June 2021
A prospective medico-legal study of physical and sexual child abuse in Alexandria governorate, Egypt
Zahraa K. Sobh 1, Heba M. Menessi 2
1 Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, University of Alexandria, 2 Violence Against Women and Children Unit in the Medicolegal Department of Ministry of Justice at Alexandria, Ministry of Justice, Egypt
DOI: 10.4328/ACAM.20353 Received: 2020-09-24 Accepted: 2020-10-29 Published Online: 2020-11-10 Printed: 2021-06-01 Ann Clin Anal Med 2021;12(6):592-597
Corresponding Author: Zahraa K. Sobh, Forensic Medicine and Clinical Toxicology, Faculty of Medicine, University of Alexandria, Champollion street, Al Attarin, Alexandria, Egypt. E-mail: z_khalifa2017@yahoo.com / zahraa.sobh@alexmed.edu.eg P: +2 01020744739 Corresponding Author ORCID ID: https://orcid.org/0000-0002-7836-9639
Aim: Child maltreatment is one of the most prevailing violations of human rights. Limited knowledge is available regarding child abuse in Arab countries includ- ing Egypt. This article highlights the medicolegal aspects of physical and sexual abuse against children under the age of 12 years in Alexandria governorate, Egypt.
Material and Methods: This is a prospective cross-sectional study that included all children under 12 years of age with reported abuse in Alexandria over a six-month period. All children underwent a general examination followed by an examination of genital and anal regions using colposcopy.
Results: The study included a total of 67 children with suspected abuse; 18% physical abuse and 82% sexual abuse. Males constituted 71.64% of the children. All children with suspected intra-familial physical violence were proved to have non-accidental traumas. Delinquents had accidental and self-inflicted injuries. Anal, vaginal, and oral penetration represented 74.54% 12.72%.and 12.72% of children with suspected sexual assaults, respectively. Medicolegal evidence was present in 29% of the children with suspected sexual abuse and all children with positive medicolegal findings were sodomy victims.
Discussion: Reported child abuse in the Alexandria governorate is the tip of the ice burg. Children’s homes are the most dangerous places in which violence took place. Intra-familial physical abuse against young children is socially acceptable that is why only serious traumas were notified. Accidental and self-inflicted injuries were reported among delinquents. Medicolegal assessment of physical trauma usually yields firm medicolegal opinion. Sexual child abuse was more reported than physical abuse; however, sexual abuse is difficult to be proved.
Keywords: Physical abuse; Sexual abuse; Child maltreatment; Alexandria; Egypt
Introduction
Child abuse and neglect (CAN) or child maltreatment is one of the most prevailing violations of human rights that endanger children worldwide. The young children are ideal victims; they could not protect themselves because of limited mental and physical development. Besides, often abuse occurs in private places where the perpetrators are children’s caregivers. The inability of the abused children to self-report violence exposes them to further assaults [1, 2].
Child abuse is a grave offense that often goes unrecognized until serious or fatal sequences has occurred. Thus, child maltreatment is the third leading cause of death in children between one and four years of age, and nearly a quarter of murdered children have been examined by physicians within a month of their death [3]. Other than the deadly outcome of child abuse, devastating short and long-term consequences might occur. Long-term sequelae of abuse might manifest as psychological disorders such as post-traumatic stress disorder (PTSD), depression, psychosis, drug dependence, and criminal behavior [4].
Child maltreatment is categorized into four major types as follows: physical abuse, sexual abuse, psychological maltreatment, and neglect. Medicolegal assessment is requested for children with suspected physical and sexual abuse to elucidate objective findings [5]. The evaluation of children with physical and sexual assaults is a challenging task. The injustice of the wrongful conviction of innocents will subject them to exaggerated penalties. On the other hand, misdiagnosis of maltreatment exposes the child to further victimization [6]. Physical child abuse is the deliberate infliction of physical trauma to the child with a high likelihood of harm. Physical abuse is suspected upon the presence of multiple injuries in various body areas at different healing stages. Non-accidental injuries are commonly discovered in protected areas, such as the abdomen, back, upper arms, and buttocks [6].
Sexual child abuse is any sexual activity with a child for the sexual gratification of an older adolescent or adult. The nature of sexual violence toward children is greatly variable and not usually involved physical contact. Sexual contact of the victim could be either libidinous acts or penetrative sexual intercourse [7].
The pattern of violence against children differs from one country to another. Also, the demographic characteristics of the victims may exhibit variations between different societies. Limited knowledge is available regarding child abuse in Arab countries including Egypt [5-7].
Providing informative data regarding child abuse is the first step for designing effective protective programs. Thus, the present study aimed to describe the pattern of violence against children under the age of 12 years with suspected physical and sexual abuse in Alexandria governorate, Egypt. The contribution of forensic examination in the verification of child abuse was studied as well.
Material and Methods
The present work is a prospective cross-sectional study that included all children under the age of 12 years with suspected physical and sexual assaults referred to the Violence against
Women and Children Unit in Alexandria for medicolegal evaluation for 6 months (from the 1 August 2018 to the end of January 2019). The study complied with codes of Egyptian Forensic Medicine Authority (EFMA) and Ethics Committee of the Faculty of Medicine, Alexandria University (IRB Number: 00012098, FWA Number: 0018699, Approval serial number: 0304059). An incent of all children and informed consent of their guardians were obtained.
Humanitarian aspects were considered during the medicolegal management of children with suspected abuse. The children were interviewed regarding the circumstances of the assault, such as the manner of violence, number, of the suspect(s) and his/her relationship to the child, venue of the assault, frequency of assault (s), and the time passed since the last incidence. Before the examination, a simple explanation of the required examination positions and procedures was provided. [8]. •Medicolegal examination:
1-General body examination:
All children were comprehensively examined for general signs of violence. Any visible injuries were documented appropriately [8].
2-Examination of the anal region and genitalia using colposcopy:
A colposcope provides clear and magnified photos of the anal region and genitalia and the captured images are considered as legal documentation [8].
The anal region was examined in the knee-chest and left lateral position for the presence of any injuries. Also, anal sphincter tone and reflex were assessed. Anal swabs were obtained if the child presented within three days following the last suspected penile-anal penetration [9].
Male genitalia were properly inspected for the presence of recent or old injuries. All relevant injuries were documented. In females, a careful genital examination was conducted in lithotomy and knee-chest positions. The perineum, pubic area, labia majora, labia minora, clitoris, posterior fourchette, fossa navicularis and hymen were inspected for any recent or old injuries. The vaginal swabs were obtained from the girls who presented within seven days following suspected vaginal penetration [9].
•Medicolegal findings:
1-Positive findings: Physical child abuse is confirmed by the presence of recent or old injuries that are consistent with the given history. Nevertheless, sexual child abuse is proved by the presence of any relevant injuries concerning the suspected sexual act. Also, the detection of spermatozoa is solid evidence that denotes the occurrence of a sexual offense [10]. 2-Negative findings: The lack of any relevant evidence concerning a suspected assault [10].
Statistical analysis:
Data were fed to the computer and analyzed using IBM SPSS software package version 20.0. The Kolmogorov-Smirnov test was used to verify the normality of the distribution of variables. Student t-test was used to compare two groups for normally distributed quantitative variables, while ANOVA was used for comparing between more than two groups and followed by the Post Hoc test for pairwise comparison. Spearman coefficient was used to correlate between quantitative variables.
Results
A total of 67 children under the age of 12 years were medicolegally examined for 6 months. Nearly three-quarters (71.64%) of the children with suspected abuse were males. Physical abuse was suspected in 12 children (18%), ranging from 3 to 11 years, with a mean age of 7.5 ± 2.94 years. Whereas, sexual abuse was suspected in 55 children (82%), ranging from 2.5 to 11.75 years, with a mean age of 8.2 ± 2.4year. There was no significant difference in the mean age of children with suspected physical and sexual abuse (t=0.879, p=0.383). Figure 1 illustrates the manners of physical and sexual assaults against children included in the current study.
A- Physical child abuse: (Table 1)
Physical assaults were attributed to one person in all cases. Three-quarters of the children were presented within three days following the last physical aggression. Half of the physical abuse of children was claimed to occur in children’s homes. The perpetrators were fathers’ wives, mothers’ husbands, and a father. Also, the physical violence was alleged to occur in custody against delinquents either during arrest or detention. Medicolegal findings:
All children with suspected physical abuse (n=12) had significant injuries, as follows:
• All children with suspected intra-familial violence (n=6) were proved to have non-accidental traumas. Four children had various injuries (dry burns, abrasions, contusions, cut wounds, bites) in different anatomical areas at different ages, and two children had massive dry burns. Thus, in the current study, child’ home was proved to be the place for all proven cases of physical abuse where the assailant was one of the family members.
• Four delinquents had fabricated wounds. These self-inflicted injuries were superficial parallel abrasions and cuts in accessible areas in the head or forearms.
• Two delinquents were accidentally injured as they resist police during arrest; one had elbow dislocation and the other had blunt head trauma.
B- Sexual child abuse:
Table 2 revealed that anal penetration was the manner of sexual assault of nearly three-quarters (74.54%) of the children with suspected sexual abuse. Vaginal and oral penetration, each was suspected in 12.72% of the cases. The suspected anal penetration was subdivided according to the penetrating part. Penetration by male organ (sodomy or penile-anal penetration) was suspected in 75.60% of children (n=31) with suspected anal penetration, whereas, in the rest of the cases fingers, pencils, and rulers were the penetrating objects.
Oral intercourse was suspected in younger children aged between 2.5 to 9 years, whereas vaginal intercourse (rape) was suspected in girls between 3.3 and 11.8 years. The anal penetration was suspected in older children aged between 6 and 12 years. The mean ages of the children with suspected oral, vaginal, and anal penetration were 6 ± 2.7, 7.5 ± 3.8, and 8.7 ± 1.8 years respectively. There was a significant difference between the mean ages of the children and three manners of penetrative sexual assaults (p= 0.012).
Regarding anal penetration, no significant difference was elucidated between the mean ages of the children and suspected penile-anal penetration (n=31) and other forms of anal penetration (n=10), the mean ages were 8.8 ± 1.8 and 8.6 ± 1.8 years respectively (p=0.977).
Considering circumstances of sexual offenses among studied children, Table 3 elucidated that sexual assaults were attributed to one person in nearly three-quarters (74.54%) of the cases. Nearly half (43.63%) of the cases were examined within three days from the last assault. The kindergartens and schools represented the commonest place for suspected sexual offenses (38.18%), where the place of the assault was the bathrooms in 18 cases, and the gardens in three cases. In such situations, the suspected persons were doormen in nine cases, clean workers in seven cases, and older students in five cases.
Medico-legal findings:
During the general examination, no injuries could be detected in 88% of the children with suspected sexual assaults. The abrasions were the only noticed injuries in 12 % of children. By local examination, the medicolegal evidence was present in less than one-third (29%) of the children with suspected sexual abuse. All cases with positive medicolegal findings were suspected of penile-anal penetration (sodomy). The evidence of penile-anal penetration was present in 16 children out of 31 children with suspected sodomy. The children with positive anal findings were as follows: seven cases with recent fissures; six cases with old anal fissures; two cases with recent anal fissures along with a positive anal swab and a case with an only positive anal swab. Diminished anal reflex and sphincter tone was present along with recent and old anal fissures (n= 15). The circumstances of sexual assaults with positive medicolegal evidence are demonstrated in Table 3. The child home was proved to be the commonest place for sexual violence (43.75%) and could be described as intra-familial sexual abuse, whereas, 37.50% of sexual assaults took place in accused homes. Two children were victimized by older students in educational institutes.
Generally, the mean age of the children with evidence for sexual assaults was significantly higher (9.6 ± 1.9) than that of those with negative findings (7.6 ± 2.3) (t= 3.220, p= 0.002). Also, there was a significant correlation between the age of the children and the positivity of the findings (r=0.410, p=0.002). Regarding sodomy, the mean age of cases with evidence of sexual offenses was significantly higher (9.5 ± 1.9) than that of those with no findings (7.9 ± 1.3) (t= 2.699, p= 0.011). Also, there was a significant correlation between the age of sodomy victims and the positivity of the findings (r=0.451, p=0.011).
Discussion
In the Arab world, child abuse is a silent hazard that might result in serious consequences [11]. In Egypt, a medicolegal examination of the children is often restricted to notified criminal cases. Public prosecution refers to those with reported physical or sexual abuse to forensic investigation. [12]. Therefore, for 6 months, only 67 children under the age of 12 years were examined in Alexandria medicolegal department to verify their exposure to violence. Alexandria is the second- largest city in Egypt, with a population of more than 5.200 million [12]. Thus, the notified child abuse in the present work in comparison to population size is the tip of the ice burg. Similarly, under-reporting of child maltreatment was mentioned by studies conducted in other Egyptian governorates such as
Cairo [13], Suez Canal [7], and El Fayoum [14]. Similarly, there was a defective reporting of child abuse in other Arab countries such as the Kingdom of Saudi Arabia (KSA) [2,6], United Arab Emirates (UAE) [15], Bahrain [16], Yemen [17], and Jordan [5]. This is could be attributed to the inability of the children to disclose their victimization due to their immaturity along with fear of consequences. Also, the close relationship between the children and their offenders exposes them to repeated unreported abuse [6,17].
The present work is concerned about violence against children under 12 years of age. Studies by Modelli et al, (2012) [18] and Silva and Barroso-Junior (2016) [19] are similarly concerned about the medicolegal investigation of maltreatment of children under the age of 12 years, because the age of 12 years is the average pubertal onset. Young children are more vulnerable to abuse than older children as a result of their marked physical and mental immaturity. Also, little children are unlikely to be engaged in willful sexual activities because of the non-development of natural sexual drive [18,19].
The reported sexual abuse outnumbered physical abuse cases in the current study that is in concordance with Al Madani et al. (2012) [6] and Al-Zayed et al. (2020) [2]. This points to serious concern about sexual violence as honor-related crimes in oriental societies. Whereas, physical violence against children is socially acceptable, that is often considered a corrective tool. Besides, community norms consider parents’ behavior toward their children as a family’s private issue, into which outsiders are not allowed to interfere [2, 6].
