (29.4%) of the deaths were preventable, six (35.3%) could not be prevented, two (11.8%) could not be decided, and for four (23.5%) a Ministry Commission’s decision is awaited. Of the five preventable deaths, four (80%) were Type one delay, and one (20%) was Type three delay. It has been determined that mothers who gave birth over the age of 35 in 2017-2020 have a 3.00 times risk of death compared to mothers who gave birth under the age of 35. This risk was found to be statistically significant (p=0.028).
Discussion: Increased maternal age is a significant risk factor, and high-risk pregnancies should be followed closely to reduce maternal mortality.
Keywords: Maternal Mortality, Maternal Mortality Rate, Maternal Age
Introduction
According to the World Health Organization, maternal death is defined as the death of a woman, pregnant or within 42 days of the termination of pregnancy, regardless of the duration and location, from direct or indirect obstetric but non-incidental causes. Deaths such as accidents, burns, homicide, electric shock, poisoning, and suicide not related to any effect of pregnancy are not considered maternal deaths.
According to the World Health Organization, maternal mortality is unacceptably high, and 2017 estimates show that around 810 women worldwide die daily from pregnancy or childbirth complications. In 2017, 295,000 women died during and after pregnancy and childbirth. The vast majority of deaths have occurred in low-resource environments, and most are thought to be preventable (1).
Maternal mortality is one of the main parameters of whether the health system works well. The maternal mortality rate is the number of maternal deaths per 100,000 live births annually. In Turkey, the Ministry of Health initiated the Maternal Mortality Prevention and Monitoring Program in 2007 to reduce maternal mortality. According to the Turkish Statistical Institute it was observed that the maternal mortality rate in Turkey, which was 16.7 in 2010, showed a decreasing trend over the years and decreased to 13.6 in 2018. Worldwide, maternal mortality monitoring systems are being developed, and maternal mortality rates are followed closely. However, the maternal mortality rates in countries that have not developed a suitable system may seem lower than they actually are, since maternal deaths cannot be determined. This shows the need for appropriate detection and monitoring systems for proper assessment (2).
Although maternal deaths are not evenly distributed worldwide, they are not evenly distributed in Turkey. While the highest maternal mortality is seen in Middle East Anatolia, it is seen that it is the lowest in East Marmara, which may be related to access to healthcare and the rural-urban divide (3).
Adiyaman is one of the cities where maternal mortality is high, and these deaths can vary significantly from year to year. This study aims to examine maternal deaths between 2017 and 2021.
Material and Methods
In this retrospective study, maternal deaths that occurred in Adiyaman between 2017 and 2021 were examined. The “Provincial Investigation Commission” decisions for maternal deaths were evaluated with the feedback decisions sent from the “Ministry of Health Maternal Deaths Preliminary Investigation Commission.”
The study was conducted in accordance with the Declaration of Helsinki and approved by the Non-interventional Clinical Research Ethics Committee of Firat University (protocol code 10293; date: July 5, 2021). Institutional permission was obtained from relevant authority, with the date 21.09.2022 and number E-13389845-771.
The maternal mortality rate in the study was calculated by dividing the number of maternal deaths by 100,000 live births. Obstetric complications cause direct maternal death due to interventions applied during pregnancy, neglect, incorrect care, or the chain of events mentioned. Moreover, indirect maternal death occurs during pregnancy due to a disease or previous diseases (pre-pregnancy) in the pregnant woman. Incoming, but not of obstetric origin, is also defined as death caused by causes exacerbated by the physiological effects of pregnancy.
In the study, variables such as the place of occurrence of deaths (province/district, home/hospital), time of occurrence (pregnancy/postpartum), preventability status, direct/indirect death decision, maternal age, and educational status, along with the variation of maternal mortality rate by years were evaluated. In addition to these data, delays related to service delivery in deaths were also examined. These:
• Primary delay: The type of delay in which the patient does not decide to get service. As an example, a pregnant woman does not apply to the physician for pregnancy follow-up.
• Secondary delay: The type of delay in which the patient decides to receive service but cannot reach the healthcare service. For example, the patient’s inability to come to the health institution due to the closure of the roads.
• Tertiary delay: It is the type of delay in which the patient comes to the health institution but cannot receive the necessary service from the health institution. For example, wrong medical practices can be given.
Statistical analysis
Analyzes were evaluated in 22 package programs of SPSS (Statistical Package for Social Sciences; SPSS Inc., Chicago, IL). The study showed descriptive data as n and % values in categorical data and mean±standard deviation (Mean±SD) values in continuous data. Chi-square analysis (Pearson Chi-square) was used to compare categorical variables between groups. The statistical significance level in the analysis was accepted as p≤0.05.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
Mothers who died between 2017-2021 were included in the study, and 17 maternal deaths occurred between these dates. Three (17.6%) mothers died in 2017, one (5.9%) in 2018, two (11.8%) in 2019, five (29.4%) in 2020, and six (35.3%) in 2021 (Table 1). When the rate of maternal deaths per hundred thousand live births is analyzed by years, it is 23.0 per hundred thousand in 2017; 7.9 in 2018; 16.8 in 2019; It was found to be 45.4 per hundred thousand in 2020, and 54.7 per hundred thousand in 2021 (Table 1).
The mean age of the mothers who died was 32.7±7.3 years, and the median was 29 (min=21-max=48). Ten (58.8%) mothers lived in the city center, and seven (41.2%) lived in the district. Four of the mothers (23.5%) had grand multiparity. Eight of the mothers (47.1%) had maternal risk factors. Five (29.4%) deaths occurred during pregnancy, and 12 (70.6%) died during puerperium. Fourteen (82.4%) deaths occurred in hospital and three (17.6%) at home. Two of the deaths (11.8%) were direct and nine (52.9%) were indirect maternal deaths, while two (11.8%) could not be decided, and a ministry commission decision is awaited for four (23.5%). Five (29.4%) of the deaths were preventable, six (35.3%) could not be prevented, two (11.8%) could not be decided, and for four (23.5%), a ministry commission decision is awaited. Of the five preventable deaths, four (80%) were type 1 delay, and one (20%) was type 3 delay (Table 2).
When analyzed by education level, two (11.8%) of the mothers were illiterate, five (29.4%) were primary school graduates, three (17.6%) were secondary school graduates, one (5.9%) was high school graduate, and six (35.3%) were university graduates (Figure 1).
When the causal distribution of maternal deaths was examined, seven (41.2%) were cardiovascular causes, one (5.9%) embolism, one (5.9%) bleeding, one (5.9%) infection, and one (5.9%) other causes, while six (35.3%) could not be diagnosed. Moreover, a ministerial decision is awaited.
When women who had a live birth in Adiyaman in 2017 were examined, it was determined that 10,623 mothers were under 35 years of age, and 2,382 mothers were 35 years of age and older. In 2017, it was determined that mothers who gave birth at the age of over 35 had 8.92 times higher risk of death compared to mothers who gave birth under the age of 35. This risk was not found to be statistically significant (p=0.088). When women who had a live birth in Adiyaman in 2020 were examined, it was determined that 8,907 mothers were under 35 years of age, and 2,071 mothers were 35 years and older. It has been determined that mothers who gave birth at the age of over 35 in 2020 have a 6.45 times higher risk of death compared to mothers who gave birth under the age of 35. This risk was found to be statistically significant (p=0.05). When women who gave live births in Adшyaman in 2017-2020 were examined, it was determined that 48,080 mothers were under 35 years of age, and 11,198 were 35 years of age and older. It has been determined that mothers who gave birth at the age of over 35 in 2017-2020 have a 3.00 times higher risk of death compared to mothers who gave birth under the age of 35. This risk was statistically significant (p=0.028) (Table 3).
Discussion
Monitoring of maternal mortality is carried out strictly in Turkey. The first reliable source of data on maternal mortality was obtained in 2005 with the National Maternal Mortality Study (NMMS) within the scope of the Reproductive Health Program, a project of the Ministry of Health. The Ministry of Health started follow-ups in 2007.
According to the NMMS conducted in 2005-2006, maternal mortality rate was 28.5 per hundred thousand. While it was 20.7 per 100,000 live births in urban areas, it was determined as 40.3 per 100,000 live births in rural areas. Again in the same study, 78.8% of maternal deaths were determined as direct and 21.2% as indirect maternal deaths. In the maternal mortality study conducted by the Public Health Institution of Turkey in 2014, the maternal mortality rate was 15.2 per hundred thousand (4). According to the National Center For Health Statistics report on the maternal mortality rates in the USA, the maternal mortality rate was 17.4 per hundred thousand in 2018, 20.1 per hundred thousand in 2019, and 23.8 per hundred thousand in 2020. Our study evaluated only Adiyaman province and calculated 5-year mortality statistics. Accordingly, the maternal mortality rate was calculated as 23 per hundred thousand in 2017, 7.9 per hundred thousand in 2018, 16.8 per hundred thousand in 2019, 45.4 per hundred thousand in 2020, and 54.7 per hundred thousand in 2021. Although there is a decrease in maternal mortality throughout the country, a significant decrease was observed in Adiyaman in 2018, but an increase was observed in 2019. Among the reasons for this change, of course, there are direct or indirect effects of the COVID-19 pandemic, but some measures and training should be taken to eliminate other possible effects. In order to increase the awareness among both institutions and the public, action plans have been created by the Adiyaman Health Directorate, and especially risky pregnant follow-ups are carried out close by the directorate and its affiliated centers. The positive results of the studies are expected to be seen in the coming years.
A high number of births is considered a risk factor for maternal death. In a multicenter study conducted in Nigeria, the risk of maternal death increased as the number of births increased. The risk of death in mothers with grand multiparity is 6.89 times higher than in those without delivery (5). Sencan et al. (4) found that 11.7% of mothers in maternal deaths in Turkey in 2014 were grand multiparous patients. In our study, 23.5% of mothers who died were found to be grand multiparous, which may be related to the decrease in mothers’ demand for healthcare services as parity increases. In order to prevent grand multiparity, it is essential to encourage the use of effective birth control methods and to provide such services free of charge to the Ministry.
The relationship between educational status and maternal death is one of the issues that has not been clarified. Yego et al. (6) in Kenya, the risk of maternal mortality increased as the level of education decreased. Kisuule et al. (7) also found that the risk of maternal death was higher in illiterate women. Alosaimi et al. (8) found no significant difference between educational status and maternal mortality. In our study, about one-third of the mothers who died were university graduates, which may be related to increasing childbearing age in women with university degrees.
Maternal age is one of the most critical risk factors for maternal mortality (9). In a study involving 144 countries, maternal mortality was examined according to the age of the mothers, and the maternal ages were categorized at five-year intervals. According to this, while the graphical representation of maternal deaths was J-shaped, it was slightly higher at ages 15-19, decreased at ages 20-24, and maternal mortality rate increased as the age group increased. Again, in the same study, the slope of the maternal mortality rate increases visibly after age 35 (10). Again, Blanc et al. (11) similarly observed a decrease in the death rate between the ages of 20-24, and the maternal mortality rate increased with age. Sencan et al. (4), in a Turkey-wide study found that maternal mortality is more common at the age of 35 and below and that mothers who gave birth at the age of over 35 carry a 3.30 times higher risk of death compared to mothers who gave birth under the age of 35.
Similarly, in our study, the number of maternal deaths under the age of 35 was found to be higher, but it was revealed that mothers over 35 years of age had a 3.0 times higher risk of death compared to those under 35 years of age. As can be seen, the risk of death increases with the mother’s age over 35, and raising public awareness regarding childbearing age is essential. However, an important pillar of this falls on the health providers. Pregnant women over the age of 35 should be considered risky pregnancies and should be followed closely.
Conclusion
Although maternal deaths in the Adıyaman province of Turkey may fluctuate over the years, they increased in 2020 and 2021 when the COVID-19 pandemic was dominant. Advanced maternal age is a significant risk factor. It is essential to take a series of measures and implement them in order to prevent the increase in maternal mortality and advanced maternal age. In order to do this, one of the primary steps is to follow the risky pregnant women closely.
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. Shennan AH, Green M, Ridout AE. Accurate surveillance of maternal deaths is an international priority. BMJ. 2022; 379(1): o2691.
2. Diguisto C, Saucedo M, Kallianidis A, Bloemenkamp K, Bødker B, Buoncristiano M, et al. Maternal mortality in eight European countries with enhanced surveillance systems: descriptive population based study. BMJ. 2022; 379(1): e070621.
3. Aygar H, Metintaş S. Bir Kalkınma Göstergesi Olarak Anne Ölümleri (Maternal Mortality As a Development Indicator). ESTÜDAM Halk Sağlığı Dergisi. 2018; 3(3): 63-70.
4. Şencan İ, Üstün YE, Sanisoğlu S, Özcan A, Karaahmetoğlu S, Keskin HL, et al. 2014 Yılı Türkiye Ulusal Anne Ölümlerinin Demografik Verilere Göre Değerlendirilmesi (Demographic Characteristics Of Turkish National Maternal Deaths In 2014). Jinekoloji-Obstetrik ve Neonatoloji Tıp Dergisi/ Journal of Gynecology-Obstetrics and Neonatology Medicine. 2016; 13(2): 45-7.
5. Ntoimo LF, Okonofua FE, Ogu RN, Galadanci HS, Gana M, Okike ON, et al. Prevalence and risk factors for maternal mortality in referral hospitals in Nigeria: a multicenter study. Int J Womens Health. 2018; 10(1): 69-76.
6. Yego F, D’este C, Byles J, Williams JS, Nyongesa P. Risk factors for maternal mortality in a Tertiary Hospital in Kenya: a case control study. BMC Pregnancy Childbirth. 2014; 14:38.
7. Kisuule I, Kaye D, Najjuka F, Ssematimba S, Arinda A, Nakitende G, et al. Timing and reasons for coming late for the first antenatal care visit by pregnant women at Mulago hospital, Kampala Uganda. BMC Pregnancy Childbirth. 2013; 13(1): 1-7.
8. Alosaimi AN, Luoto R, Al Serouri AW, Nwaru BI, Mouniri H. Measures of Maternal Socioeconomic Status in Yemen and Association with Maternal and Child Health Outcomes. Matern Child Health J. 2016; 20(1): 386-97.
9. Restrepo-Méndez MC, Victora CG. Maternal mortality by age: who is most at risk? Lancet Glob Health. 2014; 2(3): 120-1.
10. Nove A, Matthews Z, Neal S, Camacho AV. Maternal mortality in adolescents compared with women of other ages: evidence from 144 countries. Lancet Glob Health. 2014; 2(3): 155-64.
11. Blanc AK, Winfrey W, Ross J. New findings for maternal mortality age patterns: aggregated results for 38 countries. PloS One. 2013; 8(4): e59864.
Download attachments: 10.4328.ACAM.21730
Osman Küçükkelepçe, Erdoğan Öz, Osman Kurt. Maternal mortality in Adiyaman province: A five-year review. Ann Clin Anal Med 2023;14(8):731-735
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Comparative analysis of the relationship between bioelectrical impedance analysis results and laboratory data
Zeynep Ergenc 1, Hasan Ergenc 1, Cengiz Karacaer 2, Gülsüm Kaya 3, Ahmet Öztürk 4, Mustafa Usanmaz 5, Ersin Alkılıç 6
1 Department of Internal Medicine, Yalova State Hospital, Yalova, 2 Department of Internal Medicine, Sakarya University Research and Education Hospital, Sakarya, 3 Department of Quality Management, Sakarya University Research and Education Hospital, Sakarya, 4 Department of Emergency Medicine, Çorum Erol Olçok Training and Research Hospital, Çorum, 5 Department of Infectious Diseases and Clinical Microbiology, Gazi Government Hospital, Samsun, 6 Department of Pulmonology, Sinop Atatürk State Hospital, Sinop, Turkey
DOI: 10.4328/ACAM.21732 Received: 2023-04-17 Accepted: 2023-06-05 Published Online: 2023-06-16 Printed: 2023-08-01 Ann Clin Anal Med 2023;14(8):736-741
Corresponding Author: Hasan Ergenç, Department of Internal Medicine, Yalova State Hospital, Yalova, Turkey. E-mail: hasanergenc.dr@gmail.com P: +90 505 740 01 68 Corresponding Author ORCID ID: https://orcid.org/0000-0003-0519-0264
This study was approved by the Ethics Committee of Sakarya University (Date: 2021-11-04, No: 530)
Aim: In this study, we aimed to assess the relationship between demographic and laboratory data and bioelectrical impedance analysis (BIA) results in patients <40 and ≥40 years of age.