In the present work, the males constituted nearly three-quarters (71.64%) of the children with suspected child maltreatment. Over-representation of males is also mentioned by Al-Zayed et al. (2020) [2] who stated that 71% of notified child maltreatment cases in Riyadh, KSA were males. The males’ overactivity might trigger their exposure to physical violence. Besides, sodomy is the commonest sexual assault in pre-pubertal victims that explain their vulnerability to sexual abuse more than females. On the other hand, males represented 58%, 43.7%, and 46.1% of abuse victims in Bahrain [16], Dammam (KSA) [6], and Suez Canal, Egypt [7], respectively that could be attributed to samples-related variations.
Assessment of physical injuries in the current study yielded a firm medicolegal opinion in all children with suspected physical violence. Six children had abusive injures in the form of dry burns, abrasions, contusions, cut wounds, and bites in different body areas. Similar non-accidental injuries in the children were described by Al-Mahroos and Al-Amer (2011) [16] and El- Banna (2014) [20]. All children with suspected intra-familial violence were proved to have non-accidental injuries where the children’s homes were the place of physical abuse that is in agreement with Ghanem et al (2018) [21].
Regarding delinquents, two were accidentally injured during police arrest and four had fabricated wounds in the form of trivial parallel abrasions and cuts in the head and upper limbs. Self-inflicted injuries by juvenile offenders were also described by McKinnon et al. (2016) [22].
Considering children with suspected sexual assaults, the lack of signs of resistance in the majority of these children might reflect the close trustable relationship between the child and the offender who controlled the child with means other than physical violence [23]. Similarly, Modelli et al. (2012) [18] and Walker (2015) [24] reported an absence of defense injuries in a large percentage of sexually abused children.
The medicolegal evidence of penetrative sexual assault was present in less than one-third of the children that is in concordance with Walker (2015) [24] and Al-Zayed et al. (2020) [2] who did not find conclusive evidence in a large percentage of the children with suspected sexual assaults. The false allegations are unlikely in young children [25]. Many reasons could explain the high negativity of medicolegal evidence in sexual child abuse. Children might not understand what happened exactly and they could describe inter-labial (vulvar) or inter-gluteal penetration as vaginal or anal intercourse. Also, the perpetrator could be concerned to obtain sexual gratification with minimal force. Besides, the delayed presentation allows the healing of injuries and loss of evidence [23,24].
The mean age of the children with evidence of sexual assaults, in the current work, was significantly higher than that of those with negative findings. Also, a significant correlation was demonstrated between the age of the children and the positivity of the findings that is in agreement with Silva and Barroso-Junior (2016) [19]. The younger children could explain external friction or penetration trails as actual anal or vaginal penetration. Therefore, penetration reported by older children could be more likely associated with actual penetration [10,19]. The inherited challenge in the evaluation of sexual assaults is a considerable degree of uncertainty. Wide-range of normal variations and pathological conditions in genital and anal regions could simulate genuine injuries. Therefore, great caution should be taken during the interpretation of positive findings concerning sexual assaults [12].
Although the present study was restricted to the children referred for forensic investigation, the current findings serve as a valuable epidemiological reference dataset that represents a large population sector. The current results will be useful to further monitor the trend of child abuse.
Conclusions
This study concluded that the maltreatment of a young child is extremely under-reported in Alexandria. Abuse is often committed by close persons that expose the child to endless cycles of violence. Physical abuse is socially accepted in oriental societies. Thus, only serious traumas and injuries of medicolegal aspects were notified to authorities. Usually, the evaluation of physical abuse results in firm medicolegal opinions. Nevertheless, the assessment of sexual abuse among young children is a challenging and cautious interpretation of findings is mandatory.
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.
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Misuse of inhaler devices and associated factors in chronic obstructive pulmonary disease patients
Serhat Seker, Suat Konuk, Emine Ozsari, Tuncer Tug
Department of Chest diseases, Bolu Abant İzzet Baysal University, Bolu, Turkey
DOI: 10.4328/ACAM.20354 Received: 2020-10-06 Accepted: 2020-12-09 Published Online: 2020-12-23 Printed: 2021-06-01 Ann Clin Anal Med 2021;12(6):598-602
Corresponding Author: Suat Konuk, Department of Chest Diseases, Bolu Abant Izzet Baysal University, Bolu 14030, Turkey. E-mail: suatkonukk@windowslive.com P: +90 507 3410126 Corresponding Author ORCID ID: https://orcid.org/0000-0002-8240-4775
Aim: Inhaler device misuse is a common problem in the management of Chronic Obstructive Pulmonary Disease (COPD). In this study, we aimed to evaluate the incorrect use of inhaler devices and associated factors in patients with COPD.
Material and Methods: A total of 75 patients with the diagnosis of COPD were randomized. Demographic characteristics, type of device used, satisfaction with the drug, whether they received any training, and the inhalation technique were evaluated. Disease duration, pulmonologist follow-up, and device type were compared with the frequency and type of errors.
Results: Among the patients, 85.3% received information from the pulmonologist, 9.3% from another healthcare professional, and 5.3% did not receive any information about drug use; 20% of the patients were on Diskus, 4% on Turbohaler, 33.3% on capsuled devices, 37.3% pMDI, and 5.3% were on Ellipta. In total, 49.3% of patients were using their devices correctly. In patients who had 3 or more pulmonology follow-ups per year, correct installation of the device, mouth washing, and total correct use scores were significantly higher (p <0.05). Capsuled device users had significantly higher rates of performing adequate inhalation and the total score of correct use compared to pMDI users (p <0.05).
Discussion: In COPD patients, frequent follow-up and the type of device used were found to be related to correct inhaler use. Applied inhaler device training should be given by a pulmonologist both initially and during follow-up, with particular attention to the technique of using the pMDI.
Keywords: COPD; Inhaler devices; Misuse; Patient education
Introduction
Chronic obstructive pulmonary disease (COPD) is a disease characterized by the presence of airflow limitation, which is not completely reversible and is generally progressive. According to current estimates, the global burden of COPD will increase [1]. COPD was the fifth leading cause of death in the world in 2001 and is expected to be the third most common cause of death in 2020 [2]. Inhalation therapy plays an important role in the treatment of chronic obstructive pulmonary diseases, yet the correct device technique remains a barrier that can affect treatment outcomes [1]. Especially, in cases of recurring exacerbations and failure to control the disease despite treatment, the misuse of drugs plays an important role. Regardless of the type of device used, the rate of mistakes can reach 85%. For drugs to be effective, a sufficient amount of drug must be delivered to the bronchial mucosa. This is only possible with the correct technique. Among these devices, the most commonly used are pressured metered dose inhalers (pMDI) and dry powder inhalers (DPI). Hand-mouth coordination and simultaneous puff-inhalation should be achieved for patients to benefit from pMDIs effectively. A deep breathing maneuver is required for dry powder inhalers [3,4].
In this study, we aimed to evaluate the incorrect use of inhaler devices and associated factors in patients with COPD.
Material and Methods
This was a prospective study including 75 random patients who applied to the clinic of Abant University Faculty of Medicine, Department of Chest Diseases between May 2019 and August 2019 with a diagnosis of COPD and gave informed consent to participate the trial. Ethics approval was given by Abant University Faculty of Medicine with decision no:2018/126. Age, gender, education status, place of residence, duration of illness, smoking status, medicines taken, follow-up by a pulmonologist, type of device used, satisfaction with medication and adequate inhalation, correct breathing, mouth washing, and total scores were included in the study. The demographic characteristics of the patients, whether they received any training on the use of the inhaler device and who provided the training were recorded. The observation form was filled with questions about the steps of using the inhaler devices, which also inquires at what stage and why patients made mistakes. Patients’ disease duration, pulmonology follow-up, and device preparation according to device type, adequate inhalation, breath-holding, mouth washing, and total score were evaluated. Social Sciences (SPSS Inc. Chicago, IL, USA) Mac-ios version 25 software program was used to evaluate the research data. Descriptive statistics are presented as numbers and percentages for categorical variables and mean ± standard deviation for numerical variables. When the Chi-Square condition was met for categorical variables, Pearson’s Chi- Square (c2) or Fisher’s Chi-square test was used for multiple and binary group comparisons. The statistical significance level was considered significant if the p-value was less than 0.05 with a 95% confidence interval.
Results
Most of the patients in our study were male (92%) with education less than high school (90.7%) and a mean age of 69.7±9.7 years. Among our patients, 69.3% were diagnosed more than 3 years ago, device instruction was given by a pulmonologist to 85.3% of the participants; 86.6% visited their pulmonologist more than once a year and 69.3% visited their pulmonologist more than three times a year. Most of the patients used capsuled devices (33.3%) or pMDIs (37.3%) (Table 1).
Most of the patients thought their treatment was effective (77.7%), and most of them were satisfied with their medicine (78.7%) (Table 2).
Most of the patients were setting up their device correctly, performed adequate inhalation, held their breath correctly, and washed their mouths, yet looking at the total scores, half the patients were making at least one mistake (Table 2).
Comparing the individual mistakes and total score with different parameters, we found that the duration of disease did not affect the correct use of the inhalers. Frequent pulmonology follow-up improved inhaler use. Patients who were followed by a pulmonologist at least three times a year were less likely to make mistakes compared to patients who had no follow up (setting up p=0.01, mouth washing p=0.034, total score p=0.041). The device type also had a statistically significant relation with mistakes. Patients on pMDI were more likely to make inhalation mistakes (p<0.001). The total correct usage score was higher in patients using capsules, and the total misuse score was higher in patients using the pMDI (p=0.007). There was no statistically significant difference between those using capsules devices or pMDI and those using Diskus, Turbohaler, or Ellipta (Table 3).
Discussion
The main treatment for COPD is the administration of bronchodilators and corticosteroids using an inhaler. The most important advantage of using medication through inhalation is that it provides more optimal treatment by using less medication, a higher concentration of drugs can be administered more effectively to the airways and, especially, the systemic side effects of corticosteroids can be reduced [1]. The pMDIs contain active substances in liquid form in a pressure tube, after activation, the drug can reach bronchial mucosa via a deep inhalation. Hand-breath coordination and spray-inhalation synchronization are required for a correct maneuver. These devices are generally believed to be hard to use. Dry powder inhalers reach the bronchial mucosa through deep inhalation of the powder. They do not require hand- breath coordination and synchronization but are more expensive [5,6]. Errors in inhaler drug applications affect the effectiveness of treatments. Especially in the occurrence of asthma and COPD exacerbations and lack of adequate control, errors in inhaler drug applications are of great importance [7-12].
In a study published in 2018, Ozel et al. evaluated 84 patients with COPD or asthma for satisfaction and ability to use inhalation devices [13]. They found that the skill to use the devices correctly was higher in those with high school or higher education. Individuals who learned how to use the device from a pulmonologist had higher scores on the device’s correct use. It was found that the correct use of the drug is lower in patients with a disease duration of 11 years or more. The skill points were lower in pMDI users than in other devices, and mouthwash and breath-hold accuracy rates were less than 50% [13]. In our study, 78.7% of the patients were satisfied with the medication, and this rate was higher than that of Ozel et al. The reason for this may be because our patients were generally trained by a pulmonologist.
In our study, no relationship was found between disease duration and correct use rate, in contrast to the results of Ozel et al. This may be due tothe training by a pulmonologist and the frequency of follow-up in our study. Consistent with Ozel et al, our study showed a significantly higher rate of pMDI misuse, possibly due to the age of COPD patients and the difficulty of pMDI use.
In the study of 751 asthma and COPD patients, published in 2018 by Baslilar et al., the rate of non-use and misuse of the device was found to be higher in patients with disease duration of 0-3 months compared to 3 months-1 year, 1-3 years and 3 years longer. Also, in illiterate people, the rate of misuse was higher. The pMDI users made more mistakes compared to those using the Diskus, capsuled devices, and Turbohaler [14]. In our study, no relationship was found between the duration of the disease and the correct use of the drugs. The difference from Baslilar et al. is probably due to the difference between the number of patients.
In a study including 122 COPD and asthma patients published by Çörtük et al. in 2014, the correct use rate was found to be highest with Diskus at 88.2%, 85.7% with the capsuled devices, 46.3% with pMDI and the lowest in Turbohaler with 30%. There was no relationship between the duration of the disease and the correct use of the drugs [15].
In a study published by Aydemir et al. in 2012, 300 patients with COPD and asthma were evaluated for the misuse of inhaled devices, related factors, and the role of education. The correct device usage rates were 57% in Diskus, 53% in capsuled devices, 51% in Turbohaler, 55% in Easyhaler, and 13% in pMDI. Correct usage was highest with Diskus and lowest with pMDI. Correct use was significantly higher when the device training was provided by a pulmonologist compared to internal medicine specialists and pharmacists. The correct use of the drug was found to be higher in those who were followed-up by a pulmonologist [16].
A study published in 2001 by Mirici et al. investigated factors affecting the inhalation technique in 153 people with obstructive airway disease. In all devices, the most common errors were breath-holding and exhalation before the second dose. No difference was observed between the devices in terms of correct use. The person who taught patients the device caused no significant change. While the level of education increased the score of correct use, the duration of use decreased it [17]. In our study, the highest error rate was with pMDIs, and the highest correct use rate was with capsuled devices. There was no significant difference in those using other devices.
The average age in our study was 68 years, which was higher than that of Ozel, Başlılar, Çörtük et al. [13-15]. The reason for the high average may be that COPD is a lung disease affecting the advanced age group, and older age is among the risk factors for disease development. Another reason for this may be because our study did not include asthma patients.
In our study, the ratio of male patients (72.6%) was higher compared to similar studies by Çam, Mirici et al. [17,18]. Gender ratios in our study are incompatible with the literature. Possible reasons for this may be that our country is a developing country or that most of the patients in our study were living in rural areas.
In our study, a significant relationship was observed between the frequency of follow-up by the pulmonologist and the correct use of the device. Also, correct inhalation and correct use of total scores were significantly higher in patients using capsuled devices than in pMDI users. The main problem encountered with inhaler devices, including pMDIs, is the difficulties of the inhalation technique. Therefore, the correct technique should be taught by or under the supervision of a pulmonologist. All COPD patients should be treated and followed up by a pulmonologist. Applied inhaler device training should be given to patients at the beginning of the treatment and the controls, and it should be ensured that the patient is using the drug correctly. With enough focus on the problem, it seems possible to achieve a solution through regular patient education and follow-up.
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
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2. Murray CJ, Lopez AD. Alternative projections of mortality and disability by cause 1990 2020: Global Burden of Disease Study. Lancet. 1997;349(9064):1498-504.
3. Rogliani P, Calzetta L, Coppola A, Cavalli F, Ora J, Puxeddu F, et al. Optimizing drug delivery in COPD: The role of inhaler devices. Respir Med. 2017;124:6-14.
4. Lavorini F, Magnan A, Dubus JC, Voshaar T, Corbetta L, Broeders M, et al. Effect of incorrect use of dry powder inhalers on management of patients with asthma and COPD. Respir Med. 2008;102(4):593–604.
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6. King D, Earnshaw SM, Delaney JC. Pressurised aerosol inhalers: the cost of misuse. Br J Clin Pract. 1991;45(1):48-9.
7. Plaza V, Sanchis J. Medical personnel and patient skill in the use of metered dose inhalers: a multicentric study. CESEA Group. Respiration. 1998;65(3):195-8.
8. Shrestha M, Parupia H, Andrews B, Kim SW, Martin MS, Park DI, et al. Metered- dose inhaler technique of patients in an urban ED: prevalence of incorrect technique and attempt at education. Am J Emerg Med.1996;14(4):380-4.
9. Chapman KR, Love L, Brubaker H. A comparison of breath-actuated and conventional metered-dose inhaler inhalation techniques in elderly subjects. Chest. 1993;104(5): 1332-7.
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13. Ozel F, Gündüzoğlu M, Akyol AD. KOAH ve Astımlı Hastaların İnhalasyon Cihazlarını Kullanma Becerileri ve Memnuniyet Durumları (Abilities and Satisfaction of Patients with COPD and Asthma to Use Inhalation Devices). ACU Sağlık Bil Derg. 2018; 9(3):266-71.
14. Başlılar Ş, Şaylan B, Oludağ G, Sarıman N. Göğüs Hastalıkları Polikliniğine Başvuran Hastaların İnhaler Kullanım Becerilerinin Araştırılması (Investigation of Inhaler Use Skills of Patients Applying to Chest Diseases Outpatient Clinic). Türk Aile Hek Derg. 2018;22(2):66-77.
15. Çörtlük M, Kiraz K. Kronik Akciğer Hastalığı Olan Hastaların Bronkodilatatör İlaçlara Uyumu (Compliance of Patients with Lung Disease with Bronchodilator Drugs). Haran Üniversitesi Tıp Fakültesi Dergisi/ Journal of Harran University Medical Faculty. 2014;11(2):92-7.
16. Aydemir Y. İnhaler Cihazların Hatalı Kullanımı-Etkili Faktörler ve Eğitimin Rolü Araştırma (Misuse of Inhaler Devices – Effective Factors and the Role of Education Research). Solunum/ Respiratory Journal. 2013:15(1):32-8.
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Serhat Seker, Suat Konuk, Emine Ozsari, Tuncer Tug. Misuse of inhaler devices and associated factors in chronic obstructive pulmonary disease patients. Ann Clin Anal Med 2021;12(6):598-602
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Evaluation of vitamin D levels in pregnant women with familial mediterranean fever (FMF)
Harun Egemen Tolunay 1, Korkut Dağlar 2, Kudret Erkenekli 2, Dilek Şahin 1, Aykan Yücel 1
1 Etlik Zübeyde Hanım Maternity and Women’s Health Teaching and Research Hospital, 2 Dr. Zekai Tahir Burak Women’s Health Research and Education Hospital, Ankara, Turkey
DOI: 10.4328/ACAM.20356 Received: 2020-09-27 Accepted: 2020-10-26 Published Online: 2020-11-12 Printed: 2021-06-01 Ann Clin Anal Med 2021;12(6):603-606
Corresponding Author: Harun Egemen Tolunay, Etlik Zübeyde Hanım Maternity and Women’s Health Teaching and Research Hospital, Ankara, Turkey. E-mail: harunegementolunay@gmail.com P: +90 5557736303 F: +90 3125674019 Corresponding Author ORCID ID: https://orcid.org/0000-0002-8922-4400
Aim: There is an essential role of D vitamin in the fetal birth weight and bone development of the fetus. The main goal of this paper is to compare the vitamin D levels of pregnant women with familial Mediterranean fever (FMF) and normal pregnant women.
Material and Methods: Medical records of pregnant women (n=46) diagnosed with FMF and control group pregnants (n =31) were evaluated retrospectively.
Results: The vitamin D levels of pregnant women with FMF and normal healthy pregnants were 11.59 ± 6.7 ng/mL and 17.42 ± 9.36 ng/mL, respectively (p = 0,002). The birth weight of fetuses in the control group was significantly higher than the average birth weight of pregnant women with FMF (p = 0,022). Besides, a statistical difference was detected between two groups for vitamin D levels
Discussion: Pregnancies complicated by FMF could have additional morbidities. The presence of FMF in pregnancy may change the course of the pregnancy. These pregnant women have low levels of vitamin D. Pregnant women with FMF could have low fetal birth weight. Low vitamin D levels may cause this situ- ation in the pregnancy.
Keywords: Vitamin D, Familial mediterranean fever, Pregnancy, Fetal birth weight, FMF
Introduction
Familial Mediterranean Fever (FMF) is an autoinflammatory condition represented by recurrent polyserositis attacks and fever. The most accused causes are the mutations of the MEFV (Mediterranean Fever) gene, located on the q (small region of the chromosome) region of the 16th chromosome. The most devastating complication of FMF is amyloidosis, which could lead to chronic renal failure and, eventually, mortality. Besides, it may also affect other organs and tissues. Adults in the fertility period are also affected by the disease. Drug usage in this condition can be useful for the reproductive system and pregnancy period. Colchicine is the leading medical medication of choice for FMF. It is usually used to prevent and reduce the intensity of FMF exacerbations and the progress of amyloidosis. Colchicine usage in pregnant women and breastfeeding is known to be safe. The usage of colchicine has been reported to have positive effects on the frequency of fertility and pregnancy losses. Colchicine is the only effective drug, but there is still an unclarified issue regarding that there is a 30% responsiveness to the treatment with the colchicine in the FMF [1-4].
Vitamin D is structurally in the form of steroid hormones that has an essential role in the functioning of the musculoskeletal system, bone health, and human metabolism. Homeostasis of calcium and phosphorus is dependent on vitamin D. Vitamin D has immunomodulatory and pleiotropic effects. Vitamin D intake from diet has beneficial effects according to several in vivo studies conducted on laboratory animal models such as SLE, Crohn disease / ulcerative colitis, and collagen- induced arthritis. Circulating levels of vitamin D are decreased in several inflammatory conditions, according to reports of the previous studies. In cases such as cancer, muscle weakness, insulin resistance, diabetes, cardiovascular diseases, tuberculosis, and in the fight against chronic diseases, it should be carefully evaluated [5-8].
Although there are publications on the role of vitamin D and pregnancy outcomes and related conditions, the importance of vitamin D levels in pregnant women with FMF has not been evaluated to date. The purpose of this paper is to assess vitamin D levels in pregnant women with FMF.
Material and Methods
The medical records of the perinatology department at a university hospital were reviewed. Forty-eight pregnant women with FMF and 31 pregnant women with no previous disease history were enrolled in the study. Two pregnant women were excluded from the study because one of them had multiple pregnancies, and the other had D&C with own request. The diagnosis of FMF was made according to the Tel-Hashomer criteria [9]. All procedures in the study were in accordance with the latest version of the Helsinki Declaration. Besides this, institutional guidelines were also considered. The hospital’s local ethics committee approved the protocol and procedures of this study (09/14-10).
The amount of colchicine therapy in patients was 1–1.5 mg/ day, and there was no information on patients who were taking any other drugs that could affect vitamin D levels. Pregnants in both groups had no bone diseases and a history of another drug usage. We collected all blood samples from all pregnants in a similar season to avoid the seasonal change of the sun on D vitamin status. We used 25 (OH) D levels to evaluate the D vitamin status of the pregnants.
The statistical package for the social sciences (SPSS) version 20.0 for Windows was used for all statistical analyses. An independent-samples t-test was performed when the normality results were met. We used the Mann-Whitney U test to compare continuous variables. When the assumptions of the Independent t-test were not met, Mann–Whitney U tests were performed to examine the other dependent variables between patient and healthy participants. P-value <0.05 was considered statistically significant. A chi-square test was performed for independence to compare two variables in a contingency table to see if they are related.
Results
The mean age of pregnant women with FMF and the control group was 27. 35 ± 5.95 and 29.32 ± 5.90, respectively (Table 1). The mean gravida number of FMF group and control group was 2.22 ± 1.30 and 1.97 ± 1,33, respectively. The mean parity number of cases of FMF and control group was 0.72 ± 0,81 and 0.55 ± 0,81, respectively. The mean fetal birth week of cases of FMF and control group was 38.04 ± 2.56 and 38.42 ± 1,23, respectively. Basal proteinuria levels were 146 ± 108.89 mg/ dl and 156.52 ± 110.71, in the FMF group and control group, respectively. Birth weight was 2970 ± 670 gr in the FMF group and 3290 ± 310 gr in the control group. There was a statistically significant difference between the two groups in terms of birth weight (p: 0.022) (Table 2).
Healthy and patient participants were not significantly different in terms of the delivery method. Likewise, healthy and patient participants were not considerably different for body mass index (Table 3). Healthy participants were significantly different from participants with FMF for the level of vitamin D (p =0,002). The concentration of vitamin D in pregnant women with FMF was considerably lower than the healthy participants. Vitamin D levels were 17.42 ± 9.36 ng/mL and 11.59 ± 6.70 ng/mL in control group and FMF group, respectively. However, the healthy participants did not differ significantly from patient participants in terms of the levels of albumin and total protein. Albumin levels were 3.70 ± 0.45 g/dL and 3.64 ± 0.47 g/dL in healthy pregnants and FMF group, respectively. Total protein levels were 6.74 ± 0.37 g/dL and 6.62 ± 0.59 g/dL in healthy pregnants and FMF group, respectively.
Discussion
We showed that maternal serum concentrations of vitamin D are decreased in pregnant women diagnosed with FMF compared to pregnant women in the control group. Some studies have investigated the vitamin D levels in adult patients with FMF in the literature, but this is the first study, to our knowledge, that evaluates the D vitamin concentrations in pregnant women diagnosed with FMF [10].
Vitamin D deficiency is beginning to be considered a public health problem. Reduced vitamin D levels in pregnant women have been associated with poor pregnancy outcomes. Low levels of maternal vitamin D during pregnancy period have been reported to be associated with several poor newborn outcomes. These adverse outcomes include a detrimental effect on fetal bone and teeth health, intrauterine growth retardation (IUGR), preterm birth, hypertensive disorders in pregnancy, and risk of infectious conditions. Previous studies have shown different associations between maternal vitamin D status and fetal growth. Interestingly, there is some knowledge regarding the irrelevance between maternal vitamin D levels and neonatal anthropometric measures. According to some publications, neonatal outcomes are not affected by maternal vitamin D status [11-13].
Low birth weight is a leading neonatal problem and causes future morbidities. Babies with low birth weight have high risk medical problems and inguinal canal pathologies, NEC, severe respiratory problems requiring interventions. They are also candidates for surgical problems such as premature retinopathy, patent ductus arteriosus, ventriculomegaly. The causes of low birth weight could be listed as fetal, maternal, and placental. It is essential to provide proper diet and nutritional care of mothers during pregnancy [14].
It is known that the level of maternal vitamin D affects the immunity, bone development, and birth weight of the fetus. There is no consensus regarding the duration of vitamin D supplementation during pregnancy and the way of administration because of the heterogeneity of the trials of vitamin D supplementation in the pregnancy. Currently, available evidence suggests that vitamin D supplement during gravidity decreases the risk of preterm delivery, intrauterine growth retardation, teeth health of the fetus, and infectious conditions of a newborn like respiratory infections and sepsis. However, new good-designed, more extensive clinical trials are needed. The usage of low-dose vitamin D during pregnancy is considered safe for now. From the perspective of neonatal health, there is still no definitive conclusion regarding the potential long-term adverse reactions of adding vitamin D to the diet. Therefore, many randomized clinical trials are needed to monitor fetal health in pregnant women supplemented with vitamin D during pregnancy. Our study shows that decreased maternal vitamin D levels may have harmful effects on fetal birth weight in pregnant women with FMF disease [15-17].
In a trial evaluating 46 pregnant women with FMF, preterm labor rupture and cesarean frequency were increased, but preterm delivery, gestational diabetes, and preeclampsia frequency did not differ. Colchicine usage has been reported to be safe, and it reduces the abortion rate in pregnancy, according to a study conducted by Yasar et al. [18]. The preterm birth rate did not differ in the groups in our research, concordant with previously reported studies.
Limitations
The lack of PTH and calcium levels and neonatal outcomes could be listed as limitations of our study.
Conclusion
Maternal vitamin D levels have an essential role in the fetal birth weight and bone development of the fetus. Besides, it has a role in the event of fetal immunity. However, it is difficult to make conclusions about the optimal D vitamin levels required during pregnancy. Specific findings cannot be made in the usage of D vitamin during the pregnancy due to the following factors: heterogeneity of studies on this issue, the length of the duration of hypovitaminosis due to vitamin D deficiency, and other potential confusion. In light of the available data, vitamin D supplement during pregnancy reduces the incidence of preterm birth, the risk of miscarriage, low fetal birth weight, tooth decay in infants, newborn infectious diseases such as respiratory infections, and sepsis rates. These conditions are inversely proportional to the level of vitamin D. However, there is a need for well-designed, large RCTs with many participants. The safety of D vitamin during pregnancy is acceptable. The usage of low-dose vitamin D during pregnancy seems to be safe in the short term for now. What side effects vitamin D supplements will cause in gestation for a long time is based upon the research investigating the impact of neonatal health.