Material and Methods: This cross-sectional study was conducted at Ayancık State Hospital, Internal Medicine Clinic, Sinop, Turkey. This study was performed using data derived from the medical files of 674 adult patients (545 females, 129 males) with an average age of 40.15 ± 8.60 years.
Results: In patients <40 years of age, there was a moderate relationship between inbody PUM and body fat percentage (r=0.489), inbody PUM and BMI (r=-0.626), inbody PUM and fat mass (r=-0.453), BMI and body fat percentage (r=0.489), and BMI and fat mass (r=0.637). In patients aged ≥ 40 years, a strong relationship was noted between fat mass and serum glucose level (r=0.851) and body fat percentage and serum LDL levels (r=0.784). A moderate relationship was observed between fat mass and platelet count (r=0.471), fat mass and BMI (r=0.581), fat mass and body fat percentage (r=0.470), fat mass and inbody PUM (r=-0.494), inbody PUM and body fat percentage (r=-0.670), body fat percentage and fat mass (r=0.510), and body fat percentage and BMI (r=0.503).
Discussion: We suggest that BIA may provide important implications for the management of patients with obesity and metabolic disorders.
Keywords: Bioelectrical Impedance Analysis, Obesity, Fat Mass, Inflammation, Marker
Introduction
It has been proven that as people get older, their body composition changes, even if their weight does not change. According to studies, as people get older, their fat mass grows while their muscle mass declines. However, the cause of such modifications remains unknown. There is some evidence that individual organ metabolic rates are lower in elderly people than in younger people. We infer that the mass of the single organ/tissue decreases with age, as does the metabolic rate of some organs, resulting in a decrease of the metabolic rate at rest, favoring changes in body composition that contribute to an increase in fat mass (FM) and decrease in lean mass (LM) [1].
Body composition alterations have long been linked to aging and are physiologically undesirable. With age, fat accumulation and LM loss are significant alterations. The pattern and rate of age-related changes in body composition are often affected by a range of factors, including gender, ethnicity, level of physical activity, and calorie intake. Anthropometric measurements involve body mass index (BMI), abdominal waist circumference, and skinfold measurements. These measurements are rapid and low-cost. However, they have substantial flaws, such as a lack of consistency among techniques and the potential for measurement errors when measuring waist circumference and skinfold [2].
Due to the diversity of ethnicities, there are no common cutoff thresholds for waist circumference. More importantly, BMI, weight, and height alone are unable to distinguish between lean mass (LM) and fat mass (FM), as well as subcutaneous and visceral fat. Another indirect technique for the evaluation of the composition of the body is bioelectrical impedance analysis (BIA).
This approach is noninvasive and safe, and the equipment is portable, so it can be used in an ambulatory setting. The resistance of the body as a conductor of an electrical current, FM, and fat-free mass (FFM), where FFM is a charge conductor and FM is a non-conductor, are used by BIA to estimate total body water [2].
The investigation of body composition is important for understanding human energy and protein metabolism due to strategies for the measurement of energy stores and protein content. The balance between energy and protein can be observed over time, and the relationship between dynamic measures of energy and protein metabolism can be assessed via inter-individual comparisons [3].
The link between the distribution of abdominal fat and inflammatory markers is a hot topic. The leukocyte count was positively related to abdominal obesity in female obese teenagers, and this connection was stronger for subcutaneous adiposity compared to visceral adiposity [4].
Our purpose was to evaluate the relationship between hematological, biochemical, and inflammatory parameters and bioelectrical impedance analysis results in patients <40 and ≥40 years of age.
Material and Methods
Study design
This cross-sectional study was carried out in the internal medicine clinic of a state hospital between 29 November 2021-13 December 2021. The medical files of 674 adult patients (545 females, 80.1%; 129 males, 19.1%) were reviewed. The average age was 40.15 ± 8.60 years (range: 18 to 80). Demographic and clinical data consistent with age, sex, complete blood count, and serum biochemistry results as well as BIA results were extracted from the hospital database. The ethics committee approval was obtained before the study (date/no: E-71522473-050.01.04-83550-530).
Simple, quick, and reliable body composition measures are commonly necessary for medical and nutritional follow-up. Consequently, in research laboratories, hospitals, private clinics, and wellness centers, BIA constitutes a standard tool for the analysis of body composition over an extent of age and body weight [5]. Using a digital console, the subject’s sex, age, and height are manually written into the instrument, and the subject’s fat mass (FM) or percent FM is displayed instantly.
Patients were measured for body weight and height while wearing light clothing and not wearing shoes. The BMI was calculated by dividing the weight by the square of the height (kg/m2).
Blood samples were received from a peripheral vein early in the morning after an overnight fast of 8 hours. Blood samples were collected and examined on the same day using commercially available vacuum tubes. Serum biochemical parameters were measured using an autoanalyzer (Hitachi 747 autoanalyzer, Tokyo, Japan). The results of the total blood count were determined using an autoanalyzer (Sysmex XE-2100, Kobe, Japan).
Bioimpedance analysis
Within the field, the BIA method is commonly utilized to calculate LM, FM, and body fat percentage. In BIA devices, which produce a single frequency alternating current, a pair of collector electrodes assess the voltage decrease over a measured tissue bed [6].
A component of age is included in almost all published comprehensive BIA prediction systems. Because age-related effects are so significant, any new BIA descriptive component prediction models must be constructed and cross-validated in the elderly before being employed in this group [3].
The device used to measure the impedance value was a multifrequency electrical impedance analyzer (Inbody S20, Korea) with a frequency range of 1 kHz to 1 MHz and an 800A steady electrical stream through the body. The entire procedure took less than 2 minutes. All data were saved in the instrument and automatically processed by computer software. Lean mass (LM), FM, body fat percentage, and in body PUM were collected as body composition data.
Statistical analysis
The means, standard deviation, and range were utilized to present all descriptive statistical results. The Kolmogorov-Smirnov test was utilized to test the normal distribution of all variables. Since all variables were non-homogeneous, comparisons were carried out with the Mann-Whitney U test, and expressed as median, minimum, and maximum. Categorical variables were tested with the Chi-square test. Pearson’s correlation analysis was used to examine the correlation between variables. Statistical Package for Social Sciences version 12.0 was used for all calculations (SPSS Inc., Chicago, IL, USA). The level of significance was set at a p-value of <0.05.
Outcome parameters
All subjects underwent a complete medical evaluation, including the measurement of anthropometric parameters such as weight and height per standardized methods routinely performed within the outpatient clinic of our hospital’s internal medicine department. Complete blood count, as well as serum biochemical analysis, were performed. Furthermore, BIA was performed utilizing the Inbody S20 device, (Inbody S20, Korea). Correlation was sought between LM, FM, body fat percentage, Inbody PUM and WBC count, hemoglobin level, lymphocyte, neutrophil, monocyte, and platelet counts, red cell distribution width, mean platelet volume, mean corpuscular volume, serum levels of glucose, urea, creatinine, aspartate transaminase (AST), alanine transaminase (ALT), and triglycerides.
The r value and strength of correlation were interpreted as follows: 0.00-0.19: very weak; 0.20-0.39: weak; 0.40-0.69: moderate; 0.70-0.89: strong; 0.90-1.00: very strong.
Results
Our study population consisted of 674 patients (545 females, 80.1%; 129 males, 19.1%) with an average age of 40.15 ± 8.60 years (range: 18 to 80). Of 674 patients, 354 (%52.5) were younger than 40; while 320 cases (%47.5) were aged ≥40. An overview of demographic and clinical characteristics of patients <40 and ≥40 years of age is presented in Table 1.
Table 2 demonstrates the correlation analysis results between BIA results including lean mass, fat mass, inbody PUM, and body fat percentage, and laboratory markers, including hematological and biochemical results in patients younger than the age of 40. There was a moderate relationship between inbody PUM and body fat percentage (r=0.489), inbody PUM and BMI (r=-0.626), inbody PUM and FM (r=-0.453). In the same age group, there was a moderate link between BMI and body fat percentage (r=0.489) and BMI and FM (r=0.637).
On the other hand, the association between BIA results and demographic and laboratory parameters under investigation in patients aged ≥ 40 is shown in Table 3. In this group, there was a strong association between FM and serum glucose level (r=0.851), while a moderate association was observed between FM and platelet count (r=0.471), FM and BMI (r=0.581), FM and body fat percentage (r=0.470), and fat mass and inbody PUM (r=-0.494). Similarly, there was a moderate relationship between inbody PUM and body fat percentage (r=-0.670). Notably, there was a strong relationship between body fat percentage and serum LDL levels (r=0.784). A moderate relationship was noted between body fat percentage and FM (r=0.510) as well as between body fat percentage and BMI (r=0.503).
Discussion
In this study, we investigated the link between BIA results and serum hematological and biochemical parameters in patients <40 and ≥40 years of age. Our results yielded that BIA may provide important metabolic and clinical clues for obesity and other inflammatory disorders and comorbidities in patients of different age groups. The interpretation of findings derived from BIA together with laboratory data may help tailor the treatment plan in clinical practice.
The body fat distribution may aid in the determination of the risk of cardiovascular disease and for the prophylaxis and therapy of metabolic disorders associated with obesity. Adipose tissue not only regulates lipid and glucose metabolism, but also has an active endocrine function. Adipocytes, immune system cells, and endothelium secrete bioactive substances that arrange metabolic and inflammatory reactions [7].
Triglyceride increases the lipid droplet size in adipocytes, causing obesity. It also causes adipokine synthesis and secretion to be disrupted, which has been linked to obesity-induced inflammation and insulin resistance. Inflammation and insulin resistance both participate in the occurrence of metabolic complications of obesity which subsequently result in a higher rate of mortality [8].
The anatomic position of adipose tissue is pivotal for health, life expectancy, and the predisposition to various diseases [9]. BMI is a widely used metric for determining nutritional status [7]. BMI assessment, on the other hand, is not gender-specific and has destitute accuracy, particularly in patients with a lot of FFM. Diverse ethnic groups displayed remarkable differences in BMI and health outcomes, indicating that diverse cut-off values should be considered in different populations [10]. Extra anthropometric measures should also be provided since BMI does not satisfactorily depict fat distribution.
bioelectrical impedance analysis is straightforward to use because it simply takes information on body height and hip circumference. Only in obese men was the BIA positively associated with glucose and insulin concentrations, implying that the BIA and the total FM percent may be beneficial in the prediction of glucose metabolic issues [7].
Our data indicated that in patients <40 and ≥40 years of age, BIA displayed different degrees of correlation with complete blood count and serum biochemical analysis results. Age must be considered during analysis of BIA measurements in conjunction with metabolic and laboratory indicators. As a cheap and practical modality, popularization of BIA can be considered as a useful tool particularly in clinical practice for clinicians dealing with obesity and other metabolic and endocrinological disorders.
As a result, it could be used in daily clinical practice and population studies to measure cardiometabolic risk associated with fat mass as a surrogate marker of inflammation, metabolic dysfunctions, comorbidities, and complications. Furthermore, analysis of the relationship between BIA and metabolic indicators must be carried out separately in different age groups since LM, FM, and body fat percentage may display different features in people <40 and ≥40 years of age.
Chemical components, protein, water, and minerals make up fat-free mass, which do not consume energy on their own [1]. The assumption that the ingredients that constitute FFM have a similar metabolic rate is made when FFM is used as the denominator against which the resting metabolic rate is expressed. This strategy is compromised by the reality that it combines tissues and organs with drastically different metabolic rates.
In spite of their small combined weight, the brain, liver, heart, and kidneys constitute about 60% of the metabolic rate at rest [11]. Aside from the heart, aging has a noteworthy effect impact on the majority of these organs [12,13].
In adults, adiposity is related to inflammatory responses with significant contribution from visceral adipose tissue [4,13]. However, little research has been performed on the effects of the distribution of fat on metabolic and inflammatory risk factors. It would be captivating to note which aspect of fat distribution advances inflammation in obesity which brings about a high risk for cardiovascular disease. The leukocyte count is a practical and simple test that provides useful data. Consequently, establishing a link between leukocyte count and fat distribution, especially in clinical settings, may be valuable [4].
There is a strong link between white blood cells, BMI, and body fat percentage [14]. Obesity was also connected to a considerably higher WBC count in teenagers [15]. Adipose tissue serves both for energy storage and as an endocrine organ [16]. Macrophages penetrate adipose tissue at a higher level when obesity increases, possibly eliciting a pro-inflammatory response [17]. Obesity was found to be the second most common cause of leukocytosis, after smoking [18]. Since inflammation is one of the most common metabolic risk factors, understanding the link between inflammation and adiposity is crucial. Inflammation constitutes a risk factor for ischemic stroke that is free of the degree of atherosclerosis and it is also a predictor of diabetes [19,20].
In the young age group, inflammatory markers have been associated with cardiovascular risk factors such as pulse rate, systolic blood pressure, and plasma levels of fibrinogen and homocysteine [21-23]. Moreover, the WBC count can be used to predict all-cause mortality, especially due to cardiovascular disease [24]. As a result, it would be clinically useful to use a simple test to detect patients at risk in this age group.
Some restrictions of the present study are cross-sectional design, data collected from a single center, and possible impacts of socio-economical factors and ethnicity. The determination of causality is difficult in the observed associations. These limitations must be remembered during the extrapolation of our data to larger populations.
Conclusion
To conclude, BIA is a cheap, practical and non-invasive tool that may provide useful data for the relationship between metabolic indicators, obesity, and complications. This association must be separately analyzed in different age groups and validation of our preliminary findings and documentation of the clinical usefulness of BIA necessitate the implementation of further prospective multicentric trials on larger groups.
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. St-Onge MP, Gallagher D. Body composition changes with aging: the cause or the result of alterations in metabolic rate and macronutrient oxidation? Nutrition. 2010; 26(2): 152-5.
2. Al-Sofiani ME, Ganji SS, Kalyani RR. Body composition changes in diabetes and aging. J Diabetes Complications. 2019; 33(6): 451-9.
3. Heymsfield SB, Nuñez C, Testolin C, Gallagher D. Anthropometry and methods of body composition measurement for research and field application in the elderly. Eur J Clin Nutr. 2000; 54(3): 26-32.
4. Kim JA, Park HS. White blood cell count and abdominal fat distribution in female obese adolescents. Metabolism. 2008; 57: 1375-9.
5. Lazzer S, Boirie Y, Meyer M, Vermorel M. Evaluation of two foot-to-foot bioelectrical impedance analysers to assess body composition in overweight and obese adolescents. Br J Nutr. 2003; 90(5): 987-92.
6. Yahia N, Wang D, Rapley M, Dey R. Assessment of weight status, dietary habits and beliefs, physical activity, and nutritional knowledge among university students. Perspect Public Health. 2016; 136(4): 231-44.
7. Jabłonowska-Lietz B, Wrzosek M, Włodarczyk M, Nowicka G. New indexes of body fat distribution, visceral adiposity index, body adiposity index, waist-to-height ratio, and metabolic disturbances in the obese. Kardiol Pol. 2017;75(11):1185-91.
8. Global BMI Mortality Collaboration, Di Angelantonio E, Bhupathiraju ShN, Wormser D, Gao P, Kaptoge S. et al. Body-mass index and all-cause mortality: individual-participant-data meta-analysis of 239 prospective studies in four continents. Lancet. 20;388(10046):776-86.