Colchicine treatment seems to be safe in pregnant women with FMF. The vitamin D levels are decreased in pregnant women with FMF, and this clinical situation may be responsible for poor obstetric outcomes in these pregnant population. Pregnants with FMF should be encouraged to take D vitamin supplementation during pregnancy.
Acknowledgment
The authors would like to thank Dr. Halil İbrahim Yakut for his valuable contributions.
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.
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9. Livneh A, Langevitz P, Zemer D, Zaks N, Kees S, Lidar T, et al. Criteria for the diagnosis of familial Mediterranean fever. Arthritis Rheum. 1997; 40(10): 1879- 85.
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Harun Egemen Tolunay, Korkut Dağlar, Kudret Erkenekli, Dilek Şahin, Aykan Yücel. Evaluation of vitamin D levels in pregnant women with familial mediterranean fever (FMF). Ann Clin Anal Med 2021;12(6):603-606
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Reliability of the measurements of cross-sectional area and diameter of semitendinosus and gracilis tendons using 1.5 T magnetic resonance imaging
Volkan Kızılgöz 1, Ragıp Gökhan Ulusoy 2, Oğuzhan Özdemir 1
1 Department of Radiology, Kafkas University, Faculty of Medicine, 2 Department of Orthopaedics, Kafkas University, Faculty of Medicine, Kars, Turkey
DOI: 10.4328/ACAM.20357 Received: 2020-09-30 Accepted: 2020-10-29 Published Online: 2020-11-11 Printed: 2021-06-01 Ann Clin Anal Med 2021;12(6):607-611
Corresponding Author: Volkan Kızılgöz, Kafkas University, Faculty of Medicine, Department of Radiology, Kars, Turkey. E-mail: volkankizilgoz@gmail.com P: +90 5057994013 Corresponding Author ORCID ID: https://orcid.org/0000-0003-3450-711X
Aim: Hamstring tendons are widely used for anterior cruciate ligament (ACL) reconstruction. Preoperative magnetic resonance (MR) images have been used to measure the dimensions of hamstring tendons and to predict the graft size prior to ACL reconstruction. The aim of this study was to determine the reliability of measurements of the diameter and area of semitendinosus and gracilis muscle tendons using 1.5 Tesla magnetic resonance imaging (MRI).
Materials and Methods: In this retrospective study, three evaluators independently reviewed 74 knee MRI to determine the diameter and cross-sectional area of semitendinosus and gracilis tendons at three levels (medial femoral condyle, joint line and below the tibial plateau). Mean values were calculated for each reviewer and intraclass correlation coefficient (ICC) values were used to assess inter-rater agreement.
Results: There was an excellent inter-rater agreement with respect to measurements of the width and cross-sectional area of semitendinosus and gracilis tendons at all levels. The inter-rater agreement with respect to the thickness of semitendinosus and gracilis tendons ranged from good to excellent at the three levels.
Discussion: Using 1.5 T MR imaging for preoperative hamstring graft size prediction, authors found excellent inter-rater agreement with respect to the mea- sured cross-sectional area of semitendinosus and gracilis muscle tendons at three levels in this study. Even though the ICC values for tendon thickness of gracilis muscle were relatively low, the inter-rater agreement was rated as “good” in two axial planes, and “good to excellent” in one axial plane. More studies are needed to discover the exact inter-rater agreement levels for hamstring tendon measurements using 1,5 T MR images.
Keywords: Hamstring tendons; Autografts; Anterior cruciate ligament; Inter-observer variability; Magnetic resonance imaging
Introduction
The anterior cruciate ligament (ACL) plays an important role in maintaining the stability of the knee joint by restricting tibial translation in relation to the femur [1]. ACL is also one of the most frequently reconstructed ligaments [2]. ACL reconstruction is currently the standard treatment for the prevention of meniscal tears and knee laxity in athletically active persons [3]. Hamstring tendons are widely used for ACL reconstruction [4]. The use of quadruple hamstring tendon grafts for ACL reconstruction has been shown to confer adequate ligament strength and achieve good clinical results [5,6].
Prior to harvesting the graft, meticulous preoperative planning is essential to achieve successful outcomes of ACL reconstruction. Various researchers have attempted to predict tendon autograft size using patient height, weight, and other anthropometric data [7-9]. Magnetic resonance (MR) imaging is a very useful diagnostic tool for the assessment of ACL injuries. Cross-sectional MR images in the axial, coronal, and sagittal planes are useful in measuring the dimensions of knee tendons. Prediction of allograft size using MR imaging has evoked considerable interest in contemporary literature [10,11].
In the present study, we aimed to assess the reliability of area measurements of semitendinosus (ST) and gracilis (GR) muscle tendons using routine 1.5 T knee MR images. Three reviewers measured the width, thickness, and cross-sectional area of these tendons which are widely used as autografts for ACL reconstruction. In addition to the widely used measurement techniques, three axial planes were used to measure tendon dimensions and tendon area calculations.
Material and Methods
Patients
After the approval of our institutional ethics committee, all patients (n=511) who were admitted to our hospital between January and December 2019, and underwent knee MR examination were reassessed to determine the knee pathology. The requirement for informed consent of subjects was waived off by the ethics committee owing to the retrospective study design. Patients in the age-group of 18–50 years were included in this research. This age-group was chosen considering the skeletal maturity and to avoid the effect of degenerative diseases on the measurement results. Patients with any knee deformity, knee osteoarthritis, history of patellar dislocation, septic arthritis, osteonecrosis, rheumatologic diseases, or previous knee surgery were excluded from the study. Patients with ligamentous injuries, tendinopathies of the knee, and meniscal tears were also excluded. Thus, skeletally mature patients with normal MR examinations were included in this research. All eligible patients were screened against the study- selection criteria based on the consensus of two observers (V.K. and O.Ö.) after the assessment of all knee MR images. Finally, 58 patients with unilateral and 8 patients with bilateral knee MR examinations were included in this retrospective cross- sectional study. Thus, 74 knee MR imaging of 66 patients (35 female and 31 male, mean age: 32 ± 8.3 years) were reassessed to determine the width, thickness, and the cross-sectional area of semitendinosus and gracilis tendons.
MR Imaging
MR imaging was performed using a 1.5 T machine (Magnetom Essenza; Siemens, Erlangen, Germany) equipped with an 8-channel knee coil. Standard MRI protocol consisted of T1 weighted (T1W) images in the sagittal plane and proton density-weighted (PDW) images in the axial, coronal, and sagittal planes. The technical parameters of MR imaging were as follows: sagittal T1W (TR: 515 ms, TE: 14 ms, Matrix: 192 × 256, FOV: 160 mm, slice thickness: 3.5 mm, interslice gap: 0.7 mm, ETL: 55, NEX: 2); axial PDW (TR: 2500 ms, TE: 28 ms, matrix: 206 × 256, FOV: 170 mm, slice thickness: 3.5 mm, interslice gap: 0.7 mm, ETL: 69, NEX: 1); sagittal PDW (TR: 2670 ms, TE: 24 ms, matrix: 205 × 256, FOV: 190 mm, slice thickness: 3.5 mm, interslice gap: 0.7 mm, ETL: 70, NEX: 1); coronal PDW (TR: 2350 ms, TE: 26 ms, matrix: 205 × 256, FOV: 180 mm, slice thickness: 3.5 mm, interslice gap: 0.7 mm, ETL: 69, NEX: 1). MRI measurements
All measurements were performed using the picture and archiving communication system (PACS) workstation panel (Enlil PACS Viewer, Eskişehir, Turkey) provided by our university hospital. Fat saturated axial PDW images were used and three different levels were selected to perform measurements. Semitendinosus tendon width (STW) and gracilis tendon width (GTW) were measured as the widest diameter in the axial plane. The longest diameter perpendicular to the width was measured as the semitendinosus tendon thickness (STT) and gracilis tendon thickness (GTT). Freehand region of interest tool of the workstation panel was used to determine the cross-sectional area of semitendinosus tendon (STA) and gracilis tendon (GTA) in the axial plane by manually tracing the tendon borders. Axial planes at the widest point of the medial femoral condyle (MFC), at the joint line (JL), and at the first plane just below the tibial articular plateau (BTAP) were chosen to perform the measurements. To eliminate any conflict and to clarify the selection of the exact location for the measurements, the sagittal image passing through the middle of the medial condyle was chosen to determine the axial plane of the JL. Two axial images below the JL (as our slice thickness was 3.5 mm, totally 7 mm below the JL) were chosen as the BTAP level to measure the tendons. The measurements were independently performed by 3 observers (two radiologists with 15 and 21 years of experience, respectively, and one orthopedic surgeon with 25 years of experience) under × 15 magnification. The 3 observers were blinded to each other’s image interpretations and measurement results. All measurements were noted to the nearest hundredth of a millimeter (Figures 1-3).
Statistical analysis
After patient data and image acquisition, all statistical analyses were performed using IBM SPSS Statistics for Windows V.20 (IBM Corp). The mean values with standard deviation were calculated according to each observer’s measurement results. The intraclass correlation coefficient (ICC) was used to assess inter-rater reliability. A standard scale developed by Koo and Li was used to verify inter-rater agreement [12]. According to this scale, the inter-rater agreement is graded as follows: ICC<0.50, poor; 0.50–0.75, fair; 0.75–0.90, good; 0.90–1.00, excellent. All ICC values are presented with 95% confidence intervals (CI).
Results
There was an excellent inter-rater agreement with respect to all measurements (STW, STT, STA, GTW, GTT and GTA) at the MFC level. All tendon measurements at the JL and BTAP levels showed excellent agreement with the exception of GTT. For GTT measurements, “good” agreement was observed at these levels. However, the lower bounds of the 95 % CIs for STT measurements at the JL and BTAP levels were less than 0.900. The mean values of all tendon measurements (STW, STT, STA, GTW, GTT and GTA) at the MFC, JL, and BTAP levels showed excellent agreement. For GTT measurements, the lower bound of 95 % CI was less than 0.900 at each level (Table 1).
Discussion
In this study, we observed an excellent agreement between reviewers in terms of cross-sectional area measurements of semitendinosus and gracilis muscle tendons at all axial levels. The width and thickness measurements also showed excellent agreement at the MFC level, and for all other diameter measurements except GTT at the JL and BTAP levels. GTT measurements showed good agreement at the JL and BTAP levels.
The hamstring tendons have been widely used as ACL autograft in recent years. Unlike quadriceps and patellar tendon autografts, the diameter of hamstring tendons shows considerable inter-individual variability and cannot be precisely predicted prior to its harvest during surgery [13]. Previous studies have shown that anthropometric parameters such as age, sex, weight, height, and body mass index are associated with the hamstring graft size [7-9]. Graft prediction studies using MR imaging have evoked considerable interest in recent years. Researchers have sought to characterize the relationship of the diameter and cross-sectional area measurements of hamstring tendons with the actual autograft size.
Hamada et al. used axial images at the level of the JL to measure the cross-sectional area of semitendinosus muscle tendon; they found a close correlation of these measurements with the intraoperative measurements [14]. Bickel et al. measured the hamstring dimensions just below the physis or physeal scar where hamstring tendons were more tubular in shape [2]. In many other studies, similar axial planes were used to measure the diameter of hamstring muscles at the level of MFC, knee JL, or both of these axial planes [11,15]. In the study by Vardiabasis et al., gracilis tendon and semitendinosus tendon diameter at 3 cm above the medial knee JL showed the strongest correlation with the actual hamstring autograft diameter [13].
We observed that the obliqueness of hamstring tendon alignment was nearly the same for MFC level, JL, and in the first axial plane just under the tibial articular plateau. In addition, the axial planes which are close to the site of tendon insertion would not be appropriate to measure, since the distal-most edges of the tendon autograft are cut away and not used for ACL reconstruction. Moreover, after cutting the edges of the autograft, the remaining edges will be placed in the tunnel to fix the ACL reconstruction. We performed the tendon measurements on routine MR images of the knee placing emphasis on the axial planes owing to the convenience and better reproducibility of the measurements. Thus, we used three axial planes (MFC, JL, BTAP), which we perceived as being very close to the actual cross-sectional area measurements of semitendinosus and gracilis muscle tendons.
It is desirable to preoperatively predict the dimensions or cross- sectional area of muscle tendons which are planned to be used as autograft; this would ensure that these are large enough for ACL reconstruction surgery. The exact autograft diameter required to avoid ACL reconstruction failure is not absolutely clear; however, recent studies suggest that even an increase of 0.5 mm up to an autograft size of 10 mm is beneficial for the patient [16]. In several previous studies, the mean graft diameter of quadruple hamstring grafts was in the range of 7.7 mm to 8.5 mm [7,17,18]. In a meta-analysis by Conte et al. (2014), grafts ≤ 8 mm in diameter were associated with 6.8 times greater relative risk of graft failure [19]. Schlumberger et al. studied 2448 cases of four-strand doubled semitendinosus- gracilis ACL reconstruction; however, they found that no significant difference between re-ruptured and non-ruptured groups when comparing outcomes of grafts < 8 mm and > 8 mm [20]. Based on comprehensive pre- and post-operative morphological studies and follow-up of patients with ACL reconstruction, in addition to the graft size, other factors (especially the patient’s age) should be considered before reconstruction surgery [21-23].
In the 3T MRI study by Beyzadeoğlu et al. (n=51), the mean values of STW, GRW, STA, and GTA were 4.2±0.4 mm, 3.1±0.3 mm, 12.9±2.5 mm2 and 7.3±1.6 mm2, respectively [11]. In the 1.5T MRI study by Bickel et al. conducted on adolescent patients (n=26), the mean STA and GRA were 13.3±2.86 mm2 and 6.97±2.16 mm2, respectively [2]. Camarda et al.’s results (n=100) for STW and GTW were 4.2±0.4 mm and 3.3±0.4 mm, respectively, on MR images obtained with a 1.5 T scanner [10]. In another 1.5 T MRI study by Hamada et al. (n=79), the mean STA value was 10.1±2.1 mm2 [14]. Hanna et al. (n=30) assessed the correlation (r) between preoperative MR measurements and intraoperative measurements of the size of tendons. Preoperative measurements of STW and GRW showed the best correlation at the level of MFC. In addition, the sum of STA and GTA (STA+GTA) measurements showed a stronger correlation at the level of MFC compared to that at the level of JL and the average measurement value of MFC and JL (r = 0.492) [24]. Hollnagel et al. (n=68) studied the relationship between preoperative autograft size measured on MR images and intraoperative autograft size using 1.5T and 3T MR machines. The measurements of STW and STA+GTA, at the MFC level showed a stronger correlation with intraoperative results than those at the level of JL and the average measurement value of MFC and JL for both 1.5T and 3T MR imaging [25]. In our study, we observed very high ICC values of STA and GTA at all levels, and there was an excellent inter-rater agreement for MFC, JL, and BTAP levels on 1.5T MR images.
The smallest diameter measured in this research was GTT at all levels. Even the inter-rater agreement for GTT was “good” at the JL and BTAP levels; the “relatively low” agreement level may be attributable to the small sample size. On the other hand, for STT, the lower bounds of 95 % CIs were less than 0.900 and the upper bounds were more than 0.900 at the JL and BTAP levels. From a statistical perspective, the obtained ICC value with a 95 % CI implies that there is a 95 % chance of the true ICC value to lie between the lower and upper bounds of the CI. Although the ICC values obtained in this research were 0.928 at the JL level and 0.921 at the BTAP level, it would be more appropriate to deem the agreement level as “good” to “excellent”. This interpretation has previously been reported by Koo and Li [12]. Despite the high agreement levels observed in this study, some limitations of our study should be considered while interpreting the results. This study was not focused on the prediction of autograft size; nonetheless, a comparison of the preoperative diameter measurements on MR imaging with the intraoperative measurements of the graft helps verify the utility of MR imaging for predicting the actual graft dimensions. The purpose of this research was to assess the inter-rater agreement with respect to the measurement of the dimensions of semitendinosus and gracilis tendons using MR images; however, we did not assess the potential relation of these dimensions with other parameters such as weight, height, and body mass index. Furthermore, we only used MR images of normal individuals to assess the reliability of tendon measurements; comparison of the measurement results of patients with and without rupture of ACL may provide a more robust assessment of the inter- rater agreement in each patient group. This study used three experienced reviewers to assess the inter-rater agreement; the inclusion of more observers would provide a more accurate assessment of the inter-rater agreement.
Conclusion
At the MFC, JL, and BTAP levels, we observed excellent inter- rater agreement with respect to the measurements of the diameter and cross-sectional area of the semitendinosus and gracilis muscle tendons using 1.5 Tesla MR images. Among all parameters measured in this research (STW, STT, STA, GTW, GTT and GTA), the lowest ICC values were recorded for GTT.
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.
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Volkan Kızılgöz, Ragıp Gökhan Ulusoy, Oğuzhan Özdemir. Reliability of the measurements of cross-sectional area and diameter of semitendinosus and gracilis tendons using 1.5 T magnetic resonance imaging. Ann Clin Anal Med 2021;12(6):607-611
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COVID-19 and the risk to health care workers: Is it possible to prevent nosocomial transmission?
Arzu Altunçekiç Yıldırım 1, Celali Kurt 1, Ali Aygün 2, Yeliz Çetinkol 3, Şükran Kaygısız 4, Hakan Timur 5
1 Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, 2 Department of Emergency Medicine, Faculty of Medicine, 3 Department of Medical Microbiology, Faculty of Medicine, 4 Department of Neurology, Faculty of Medicine, 5 Department of Obstetrics & Gynaecology, Faculty of Medicine, Ordu University, Ordu, Turkey
DOI: 10.4328/ACAM.20359 Received: 2020-10-05 Accepted: 2021-01-14 Published Online: 2021-01-23 Printed: 2021-06-01 Ann Clin Anal Med 2021;12(6):612-616
Corresponding Author: Arzu Altunçekiç Yıldırım, Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Ordu University, 52200, Ordu, Turkey. E-mail: arzaltu@gmail.com P: +90 452 225 01 86 GSM: +90 505 3745836 F: +90 452 225 01 90 Corresponding Author ORCID ID: https://orcid.org/0000-0003-1141-9838
Aim: Health employees are the key point in the struggle against the disease and in-hospital transmission during the 2019 coronavirus disease (COVID-19) pandemic. Hospital contamination poses a serious risk for both healthcare personnel and social transmission. In our study, we aimed to evaluate the COVID-19 positivity and prevention strategies in healthcare personnel.
Materials and Methods: The SARS-CoV-2 PCR results examined among health employees for all reasons were retrospectively collected. Combined nasopha- ryngeal and oropharyngeal swab samples were used. Real-time PCR was used for testing. With the epidemic, the pandemic preparation process started in our hospital. All in-hospital organization was prepared in steps. Training programs and practical applications were put into practice.
Results: Among 1054 active health personnel, 682 underwent 876 tests. Only 2 people (0.3%) were identified as positive for SARS-CoV-2 on PCR tests. In the total number of tests, the positivity rate was identified as 0.22%. In this period, no health employee developed severe disease, and no personnel died due to COVID-19.
Discussion: Creating effective health strategies with a preparation process, together with in-hospital organization and training, and the use of appropriate and sufficient personal protective equipment, are highly effective in protecting healthcare personnel and preventing hospital-borne transmission.
Keywords: Coronavirus; Polymerase chain reaction; Healthcare workers
Introduction
Emerging in Wuhan city in China and following the recognition of pneumonia patients linked to the novel coronavirus (SARS- CoV-2), the disease rapidly spread and was declared a pandemic on 11 March 2020 by the World Health Organization. Currently, as of 12 June 2020, there are more than 7.5 million confirmed cases around the world and over 420 thousand deaths reported. Though the disease is generally known to be transmitted by droplets and contact, many studies have shown that droplets may travel long distances, even up to 8 m, in some situations, and may remain suspended in the air for up to 3 hours in situations involving aerosols [1]. Additionally, it is known that though a significant proportion of people may carry the virus and transmit the disease, they may not have any clinical symptoms [2]. This situation has caused many health personnel to catch the disease in hospital environments, where many medical procedures and interventions are performed in countries where patients infected with SARS-CoV-2 are intensely found.
In the period when people were recommended to stay at home with the aim of protecting themselves and preventing the spread of the disease, health employees were required to work in spite of all risks. During the pandemic, health employees caring for and treating patients with 2019 coronavirus disease (COVID-19) were at special risk. Personnel not working in pandemic clinics and wards were at risk due to the asymptomatic progression of the disease and a lack of COVID-19 diagnosis, patients with different diagnoses in the hospital, and work colleagues. Infected health employees could not work during the critical period due to the disease or may cause serious results due to being a source for the spread of the disease if not diagnosed. As a result, they were required to undergo screening when necessary with sensitive monitoring of symptoms. In fact, employees in some units undergo screening tests at certain periods, even if asymptomatic was debated [3]. In our study, we aimed to evaluate the results of the SARS- CoV-2 polymerase chain reaction (PCR) test applied to healthcare professionals in our hospital, nosocomial Covid-19 transmission and prevention strategies.
Material and Methods
The study was planned observationally, retrospectively and cross-sectionally and was conducted between March and June 2020. Education and Research Hospital is a tertiary hospital with a total of 260- bed capacity, including 26 in intensive care units. The hospital has a total of 1054 active employees, including 167 doctors, 229 nurses, 133 midwives, 32 laboratory employees, 28 radiology unit employees, 91 administrative and technical personnel, 85 data entry personnel, 32 security guards, 119 cleaning personnel and 138 other personnel. The study included data for personnel in contact with patients and patient areas and excluded data from management and office staff. Personnel with symptoms suspected of being infected with COVID- had samples taken immediately, while personnel with risky contact with COVID-19 patients had samples taken when symptoms developed or on the seventh day after contact. In this process, the guideline instructions of the ministry of health were implemented. Additionally, from 1 May 2020 to 10 May 2020, samples were taken from symptom-free personnel for screening purposes. Samples were taken with a single sample stick from both the pharynx and the deep nasopharyngeal region. The fluids carrying the virus were sent to the laboratory in accordance with cold chain rules and tested with real-time reverse transcriptase PCR on the same day ( Roche LightCycler® 480, Mannheim, Germany). One of the RT-PCR kits, the Bio-Speddy® (Bioeksen R&D Technologies Inc. COVID-19 RT-qPCR Detection Kit v2.0, Istanbul, Turkey), is determined valuable by the Turkish Ministry of Health and used throughout the COVID-19 pandemic).
All analyses were conducted using the statistical package program, the Statistical Package for Social Sciences (IBM SPSS for Windows, Ver.22) was used in the calculations. Means and standard deviations were obtained for continuous variables, while categorical variables were summarized using frequency and percentage. Student’s t-test was applied to assess the differences between numerical variables. The chi-square test was used to compare categorical variables.
The study was approved by the Regional Ethics Committee (2020/143) and was conducted according to the Helsinki Declaration. In addition, permission was obtained from the Republic of Turkey Ministry of Health.
Results
During the whole process, 682 health personnel underwent 876 PCR tests. Among these, 16 were symptomatic, 178 were contact screening (filiation) and 682 were in the planned screening week. Nonspecific ally, all symptomatic workers had mild symptoms such as sore throat and malaise. Among the total test count for health employees, the positivity rate was identified as 0.22%. The distribution and demographic data of tested personnel are presented in Table 1. Positive cases were in the symptomatic group, and their rate within the symptomatic group was 0.3%. One of the positive personnel had a history of out-of-hospital contact. In the other personnel, hospital infection could not be ruled out.
Among 178 contact histories, 26% (n = 46) had high, 46% (n = 81) had medium and 28% (n = 51) had low-risk contact. Chloroquine treatment was initiated in the high-risk group with a guide recommendation. No disease was detected in the cases that were followed up with contact. Routine testing was not performed for those in the low-risk group, and no disease developed during follow-up.
Since March 15, out of 207 patients admitted to the pandemic wards, 129 had COVID-19 diagnosis. Among COVID-19 diagnosed patients, 83 were PCR positive, and 46 had clinical and radiological compatibility. The internal capacity of the hospital decreased significantly due to decisions taken in the pandemic period (non-urgent surgeries were postponed, outpatient treatment was preferred except for mandatory cases, the number of outpatient clinic appointments was reduced). The workload for January and February and during the pandemic period is given in Table 2.
Additionally, in-service training beginning before the identification of COVID-19 cases in Turkey continued throughout the whole period. During this period, a total of 1653 participants attended 44 training sessions. Training topics were determined as Ministry of Health COVID-19 guidelines, hand hygiene, isolation methods, use of personal protective equipment, sample taking and transport for SARS-CoV-2 PCR tests, waste management, hospital cleaning and disinfection, organizational action plan for the pandemic and infection control precautions in a variety of units. Sessions were performed for each topic at different times to encompass all personnel. Throughout the process, one-to-one trainings were carried out in clinics by paying attention to protective measures, and the continuity of the training was ensured.
From the beginning of March to the middle of June, 200 thousand medical masks, 17 thousand disposable aprons, more than 3 thousand disposable overalls and 12 thousand N95 masks were used. Total use exceedsthese numbers because materials like washable aprons, glasses, and face shields were reused after appropriate cleaning and disinfection. Additionally, material donations were given to the hospital by other public and civil society organizations. There was no lack of personal protective equipment in clinics.
In order to quickly identify the personnel who have contact with the positive case and to take the necessary precautions, a team was formed under the presidency of an infection physician and a personnel health nurse. The phone number was announced to all staff and this team was accessible 24 hours a day. Contacts were recorded with the forms created. Active and rapid changes were made in the working order. Thus, the contagion was prevented, and the service was provided in this process.
Discussion
COVID-19 was detected in two of 1054 healthcare workers from the beginning of the outbreak until June 2020. One of these staff members tested due to being symptomatic was a radiography technician. After the SARS-CoV-2 PCR test was positive, all of their colleagues were screened and monitored for symptoms. None of them developed the disease or tested positive. Nosocomial infection was not considered due to a lack of hospital-acquired focus and a history of out-of-hospital contact. The other personnel identified positive for SARS- CoV-2 on PCR was a nurse responsible for the gynecology and obstetrics clinic. She had suspicious contact with a patient who was followed up for pregnancy on the 5th day of her hospitalization and was diagnosed with COVID-19, and she had mild symptoms. All other personnel in contact with the same patient were screened and all tested negative. The nurse who was positive had not had long-duration or high-risk contact with the patient, but had performed an intravaginal application. Our nurse developed very mild symptoms lasting only one day. Both personnel did not have pneumonia findings identified on tomography, and both were isolated and administered 5-day hydroxychloroquine treatment.
The other 14 people who were tested for symptoms were negative and their symptoms did not persist. Therefore, tomography evaluation was not required.
Since the beginning of the pandemic, studies have reported about infected health personnel. These rates display differences between countries and health facilities. A study in China reported that 3.5% of total patient numbers were health employees, while another study reported 3.8% were health employees [4,5]. In the United States of America, 3% of 315,531 patients confirmed as for 9 April were health workers [6]. However, this publication noted that there were serious deficiencies in the reporting forms as to whether confirmed cases were health workers or not. A screening study of 1032 asymptomatic health workers in England obtained 3% positive PCR test results [7]. A study of 1666 PCR test results from 1654 symptomatic personnel again in England identified 240 (14%) health workers were positive for SARS-CoV-2 [8]. One of the countries most affected by the pandemic was Italy that reported nearly 20% of health workers in a center were infected [9].
Strict implementation of infection control measures is essential both to reduce the risk of nosocomial infections of healthcare professionals and not to be a source of contamination [10].
If hospitals, which are diagnosis and treatment centers, do not take the necessary precautions, they may become a focus for disease transmission. Early diagnosis in health workers is very important from this aspect, though periodic screening of select groups is debated. Thus, symptomatic personnel may avoid unnecessary quarantine, and loss of labor and transmission by atypical, mild and asymptomatic cases may be prevented [11]. In the 2.5-month period from the moment the disease first emerged in China on December 31, 2019 until the moment it was first identified in our country on March 11, Turkey monitored the progression of the pandemic and new scientific data, and made preparations in light of experiences in other countries. As a result of precautions taken, the virus entered our country late, which provided significant advantages. The low number of infected health employees in our hospital was our priority target during preparation for the pandemic. There were three main factors in this situation, which can be qualified as a success.