9. Fox CS, Massaro JM, Hoffmann U, Pou KM, Maurovich-Horvat P, Liu CY, et al. Abdominal visceral and subcutaneous adipose tissue compartments: association with metabolic risk factors in the Framingham Heart Study. Circulation. 2007; 116(1): 39-48.
10. Rahman M, Berenson AB. Accuracy of current body mass index obesity classifcation for white, black, and Hispanic reproductive-age women. Obstet Gynecol. 2010;115(5):982-8.
11. Gallagher D, Belmonte D, Deurenberg P, Wang Z, Krasnow N, Pi-Sunyer FX, et al. Organ-tissue mass measurement allows modeling of REE and metabolically active tissue mass. Am J Physiol. 1998; 275(2): E249-58.
12. He Q, Heshka S, Albu J, Boxt L, Krasnow N, Elia M, et al. Smaller organ mass with greater age, except for heart. J Appl Physiol (1985). 2009;106(6):1780-4.
13. Panagiotakos DB, Pitsavos C, Yannakoulia M, Chrysohoou C, Stefanadis C. The implication of obesity and central fat on markers of chronic inflammation: The ATTICA study. Atherosclerosis. 2005; 183(2): 308-15.
14. Zaldivar F, McMurray RG, Nemet D, Galassetti P, Mills PJ, Cooper DM. Body fat and circulating leukocytes in children. Int J Obes (Lond). 2006; 30(6): 906-11.
15. Visser M, Bouter LM, McQuillan GM, Wener MH, Harris TB. Low-grade systemic inflammation in overweight children. Pediatrics. 2001;107(1):E13.
16. Hutley L, Prins JB. Fat as an endocrine organ: relationship to the metabolic syndrome. Am J Med Sci. 2005; 330(6): 280-9.
17. Weiss R, Caprio S. The metabolic consequences of childhood obesity. Best Pract Res Clin Endocrinol Metab. 2005; 19(3): 405-19.
18. Herishanu Y, Rogowski O, Polliack A, Marilus R. Leukocytosis in obese individuals: possible link in patients with unexplained persistent neutrophilia. Eur J Haematol. 2006; 76(6): 516-20.
19. Cao JJ, Thach C, Manolio TA, Psaty BM, Kuller LH, Chaves PH, et al. C-reactive protein, carotid intima-media thickness, and incidence of ischemic stroke in the elderly: the Cardiovascular Health Study. Circulation. 2003; 108(2): 166-70.
20. Freeman DJ, Norrie J, Caslake MJ, Gaw A, Ford I, Lowe GD, et al. C-reactive protein is an independent predictor of risk for the development of diabetes in the West of Scotland Coronary Prevention Study. Diabetes. 2002; 51(5): 1596-600.
21. Barbeau P, Litaker MS, Woods KF, Lemmon CR, Humphries MC, Owens S. Hemostatic and inflammatory markers in obese youths: effects of exercise and adiposity. J Pediatr. 2002; 141(3): 415-20.
22. Cook DG, Mendall MA, Whincup PH, Carey IM, Ballam L, Morris JE, et al. C-reactive protein concentration in children: relationship to adiposity and other cardiovascular risk factors. Atherosclerosis. 2000; 149(1): 139-50.
23. Ford ES. C-reactive protein concentration and cardiovascular disease risk factors in children: findings from the National Health and Nutrition Examination Survey 1999-2000. Circulation. 2003; 108(9): 1053-8.
24. Tamakoshi K, Toyoshima H, Yatsuya H, Matsushita K, Okamura T, Hayakawa T, et al. White blood cell count and risk of all-cause and cardiovascular mortality in nationwide sample of Japanese–results from the NIPPON DATA90. Circ J. 2007;71(4):479-85.
Download attachments: 10.4328.ACAM.21732
Zeynep Ergenc, Hasan Ergenc, Cengiz Karacaer, Gülsüm Kaya, Ahmet Öztürk, Mustafa Usanmaz, Ersin Alkılıç. Comparative analysis of the relationship between bioelectrical impedance analysis results and laboratory data. Ann Clin Anal Med 2023;14(8):736-741
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Male gender is a risk factor for high-risk colorectal polyps
Enver Avcı 1, Serden Ay 2
1 Department of Gastroenterology, 2 Department of General Surgery, KTO Karatay University Medical School Medicana Affilated Hospital KTO, Konya, Türkiye
DOI: 10.4328/ACAM.21739 Received: 2023-04-24 Accepted: 2023-05-30 Published Online: 2023-06-10 Printed: 2023-08-01 Ann Clin Anal Med 2023;14(8):742-746
Corresponding Author: Enver Avcı, Department of Gastroenterology, KTO Karatay University Medical School Medicana Affilated Hospital, 42000, Konya, Türkiye. E-mail: enver.a.dr@gmail.com P: +90 507 239 67 65 Corresponding Author ORCID ID: https://orcid.org/0000-0002-3065-2419
This study was approved by the Ethics Committee of Konya Medicana Hospital (Date: 2022-01-28, No: 2022/01)
Aim: Almost all colorectal cancers originate from polyps. Polyps are divided into two groups: neoplastic and non-neoplastic. The most commonly detected polyps are adenomatous polyps, and some of them have a high risk of malignancy. In our study, we aimed to investigate the effect of age and gender on high-risk colorectal polyps.
Material and Methods: We retrospectively reviewed the colonoscopy procedures performed in our Endoscopy Unit between January 2018 and January 2022. Demographic information of patients and colonoscopy reports were re-examined from the hospital information system.
Results: In 1474 colonoscopy procedures, 289 polyps were detected in a total of 204 (13.8%) patients. 61.7% of the patients were male and 38.3% were female. The age range in which polyps were detected most frequently was 60-69 years (28%). There were more polyps in the distal colon than in the proximal. In the histopathological examination, 50.95% of the polyps were adenomatous polyps, followed by hyperplastic polyps with 46%. 20% of the patients had high-risk polyps. High-risk adenomas were statistically significantly higher in men than in women (p=0.026).
Discussion: High-risk adenomas are more common in men. Colon cancer mostly consists of polyps. For this reason, we believe that men should be insisted and encouraged for more screening.
Keywords: High-risk Colorectal Polyps, Colorectal Cancer, Male Gender
Introduction
All formations in the gastrointestinal tract with or without stems, small or large, with or without stems from the epithelium to the lumen, with regular or irregular borders, are called polyps. They are often symptom-free and sometimes present with symptoms of hemorrhage, abdominal pain and obstruction [1]. Polyps are important because they are precursor lesions of colorectal cancers (CRC). Colorectal cancers are a deadly type of cancer that is detected second in women and third in men among all cancers [2].
Colorectal polyps are divided into two main groups: Neoplastic polyps and non-neoplastic polyps. Non-neoplastic polyps include hyperplastic polyps, inflammatory polyps, mucosal polyps, juvenile polyps and Peutz-Jeghers polyps [3].
Hyperplastic polyps are the most common type of non-neoplastic polyps in the colon [4]. They usually appear in the distal colon and resemble adenomatous polyps in appearance. They are usually sesile and dimunitive in nature and rarely exceed 10 mm [5,6].
Neoplastic polyps have the potential to become cancerous and have two main types: adenomatous polyps and sessile serrated polyps. Adenomatous polyps are precancerous lesions originating from the colon epithelium. Adenomatous polyps constitute 85-90% of the polyps that evolve into cancer. However, approximately 10% of all adenomatous polyps turn into cancer, and this process requires at least 7-10 years [7]. Adenomatous polyps are classified according to their histopathological features as tubular, villous and tubulovillous [3]. Histology of the adenoma for cancerization (villous structure, severity of dysplasia), size of 10 mm and above, and three or more are the most important factors determining the risk [8].
In our study, we aimed to investigate the effect of age and gender on high-risk colorectal polyps.
Material and Methods
The study included a retrospective single-center examination of patients who underwent colonoscopy for any reason in the endoscopy unit of our hospital between January 2018 and January 2022. The study followed Helsinki Declaration Principles and local ethics committee approval Konya Medicana Hospital Ethics Commitee Date:28.01.2022, Number: 2022/01 was obtained.
For colonoscopy, colon cleansing was performed by giving oral 500 ml sennoside solution and rectal 210 ml sodium phosphate enema after a watery diet 48 hours before the procedure. After the patients gave their consent by reading the procedure information form, it was performed by a single gastroenterologist with Fujifilm EC760-R colonoscope (Fujifilm Medical Systems Inc., Tokyo, Japan) accompanied by sedation with midazolam, fentanyl and propofol. Detected polyps were excised by forceps, snare or endoscopic mucosal resection and then sent to the pathology laboratory in solution with formaldehyde.
Demographic information of patients and colonoscopy reports were re-examined from the hospital information system. Demographic information such as age, gender and disease history of the patients were recorded. According to colonoscopy reports, the location of the polyps was divided into the rectum, sigmoid colon, descending colon, transverse colon, ascending colon and cecum. The number of polyps in each region, the size of the polyps and the histopathological features of the polyps were recorded in the registration form. Histopathologically, polyps with any of the following three criteria were included in the high-risk group (3):
i. adenoma size ≥10 mm,
ii. prominent villous component,
iii. high-grade dysplasia,
iv. number of adenomas ≥3.
Criteria for exclusion from the study were inflammatory bowel disease, familial polyposis syndrome and the presence of colon cancer.
Data were statistically analyzed using SPSS 22.0 for Windows program (IBM Corp. Armonk, NY, USA) and were presented as average, percentage and standard deviation. The Chi-Square test was used for statistical significance between age, gender and risky polyps.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
The files of 1503 patients who underwent colonoscopy were retrospectively scanned. After excluding 27 (1.8%) patients with adenocarcinoma, 1 (0.07%) patient with familial adenomatous polyposis (FAP) and 1 (0.07%) patient with attenuated FAP were excluded from the study; a total of 289 polyps were analyzed in 204 (13.8%) of the remaining 1474 patients. The most common indication for colonoscopy was constipation (27%) (Table 1). The youngest of the patients with polyps was 31 years old, the oldest was 89 years old, and the median age was 62 years; 79 (38.7%) patients were female wit the median age of 62 (32-88) years, while 125 (61.3%) were male with the median age of 62 (31-89) years. 80% of the patients with polyps were over 50 years of age, and the most common age range with polyps was 60-69 (28%) and at least 30-39 (4.4%) years of age (Figure 1). When the polyps were evaluated according to their size, 221 (76.5%) were ≤ 5 mm, 38 (13.1%) were 6-9 mm, 20 (6.9%) were 10-20 mm and 10 (3.5%) were ≥20 mm (Figure. 2). Of the 204 patients included in the study, 132 (64.7%) had a single polyp and 72 (35.3%) had more than one polyp. When the polyps were evaluated according to their localization, most polyps were in the rectosigmoid region (48.5%) and the least in the cecum (5.5%). According to their histopathological features, adenomatous polyps were detected with a maximum of 147 (50.95%) units, followed by hyperplastic polyps with 133 (46%) units (Table 2). Hyperplastic polyps were significantly larger on the left side than on the right side. When polyps were classified according to their risk, a total of 41 (20%) patients were in the high-risk polyp group and 163 (80%) patients were in the low-risk group. The median age of high-risk patients was 69 years, while the median age of low-risk patients was 59 years. There was no statistically significant difference between the two groups in terms of age (p=0.101). High-risk polyps were present in 32 (27%) of men and 9 (13.9%) of women. High-risk polyps were statistically significantly higher in men than in women (p=0.026) (Figure 3).
Discussion
The most important finding of this study is that high-risk polyps are more common in men than women.
Most colorectal polyps are adenomatous polyps from the group of neoplastic polyps and constitute approximately 70% of all colon polyps [3]. Colonic adenomas are typically asymptomatic and are most commonly found through imaging studies of the colorectal for other causes [9]. Adenomas are classified according to their shape as sessile, pedunculated, or flat [3]. Histologically, they are classified according to their pattern as tubular, villous, or tubulovillous [1]. An adenoma is considered villous if it has at least 75% villous structure, tubular if it has <25% villous structure, and tubulovillous if it is between the two (25-75% villous architecture) [3]. The risk of malignancy increases from the tubular structure to the villous structure. In general, the size of an adenoma is related to the histological type, the larger the villous structure, the larger the polyp. Tubular adenomas are usually stalked, while villous adenomas are usually sessile [3]. Although the prevalence of adenomatous polyps varies, especially advanced age is known as a major risk factor. In addition, male gender, race and abdominal obesity are also considered risk factors for adenomatous polyps [1]. In our study, 50.95% of the polyps we resected were adenomatous polyps. This rate was lower than in the literature. We think that the reason for our relatively low rate of adenomatous polyps is related to our high rate of hyperplastic polyps. We do not know the reason for the high hyperplastic rate. However, most of these polyps are of diminutive size [5,6]. When the colon is completely swollen by air insufflation during a colonoscopy, this tends to flatten or press on hyperplastic polyps, making it difficult to detect hyperplastic polyps [10]. The adequate colon cleansing of our patients and the fact that the procedures are performed in accordance with the guidelines with at least 7 minutes of withdrawal time with a high-definition colonoscope may have enabled us to notice very small lesions in the colon. We believe that our high detection of hyperplastic polyp ratio may be related to these parameters.
The cancerous potential of adenomas is related to the size, type and degree of dysplasia of the polyp, and the number of polyps. Adenomas are classified as high-risk or low-risk according to the presence of these features [3]. These high-risk adenomas have a higher risk of becoming cancerous than other adenomas. The presence of advanced adenoma in the distal colon was associated with an approximately 5-fold higher rate of metachronous proximal colon cancer than in the general population [9]. Most colorectal cancers occurring within 5 years after polypectomy are thought to develop because high-risk adenomas cannot be identified or completely removed during the first colonoscopy [11]. High-grade dysplasia has the highest risk of becoming cancerous, with an annual rate of 37%, followed by the presence of a villous component at a rate of 17% [12]. Adenomas larger than 10 mm in diameter have the potential to contain cancer and carry a risk of metachronous cancer [13], and a size of at least 10 mm provides a 3% risk. [12]. In addition, both the number of adenomas in the index colonoscopy and the number of adenomas during the lifetime of the person are important risk factors for colorectal cancer. Patients with 3 or more tubular adenomas smaller than 10 mm have a greater risk of advanced neoplasia than patients with 1 or 2 tubular adenomas smaller than 10 mm at baseline. The risk of metachronous advanced adenoma increases with a baseline number of adenomas [14]. In our study, the rate of high-risk polyps was 20%, and high-risk polyps were found to be statistically significantly higher in men than in women (p=0.026), but there was no significant difference according to age (p=0.101). Betes et al. reported that male gender, older age, and high body mass index were risk factors for high-risk adenoma. Male gender was significantly associated with the highest risk of advanced adenoma after adjusting for other variables in the model. As a result of this analysis, they suggested a scoring system with 2 points for the male gender and zero points for the female gender [15]. Greenspan et al. reported older age and male gender as important independent variables associated with advanced adenoma detection [16]. In a large study conducted by Regula J et al. on 50 thousand 148 patients, it was reported that high-risk adenomas were higher in men than in women in all age groups. However, they did not find a relationship with age [17]. On the contrary, Stegaman et al. found a relationship between age and advanced adenoma, but could not find a relationship between gender and advanced adenoma [18]. We are of the opinion that there is a need for more work on this issue.
The most important limitation of this study is that other parameters of the patients such as body mass index and smoking could not be evaluated.
Conclusion
This study showed that high-risk adenoma is more common in males. The higher incidence of colorectal cancer in men may be due to this situation. Also, most patients avoid the procedure because of pre-colonoscopy preparation and sedation. Process avoidance behavior is even more common in men. For these reasons, we are of the opinion that more insistence and encouragement should be made on screening in men.