1. Organization: Firstly, a pandemic committee chaired by hospital management (chief physician and assistants) was created. The committee included infectious disease experts, emergency medicine experts, chest diseases experts, intensive care experts, microbiology expert, head of nursing services and infection control nurses, and the administrative financial services manager. During this process, all decisions were made by this committee and published in written form. With no COVID-19 patients in our country or city, hospital departments, triage areas, wards and clinic areas were defined. Plans were prepared in three stages according to the pandemic level, and the transition from the first stage to the second and third stage implementations occurred according to patient numbers over time. Additionally, personnel who would work in COVID-19 wards, clinics and in shifts were determined. Apart from infectious diseases and chest diseases experts, all other internal medicine and surgical branch doctors were included in the process, and responsibilities were shared to prevent some doctors from being overloaded. Hospital cleaning procedures were reviewed and reorganized. Radiography, tomography, laboratory processes, surgeries and intensive care units were organized. All non-emergency surgeries and interventional procedures were postponed. The number accepted for clinical appointments was reduced and health personnel began to work on a rotational basis. The number of patient caregivers and visitors in the hospital was limited. In this process, the decrease in the number of non-COVID patients enabled more effective service to the COVID patient group and healthcare personnel to work more carefully (Table 2). Also, an additional service building was created separately from the main building to monitor COVID-19 diagnosed or suspected patients. Apart from pandemic wards, patients admitted for diagnoses other than COVID-19 and caregiving personnel were reorganized. All patients and health workers were made to use masks, personnel used gloves, and meticulous hand hygiene was ensured.
2. Training: The Turkish Ministry of Health has published guidelines for the diagnosis, treatment and prevention of COVID-19 for health workers. Based on the Ministry of Health guidebook, theoretical training on the clinical and laboratory features of the disease, transmission and protection routes and applied training on protective equipment and use was completed to encompass all personnel.
3. Use of personal protective equipment: The indispensable and most important point in the protection of health personnel dealing with patients with COVID-19 diagnosis or suspicion is the use of protective equipment. In the pandemic preparation stage, the organization reviewed personal protective material stocks and purchases were completed according to the third stage of the pandemic action plan. Interventions ensured that no protective material deficiency was experienced by personnel in any period. At the same time, unnecessary consumption caused by panic was prevented during a period when the number of patients had not increased yet.
It was determined which protective material was to be used in which way during which medical applications. The use of an N95 mask is recommended for aerosol-generating procedures such as bronchoscopy, endotracheal aspiration and taking nasopharyngeal swabs [12]. The use of medical masks by patients has been shown to reduce the spread of coronavirus and other respiratory tract viruses [13]. Additionally, a meta- analysis observed that the use of medical masks during routine patient procedures, which do not create aerosols was not different from N95 masks in terms of protection [14]. We made it mandatory for all personnel, patients and visitors in all hospital areas to wear medical masks.
When creating health strategies, ensuring effective infection control plays a key role in situations with epidemic disease, especially [15]. During the severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and Ebola epidemics, countries in Asia and West Africa had weak strategies for infection control in health facilities, and as a result, they experienced multiple cross-contamination, death and financial losses. These strategy deficiencies were identified as case identification, training inadequacy, isolation deficiency, communication deficiency, limited personnel policies and delayed response to the epidemic [16].
The limitations of the study are sensitivity problems in identifying SARS-CoV-2 on the PCR test, which may vary according to the region the sample was taken from, sampling technique and period of the disease. Apart from personnel with symptoms and continuing complaints, only one sample was used, despite negative tests. Additionally, antibody tests could not be used.
Conclusion
In conclusion, health employees are important for the struggle with COVID-19, while at the same time they are under serious risk. Additionally, they play a key role in in-hospital transmission. Considering the frequency of asymptomatic cases, periodic screening may come to the agenda wherever possible. In this process, we experienced the importance of determining organizational pandemic strategies before the pandemic wave and effective organization by making the necessary preparations. We think that in this way, we can fight the epidemic more effectively and prevent hospital infections.
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
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6. Burrer SL, de Perio MA, Hughes MM, Kuhar DT, Luckhaupt SE, McDaniel CJ, et al. Characteristics of health care personnel with Covid-19 – United States, February 12-April 9, 2020. Morb Mortal Wkly Rep. 2020; 69(15): 477–81.
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Arzu Altunçekiç Yıldırım, Celali Kurt, Ali Aygün, Yeliz Çetinkol, Şükran Kaygısız, Hakan Timur. COVID-19 and the risk to health care workers: Is it possible to prevent nosocomial transmission? Ann Clin Anal Med 2021;12(6):612-616
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Comparison of the clinical and radiological results of posterior cruciate ligament-retaining and posterior cruciate ligament-stabilized knee arthroplasties
Sezgin Bahadır Tekin 1, Mehmet Ömer Arpacıoğlu 2
1 Department of Orthopedics, Dr. Ersin Arslan Education and Research Hospital, 2 Department ofOrthopedics, Gaziantep University/Retired, Gaziantep, Turkey
DOI: 10.4328/ACAM.20360 Received: 2020-10-02 Accepted: 2020-11-01 Published Online: 2020-11-15 Printed: 2021-06-01 Ann Clin Anal Med 2021;12(6):617-620
Corresponding Author: Sezgin Bahadır Tekin,Department of Orthopedics, Dr. Ersin Arslan Education and Research Hospital, Gaziantep, Turkey. E-mail: sezgintekin1988@hotmail.com P: +90 5317916686 Corresponding Author ORCID ID: https://orcid.org/0000-0003-4740-9949
Aim: Total knee arthroplasty (TKA) is one of the most successful orthopedic surgeries. To further improve these outcomes, researchers have developed vari- ous types of prosthetics. This study aims to compare the clinical and radiological results of the common posterior cruciate ligament (PCL)-retaining (CR) and PCL-stabilized (PS) knee arthroplasties.
Material and Methods: We retrospectively evaluated the data of patients that were diagnosed with gonarthrosis in our clinic and who underwent knee replace- ment. The patients were evaluated using the American Knee Society score (AKSS) and radiographic assessment.
Results: There were a total of 115 subjects. Fifty-nine knees of 54 patients and 80 knees of 61 patients were included in the study. Forty-six of the 54 patients in the ligament-retaining group were female (86%) and 8 were male (14%). Fifty-two of the 61 patients in the ligament-stabilized group were female (85%) and 8 were male (15%).
The mean age was 67.4 years (54-82) in the ligament-retaining group and 65.4 years (42-85) in the ligament-stabilized group. The mean follow-up time in both groups was 32.6 months (12-98).
Discussion: The comparison of PCL-retaining and PCL-stabilized knee arthroplasties revealed that the ligament-stabilized group was superior in terms of the range of motion. The radiological examination revealed a difference in component alignment. The two groups did not differ significantly regarding other parameters.
Keywords: Knee; Arthroplasty; Prosthesis; PCL; Cruciate
Introduction
Total knee arthroplasty aims to achieve two main objectives: to reduce pain and improve knee function, and to provide proper alignment [1]. However, researchers have been constantly discussing possible treatment options to achieve these goals. Each type of prosthesis has its own set of advantages and disadvantages [2-6]. The most popular knee prosthesis designs include PCL-retaining and PCL-stabilized knee arthroplasties [7]. These two types of prostheses have similar geometric designs in general; however, many researchers have studied the two approaches, especially in the context of the role of the posterior cruciate ligament. PCL-retaining and PCL-stabilized knee arthroplasties are not only different in concept but also in practice. However, the surgeon’s choice of the prosthesis depends more on surgeon’s experience, than the attributes of the prosthesis type [8]. We designed this study considering that the clinical and radiological outcomes of these inherently different designs will also be distinct.
This study aims to compare the clinical and radiological results of the PCL-sacrificing and PCL-sparing knee arthroplasties.
Material and Methods
The study included patients who presented to our clinic with knee pain and were diagnosed with gonarthrosis radiologically, who had previously tried conservative methods of treatment, but had undergone knee arthroplasty as they no longer responded to conservative treatment. The patients that were operated with revision systems and those whose data were not found were excluded from the study.
All subjects were preoperatively evaluated with both AP and PA weight-bearing radiography of the knee. Other than routine monitoring of the patients with comorbidities, all patients were evaluated for infection parameters before surgery. Preoperative sedimentation rate and C-reactive protein levels were evaluated. All patients were preoperatively administered cefazolin 1 g IV 30 minutes before surgery and postoperatively continued to use cefazolin for 3 days. In all patients, a midline incision was made, and bony structures were revealed with a medial parapatellar incision. A tourniquet was used in all patients during the operation. Smith & Nephew cemented knee replacements were used in all patients. The patellar joint surface was not replaced in any of the subjects. However, patellar denervation was achieved with electrocautery in all subjects. All operations were performed by the same surgeon. General anesthesia was applied to 12 ligament-stabilized patients and 3 ligament- retaining patients, all other patients were operated on under spinal anesthesia.
Postoperative surgical drains were used. The drains were removed on postoperative day 1, and the patients were mobilized with walkers. All of the patients were evaluated according to the American Knee Society criteria. Also, patients in both groups were evaluated using the criteria of radiographic assessment of total knee arthroplasty. This study was approved by the Ethics Committee of the Gaziantep University Medical Faculty.
Statistical analysis
The compliance of numerical data with normal distribution was tested using the Shapiro-Wilk test. The Student’s t-test
was used to compare variables that fit a normal distribution in the two groups. SPSS 22.0 package program was used in the analyzes. P <0.05 was considered significant.
Results
The study includes patients that underwent total knee replacement in our clinic between 2006 and 2017. Fifty-four of 115 patients had posterior cruciate ligament-retaining knee arthroplasty, whereas 61 had posterior cruciate ligament- stabilized knee arthroplasty. Fifty-nine knees of 54 patients and 80 knees of 61 patients were included in the study.
Forty-six of the 54 patients in the ligament-retaining group were female (86%) and 8 were male (14%). Fifty-two of the 61 patients in the ligament-stabilized group were female (85%) and 8 were male (15%).
The mean age was 67.4 years (54-82) in the ligament-retaining group and 65.4 years (42-85) in the ligament-stabilized group. The mean follow-up period for both groups was 32.6 months (12-98).
Fifty-two of the 54 ligament-retaining patients were operated for primary osteoarthritis, while 3 patients were operated for underlying rheumatoid arthritis. Fifty-nine of the 61 ligament- stabilized patients were operated for primary osteoarthritis, 1 for rheumatoid arthritis, and 1 for post-traumatic arthritis. Five ligament-retaining patients underwent arthroplasty of both knees. Nineteen patients that were performed ligament- stabilized prosthesis underwent arthroplasty of both knees. The mean preoperative AKSS knee score (including pain, range of motion, and stability) of the 59 knees of the 54 patients in the ligament-retaining group was 48.4 ± 8.1 (36-72), whereas the mean postoperative AKSS knee score was 93.3 ± 4.6 (76- 100). The mean preoperative AKSS knee score of the 80 knees of the 61 patients in the ligament-stabilized group was 43.7 ± 5.9 (38-71), whereas the mean postoperative AKSS knee score was 95.0 ± 6.9 (78-100). In light of these data, the postoperative AKSS knee scores of the ligament-sparing and ligament-sacrificing groups are not significantly different (p = 0.129) (Table 1)
The mean preoperative AKSS function score ligament- retaining group was 31.2 ± 11.7 (15-60) whereas the mean postoperative AKSS function score was 84.8 ± 9.06 (60-100). The mean preoperative AKSS function score of the ligament- stabilized group was 35.08 ± 4.9 (10-60), whereas the mean postoperative AKSS function score was 82.2 ± 8.9 (60-100). This assessment indicated that the outcomes of the two groups were not significantly different (p = 0.128) (Table 2).
Another parameter that we used to evaluate our subjects was the pre- and postoperative knee range of motion. The mean preoperative knee flexion value was 73.42 ± 14.18 degrees (50-105) for the ligament-sparing group and 77.1 ± 7.6 degrees (40-105) for the ligament-sacrificing group. The mean postoperative knee flexion value was 107.67 ± 8.45 degrees (90-120) for the ligament-retaining group and 117 ± 8.03 degrees (90-120) for the ligament-stabilized group (p = 0.001). Preoperative joint assessment revealed the mean knee alignment of the PCL-retaining group was an 8.9-degree varus (ranging from 5-degree valgus to a 20-degree varus). The mean preoperative knee alignment of the PCL-stabilized group was
a 9.7-degree varus (8-degree valgus to 20-degree varus), and the mean postoperative knee alignment was a 4.75-degree valgus (10-degree valgus to 2-degree varus). The radiographic assessment revealed that the mean alpha angle value of the PCL-retaining group was 94.5 degrees (90-103) and the mean beta angle value was 88.3 degrees (84-93). The mean gamma angle value was calculated as 5.2 degrees (0-10) and the mean theta angle value was calculated as 86.7 degrees (80-94). In the PCL-stabilized group, the mean alpha angle value was calculated as 93.4 degrees (89-99), the mean beta angle value was 89.2 degrees (86-92), the mean gamma angle value was 88.3 degrees (84-92), and the mean theta angle value was 4.3 degrees (0-11). In light of these findings, we saw that the alpha angle values of the two groups were not significantly different; however, the beta, theta, and gamma angles were significantly different (p = 0.001).
None of the subjects developed embolism and only one patient in the ligament-stabilized group required revision surgery due to late infection.
Discussion
There are several evidence level I and II studies comparing ligament-sparing and ligament-stabilized prostheses [9-15]. Many studies concluded that the two approaches were not significantly different in clinical scores, range of motion, and quadriceps healing outcomes, and only two studies reported a better range of motion outcome in ligament-stabilized prostheses [16].
Four studies compared the long-term results of ligament- retaining and stabilized prostheses. Two studies indicated no difference, and the remaining two found that the ligament- retaining approach had better prosthesis survival outcomes [16,17].