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. Øines M, Helsingen LM, Bretthauer M, Emilsson L. Epidemiology and risk factors of colorectal polyps. Best Pract Res Clin Gastroenterol. 2017; 31(4): 419-24.
2. Granados-Romero JJ, Valderrama-Trevino AI, Contreras-Flores EH, Barrera-Mera Baltazar, Enriquez MH, Uriarte-Ruiz K, et al. Colorectal cancer: a review. Int J Res Med Sci. 2017; 5(11): 4667-76.
3. Naini BV, Odze RD. Advanced precancerous lesions (APL) in the colonic mucosa. Best Pract Res Clin Gastroenterol. 2013; 27(2): 235-56.
4. Carr NJ, Mahajan H, Tan KL, Hawkins NJ, Ward RL. Serrated and non-serrated polyps of the colorectum: their prevalence in an unselected case series and correlation of BRAF mutation analysis with the diagnosis of sessile serrated adenoma. J Clin Pathol. 2009; 62(6): 516-8.
5. Jass JR. Hyperplastic Polyps and Colorectal Cancer: Is There a Link. J Clin Gastroenterol Hepatol. 2004; 2(1): 1-8.
6. Hyman NH, Anderson P, Blasyk H. Hyperplastic Polyposis and the Risk of Colorectal Cancer. Dis Colon Rectum. 2004; 47(12): 2101-4.
7. Keum N, Giovannucci E. Global burden of colorectal cancer: emerging trends, risk factors and prevention strategies. Nat Rev Gastroenterol Hepatol. 2019; 16(12): 713-32.
8. Winawer SJ, Zauber AG. The advanced adenoma as the primary target of screening. Gastrointest Endosc Clin N Am. 2002; 12(1): 1-9.
9. Levine JS, Ahnen DJ. Adenomatous Polyps of the Colon. N Engl J Med. 2006; 355(24): 2551-7.
10. Tamura S, Ueta H, Miyamoto T, Mizuta H, Onishi S. Depressed-type hyperplastic lesion in the colon. Endoscopy. 2004; 36(12): 1131.
11. Winawer SJ, Zauber AG, Fletcher RH, Stillman JS, O’Brien MJ, Levin Bernard, et al. Guidelines for colonoscopy surveillance after polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer and the American Cancer Society. Gastroenterology. 2006; 130(6): 1872-85.
12. Risio M. Reprint of: The natural history of adenomas. Best Pract Res Clin Gastroenterol. 2010; 24(4): 397-406.
13. Winawer SJ, Zauber AG, O’Brien MJ, Ho MN, Gottlieb L, Sternberg SS, et al. Randomized comparison of surveillance intervals after colonoscopic removal of newly diagnosed adenomatous polyps. The National Polyp Study Workgroup. N Engl J Med. 1993; 328(13): 901-6.
14. Lieberman DA, Weiss DG, Harford WV, Ahnen DJ, Provenzale D, Sontag SJ, et al. Five-year colon surveillance after screening colonoscopy. Gastroenterology. 2007; 133(4): 1077-85.
15. Betes M, Muñoz-Navas M A, Duque J M, Angos R, Macias E, Subtil JC, et al. Use of colonoscopy as a primary screening test for colorectal cancer in average risk people. Am J Gastroenterol. 2003; 98(12): 2648-54.
16. Greenspan M, Rajan KB, Baig A, Todd B, Sohrab M, Joshua M. Advanced adenoma Detection Rate Is Independent of Nonadvanced Adenoma Detection Rate. Am J Gastroenterol. 2013; 108(8): 1286-92.
17. Regula J, Rupinski M, Kraszewska E, Polkowski M, Pachlewski J, Orlawska J, et al. Colonoscopy in colorectal-cancer screening for detection of advanced neoplasia. N Engl J Med. 2006; 355(18): 1863-72.
18. Stegeman I, Wijkerslooth TR, Stoop EM, Leerdam ME, Dekker E, Ballegooijen, et al. Colorectal cancer risk factors in the detection of advanced adenoma and colorectal cancer. Cancer Epidemiol. 2013; 37(3): 278-83.
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Ductal spasm during percutaneous device occlusion of the patent ductus arteriosus; nightmare of the cath-lab: “winking ductus”
Fatma Sevinc Sengul 1, Ibrahim Cansaran Tanidir 2, Alper Guzeltas 1
1 Department of Pediatric Cardiology, Istanbul Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, 2 Department of Pediatric Cardiology, Istanbul Basaksehir Cam and Sakura City Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.21760 Received: 2023-05-19 Accepted: 2023-07-03 Published Online: 2023-07-09 Printed: 2023-08-01 Ann Clin Anal Med 2023;14(8):747-752
Corresponding Author: Fatma Sevinc Sengul, Department of Pediatric Cardiology, Istanbul Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, Halkali, Istanbul, Turkey. E-mail: doganfatmasevinc@gmail.com P: +90 212 692 20 00 F: +90 212 471 94 94 Corresponding Author ORCID ID: https://orcid.org/0000-0001-6791-3777
This study was approved by the Ethics Committee of Istanbul Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital (Date: 2022-11-28, No: 2022-67)
Aim: The occurrence of intermittent spasms and subsequent patency of the patent ductus arteriosus (PDA) has been infrequently documented in older children. This study aims to present our experience with ductal spasms observed during transcatheter occlusion procedures for PDA.
Material and Methods: A retrospective analysis was conducted on transcatheter PDA occlusions (n=544) performed at our clinic between 2010 and 2022.
Results: Eleven patients (2%) were identified to have experienced ductal spasms during the transcatheter PDA occlusion procedure. Nine patients were born prematurely between 25 and 35 weeks of gestation, while two were born at full term. The median age at the time of the procedure was 17 months (range: 10-87 months). Eight patients received supplemental oxygen during the procedure. Device embolization occurred in two patients; however, the embolized devices were successfully retrieved, and larger devices were subsequently implanted. Closure of the PDAs was achieved using Amplatzer Vascular Plug-2 (n=10) and Amplatzer Duct Occluder-2 (n=1).
Discussion: Ductal spasm primarily manifests in preterm infants, even during infancy, particularly those receiving oxygen therapy. It is imperative to minimize the use of oxygen during transcatheter PDA occlusion procedures. Preoperative echocardiographic measurements consistently demonstrate superior reliability compared to angiographic measurements. Therefore, they should be given due consideration when assessing and selecting an appropriate device. Double-disk devices may be preferable for closing the ductus in patients at risk of PDA spasm or with a history of PDA spasms.
Keywords: Patent Ductus Arteriosus, Prematurity, Ductal Spasm, Transcatheter Closure
Introduction
Patent ductus arteriosus (PDA) is one of the most prevalent congenital heart diseases observed across all age groups. In most full-term infants, the ductus arteriosus closes functionally within a few hours following birth, and anatomical closure typically occurs within 2 to 8 weeks. Nevertheless, the persistence of an open ductus beyond 72 hours of postnatal age, known as a persistent ductus arteriosus, is frequently encountered in nearly 50% of premature infants [1]. However, the incidence of delayed closure is comparatively less frequent in neonates born at full term. Intermittent spasms and subsequent patency of ductus rarely occur in premature cases following pharmacological ductal closure. Such a phenomenon has been described in term neonates; however, it is extremely rare in older children and has been presented in a few case reports in the literature [2, 3, 4]. However, transcatheter occlusion, an emerging standard procedure, can be complicated by rare ductal spasm during cardiac catheterization, causing procedural failure, underestimation of duct and device size, and potential embolization [1, 3].
In this report, we present our experience concerning the occurrence of ductal spasms during transcatheter occlusion of PDA, where the presence of spasm complicated the procedure and influenced the selection of an appropriate device for these patients.
Material and Methods
A retrospective analysis was conducted, encompassing a total of 544 cases of transcatheter occlusion of PDA performed at our clinic between 2010 and 2022. The study was planned in accordance with the Declaration of Helsinki after obtaining the required approval from the local ethics committee (no: 2022-67, expiry date: 28.11.2022).
Device occlusion was conducted in patients with significant left-to-right shunting via PDA, which results in echocardiographic parameters of left atrial and/or left ventricular volume overload. Before the procedure, the interventional cardiologist conducted comprehensive physical examinations and echocardiographic assessments on the same day. All patients exhibited continuous heart murmurs consistent with a PDA, accompanied by echocardiographic evidence of left-heart volume overload.
Cardiac catheterization procedures were carried out under general anesthesia while patients were ventilated with a laryngeal mask. Vascular access was obtained using the modified Seldinger technique. Baseline hemodynamic measurements, including mean pulmonary artery and aortic pressures, were recorded prior to the initiation of the procedure. Biplane aortic angiograms were subsequently performed to evaluate the characteristics of the PDA, encompassing measurements of aortic and pulmonary side diameters, the narrowest segment, and length. Based on these observations, an appropriate device was selected in accordance with established guidelines [5]. Antegrade delivery from the venous circulation was the preferred method for device deployment, whereas retrograde deployment was infrequently employed. Subsequent to device deployment, angiography in the descending aorta through the delivery catheter was conducted to confirm the final positioning of the device relative to the pulmonary arteries. If the device was deemed to be satisfactorily positioned, it was released accordingly.
The presence of significant ductal spasms was defined based on the following observations:
1. Echocardiographic examination revealed a notably larger PDA prior to the angiographic procedure.
2. Initial aortic angiogram indicating minimal flow through the PDA.
3. Relief of the spasm was observed in angiography that was performed 15-20 minutes after the initiation of aorta-to-pulmonary artery flow.
For cases exhibiting ductal spasm, a comprehensive collection of data was recorded, including gestational age, birth weight, age at the time of the procedure, physical examination findings, echocardiographic findings before and during catheterization, angiographic data, details regarding the type and diameter of the PDA after spasm relief, device specifications, and recent echocardiographic follow-up information.
Statistics
Statistical analysis was conducted employing SPSS 25 software (SPSS, Chicago, IL, USA). Categorical variables were presented as total counts, mean values accompanied by the standard deviation (SD) in cases where the data followed a normal distribution or as medians with ranges (minimum to maximum) in instances where the data did not exhibit a normal distribution.
Ethical Approval
Ethics Committee approval for the study was obtained. Informed consent was obtained from the patient’s parents.
Results
A total of eleven patients (2%) exhibiting ductal spasms during transcatheter occlusion of PDA were identified. Among them, nine patients were born within the gestational age range of 25 to 35 weeks, while the remaining two were born at full term (Figure 1). The median age at the time of the procedure for patients experiencing ductal spasms was 17 months, ranging from 10 to 87 months. Comprehensive demographic and clinical data of these patients are summarized in Table 1.
Echocardiographic assessments revealed minimum ductus diameters ranging from 3 to 6.4 mm. Notably, in 10 out of 11 patients, the occurrence of spasm preceded the passage of the catheter through the PDA. Eight of the patients who experienced ductal spasm were receiving oxygen during the procedure. Subsequently, upon re-auscultation, a reduction in murmur intensity was observed concomitant with the onset of ductal spasm in all patients. Following the relief of the spasm, minimal PDA diameters ranged from 2.8 to 5.6 mm, with a median value of 3.5 mm. Deployment of the devices took place anterogradely from the venous circulation in nine cases, while the retrograde route was employed in the remaining two instances. Detailed cardiac catheterization findings are presented in Table 2.
During percutaneous occlusion procedures for PDA conducted between 2010 and 2016, all patients underwent oxygen ventilation administered by the anesthesiologist. Within this specified period, we observed the occurrence of ductal spasms in seven patients, all of whom were premature infants. During the occurrence of ductal spasm, a remarkable decrease in murmur and precordial thrill was observed, coinciding with a concomitant reduction in the flow of the PDA into the pulmonary artery as evidenced by echocardiographic evaluations. Subsequently, upon realizing that the patients were receiving oxygen, the administration of supplemental oxygen was promptly discontinued. The continuous murmur reappeared after a waiting period of 15 to 20 minutes. Notably, following the relaxation of the PDA, all devices were successfully deployed without any residual shunting. For six patients (except patient number six), ductal spasms occurred before the catheter crossed the ductus.
Our prior experience with ductal spasms was limited before the year 2016. In two patients, device embolization occurred. Specifically, in patient 6, successful deployment of a 5.5 mm Nit-Occlud® PDA-R device (PFM Medical, Cologne, Germany) resulted in minimal residual flow. However, the subsequent day witnessed the embolization of the device to the descending aorta. The embolized device was effectively retrieved using an Amplatz Gooseneck snare (Microvena, St. Paul, MN, USA), and the duct was subsequently occluded using an 8 mm Amplatzer Vascular Plug 2 (St. Jude Medical, Inc., St. Paul, MN, USA).
In the case of the 7th patient, the ductus was successfully occluded using an 8 mm AVP-2 device. However, the device embolized to the right pulmonary artery on the following day. The embolized device was promptly extracted, and closure of the PDA was subsequently accomplished by employing a 10 mm AVP-2 device (Figure 2). In these two cases, during the initial procedure, we observed that the angiographically measured diameter of the duct was smaller than the expected size. Consequently, a small-sized single-disc device was employed for patient 6, while a small double-disc device was utilized for patient 7. Upon retrieving the embolized devices the subsequent day, a double-disc device was implemented for duct occlusion in both patients. After this unpleasant yet instructive experience, ductal occlusion procedures were subsequently guided not only by small angiographic measurements but also by echocardiographic measurements or angiographically relieved ductal measurements, and then double-disc devices were used.
Following these distressing events, we provided guidance to the anesthesiologist to refrain from administering oxygen to patients scheduled for PDA occlusion prior to the procedure. In patients who underwent ductal occlusion after 2016, the anesthesiologist diligently focused on minimizing the inhaled oxygen fraction to 21% whenever feasible. However, despite these precautions, an additional four cases of ductal spasms were encountered. The first case was a seven-year-old female patient (patient 8), who was born prematurely at 30 gestational weeks weighing 1480 grams. She was ventilated with 21% FiO2 during the procedure. The second case was a three-year-old girl (patient 9). She was born full term at the 38th gestational week, weighing 2300 grams, but required supplemental oxygen during the procedure due to excessive secretion. The penultimate patient (patient 10) was a one-year-old male with a history denoting full-term delivery (40th gw, 3500 g). This patient did not necessitate supplemental oxygen, though he experienced emesis during the induction of anesthesia despite maintaining normotensive arterial pressure. The last patient (patient 11) was a one-year-old female infant, born prematurely at 29 gestational weeks and weighing 1440 grams, and she did not require supplemental oxygen support during the procedure.
Over the years, our awareness of the disease was heightened, and none of the patients with ductal spasm were seen after 2018, indicating an enhancement in our approach. Concerning follow-up, no severe complications occurred in any patient. All patients were asymptomatic and had normal left-heart volumes without a residual ductus arteriosus or an obstruction to the branch pulmonary artery and aortic flows.
Discussion
Ductal spasm is a condition that occurs during transcatheter occlusion and may be an unpredictable cause of procedural failure. Successful percutaneous closure of the patent ductus arteriosus (PDA) relies heavily on an accurate assessment of the ductal morphology, which includes a detailed understanding of its length, the narrowest segment, and the overall shape and configuration. The importance of a judicious selection of an appropriate occlusion device for a successful procedure cannot be overstated.
The onset of ductal spasm, whether spontaneous or induced by manipulation of the duct, presents a challenging variable that might lead to an underestimation of the ductus arteriosus dimensions. This miscalculation may lead to the selection of an inappropriate occlusion device and the unintentional embolization of devices, as seen in prior studies [1, 3]. The sporadic spasm of the ductus beyond neonatal stages was first observed through auscultatory changes and subsequently confirmed via echocardiography and angiography [3, 6, 7, 8]. Even though the precise mechanisms that trigger the vascular reactivity of the ductus arteriosus are yet to be unraveled entirely, a number of physiological, hemodynamic, and pharmacological factors have been proposed as possible contributors to the patency or constriction of the ductus arteriosus. The presence of smooth muscle cells at the pulmonary artery end of the ductus suggests the potential site of narrowing in affected cases [5, 8, 9]. Specific triggers, such as catecholamines, have been shown to potentially induce ductal constriction, particularly in children with a history of low birth weight and a potentially lower gestational age [10]. Moreover, agents like oxygen, bradykinin, histamine, 5-hydroxytryptamine, and acetylcholine have been found to influence ductal constriction according to numerous studies [3, 5, 7, 9, 10, 11, 12].