The role of the posterior cruciate ligament is still debated. This is due to the role of the posterior cruciate ligament in knee kinematics. The posterior cruciate ligament is the structure that provides femoral rollback movements, a physiological movement of the distal femur. In addition, it contributes to the stability of the knee joint and knee joint proprioception due to its mechanoreceptors. In PCL-stabilized designs, the geometry of the articular surface of the prosthesis resists displacement. The prosthesis resists the subsequently developing stress, and this causes the stress to load onto the cement-bone interface. Researchers speculated that this would cause PCL-sacrificing prosthesis to fail [18]. Regardless, we found that the functional outcomes of the two groups were similar, and that only in terms of the range of motion, PCL-stabilized prosthesis was superior. The literature indicates several factors that might influence the postoperative outcome of total knee arthroplasty. These include age, obesity, and gender [19]. In order to reduce the bias that may be caused by these factors in our results, we tried and selected patients in the two groups to be similar and homogeneous. In this way, we aimed to obtain more accurate data.
In our study, the success rates of PCL-retaining and PCL- stabilized approaches were similar. The literature indicates that rheumatoid arthritis, post-traumatic arthritis, and previous surgery or patellectomy are all indications for using the PCL- stabilized approach for better outcomes [20]. However, this choice is still associated with the surgeon’s preference and experience. Although some of our subjects had underlying diseases, we could not include these factors into comparison due to the insufficient number of subjects.
The most feared complications of total knee replacement are infection and thromboembolism [21]. In our study, none of the subjects developed embolism, and only one patient in the ligament-sacrificing group required revision surgery due to late urinary infection.
Studies report successful clinical and radiological outcomes for knee prosthesis surgeries [22]. We also conducted a comparative analysis of the radiological results and found that, while the alpha angles of the two groups were statistically similar, the other parameters were not. It should be kept in mind that this outcome may vary depending on the surgical technique, preoperative planning, and joint deformity.
Our study has several limitations. The first limitation of our study is its retrospective nature. The second limitation is that, despite having a sizable number of patients, similar studies in the literature have significantly larger samples.
We conclude that both PCL-retaining and PCL-stabilized knee arthroplasties have good clinical outcomes. The clinical and radiological results of both approaches are satisfactory. The decision for the surgical approach should be based on the surgeon’s experience, preference, and the preoperative characteristics of the patient.
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
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4. In Y, Kim JM, Woo YK, Choi NY, Sohn JM, Koh HS. Factors affecting flexion gap tightness in cruciate-retaining total knee arthroplasty. J Arthroplasty. 2009;24(2):317-21.
5. Mikulak SA, Mahoney OM, dela Rosa MA, Schmalzried TP. Loosening and osteolysis with the press-fit condylar posteri- or-cruciate-substituting total knee replacement. J Bone Joint Surg Am. 2001;83(3):398-403.
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Download attachments: 10.4328_ACAM.20360
Sezgin Bahadır Tekin, Mehmet Ömer Arpacıoğlu. Comparison of the clinical and radiological results of posterior cruciate ligament-retaining and posterior cruciate ligament-stabilized knee arthroplasties. Ann Clin Anal Med 2021;12(6):617-620
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Can the novel inflammatory markers be used in the prediction of Gestational Diabetes Mellitus or to strengthen the screening test?
Deniz Simsek, Yasin Altekin
Department of Obstetrics and Gynecology, Bursa Yuksek Ihtisas Training and Research Hospital, University of Health Sciences, Bursa, Turkey
DOI: 10.4328/ACAM.20362 Received: 2020-10-04 Accepted: 2020-11-03 Published Online: 2020-11-15 Printed: 2021-06-01 Ann Clin Anal Med 2021;12(6):621-625
Corresponding Author: Deniz Simsek, Mimar Sinan Mah. Emniyet Cad. Polis Okulu Karşısı Yıldırım, Bursa, Turkey. E-mail: drdenizsimsek@gmail.com P: +90 224 294 40 00 – 4037 F: +90 224 366 69 25 Corresponding Author ORCID ID: https://orcid.org/0000-0002-0975-9457
Aim: The pathophysiology of Gestational diabetes mellitus (GDM) has not been exposed properly, however, some clues designate the systematic inflamma- tion. New inflammatory markers such as mean platelet volume (MPV), neutrophil- to- lymphocyte ratio (NLR), platelet- to-lymphocyte ratio (PLR), and platelet distribution width (PDW) might play a crucial role in predicting or diagnosing GDM.
In this study, we aimed to evaluate the possible association between the CBC parameters (MPV, PDW, NLR, PLR values) which were sampled on the test day of the glucose challenge test and GDM.
Material and Methods: Pregnant women who underwent 50 gr GCT were evaluated. Among them, patients with an abnormal 100 g oral glucose tolerance test (OGTT), and normal OGTT results were recruited in groups 1 and 2, respectively.Women with normal GCT were included in Group 3 as controls. Patients who had complete hemogram count on the day of GCT or OGTT were reviewed.The MPV, NLR, PLR and PDW parameters were analyzed statistically between groups.
Results: A total of 9819 patients were screened with 50gr GCT over a 3-year period. The distribution of patient numbers within the groups in groups 1, 2, and 3 was 167, 400, and 610 patients, respectively. There was no statistically significant difference between Group 1 and Group 2 for NLR, PLR, Platelet, MPV, PDW, neutrophil, lymphocyte, and hemoglobin (p>0.05). Healthy patients had higher MPV and lower PDW values than patients with GDM, which differed significant.
Discussion: Neither the novel inflammatory markers PLR, and NLR, nor the platelet parameters PDW, and MPV seemed to be beneficial to predict GDM or strengthen the 50g glucose challenge test during the routine screening period. These markers might be related with chronic circumstances, and the usefulness of novel inflammatory markers might be revealed in the near future.
Keywords: Inflammation marker; Neutrophil-to-lymphocyte ratio, Mean platelet volume; Gestational diabetes mellitus; Platelet-to-lymphocyte ratio; Platelet distribution width
Introduction
Gestational diabetes mellitus (GDM) is carbohydrate intolerance resulting in hyperglycemia which is primarily diagnosed during pregnancy. Physiological changes in pregnancy induce peripheral resistance to insulin to ensure a sustained supply of glucose to the fetus resulting in a 250% increase in insulin production [1]. The circumstances that cannot respond to these changes would cause GDM. The pathophysiology of GDM has not been elucidated properly. Recent studies emphasize that systematic inflammation may play a key role in susceptibility to GDM [2, 3]. The factors that initiate the primary inflammation are controversial. The type of the inflammation, acute or chronic, in gestational mellitus is controversial. However, several serum markers were investigated to identify the responsible elements, so that prediction or prevention of DM or GDM could be possible. In recent years, physicians have intensified their attention on hemogram parameters for systemic inflammation. Neutrophil- to- lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are considered as novel markers of systemic inflammation [4, 5]. These parameters could be achieved using a complete blood count (CBC) test, which is inexpensive, feasible, and accessible. Other CBC parameters, which could give precious information about diabetes are mean platelet volume (MPV) and platelet distribution width (PDW) [6, 7]. Several studies have depicted that these parameters could be correlated with DM and GDM, especially with accompanying microvascular complications [8, 9]
There is no consensus regarding the optimal approach for screening gestational diabetes mellitus. One-step and two-step approaches were recommended and utilized for GDM screening and diagnosis. The American College of Obstetricians and Gynecologists (ACOG) continues to recommend a two-step approach using the Carpenter-Coustan criteria cutoffs [10]. In our hospital, all patients with low risk of GDM are screened using a two-step approach between the 24th and 28th weeks of gestation. If the patient has an increased risk factor for GDM, a 75gr glucose load challenge test is performed regardless of the gestation week. Consumption glucose for a gestational diabetes test can make patients feel like it could harm the baby or themselves, which may be most related to obtaining information from the media or from unreliable sources. Many patients may hesitate to undergo glucose load tests, especially for repeated intravenous blood samplings [11]. Several studies were conducted to evaluate the prediction or association between CBC parameters and GDM with few participants. We aimed to evaluate the possible association between CBC parameters (MPV, PDW, NLR, PLR values), which were sampled on the day of testing the glucose challenge test and GDM.
Material and Methods
A retrospective cohort study was designed after approval of the local ethics committee in Bursa Yuksek Ihtisas Training and Research Hospital, University of Health Sciences. Women who had a 50 g glucose challenge test (GCT) without starvation at 24 -28 weeks of gestation between June 2016 and September 2019, were reviewed. All women with plasma glucose values between 140 and 199 mg/dl after 1 hour following the 50 g glucose intake were advised to undergo a 3-hour 100-gram oral glucose tolerance test (OGTT) after a 3-day standard diet, which was comprised of a daily intake of at least 250 g carbohydrates. Initially, a blood sample was obtained after 8-10 hours of fasting. After measuring fasting blood glucose, patients were instructed to take 100 g of glucose. Blood samples were repeated at one-hour intervals a total of three times. GDM diagnosis was established based on Carpenter- Coustan criteria after OGTT if two or more blood glucose values were higher than the defined cutoff values, namely, fasting blood glucose levels ≥ 95 mg/dL and blood glucose levels of ≥180 mg/dL, ≥155 mg/dL and ≥ 140 mg/dL during the first, second, and third hours, respectively [12]. Venous blood glucose levels were measured by the Cobas® e 602 modules (Roche, New Jersey, USA).
Patients who had a complete hemogram count (CBC) test on the day of GCT or OGTT were recruited into the study. Patients with a family history of DM, previous history of GDM, previous delivery of macrosomia, unexplained fetal loss, elevated risks of GDM including metabolic syndrome, polycystic ovary syndrome, use of corticosteroids, and patients with multiple pregnancies were excluded from the study because these patients underwent directly 75 gr or 100gr OGTT regardless of the gestational week in our hospital. Patients who had any concomitant disease that can affect complete blood count like anemia (Hb< 10.5 gr/dl), leukocytosis (white Blood Cell >15.000 μl/ml), thrombocytopenia (Platelets < 150.000 μl/ ml), auto-immune disease, chronic inflammatory disease or hematological disorders were also excluded.
All laboratory data and patient information were retrieved from Bursa Yuksek Ihtisas Training and Research Hospital database. All venous blood samples for CBC examination were collected in 2 mL EDTA tubes and analyzed using an automated hematology analyzer (Mindray BC-6800 Plus, Shenzhen, China) within 1 hour to avoid time-dependent ultrastructural morphological changes in platelets. In our laboratory, the normal range for MPV and is taken as 7,8–11 femtoliters (fl).
Patients were divided into three groups. Group 1 consisted of the patients diagnosed with GDM. The diagnosis was confirmed by two or more blood glucose values that were higher than the defined cutoff values in OGTT, which was performed after an abnormal GCT test (plasma glucose value between 140 and 199).
Group 2 consisted of patients with false positive GCT, which was defined as normal OGTT (all values were normal or only one value was higher than the cutoff values) after abnormal GCT (plasma glucose value was between 140 and 199).
Group 3 consisted of the patients with plasma glucose values < 140 mg/dl in GCT (healthy control group).
Complete blood count parameters (MPV, PDW, platelet, hemoglobin, NLR, PLR) which were sampled on the day of GCT or OGTT, were reviewed for each patient.
Primarily we aimed to investigate the difference between these groups in terms of CBS parameters to find out a proper threshold for GDM to prevent glucose-consuming tests.
The study sample size determination was calculated by evaluating similar studies with a statistical power analysis program. As a result, to achieve 80% power with 5% type 1 error to detect a minimum clinically significant difference, at
least 114 individuals must have been included in each group. Statistical analysis was performed using the SPSS 24.0 software for Windows. The normal distribution of continuous variables was evaluated using the Shapiro-Wilk test. Skewness and kurtosis values were also used to determine the normality of the population. Due to the normality results, patients’ data were compared between three groups with a one-way ANOVA test. Levene’s test was used to assess the homogeneity of the variances. An overall p-value of less than 0,05 was considered statistically significant.
Results
The total number of patients who were screened with 50g GCT between 24-28 weeks over a 3-year period was 9819. Among these, GCT test results of 1259 patients were between 140 and 199. The number of patients who underwent OGTT was 690. The rest of the patients either declined the diagnostic test or underwent the testing in another health center. One hundred ninety-six patients were diagnosed with GDM (Group 1) after OGTT. Twenty-nine patients were excluded from the study due to exclusion criteria (11 did not have a CBC test, 2 had twin pregnancy, 8 had anemia, 3 had leukocytosis and 5 had thrombocytopenia). Four hundred ninety-four patients had a normal diagnostic test with abnormal screening test (false positive GCT), and 400 of them were included in the study. Ninety-four patients were excluded (27 did not have CBC test, 7 had twin pregnancy, 36 had anemia, 9 had leukocytosis and 15 had thrombocytopenia) due to exclusion criteria. Six hundred and ten patients with normal screening tests were included in the study as a control group (Group 3).
Patients with GDM were older than the rest. Patients in Group 2 were also older than healthy controls. Evaluation CBC components revealed that there was no statistically significant difference between groups.
The novel inflammatory parameters such as NLR and PLR were higher in groups 1 and 2; however, these levels did not differ significantly. Mean platelet volume and the platelet distribution width were the only parameters that differed significantly in the present study. MPV was higher in healthy subjects than the false positive GCT groups and GDM groups, which differed significantly. Opposite of MPV, PDW was lower in healthy, and this difference was significant.
Laboratory results of the patients and comparison of the parameters with p-values were evaluated in Table 1.
The main determinants of gestational diabetes were evaluated via correlation analysis. It was revealed that age (as expected) and PDW positively, and MPV negatively correlated with GCT values; however, these correlations were weak (r<0.4). Correlation analysis of the parameters with age was evaluated. MPV, PDW, PLR were associated with age, yet this correlation was very weak (r<0.2). The correlation between parameters with GCT and age was evaluated in Tables 2 and 3.
Discussion
Gestational diabetes mellitus emerges due to the insufficient response with an adequate amount of insulin secretion to physiological changes during pregnancy. The prevalence of the disease bears an increasing trend due to the increasing risk factors. Causes of insulin resistance such as obesity, polycystic ovary syndrome, genetic history of diabetes, advanced age, and steroid consumption are major risk factors of GDM. Placental growth hormone, corticotropin-releasing hormone, placental lactogen, tumor necrosis factor-α (TNF-α), and progesterone initiate an adequate metabolic environment for the necessity of the fetus. The effect of these hormones arises apparently during the late second trimester of the pregnancy. Thus, almost all the obstetrician associations recommend performing GDM screening tests during 24-28 weeks of gestation.