While the ductus arteriosus reactivity in older children is considered an uncommon phenomenon and has been sparsely documented in the literature, it is known to occur [3, 6, 7, 10]. However, some professionals have doubts about the likelihood of duct diameter changes occurring without any direct or indirect manipulation of the ductus arteriosus [6]. Notable instances include Cokkinos et al.’s report of the intermittent disappearance of a PDA murmur in a ten-year-old patient [2], as well as a documented case from Germany revealing the reactivity of a patent arterial duct in a one-year-old infant during a routine echocardiographic study [6]. In our study, similar to other reports, ductal spasm occurred without catheter manipulation in most of the patients (n=10, 91%). Nonetheless, several case reports present a different viewpoint. In these reported cases, catheter-induced vasospasm was considered as a possible causative factor [3, 7]. In our series, we encountered a case where ductal reactivity likely occurred subsequent to direct manipulation of the duct.
Prematurity appears to be the prevailing associated anomaly in the vast majority of previously reported cases [3, 10, 11]. For instance, Batlivala et al., in their research, identified seven cases of ductal spasms out of 331 (2.1%), all of whom were prematurely born. The median age of these patients was 12 months, with a median gestational age of 28 weeks [10]. In our own series spanning 13 years and covering 544 ductal occlusions, we encountered 11 cases (2%) of ductal spasms. Among the 16 patients who underwent transcatheter occlusion for PDA in our research, nine had a history of preterm delivery and later developed ductal spasms. Conversely, the other two infants who experienced a ductal spasm were born after completing 37 weeks of gestation. In our patient group, the median age at the time of intervention was 17 months.
Studies have indicated that the ductus arteriosus musculature demonstrates sensitivity to oxygen, a potent constrictor for the fetal PDA [10, 12]. In the report by Phyu et al., they shared their experiences about ductal spasms that occurred during transcatheter occlusion in two children without any catheter manipulation and stated that the cause of spasms could be oxygen or catecholamines [12]. Until 2016, we routinely administered oxygen during transcatheter ductal occlusion procedures. However, frequent occurrences of ductal spasms led us to decrease inhaled oxygen levels, aiming for a FiO2 of 0.21. Of the eight patients who experienced ductal spasms during our study, seven were preterm infants, and one was a full-term infant, all initially receiving oxygen supplementation. These findings suggested that oxygen may play a role in the development of ductal spasms.
One of the risks of PDA spasm is device embolization due to inappropriate device selection, as stated in the literature [1, 3, 9, 12]. Among our patient cohort, two experienced embolization of the occlusion device due to undersizing. The remaining nine patients received relatively large, double-disc ductal occlusion devices. We advise a minimum 15-minute waiting period if a ductal spasm transpired prior to the catheter crossing the ductus for spasm relief and assessment of any underlying causes. Ensuring appropriate occlusion device selection necessitates careful echocardiographic measurements and proactive steps to prevent device undersizing.
Tomita et al. explored the effect of catecholamines on the ductus arteriosus, proposing a hypothesis that the sympathetic response initiated during crying might contribute to the temporary occlusion of the PDA. Within this investigation, the intravenous administration of epinephrine, norepinephrine, and dobutamine substantially constricted the ductus arteriosus within a span of 10 to 15 minutes post-injection, demonstrating a discernible contraction at the pulmonary artery end of the ductus arteriosus [11]. A noteworthy case in our study involved a full-term infant who underwent the procedure with a FiO2 of 0.21. Following anesthesia induction, the patient experienced vomiting. There was a reduction in the ductal diameter from an initial echocardiographic measurement of 3.5 mm to 2 mm during the procedure, prompting contemplation of the potential impact of catecholamines on ductal constriction.
All of our cases presented with murmurs indicative of PDA during pre-procedural auscultation. However, the absence of a ductal murmur during a spasm underlines the importance of a comprehensive examination to avert misinterpretation based solely on catheterization data. We strongly advocate routine patient evaluation prior to procedures to ensure accurate diagnostic information.
Our findings indicate that ductal spasms may initiate spontaneously or in response to oxygen supplementation, adrenergic stimuli (such as vomiting), or ductal manipulation via catheter or wire. This occurrence seems more prevalent among oxygen-receiving preterm infants, yet it can also arise in term infants. Despite historical evidence highlighting the primary manifestation of ductal spasm in neonates, it may also occur in older age groups. Thus, clinicians must consider the potential for ductal spasm when disparities emerge between clinical examination, echocardiography findings, and catheter angiography results.
Study limitations
This study has certain limitations to consider. As an observational investigation, it focused on a relatively small cohort of patients experiencing ductal spasm, with all data collected retrospectively from a single medical center. This may influence the overall generalizability and applicability of the findings.
Conclusions
Ductal spasm predominantly manifests in preterm infants, even during the early stages of infancy, particularly in those receiving oxygen therapy. It is strongly recommended to minimize the use of oxygen during transcatheter PDA occlusion procedures. Preoperative echocardiographic measurements consistently exhibit greater reliability compared to angiographic assessments. Hence, these measurements should be considered when determining the appropriate device selection. Double-disk devices can be preferred to close the ductus in patients with ductal spasm or risk of ductal spasm.
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
The authors declare no conflict of interest.
References
1. Backes CH, Cheatham SL, Deyo GM, Leopold S, Ball MK, Smith CV, et al. Percutaneous Patent Ductus Arteriosus (PDA) Closure in Very Preterm Infants: Feasibility and Complications. J Am Heart Assoc. 2016; 5(2): e002923.
2. Cokkinos DV, Leachman RD, Lufschanowski R. Intermittent disappearance of a patent ductus arteriosus murmur: Case report and review of the literature. Tex Heart Inst J. 1982; 9: 57–60.
3. Lozier JS, Cowley CG. Reactivity of the ductus arteriosus: Implications for transcatheter therapy. Catheter Cardiovasc Interv. 2004;61(2):268-70.
4. Sarquella-Brugada G, Mivelaz Y, Dahdah N. Hemodynamic changes alert to spontaneous ductus arteriosus spasm. Rev Esp Cardiol (Engl Ed). 2013;66(9):743.
5. Alkamali AM, Hassan AA. Patent Ductus Arteriosus Closure. In: Butera G, Chessa M, Eicken A, Thomson J, editors. Cardiac Catheterization for Congenital Heart Disease. Cham: Springer; 2021. p. 585-602.
6. Galal M, Turkistani H, Sultan A. Change of size and type of patent ductus arteriosus in a one year old infant during routine echocardiographic study. Images Paediatr Cardiol. 2008; 10(2): 6-10.
7. Kannan BR, Sadhananthan AK, Kumar RK. Severe spasm of a large patent ductus arteriosus. Indian Heart J. 2005; 57(3): 274.
8. MacDonald ST, Bhindi R, Ormerod O, Wilson N. Ductus arteriosus spasm. JACC Cardiovasc Interv. 2009;2(1):73.
9. Tzifa A, Tulloh R, Rosenthal E. Spontaneous spasm of the arterial duct: a pitfall for transcatheter occlusion. Heart. 2005; 91(1): 31.
10. Batlivala SP, Glatz AC, Gillespie MJ, Dori Y, Rome JJ. Ductal spasm during performance of transcatheter ductal occlusion. Catheter Cardiovasc Interv. 2014; 83(5): 762-7.
11. Tomita H, Fuse S, Chiba S. Catecholamine-induced ductus arteriosus constriction in children. Am J Cardiol. 1996; 77(15): 1372-5.
12. Phyu HL, Oo KM. Ductal arterial spasm: a nightmare. Cardiol Young. 2020; 30(3): 422-3.
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Fatma Sevinc Sengul, Ibrahim Cansaran Tanidir, Alper Guzeltas. Ductal spasm during percutaneous device occlusion of the patent ductus arteriosus; nightmare of the cath-lab: “winking ductus”. Ann Clin Anal Med 2023;14(8):747-752
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Comparison of the results of computerized tomography of the hips in adult patients with unilateral high hip dislocation
Ahmet Atilla Abdioğlu 1, Servet Kerimoğlu 2, Ali Küpeli 3, Polat Koşucu 4
1 Department of Orthopedics and Traumatology, Fatih State Hospital, 2 Department of Orthopedics and Traumatology, Faculty of Medicine, Karadeniz Technical University, 3 Department of Radiology, Kanuni Education and Research Hospital, 4 Department of Radiology, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey
DOI: 10.4328/ACAM.21768 Received: 2023-05-27 Accepted: 2023-07-03 Published Online: 2023-07-15 Printed: 2023-08-01 Ann Clin Anal Med 2023;14(8):753-758
Corresponding Author: Ahmet Atilla Abdioğlu, Department of Orthopedics and Traumatology, Fatih State Hospital, 61100, Trabzon, Turkey. E-mail: ahmetatilla@hotmail.com P: +90 505 925 31 87 Corresponding Author ORCID ID: https://orcid.org/0000-0002-0206-8135
This study was approved by the Ethics Committee of Karadeniz Technical University Faculty of Medicine (Date: 2013-04-08, No: 2013/19)
Aim: Since the joints of adult patients with developmental dysplasia of the hip (DDH) differ significantly from normal anatomy, surgery in these patients poses many additional challenges. The aim of this study was to quantify the anatomical differences between the hips of individuals with normal hips on one side and high hip dislocation on the other side.
Material and Methods: Twenty computed tomography images of unoperated patients with one normal hip and one high hip dislocation (Hartofilakidis type C) were retrospectively analyzed. The acetabulum was analyzed with seven measurements and the femur with 16 measurements.
Results: The mean acetabular volume of the normal side was 2.3 times that of the dislocated side, the depth was 1.5 times that of the dislocated side, the anteroposterior diameter was 1.58 times that of the dislocated side, and the mean posterior lip thickness was 3.61 times that of the dislocated side. The femoral cortical thickness of the dislocated hip was thinner, the femoral anteversion angle was higher and the trochanter minor was more retroverted than the normal side. Although the total length of the dislocated side was less, we observed that the femur of the dislocated side was longer distally than the trochanter minor.
Discussion: Patients with unilateral high DDH had significant changes in both the acetabulum and the intact side. We recommend a thorough pre-assessment and preparation to prevent complications during total hip arthroplasty surgery as part of DDH treatment.
Keywords: Developmental Hip Dysplasia, Dislocation Height, Hartofilakidis Type C, Computed Tomography, Total Hip Arthroplasty
Introduction
Developmental dysplasia of the hip (DDH) is a broad term that encompasses all problems ranging from hip instability to total dislocation, in which the femoral head-acetabulum connection is completely lost [1,2]. Various classification systems exist for DDH [3,4].
In populations subjected to standard postnatal ultrasonography screening, the incidence of dysplasia ranges from 25 to 50 per 1000 [1,5]. Although DDH can be detected and treated early using advanced screening, diagnosis, and treatment procedures, it is a health concern that can cause major complications for the patient if not detected and addressed [1,5]. Patients with untreated DDH are more likely to develop osteoarthritis in the affected hip joint [6]. DDH can result in symptoms such as discomfort, limited movement, limb length inequality, and limping [3,6]. Since the tissues of patients with osteoarthritis secondary to DDH differ greatly from normal hip anatomy, the surgeries to be undertaken in the treatment provide numerous extra challenges [3,7-9].
The goal of our study was to use quantitative data to identify the anatomical differences between the two hips in patients with unilateral DDH and to gain a better understanding of the difficulties that might arise during treatment.
Material and Methods
The study included patients who were advised to undergo computed tomography (CT) conducted for the purpose of planning prior to total hip arthroplasty (THA) surgery at the Orthopedics and Traumatology clinic within a year. The study was approved by the ethics committee of Karadeniz Technical University Faculty of Medicine on 08.04.2013 with the number 2013/19 and informed consent was obtained from the patients. Twenty hips from ten different patients were evaluated.
The study comprised patients with high hip dislocation in just one hip joint (Hartofilakidis classification Type C) and no disease in the other hip joint. Patients over the age of 18 with no other systemic diseases were included. None of the patients underwent orthopedic surgery. Multislice computed tomography images were obtained using “Siemens Somatom Plus” and “Toshiba Prime Aquilion TSX-303A”. The imaging was obtained with the patient in a supine position, with the patella facing the ceiling. The cross-sectional area was measured from the level of the superior crista iliaca to the distal femoral articular surface. Sections were taken every 1 millimeter. Coronal and sagittal reconstruction pictures were created from the axial plane images. The measurements were obtained from these images. Dislocated hip measurements were taken from actual acetabulum. Each patient’s measurement was repeated three times by the same radiologist, randomly and blinded to patient information. To acquire precise results, each patient’s measurements were obtained three times, and the arithmetic average of the data was taken. Units used were millimeters for length, degrees for angles, and cubic centimeters for volume.
Femoral measurements (FM): distance from femoral head to trochanter minor (FM1), distance between trochanter major and intercondylar notch (FM2), distance between femoral head and intercondylar notch (FM3), femoral anteversion angle (FM4), angle of the trochanter minor long axis relative to the femoral condyles (FM5), anteroposterior canal diameter at half the distance between the trochanter major notch (FM6), diameter of the medio-lateral canal at half the distance between the trochanter major notch (FM7), anteroposterior canal diameter at the level where the trochanter minor is most protruding (FM8), diameter of the medio-lateral canal at the level where the trochanter minor is most protruding (FM9), antero-posterior canal diameter at the level of the proximal quarter of the distance between the trochanter major notch (FM10), diameter of the medio-lateral canal at the level of the proximal quarter of the distance between the trochanter major notch (FM11), the narrowest canal diameter of the femur (FM12), distance from the narrowest canal diameter of the femur to the minor (FM13), average cortical thickness 2 cm distal to the trochanter minor (FM14), diameter of the antero-posterior canal 2 cm distal to the trochanter minor (FM15) and diameter of the medio-lateral canal 2 cm distal to the trochanter minor (FM16) [12-15,25].
Acetabulum measurements (AM): acetabular anteversion angle (AM1), acetabulum depth (AM2), anteroposterior diameter (AM3), medial bone thickness (AM4), anterior lip thickness (AM5), posterior lip thickness (AM6) and acetabulum volume (AM7) [10,11,20-24].
The acetabular anteversion angle (AM1) was measured in axial sections by drawing a line perpendicular to the line joining the most posterior ends of the iliac bones and crossing it through the anterior and posterior lip tips at the level where the real acetabulum is deepest [10,11].
The patients’ axial images were transferred to the Vizard and Vitrea workstations. Images of 3D volume rendering coronal and sagittal reconstruction were created. The acetabular fossa’s borders were delineated in the axial, coronal, and sagittal planes on these pictures, and its volume (AM7) was estimated.
Statistical Analysis
Measurement and calculations obtained were statistically analyzed. Percentage (%), mean and standard deviation were used for descriptive data. Data normality was evaluated using the Kolmogorov-Smirnov test. Comparison of normally distributed data was conducted using Student’s t test. The analysis was conducted using SPSS v. 21.0 (IBM Corp., Armonk, NY, USA).
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
The median age of patients included in the study was 41.6 (22 – 59) years, of which 10% were male and 90% were female. An example case is shown in Figure 1, which shows a diagram of the methods of femur length measurement, as well as some of the horizontal sections at various levels where the canal diameter was measured. Femoral measurement data are shown in Table 1. The acetabulum measurement diagram of a sample case is shown in Figure 2. Acetabulum measurements are shown in Table 2.
The mean of FM 4 was 33.61 degrees on the normal side and 26.38 degrees on the dislocated side, although the difference was not statistically significant.
When the angulation of the minor trochanter, the diameter of the mediolateral canal in the middle of the femur, the diameter of the mediolateral canal at the level of the trochanter minor, the diameter of the narrowest canal of the femur, and the cortex thickness values 2 cm distal to the trochanter minor were compared between normal and dislocated hip, a statistically significant difference was found.
Average FM 14 was 1.25 times greater on the normal side compared to the dislocated side.
The distance between the trochanter minor and the intercondylar notch of the femur was calculated as 345.27 mm on the normal side and 350.54 mm on the dislocated side. On average, the distance on the dislocated side was 5.27 mm longer.
Figure 3 shows the level- by- level changes in the comparative images of 2 cm-spaced axial sections from the trochanter major to the level of the intercondylar notch on the dislocated and intact hip sides of one patient.
A statistically significant difference in acetabulum depth, anterior posterior diameter of acetabulum, anterior lip thickness, posterior lip thickness, and acetabulum volume was identified when normal and dislocated hip measurements were compared. The mean acetabulum depth on the normal side was 1.50 times that of the dislocated side, the normal side’s mean anterior-posterior diameter was 1.58 times that of the dislocated side, the normal side’s mean anterior lip thickness was 2.33 times that of the dislocated side, and the normal side’s average posterior lip thickness was 3.61 times that of the dislocated side. The average acetabulum volume on the normal side was 25.82 cm3 and 11.21 cm3 on the displaced side. The intact side acetabulum volume was found to be 2.30 times that of the dislocated side.
Discussion
Total hip arthroplasty (THA) surgery performed in the treatment of degenerative osteoarthritis caused by DDH is very challenging and has a high complication rate due to existing large bone deformities [7,9,12].
The femoral length was found to be 6.84 mm shorter on the dislocated side. Similar to our results, an average of 9 mm shortness was reported in a similar study [13].
Although the entire femur length is shorter on the dislocated side, this shortness is attributed to the portion proximal trochanter minor, and the situation is inverted distal to the trochanter minor, with the femur length distal to the trochanter minor being longer in the dislocated hip when compared to the normal side. The distal side of the trochanter minor was, on average, 5.27 mm longer on the dislocated side compared to the normal side. We believe that this finding is critical for precise leg length modification in THA applications.
Femoral anteversion angles have been reported in the literature as being 13 degrees in normal hips, 38.4 degrees in Crowe Type 3-4 hips, 37 degrees in Crowe Type 4 hips, an average of 22.2 degrees in CHD, 41 degrees in Crowe type 4a hips, and 29 degrees in Crowe type 4b hips [12-16]. In our study, femoral anteversion angles were found to be 33.61 degrees on the normal side and 26.38 degrees on the dislocated side, and these values demonstrate increased femoral anteversion similar to other studies on DDH hips. However, the variability of the angles suggests that it may be caused by the pressure of the pelvis on the dislocated femoral head at different angles in different positions. The values for the normal side in our study indicate a higher femoral anteversion than the measurements in normal hips in other studies [12,13,15,16]. These findings suggest that the dislocated side may impact the intact hip over time, or that the excess of femoral anteversion in the normal hips may be substantial from the beginning.
When the rotational position of the trochanter minor relative to the distal femur was examined, it was discovered that it was substantially retroverted in the dislocated hip joint. This was assumed to be owing to the variable anatomical structure and placement of the proximal femur in DDH patients, as well as the diversity of the iliopsoas muscle’s angle of attraction on the trochanter minor. We believe this is critical and should not be overlooked during THA.
One study reported that the intramedullary anteroposterior diameter was greater than the mediolateral diameter at the isthmus level in both normal and dysplastic femurs, and the trochanter minor was 40 mm distal and the mean anteroposterior canal diameter was greater than the mediolateral diameter at the isthmus level in Crowe Type 3-4 patients [13,15]. In our study, the mediolateral diameter was observed to be larger than the anteroposterior diameter on both the dislocated and normal sides at the level of the trochanter minor. Both on the dislocated and on the normal side, the anteroposterior diameter was larger than the mediolateral diameter at all levels, distal to the trochanter minor.
The diameter of the femoral intramedullary canal is one of the most significant features for prosthesis fixation and plays an important role in the selection of the suitable prosthesis prior to the operation and, therefore, in stability [17]. A study reported that all canal diameters in Crowe 4 patients were found to be smaller than in the normal control group [12]. Similarly, we discovered that the canal width in the proximal was narrower in both directions compared to the normal side. The diameter of the femoral canal was observed to be wider on the dislocated side compared to the normal side as it progressed distally from 20 mm below the trochanter minor, contrary to the literature findings. It will be very helpful to know that the femoral canal can be of varying widths at various levels in order to minimize issues with femoral stem fixation distal to the osteotomy line, especially in patients who require femoral shortening after THA.
In many studies, canal diameters at the isthmus level were found to be narrower on the dislocated side [12,13,15]. The canal diameter of the dislocated side at the isthmus level was found to be substantially larger than that of the normal side in our study. We believe this is due to the differentiation in the normal bone growth of the femur as a result of the patients’ impairment of load distribution in the extremities due to DDH.
The dislocated femur in adults with unilateral high hip dislocation is hypoplastic when compared to the normal side [18]. In these patients, decreased canal width and thin cortical thickness may result in femoral fractures during THA [7,8]. The dislocated side was observed to have a substantially thinner mean cortical thickness at a level of 20 mm distal to the trochanter minor. The degradation of various functions, ranging from body posture to gait physiology, caused by high dislocations allows patients to place less strain on the extremities on the dislocated side, resulting in insufficient bony development on that side. The femurs of Crowe type 4 DDH patients were compared to other DDH femurs in a study, and it was reported that the femoral structures of high dislocation patients were significantly different, and therefore the readily available prostheses may not be the best option for these patients [19]. This should be taken into consideration during THA and precautions should be taken against possible femoral fracture complications.
A reduced hip joint is very important for the natural development of the anatomical structure of the acetabulum, and the normal acetabular anteversion angle has been found to be 20, 19.9, 23, 21.3, 21.4 degrees in different studies [10,14,20-22]. In our study, the acetabular anteversion angle in the reduced hips patients with unilateral dislocation was observed to be 28.15 degrees, higher than similar reports in the literature. This finding demonstrates that the developmental process of the normal hip may be affected in patients with high hip dislocation on one side or that the normal hip joint may have minor acetabular dysplasia.
Acetabular anteversion values for hips with DDH have been reported to be 22 degrees for Crowe Type 2 hips, 24.4 degrees for hips with DDH, and 34 degrees for Crowe Type 4 hips [11,14,23]. In our study we found an average acetabular anteversion angle of 24.24 degrees, similar to reports in the literature.
In patients with high hip dislocation, the pelvic bones on the dislocated side are smaller and the acetabulum walls are thinner than those on the normal side [13,23]. The acetabular length, height, width, and depth of DDH hips were shown to be substantially smaller than those of normal persons when compared to those with Crowe type 4 CHD [23]. Similar to previous reports, we found that in dislocated hips, the anterior-posterior diameter, anterior lip and posterior lip thickness, and depth of the dislocated acetabulum were smaller and thinner when compared to those of the normal side. When comparing the normal side to the dislocated side, the largest anatomic defect was observed in the posterior lip thickness.
Inappropriate application of the acetabular component during THA is complicated by acetabulum variations in terms of both volume and bone structure [11,14,20,23,24]. A study comparing Crowe type 4 DDH to normal people discovered that normal hip volume was more than four times that of those with DDH [23]. The volume of the acetabulum of the normal side was found to be 2.3 times that of the dislocated side in our study. This considerable difference highlights the importance of a reduced hip joint in acetabulum volumetric development and hence the forces transferred to the acetabulum.
Our research has some limitations. Our study included a relatively small number of patients. It should be noted, however, that adult patients with a high dislocation on one side (Hartoflakidis classification C) and a normal side on the other side are quite rare. The study’s most notable aspect is that it is the first extensive research of its kind undertaken in our country. The study can be advanced in the future by increasing the number of patients, adding subgroups, adding other systemic disease parameters, and including different angles and ratios.
Conclusion
Changes in both the dislocated and normal sides were revealed in patients with unilateral high DDH, and the measures differed significantly. Since the normal hips of the patients in our study differed from the typical hip values in the literature, it was assumed that the other hip joints of the patients with DDH in one hip should be addressed with caution.
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
The authors declare no conflict of interest.
References
1. Committee on Quality Improvement. Clinical practice guideline: early detection of DDH of the hip. Pediatrics. 2000; 105(4):896–905.
2. Vaquero-Picado A, González-Morán G, Garay EG, Moraleda L. Developmental dysplasia of the hip: update of management. EFORT Open Rev. 2019; 4(9): 548-56.
3. Crowe JF, Mani VJ, Ranawat CS. Total hip replacement in congenital dislocation and dysplasia of the hip. J Bone Joint Surg, 1979; 61-A:15-23.
4. Hartofilakidis G, Stamos K, Karachalios T, Ioannidis TT, Zacharakis N. Congenital hip disease in adults. J Bone Joint Surg, 1996; 78-A(5):683-92.
5. 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.
6. Ganz R, editor. Overview on Developmental Dysplasia of the Hip. Modern Hip Preservation: New Insights In Pathophysiology And Surgical Treatment. Switzerland: Springer; 2022.p.23-36.
7. Sağlam N, Şener N, Beksa B, Tüzün ÜR. Total hip arthroplasty and problems encountered in patients with high-riding developmental dysplasia of the hip. Acta Orthop Traumatol Turc. 2002;36(3): 187-94.
8. Yang S, Q Cui. Total hip arthroplasty in developmental dysplasia of the hip: Review of anatomy, techniques and outcomes. World J Orthop, 2012; 3(5): 42-8.
9. Köken M, Güçlü B, Çetin İ. Long-term results of total hip arthroplasty with transverse subtrochanteric shortening osteotomy in developmental high dislocation of the hip. Acta Orthop. Belg. 2020;86(Suppl.3) 77-82.
10. Stem ES, O’connor MI, Kransdorf MJ, Crook J. Computed tomography analysis of acetabular anteversion and abduction. Skeletal Radiol. 2006; 35(6):385-9.
11. Altıntaş F, Gökçe A, Güven M, İnan M. Analyzing acetabular deficiency by computed tomography in osteoarthritis after Crowe type 2 developmental dysplasia of the hip. Jt Dis Relat Surg, 2009; 20(3):127-30.
12. Yang Y, Liao W, Yi W, Jiang H, Fu G, Ma Y, et al. Three-dimensional morphological study of the proximal femur in Crowe type IV developmental dysplasia of the hip. J Orthop Surg Res. 2021; 16(1):621.
13. Sugano N, Noble PC, Kamaric E, Salama JK, Ochi T, Tullos HS. The morphology of the femur in developmental dysplasia of the hip. J Bone Joint Surg. 1998; 80(4): 711-9.
14. Akiyama M, Nakashima Y, Fuji M, Sato T, Yamamoto T, Mawatari T, et al. Femoral anteversion is corelated with acetabular version and coverage in Asian women with anterior and global deficient subgroups of hip dysplasia: a CT study. Skeletal Radiol, 2012;41(11):1411-8.
15. Argenson JN, Ryembault E, Flecher X, Brassart N, Parratte S, Aubaniac JM. Three- dimensional anatomy of the hip in osteoarthritis after developmental dysplasia. J Bone Joint Surg. 2005; 87(9):1192-6.
16. Paluska SA. An overview of hip injuries in running. Sports Med. 2005;35(11): 991-1014.
17. Li Y, Lin J, Zhang J, Li J, Yao X, Zhuang H, et al. Significance of proximal femoral computed tomography scanning in the prediction of femoral prosthesis before total hip arthroplasty. Eur J Orthop Surg Traumatol. 2013;23(1):67-72.
18. Hartofilakidis G, Stamos K, Loannidis T. Low friction arthroplasty for old untreated congenital dislocation of the hip. J Bone Joint Surg. 1988;70-B:182-6.
19. Liu S, Zuo J, Li Z, Yang Y, Liu T, Xiao J, et al. Study of three-dimensional morphology of the proximal femur in developmental adult dysplasia of the hip suggests that the on-shelf modular prosthesis may not be an ideal choice for patients with Crowe type IV hips. Int Orthop. 2017; 41(4):707-13.
20. Perreira AC, Hunter JC Laird T, Jamali AA. Multilevel measurement of Acetabular version using 3-D CT-generated models: implications for hip preservation surgery. Clin Orthop. 2011; 469(2):552-61.
21. Murphy SB, Kijewski PK, Millis MB, Harless A. Acetabular dysplasia in the adolescent and young adult. Clin Orthop. 1990; 261:214-23.
22. Maruyama M, Feinberg JR, CapelloWN, D’Antonio JA. The Frank Stinchfield award: morphologic features of the acetabulum and femur: anteversion angle and implant positioning. Clin Orthop Relat Res. 2001; 393:52-65.
23. Yang Y, Ma Y, Li Q, Lin B, Dong H, Zheng Q. Three-dimensional morphological analysis of true acetabulum in Crowe type IV hip dysplasia via standard-sized cup-simulated implantation. Quant Imaging Med Surg. 2022;12(5):2904-16.
24. Wang Z, Li H, Zhou Y, Deng W. Three-dimensional femoral morphology in Hartofilakidis type C developmental dysplastic hips and the implications for total hip arthroplasty. Int Orthop. 2020;44(10):1935-42.
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Ahmet Atilla Abdioğlu, Servet Kerimoğlu, Ali Küpeli, Polat Koşucu. Comparison of the results of computerized tomography of the hips in adult patients with unilateral high hip dislocation. Ann Clin Anal Med 2023;14(8):753 -758
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Evaluation of the effect of COVID-19 on static balance in healthy young individuals
Gamze Taşkın Şenol, İbrahim Kürtül, Abdullah Ray, Gülçin Ahmetoğlu
Department of Anatomy, Faculty of Medicine, Bolu Abant Izzet Baysal University, Bolu, Turkey
DOI: 10.4328/ACAM.21782 Received: 2023-06-07 Accepted: 2023-07-17 Published Online: 2023-07-21 Printed: 2023-08-01 Ann Clin Anal Med 2023;14(8):759-762
Corresponding Author: Gamze Taşkın Şenol, Department of Anatomy, Faculty of Medicine, Bolu Abant Izzet Baysal University, 14030, Bolu, Turkey. E-mail: rumeysagamzetaskin@ibu.edu.tr P: +90 537 740 76 40 Corresponding Author ORCID ID: https://orcid.org/0000-0001-5587-1055
This study was approved by the Clinical Research Ethics Committee of Bolu Abant Izzet Baysal University (Date: 2022-09-06, No: 2022/179)
Aim: It is known that COVID-19 infection has various physiological effects. And, it also has negative effects on the balance. This study focused on evaluating the static balance of healthy individuals who either had or did not have a history of COVID-19.
Material and Methods: The study included 30 individuals who were previously diagnosed with COVID-19 infection (positive PCR test), who recovered later on, and 30 individuals as a control group. After the dominant foot of both groups was determined, the flamingo balance test was used to evaluate static balance, and Dizziness Handicap Inventory (DHI) was applied to the group that had a COVID-19 infection history.
Results: A significant difference was found between dominant foot balance and non-dominant foot balance in individuals who had COVID-19 and in the control group.
Discussion: The severity of recent cases of COVID-19 disease that affect the balance system has risen significantly. This study showed that individuals with COVID-19 have problems with static balance compared to those without COVID-19. In our estimation, post-recovery rehabilitation programs for people who have had COVID-19 should include balancing exercises.
Keywords: COVID-19, Static Balance, Dizziness Handicap Inventory, Flamingo Balance Test, Vestibular System
Introduction
COVID-19 disease emerged in China in December 2019. The most common symptoms of COVID-19, which initially causes respiratory function disorders were fever, cough, loss of taste and/or smell [20]. Recent studies have revealed the fact that it possesses certain neurological effects on the nervous and muscular systems [19, 20]. Yet, it has not been fully clarified what kind of an effect this disease has on the peripheral and central vestibular system [19, 25].
Static balance is the ability to maintain posture swing with minimal movement on a stable support surface. Obtaining and maintaining optimum posture basically occurs through the integrity of visual, somatosensory and vestibular information [2]. The vestibular organ in the membranous labyrinth and the vestibular nuclei in the medulla oblongata and the pathways between these structures function as the vestibular system. Utricle and saccule, which are also known as otolith organs in this system, position the head according to the posture of the body and thus maintain static balance [11].
Since the disease shows its first and main effects on the respiratory system, studies conducted in the literature have focused primarily on it. Although the pathophysiology of its effect on the auditory and vestibular system is not fully known, there have been accumulating reports indicating its negative effect on balance [12, 16]. Likewise, this study aims to document the effects of the COVID-19 disease on static balance in healthy young individuals by interpreting the results of DHI.
Material and Methods
The study was conducted on the students of the Faculty of Medicine. The study was approved by Bolu Abant Izzet Baysal University Clinical Research Ethics Committee (Decision Date: 06.09.2022, Decision Number: 2022/179). After signing the informed consent form, 30 (15 females, 15 males) individuals between the ages of 18 and 22 who had been diagnosed with COVID-19 with a positive PCR (Polymerase Chain Reaction) test and 30 (15 females, 15 males) individuals between the ages of 18 and 22 with a negative PCR test for COVID-19 were included in the study.
Inclusion criteria were age between 18 and 22, having COVID-19 positive diagnosis with PCR test (study group), having negative COVID-19 diagnosis with PCR test (control group), no hearing loss or a history of ear surgery, no history of balance disorder or a disease of the vestibular system, no using medication affecting the central nervous system.
With reference to Turkish validity and reliability study [1], DHI with 25 questions was administered to the group whose PCR test results were positive to evaluate the effects of dizziness on the participants and to find out balance problems. Dizziness Handicap Inventory (DHI) is among the useful test methods frequently used as reported in the literature [1, 10] to evaluate the complaint of dizziness and balance problems.
Possible answers to the inventory are yes (4 points), no (0 points), and sometimes (2 points). The scores have been evaluated as mild between 16 and 34; as moderate between 36 and 52; as severe when >54. High scores are interpreted as the patient’s complaint of dizziness preventing an advanced level of life.
In order to evaluate static balance, the dominant foot of individuals was determined. While determining the dominant foot, the participants were asked to hit the ball that was steady on a flat surface. The foot that the participants used first and most comfortably was noted as the dominant foot [6]. After the dominant foot was determined, the Flamingo balance test was applied to the dominant and non-dominant foot to evaluate static balance. For this test, the participants were asked to stand on a 50 cm long, 3 cm wide and 4 cm high standard balance board for a minute with their eyes open. The number of times the participants lost their balance within the predetermined time was reported, and the stopwatch was stopped each time the participants fell [6].
Statistical Analyses
Statistical analyses were conducted with Minitab® 21.2 (64-bit) program. The normality of the distribution of variables was tested with the Anderson-Darling test. Mean and standard deviation (sd) values of parametric variables and median, minimum (min.) and maximum (max.) values of non-parametric variables were calculated. Intergroup differences of non-parametric variables were tested with the non-parametric Mann- Whitney U test. p<0.05 was considered significant.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
The mean and sd values of parametric variables, median, min, and max values of non-parametric variables, and p-value of the Mann-Whitney U test, used for finding out the difference between individuals who had COVID-19 and those who did not, are shown in Table 1. BMI, balance on the dominant foot (DFB) and balance on the non-dominant foot (NDFB) were measured.
Upon the analyses conducted for DFB, the median value was found to be 4.00 in individuals who had COVID-19 and 4.00 in individuals who did not have COVID-19. A statistically significant difference was found between individuals who had COVID-19 and those who did not in the variable for which the Mann-Whitney U test was applied.
Upon the analyses conducted for NDFB, the median value was found to be 8.00 in individuals who had COVID-19 and 4.00 in individuals who did not have COVID-19. A statistically significant difference was found between individuals who had COVID-19 and those who did not in the variable for which the Mann-Whitney U test was applied. Upon the analyses conducted for DHI, the mean and standard deviation were 13.53 and 5.76 for the individuals who had COVID-19. It was predicted to be 2.16 and 0.83 for individuals who did not have COVID-19. The distribution of this variable is shown in Figure 1.
Discussion
The vestibular system is of great importance to perform tasks of locomotor movements related to balance and to ensure their orientation [22]. Postural balance and stability is a system that coordinates changes occurring spontaneously or with an external intervention by keeping the body’s center of mass constant [9]. As with other types of viruses, coronaviruses have been shown to affect the olfactory nerves by showing herpes simplex virus DNA in vestibular nerve fibers [11]. When the literature is reviewed, in addition to symptoms such as fever, headache, upper respiratory tract symptoms, muscle pain, joint pain, diarrhea, loss of taste and smell in COVID-19 patients, it has been reported that there are also symptoms affecting balance system [4, 5, 12, 15, 16]. In our study, dizziness and balance disorders have been observed in people who had COVID-19.
Recently, enough literature has accumulated on the COVID-19 disease affecting the balance system. In a case report conducted in 2020, it was reported that the PCR test of a patient who was referred to the emergency service with sudden and severe dizziness, nausea and vomiting, was positive [15]. Again, the first acute cerebellitis case evaluated in the literature related to COVID-19 reported complaints of moderate ataxia and dizziness and as a result restriction of daily activities in a 47-year-old male patient. On cerebellar examination, impaired tandem gait, large sole and ataxic gait have been reported [4]. In a COVID-19 patient who underwent eye examination at regular intervals, even approximately three weeks after the first known symptoms of COVID-19 (fever, cough, sore throat, runny nose, etc.), dizziness and nystagmus continued for a while [5]. In individuals with COVID-19, the virus affects the inner ear directly, causing the involvement of the central vestibular system and its connections, hypoxia and coagulation. It has also been reported that specific utricle and saccule disorder causes symptoms such as tingling, tremors and falling sensation in diagnosed individuals [23]. Evaluation of neurological observations in COVID-19 patients has shown that balance has decreased in these patients. In our study, balance assessment was performed with the static balance test for the dominant and non-dominant foot and also with DHI. A significant difference was found between the groups.
A study conducted on 150 children between the ages of 8 and 12 in Spain evaluated balance performances before and after the COVID-19 quarantine. It was found that postural balance in children worsened after the quarantine. It was also found in this literature that physically active children showed a statistically significant deterioration after the quarantine period compared to non-active children. As a result, a significant decrease was found in balance performance after the quarantine period and regular physical activity benefited postural control [17]. Another study performed on individuals between the ages of 20 and 40 in Iran assessed the static balance in individuals diagnosed with COVID-19, the conditions of these individuals one and three months after their recovery and in the control group. While the postural disorders in some tests were found to be higher in the third month after infection compared to the first month, no significant difference was found. A significant difference was found between the control group and patient groups in most of the tests. These findings suggest that COVID-19 disease, induces postural deviation in COVID-19 patients [18]. In our study, a separate test was not performed to evaluate postural instability, and we think that balance disorder also affects postural instability. We think that studies evaluating postural instability should be done in the future.
In a study conducted in 2021, examining the effect of prone position on oxygenation and static respiratory system compliance, and in a study conducted in 2022 researching COVID-19-related acute respiratory distress syndrome, COVID-19 was found to have effects on the vestibular system [7, 21]. In another study evaluating static and dynamic balance in healthy individuals and individuals with COVID-19, it was emphasized that balance variables affected the quality of life [13]. In research conducted on healthy individuals, no statistically significant difference was found between balance performance results on the right-left and dominant-non-dominant single foot [8, 14].
In the DFB and NDFB tests conducted to evaluate static balance in our study, a significant difference was found between the groups, which had COVID-19 and those who did not have COVID-19. DHI, which was developed in 1990 [10], is an inventory evaluating dizziness and balance disorders and is the most used inventory for this purpose.
In addition, it is thought that in DHI, the described vestibular symptoms are not specific to any disease. For this reason, we used this inventory in our study.
The first study that used DHI to evaluate the complaints of COVID-19 patients who experienced balance problems and the effects of this on quality of life was conducted in Turkey in 2021 [3]. As a result of the evaluation, the total mean score of the inventory was found as 35.90 [3]. In a study conducted in 2023 examining the effects of COVID-19 on vestibular system with DHI, 50 individuals diagnosed with COVID-19 were evaluated. As a result of the inventory conducted during the infection, while the score was found to be 16.04 (10.5-21.5), this score was found to decrease in the period after infection [25]. In a study conducted in 2022 to evaluate the effects of COVID-19 on vestibulo-ocular system with DHI, the mean score was found to be 18 [24]. In our study, while the mean score was found to be 13.53 in individuals who had COVID-19, it was 2.16 in individuals who did not have COVID-19. A mild balance disorder was found in individuals who had COVID-19. Overall, the DHI data and the results were found to be consistent with the literature.
Vestibular system functions were found to decrease in patients. Weakness in vestibular system can cause postural control disorders, causing dizziness, which in turn leads to an increased possibility of falls. For these reasons, we believe that balance exercises should be added to post-recovery rehabilitation programs for individuals who had COVID-19. It is important to prevent falls, especially in individuals with advanced age. There is also a need to conduct further studies on different age groups to focus on balance problems in COVID-19 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
The authors declare no conflict of interest.
References
1. Özer F, Özer C, Yavuz H. COVID-19 ve odyovestibüler sistem (COVID-19 and audiovestibular system). KBB ve BBC Dergisi. 2020; 28(2): 56-60.
2. Niazkar HR, Zibaee B, Nasimi A, Bahri N. The neurological manifestations of COVID-19. Neurol Sci. 2020; 41(7): 1667-71.
3. Zaubitzer L, Ludwig S, Berkemann M, Walter B, Jungbauer F, Held V, et al. The effects of COVID-10 on the vestibular system. Front Neurol. 2023; 14: 1134540. DOI: 10.3389/fneur.2023.1134540.
4. Çoban O. Denge yetisinin incelenmesi (Examination of Balance Ability). Çanakkale Onsekiz Mart Üniversitesi Spor Bilimleri Dergisi/ Çanakkale Onsekiz Mart University Journal of Sport Sciences. 2021; 4(3): 58-80.
5. Karimi-Galougahi M, Naeini AS, Raad N, Mikaniki N, Ghorbani J. Vertigo and hearing loss during the covid-19 pandemic – is there an association? Acta Otorhinolaryngol Ital. 2020; 40(6): 463-5.
6. Mao L, Jin H, Wang M, Hu Y, Chen S, He Q, et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol. 2020; 77(6): 683-90.
7. Kong Z, Wang J, Li T, Zhang Z, Jian J. 2019 Novel coronavirus pneumonia with onset of dizziness: A case report. Ann Transl Med. 2020; 8(7): 506.
8. Canbal M, Cebeci S, Duyan G, Kurtaran H, Arslan I. Baş dönmesi engellilik envanterinin Türkçe geçerlilik ve güvenilirlik çalışması (A study of reliability and validity for the Turkish version of dizziness handicap inventory). Turkish Journal of Family Medicine and Primary Care. 2016; 10(1): 19-24.
9. Jacobson GP, Newman CW. The development of the dizziness handicap inventory. Arch Otolaryngol Head Neck Surg. 1990; 116(4): 424-7.
10. Göktepe M. Futbolcularda dominant ve non-dominant ayak statik denge parametrelerinin karşılaştırılması (The comparison of dominant and non-dominant foot static balance parameters of soccer players). International Journal of Science Culture and Sport. 2016; 4(1): 260-9.
11. Peterka RJ. Sensory integration for human balance control. Handb Clin Neurol. 2018; 159(3): 27-42.
12. Horak FB. Postural orientation and equilibrium: What do we need to know about neural control of balance to prevent falls? Age Ageing. 2006; 35(2): 7-11.
13. Fadakar N, Ghaemmaghami S, Masoompour SM, Shirazi Yeganeh B, Akbari A, Hooshmandi S, et al. A first case of acute cerebellitis associated with coronavirus disease (COVID-19): A case report and literature review. Cerebellum. 2020; 19(6): 911-4.
14. García-Romo E, Blanco R, Nicholls C, Hernández-Tejero A, Fernández-de-Arévalo B. COVID-19 presenting with nystagmus. Arch Soc Esp Oftalmol (Engl Ed). 2021; 96(4): 224-6.
15. Malayala S V, Raza A. A case of COVID-19 induced vestibular neuritis. Cureus. 2020; 12(6): 1-6.
16. Silva TD da, Oliveira PM de, Dionizio JB, Santana AP de, Bahadori S, Dias ED, et al. Comparison between conventional intervention and non-immersive virtual reality in the rehabilitation of individuals in an inpatient unit for the treatment of COVID-19: A study protocol for a randomized controlled crossover trial. Front Psychol. 2021; 12: 622618. DOI: 10.3389/fpsyg.2021.622618.
17. Martínez-Córcoles V, Nieto-Gil P, Ramos-Petersen L, Ferrer-Torregrosa J. Balance performance analysis after the COVID-19 quarantine in children aged between 8 and 12 years old: Longitudinal study. Gait Posture. 2022; 94: 203-9.
18. Mehrjou F, Majlesi M. The comparison of static balance in COVID- 19 recovered patients and healthy individuals. Journal of Advanced Sport Technology. 2022; 6(1): 113-22.
19. Park J, Lee HY, Lee J, Lee SM. Effect of prone positioning on oxygenation and static respiratory system compliance in COVID-19 ARDS vs. non-COVID ARDS. Respir Res. 2021; 22(1): 1-12.
20. Grasselli G, Tonetti T, Protti A, Langer T, Girardis M, Bellani G, et al. Pathophysiology of COVID-19-associated acute respiratory distress syndrome: a multicentre prospective observational study. Lancet Respir Med. 2020; 8(12): 1201-8.
21. Lee KJ, Seo KW, An KO. Effects of the non-face-to-face learning on health-related physical fitness and balance in adolescents according to Covid-19. Exercise Science. 2021; 30(2): 229-36.
22. Greve J, Alonso A, Bordini ACPG, Camanho GL. Correlation between body mass index and postural balance. Clinics (Sao Paul). 2007; 62(6): 717-20.
23. Lin WH, Liu YF, Hsieh CCC, Lee AJY. Ankle eversion to inversion strength ratio and static balance control in the dominant and non-dominant limbs of young adults. J Sci Med Sport. 2009; 12(1): 42-9.
24. Eğilmez OK, Özçelik Korkmaz M, Güven M. Denge bozukluğu bulunan COVID-19 hastalarının baş dönmesi engellilik envanteri ile değerlendirilmesi (Evaluation of COVID-19 patients complaining of balance disorders with the dizziness handicap inventory). Sakarya Med J. 2021; 11(3): 500-6.
25. Toker ÖG, Özdemir S, Behmen MB, Hüsam H, Aksoy F. COVID-19’un vestibülooküler sistem üzerine etkileri (Effects of Covid-19 on vestibulo-ocular system). KBB-Forum. 2022; 21(4): 236-43.
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Gamze Taşkın Şenol, İbrahim Kürtül, Abdullah Ray, Gülçin Ahmetoğlu. Evaluation of the effect of COVID-19 on static balance in healthy young individuals. Ann Clin Anal Med 2023;14(8):759-762
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Comparison of pre- and post-education video laryngoscope and direct laryngoscope skills of medical school students: A manikin study
Seval Komut, Nurullah Çorakyer, Ali Kemal Erenler
Department of Emergency Medicine, Faculty of Medicine, Hitit University, Çorum, Turkey
DOI: 10.4328/ACAM.21794 Received: 2023-06-15 Accepted: 2023-07-17 Published Online: 2023-07-21 Printed: 2023-08-01 Ann Clin Anal Med 2023;14(8):763-767
Corresponding Author: Seval Komut, Department of Emergency Medicine, Faculty of Medicine, Hitit University, 19040, Çorum, Turkey. E-mail: drsevalkomut@hotmail.com P: +90 364 222 11 00 Corresponding Author ORCID ID: https://orcid.org/0000-0002-9558-4832
This study was approved by the Non-Interventional Research Ethics Committee of Hitit University (Date: 2023-02-28, No: 2023-01)
Aim: Video laryngoscope (VL) has a lot of advantages over direct laryngoscope (DL). In this study, our aim was to compare the skills of medical students with VL and DL before and after education.
Material and Methods: The 5th-grade students performed VL and DL before and after education. Success rates and timings were recorded pre- and post-education. Then, the groups were compared.
Results: A total of 104 Medical school students were involved in the study. The rates of students who were successful in video laryngoscopy pre-education were significantly higher than the rates of students who were successful in DL (61.5% vs 36.5%, respectively). The rates of students who were successful in post-education DL and VL applications were not different. The post-education completion times of DL and VL were significantly reduced when compared to pre-education completion times. There was not any statistical significance between the completion times of DL and VL after the education. Of the students, 61 (58.7%) who were unsuccessful in DL pre-education were successful post-education. The effect of education was statistically significant (p<0.001). Thirty-five (33.7%) students who were unsuccessful in VL pre-education were successful post-education. The effect of education was statistically significant (p<0.001).
Discussion: Video laryngoscope is a viable option for inexperienced users. More emphasis should be placed on this procedure within medical education.
Keywords: Direct Laryngoscopy, Video Laryngoscopy, Manikin Model, Airway Management
Introduction
Tracheal intubation is used as a common airway method when basic airway methods are insufficient. There are many studies showing that video has a better chance of success on the first try in emergency airway management [1]. Over the past 30 years, laryngoscopes have also developed in parallel with the development of technology particularly with regard to computer and fiber optic technology. Each new development in visualization builds on the development of the previous technology. Considering the good patient outcomes, it seems that video laryngoscope (VL) has been gaining popularity rapidly recently. However, the question remains related to its daily use [2]. Although VLs are available in many clinical settings, it remains unclear if their use reduces the incidence of failed tracheal intubation compared with conventional direct laryngoscopy (DL) in routine airway management [3]. Early studies of VL focused on the novice laryngoscopist or the patient predicted to be difficult to intubate by DL. However, today it is discussed that video should be used as a priority [4]. In this study, we aimed to compare the ease of use and learnability of VL and DL among medical students. In addition, in this study, we compared the success of both methods in intubation interventions performed by medical students before and after education and their preference by students.
Material and Methods
Ethical approval for the study was granted by the Non-Interventional Research Ethics Committee of Hitit University (decision no: 2023-01, dated: 28.02.2023). We conducted this study among 5th-grade students at a university hospital. The study was conducted between 01/01/2022 and 01/01/2023. A total of 140 students were involved in the study. Written consent was obtained from the students. Demographical properties, chronic diseases, perspectives on procedures were recorded. The students performed VL (McGrath®) and DL (MAC 2®) before and after education. Each education period was restricted to 15 minutes of theoretical and practical demonstration. Success rates and timings were recorded pre- and post-education. Then, the groups were compared.
Statistical analyses
Statistical analyses of the data collected in our study were conducted using the SPSS (Version 22.0, SPSS Inc., Chicago, IL, USA) software. Descriptive statistics were reported using numbers (n) and percentage (%) for categorical variables, and mean ± standard deviation (min – max) for numerical variables. Proportion comparisons between categorical variables were performed with the Chi-square test. Proportion comparisons between the categorical variables before and after the training were performed with the Mc-Nemar test. The conformity of the numerical data to the normal distribution was examined using the Shapiro-Wilk and Kolmogorov-Smirnov tests. The homogeneity of variances was evaluated with Levene’s test. Comparison of numerical data between two independent groups was performed with Student’s t-test, since parametric test assumptions were met.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
A total of 104 medical school students were involved in the study. The mean age of the students was 23.23±0.95 years (min-max: 21-26). Of these students, 34.6% (n=36) were male and 65.4% (n=68) were female; 62.5% (n=65) of the students had an ophthalmic disease; 50% (n=18) of male students and 69.1% (n=47) of female students declared an ophthalmic disease. There was no statistical significance between genders in terms of ophthalmic disease (p=0.055). Of the students, 39.4% (n=41) stated that they had received training in airway management in the past. When their experiences on devices were investigated, 69.2% (n=72) were educated in DL and 26% (n=27) were educated in VL. When students were asked: “Which method would you prefer?”, 72.1% (n=75) answered as VL and 27.9 (n=29) answered as DL. Of the male students, 69.4% (n=25) preferred VL and 30.6% (n=11) preferred DL. Of the female students, 73.5% (n=50) preferred VL and 26.5% (n=18) preferred DL. There was no statistical significance between genders in terms of method choice (p=0.659). Both individuals from two genders preferred DL.
Statistical data regarding the comparison of DL and VL procedure success pre- and post-education for DL and VL are presented in Table 1. Pre-education DL intervention was successful in 7 students on the 1st attempt, in 19 students on the 2nd attempt and in 12 students on the 3rd attempt. The overall success rate was 36.5% (n=38). Pre-education VL intervention was successful in 33 students on the 1st attempt, in 21 students on the 2nd attempt and in 10 students on the 3rd attempt. The overall success rate was 61.5% (n=64). Bar graphs show the number of students according to the seconds of successful completion of direct and video laryngoscopy before and after the training (Figure 1, 2).
The rates of students who were successful in VL pre-education were significantly higher than the rates of students who were successful in DL (p<0.001, Table 1). After the education, a total of 96 (92.3%) students successfully completed DL, 42 on the first attempt, 38 on the 2nd attempt, and 16 on the 3rd attempt. A total of 96 (92.3%) students successfully completed the post-training VL application, 57 on the 1st attempt, 29 on the 2nd attempt and 10 on the 3rd attempt. The success rates of students who were successful in post-education DL and VL applications were not statistically different (p=1.000, Table 1).
Statistical findings for the comparison of the success time of direct and VL applications by students pre- and post-education are presented in Table 2. The time to complete DL pre-education was 26.29±3.81 (21-30) on the 1st attempt, 25.68±5.62 (14-30) on the 2nd attempt, and 26.17±3.85 (20-30) on the 3rd attempt, in total of 25.95±4.71 (14-30).
The time to complete the pre-education VL application was 22.7±5.85 (11-30) on the 1st attempt, 21.95±6.83 (12-30) on the 2nd attempt, and 21.40±7.96 (5-30) on the 3rd attempt, with a total of 22.25±6.44 (5-30) times. DL completion times of students’ pre-education were significantly higher than VL completion times (p=0.003, Table 2). The time to complete the DL application post-education was 20.19±6.57 (5-30) on the 1st attempt, 19.92±7.34 (7-30) on the 2nd attempt, and 20.88±5.73 (11-30) on the 3rd attempt, with a total of 20.20±6.70 (5-30) times. The time to complete the VL application post-education
was 18.95±7.23 (6-30) on the 1st attempt, 18.76±8.39 (5-30) on the 2nd attempt, and 19.3±5.83 (8-25) on the 3rd attempt, with a total of 18.93±7.41 (5-30) times.
There was no statistical significance between the completion times of DL and VL after the education (p=0.214, Table 2). The post-education completion times of DL were significantly reduced compared to pre-education completion times (p<0.001, Table 2). The post-education completion times of VL were significantly reduced compared to pre-education completion times (p=0.004, Table 2).
In order to determine the effect of training on laryngoscopy success, the success rates pre- and post-education were compared; DL and VL results are presented in Table 3. Of the students, 61 (58.7%) who were unsuccessful in DL pre-education were successful post-education. The effect of education was statistically significant (p<0.001, Table 3). Thirty-five (33.7%) students who were unsuccessful in VL pre-education were successful in post-education. The effect of education was statistically significant (p<0.001, Table 3).
Discussion
The results of our study revealed that all students prefer VL. The overall success rate was higher with VL in both pre- and post-education groups. There was no statistical significance between the completion times of DL and VL after the education. Direct laryngoscopic completion times of students pre-education were significantly higher than VL completion times.
Since we conducted our study among students, we preferred to use an endotracheal intubation manikin to avoid any patient harm. In another manikin simulator study, 28 anesthetists and 28 anesthesia nurses performed a tracheal intubation with VL and DL on a manikin simulator during ongoing chest compressions by a mechanical resuscitation device. First-pass success rate was 100% in the video laryngoscopy group and 67.8% in the direct laryngoscopy group. The median time for intubation was 27.5 seconds in the VL group and 30.0 seconds in the DL group. Similar to our results, the manikin study on tracheal intubation during ongoing chest compressions demonstrated that VL had a higher first-pass success rate and shorter time to successful intubation compared to DL [1].
In a meta-analysis comparing VL and DL, 64 studies with 7044 adult participants were included. Video laryngoscope was found to be associated with significantly fewer laryngeal or airway traumas [5].
Video laryngoscopes may reduce the number of failed intubations, particularly among patients presenting with a difficult airway. They concluded that VL may improve the glottic view and may reduce laryngeal/airway trauma [6].
Our study has shown that video is easier to apply and preferred by students in first attempts and in uneducated individuals.
In a study, 150 patients were subdivided into two groups according to the intubation method: the VL group and the DL group. The duration for the vocal cord appearance was significantly shorter in the VL group than in the DL group. Also, the beginning of intubation to full ventilation of the lungs was significantly shorter in the VL group than in the DL group [7]. Another multi-centered study with 2092 adult patients demonstrates that using VL compared with DL improved first-pass tracheal intubation success in patients having elective surgery. As a result, the authors recommended practitioners to use this device as their first choice for tracheal intubation [3]. In our study, we revealed that the success rate of the VL is higher, although it was not determined after the training between video and the other in terms of duration in post-education trials.
In a meta-analysis, first pass success was higher in VL than in DL. Clinical trials showed a shorter time to achieve successful intubation with the VL. Video laryngoscope was also superior in terms of avoiding cessation of chest compressions. In concordance with our study, it was concluded that when clinicians with limited intubation experience have to perform tracheal intubation during advanced life support, the use of the VL improved intubation. It was also concluded that CPR performance improved with VL compared to DL [8].
Despite these advantages, however, the success of VL in the congenital difficult airways is controversial. In a study in which Pierre Robin Syndrome was created, VL was less successful compared to DL [9]. Additionally, a study with paramedics reported that VL caused longer endotracheal intubation time. The intubation times performed by paramedics in UESCOPE® and ProVu® were significantly longer than those with the I-view and Macintosh laryngoscopes [10]. Video laryngoscope also helps reduce the number of intubation attempts. A study with 94 participants revealed that the success rate of VL during the first attempt was significantly higher. View of the vocal cords was significantly better, and perceived subjective safety was increased using VL [11]. In a study, anesthesia residents performed VL and DL on pediatric patients. A total of 105 intubations with the VL and 106 DL were performed by the residents. The success rate on the first attempt with the VL was 81%, and the success rate on the first attempt within a given time limit of 30 s was 45%, which was lower than with DL (93% and 77%). However, intubation with DL was significantly faster. The authors concluded that VL took longer time to intubate compared to DL. As a result of this pediatric manikin model, they did not recommend VL for learning pediatric intubation by residents [12]. Despite the mentioned disadvantages of VL in some studies, it also has superiorities to DL such as allowing a distance between the patient and the physician [13]. In the pandemic era, this phenomenon becomes even more important. As an observational result of our study, we determined that participants could achieve advanced airway with VL from a distance. In the DL group, contrarily, participants needed to get closer to the patient for a better view, which may cause overexposure to potential viral spread.
Our study revealed that VL is more advantageous for uneducated and inexperienced performers. However, more solid data are needed to say that it should completely replace DL. Education on DL to medical students should continue, but their experience with video should also be increased. Video laryngoscope should be considered not only as a good alternative but also as an essential tool for advanced airway management.
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
The authors declare no conflict of interest.
References
1. Steffen R, Hischier S, Roten FM, Huber M, Knapp J. Airway management during ongoing chest compressions–direct vs. video laryngoscopy. A randomised manikin study. Plos One. 2023;18(2):e0281186.
2. King D, Blair A. The Evolution of Equipment and Technology for Visualising the Larynx and Airway. Adv Exp Med Biol. 2023;1406:61-78.
3. Kriege M, Noppens RR, Turkstra T, Payne S, Kunitz O, Tzanova I, et al. A multicentre randomised controlled trial of the McGrath™ Mac videolaryngoscope versus conventional laryngoscopy. Anaesthesia. 2023;78(6):722-9.
4. Aziz MF, Berkow L. Pro-Con Debate: Videolaryngoscopy Should Be Standard of Care for Tracheal Intubation. Anesth Analg. 2023;136(4):683-8.
5. Hansel J, Rogers AM, Lewis SR, Cook TM, Smith AF. Videolaryngoscopy versus direct laryngoscopy for adults undergoing tracheal intubation: a Cochrane systematic review and meta-analysis update. Br J Anaesth. 2022;129(4):612-3
6. Lewis SR, Butler AR, Parker J, Cook TM, Schofield-Robinson OJ, Smith AF. Videolaryngoscopy versus direct laryngoscopy for adult patients requiring tracheal intubation: a Cochrane Systematic Review. Br J Anaesth. 2017;119(3):369-83.
7. Tör IH, Ural SG. Airway management during the COVID-19 pandemic: macintosh laryngoscopy vs. video laryngoscopy. Eur Rev Med Pharmacol Sci. 2023;27(6):2679-85.
8. van Schuppen H, Wojciechowicz K, Hollmann MW, Preckel B. Tracheal Intubation during Advanced Life Support Using Direct Laryngoscopy versus Glidescope® Videolaryngoscopy by Clinicians with Limited Intubation Experience: A Systematic Review and Meta-Analysis. J Clin Med. 2022;11(21):6291.
9. Shaylor R, Weiniger CF, Rachman E, Sela Y, Kohn A, Lahat S, et al. A Prospective Observational Crossover Study Comparing Intubation by Pediatric Residents Using Video Laryngoscopy and Direct Laryngoscopy on a Pierre Robin Simulation Manikin. Pediatr Emerg Care. 2023;39(3):159-61.
10. Kluj P, Fedorczak A, Fedorczak M, Gaszyński T, Kułak C, Wasilewski M, et al. Comparison of Three Video Laryngoscopes and Direct Laryngoscopy for Emergency Endotracheal Intubation While Wearing PPE-AGP: A Randomized, Crossover, Simulation Trial. Healthcare. 2023; 11(6):884.
11. Salis-Soglio NV, Hummler H, Schwarz S, Mendler MR. Success rate and duration of orotracheal intubation of premature infants by healthcare providers with different levels of experience using a video laryngoscope as compared to direct laryngoscopy in a simulation-based setting. Front Pediatr. 2022;10:1031847.
12. Epp K, Zimmermann S, Wittenmeier E, Kriege M, Dette F, Schmidtmann I, et al. Video Laryngoscopy Using King Vision™ aBlade™ and Direct Laryngoscopy in Paediatric Airway Management: A Randomized Controlled Study about Device Learning by Anaesthesia Residents. J Clinl Med. 2022; 11(19):5676.
13. Erenler AK, Komut S, Çapraz M, Baydin A. Airway management in patients with COVID-19: an updated guide for clinicians in the emergency department. Reviews and Research in Medical Microbiology. 2022;33(4): 248-52.
Download attachments: 10.4328.ACAM.21794
Seval Komut, Nurullah Çorakyer, Ali Kemal Erenler. Comparison of pre- and post-education video laryngoscope and direct laryngoscope skills of medical school students: A manikin study. Ann Clin Anal Med 2023;14(8):763-767
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