Recent studies declared the benefits of the GCT and OGTT without any harm to the fetus and pregnant women; however, some patients have a prejudice about the test. GCT could be a more reasonable option, and OGTT might be occasionally challenging for patients with blood testing done four times and high glucose levels. Every single day as the novel diagnostic tests evolve, patients request a test without any intervention. They require a test without consuming glucose or other molecules. We aimed to investigate whether CBC parameters could benefit to GDM diagnosis.
Our findings revealed that patients with GDM are significantly older than healthy participants, and this is consistent with the literature since age is the major risk factor for GDM. Patients with GDM were also significantly older than patients with false-positive GCT. There is no consensus on this data. When evaluating the number of participants and the including criteria of the studies, it was found that the present study included the largest number of participants compared to other studies in the literature [13-15], and this is the strength of our study. We also depicted that patients with false positive OGT were older than healthy controls. In this regard, increased age might affect the response of the pancreatic beta cells to acute glucose consumption.
Physiological changes in pregnancy have an impact on complete blood count parameters [16]. Leukocytosis with increased lymphocytes is normal. Any disease could affect the distribution of blood components. To diminish this effect, we excluded participants with anemia, leukocytosis, thrombocytopenia, or thrombocytosis [17]. The levels of the neutrophils, lymphocytes, and hemoglobin did not affect due to gestational diabetes status. Comparing the NLR and PLR which were determined as novel inflammatory markers, we found no statistically significant difference between all groups. The mean values of these parameters were higher in GDM and false positive patients than the healthy control group, with no statistically significant difference. Even though NLR and PLR are supposed to be inflammatory markers, there is no consensus as to whether they are indicative of acute or chronic inflammatory processes. Recently, NLR and PLR have represented a statistical significant difference in patients with chronic diseases with concomitant end organ failure [18-20]. Aktulay et al. declared a significantly increased NLR and PLR in patients with GDM although they included only 29 patients in each group [21]. These markers have also been evaluated as predictors of GDM during the first trimester of pregnancy, yet the studies depicted no benefit on this subject [22, 23]. In the light of the studies, NLR and PLR may be beneficial in chronic situations. Thus, due to our findings, NLR and PLR were not beneficial for distinguishing patients with GDM. On the other hand, GDM seems to be an acute illness, which exposes itself in the late second trimester of the pregnancy. We do not think that this disease can be detected using chronic inflammation markers.
The other CBC markers, which were investigated in GDM and DM, were thrombocyte parameters (Platelet count, MPV, PDW). Authors have investigated MPV as a predictor for GDM or to follow up serum glucose regulation. One of the major aims of the present study was the use of MPV and PDW as a diagnostic tool for GDM with a study with broad participation. Due to the result of our study, no statistically significant difference has occurred comparing MPV, PDW, and platelet counts between GDM patients and false-positive GCT patients. Although the mean values in all groups were within the normal MPV range, the healthy controls had a higher mean level than the false positive GCT group and also GDM group. This result was contrary to many articles [23-25]. A meta-analysis declared that MPV values were significantly higher in GDM patients; however, authors also remarked the heterogeneity of the studies and a possible bias [6]. When comparing studies in the literature with our study, the interesting fact was that our study not only had one of the largest numbers of participants, but also had clear and strong inclusion and exclusion criteria. We have stated that using MPV values did not seem beneficial to diagnose or predict GDM at late second trimester of the pregnancy. Scanning tests were proposed to be performed between 24-28-week of gestation. During this period of the pregnancy, the maximum effect of the pregnancy diabetogenic hormones on metabolism was possible. Thus, in this period, the influence of diabetes on the CBC parameters might not be initiated.
PDW, which was another test for thrombocyte function, was also investigated as a marker for GDM. The difference was significantly higher in patients with abnormal GCT (GDM and false positive GCT) than healthy control conversely to MPV values. Comparing GDM patients and the false positive group, it wasfoundthatPDWwasnotagoodmarkerfordistinguishing GDM patients as well. There is still no consensus on the effect of GDM on MPV and PDW [24, 25]. More studies examining PDW in GDM are required for this issue.
A correlation analysis was calculated to find whether the parameters might be a good diagnostic tool. Age, MPV and PDW were correlated with GCT results, with weak or very weak correlation. Age was also analyzed particularly with the CBC parameters. The result was the same as a very weak correlation; however, the strengths of these correlations were also very weak.
In conclusion, neither the novel inflammatory markers PLR, and NLR nor the platelet parameters PDW, and MPV were beneficial to predict GDM or strengthen the 50g glucose challenge test during the routine screening period. These markers may be related to chronic circumstances.
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.
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Evaluation of “white code” notifications at the training and research hospital between 2015 and 2019
Mustafa Çalık 1, Melike Mercan Başpınar 2, Serpil Soyudoğru 1
1 Department of Emergency Medicine University Of Health Sciences Gaziosmanpasa Training And Research Hospital, 2 Department of Family Medicine University Of Health Sciences Gaziosmanpasa Training And Research Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.20364 Received: 2020-10-06 Accepted: 2020-11-07 Published Online: 2020-11-20 Printed: 2021-06-01 Ann Clin Anal Med 2021;12(6):626-632
Corresponding Author: Mustafa Çalık, Department of Emergency Medicine, University of Health Sciences, Gaziosmanpaşa Training and Research Hospital, Osmanbey Street, 621 Street, 34255, Gaziosmanpaşa, İstanbul, Turkey. E-mail: drmustafacalik@yahoo.com P: +90 2129453000 Corresponding Author ORCID ID: http://orcid.org/0000-0002-3184-2943
Aim: This study has been carried out as part of the activities to define Workplace Violence (WPV) based on the white code system according to age, gender, types, sources, time-periods, and groups in health care professionals (HCPs). The white code notification is a government support system including a web ad- dress, a call center serving all day, and free legal support for HCPs.
Material and Methods: A retrospective data-based study was realized by including 316 white code notifications at Gaziosmanpaşa Training and Research Hospital in Istanbul, Turkey, between January 3, 2015 and January 1, 2019. The statistical significance level of tests was accepted as p<0.05 using statistical software SPSS version 22.
Results: Samples consisted of 316 (mean age=31 ±6.8 years) HCPs (49% male, 51% female) who were reported in white code applications for four years. WPV was distributed as doctors in 160/316 (50.6%), nurses in 65/316 (20.6%), security personal in 50/316 (15.8%), secretary in 29/316 (9.2%) cases respectively. Nurses and medical secretaries exposed to violence aged under 30 years had a significantly higher rate than those aged ≥30 years old (p=0.002). The highest prevalence of violence in the hospital was in polyclinic rooms (66.5%). Distribution of WPV based on departments was as follows: emergency medicine (36.4%), pediatrics (16.5%), and internal medicine (7.3%). In this study, the most common type of violence was insult plus verbal threat (39.6%) and the most common reason was the waiting-line problem (21.8%). WPV was highest in the summer season (30.4%), around 12:00-16:00 hours (28.2%), and peaked in September (10.8%) and December (10.8%). WPV was shown increased in 2018 (31.6%) than that of 2015 (19.9%), 2016 (24.1%), and 2017 (24.4%) especially in doctors (p=0.002) and female HCPs (p<0.001).
Discussion: The results of this research show the importance of increasing white code cases, especially the percentage of doctors and female HCPs. The impli- cations of this study are expected to provide feedback in describing increased WPV to health workers. Institutions should train staff to handle violence, provide a therapeutic environment, simplify the reporting process, and encourage reporting of all types of violence.
Keywords: White code; Health care professionals; Workplace violence
Introduction
The World Health Organization (WHO) describes workplace violence (WPV) as incidents where a person is abused, threatened, or assaulted in a a working environment. Though health care workers are known to be particularly at risk of exposure to workplace violence, attention has been drawn to this problem only in recent years (Wiskow C. Guidelines on workplace violence in the health sector. World Health Organization/International Labour Office. 2003;40.) Nowadays, the trend of violence against physicians is like a new viral epidemic according to some authors [1].
The term “verbal violence” might be defined as an attempt to attack another person using harsh words, cursing, an aggressive manner of speech, threats, or any other manner of speech that is unacceptable but does not lead to physical injury. “Physical violence” might be defined as any form of attack that has a physical component [2].
The United States Government Accountability Office reported in 2016 that healthcare workers experienced violence-related injuries at a rate five times higher than workers in other industries [3]. In Turkey, of the12 944 health workers in a national survey, 43.2% have experienced verbal violence, 6.8% physical violence. Mobbing and sexual harassment have been identified in 2.4% to 1% [4, 5] and studies have shown that 44.7% of all HCPs are victims of violence every year [6]. Unfortunately, over the past decade, five doctors were killed by patients or patients’ relatives [7]. A total of 65 studies reported a one-year prevalence of WPV against HCPs perpetrated by patients or visitors, with prevalence estimates ranging from 2.75% to 88.31%[8].
Background
In the tenth development plan between 2014-2018 in our country, it was decided to develop approaches to the provision of medical care, taking into account the effectiveness of clinical interventions, the safety and satisfaction of patients and health professionals. The implementation of different colored codes (blue code in 2008, pink code in 2009, white code in 2011, and red code in 2015) was launched by the Ministry of Health policies. Code White is an emergency warning code created to respond to an action as soon as possible in the presence of violence risk/interference with staff working in the health institution and organization or in case of violence (Sağlıkta Ulusal Renkli Kodlara (URK) İlişkin Yeni Düzenleme/ New Regulation on National Color Codes in Health (URK) 2013). The web address www.beyazkod.saglik.gov.tr was created with the 113 White Code Call Center, which will serve 7 days and 24 hours, and a technical and administrative infrastructure related to the white code system has been requested in each hospital (Çalışan Güvenliği Genelgesi/ Employee Safety Circular (14.05.2012) – TC Sağlık Bakanlığı/ TR Ministry of Health ). Aim
In this study, the primary aim is to estimate the distibution of HCPs who experienced aggression and violence based on white code notifications by years, and the secondary aim is to observe characteristics (age, gender, department, reason, violence type, seasonality, etc.) associated with an increased risk of WPV.
Material and Methods
Study population and design
We conducted a retrospective analysis for the last four years between January 3, 2015 and January 1, 2019. We have applied for permission from the hospital management and ethics committee for using data. The demographic and clinical data of 316 white code victims aged ≥18 years were analyzed. Evaluation of WPV
The types of aggression were listed as verbal threats, physical violence, damage to property, insult, and/or combinations of these. The time of WPV was noted as hour, day, month, season, and year, while the WPV area was classified including information about the department of abused HCPs, as a polyclinic room, service floor, intervention room, and other locations.
Selection Criteria
The white code list used in the study was retrospectively collected at the “Employee Rights and Security” unit of the hospital, and the white code incident forms collected in the “White Code Unit”. We discussed these results in light of recent legal reforms and researched evidence-based administrative data. The study included all cases in the 2015-2019 period. Classification of HCPs
Occupational groups were classified using the International Standard Classification of Occupations (ISCO-08) with modifications (ILO, ISCO-08—International Standard Classification of Occupations, 2012). The main groups of two branches were health professionals (medical doctors, nursing and midwifery professionals, paramedical practitioners, other health professionals such as dentists, pharmacists, physiotherapists, dieticians, audiologists, etc.), health associate professionals (medical and pharmaceutical technicians, nursing and midwifery associate professionals, other health associate professionals such as ambulance workers, etc.) and personal care workers. At the end of the study, occupation groups were revised with less grouping for statistical comparisons. Statistical data analysis
Data were prepared by Microsoft Excel 2016 program and analyzed with statistical software SPSS version 22. The analyses were summarised using pie charts, tables, mean, median, and frequencies and were presented in tables and graphs. The Chi-Square test was used to compare groups and categorical variables. It was set at 80% power with an alpha error = 0.05. The sample size was calculated using the G-power program.
Ethical aspects
Taksim Training and Research Hospital Clinical Research Ethics Committee approved this study on May 28, 2020 ( Approval no:92).
Results
The distribution of white code cases in hospitals by years was 2.8% (63/2183) in the 2015-2016 period, 3.8% (76/1978) in the 2016-2017 period, 3.9% (77/2000) in the 2017-2018 period, and 5.5% (100/1817) in the 2018-2019 period, respectively. Table 1 shows the medical demographics of screened 51% of females 49% of males, and a total of 316 white code cases aged 31 ±6.8 (median=30) years during the period 2015-2019. Most of all white code notifications were from doctors (50.6%), exposed in polyclinic areas (66.5%), and in the emergency departments (36.4%). The rate of white code was highest in the summer season (30.4%), around 12:00-16:00 hours (28.2%), and peaked in September (10.8%) and December (10.8%); 72.3% of the nurses ( 47/65) and 69% of the secretaries (20/29) were under the age of 30 in cases of violence. There was a significant difference between younger and older nurses/ secretaries (p=0.02).
In this study, the most common violence resource was visitors/ partners (63.3%), the most common type of violence was Insult+ Verbal threat (39.6%), and the most common reason was the waiting-line problem (21.8%) (Table 2). WPV sources were distributed as follows: only the patient in 21.5% of cases, only visitors/relatives in 63.3%, both patients and their visitors/ relatives in 15.2% of all cases. Female gender was significant among locations of WPV (p=0.001), occupational groups (p<0.001), resource of violence (p=0.02), medical departments (p<0.001) and reasons of violence (p=0.001). Female doctors (28%) had more often white code from male doctors (22.5%), female nurses (15.5%) than male nurses (5%), male security personnel (14.2%) than female security personnel (1.6%). While code alerts of male (33%) and female (33%) HCPs from the polyclinic room was similar, women reported more white codes from the service floor (12%) and intervention room (5%) comparing with males ( 8.5% service floor and 2% intervention room, respectively). Female HCPs had a higher rate of white code exposed by woman patients (7.2% female HCP, 2.5% male HCP) or woman patient plus her visitors (3.2% female HCP 2%, male HCP) than that of other groups. White code rate at the Emergency department was higher in male HCPs (23.5%) than that of female HCPs (13%). Female HCPs had higher rates for style problems in communication, waiting-line problem, the problem with opposing doctor’s directives, and treatment dissatisfactions than that of male HCPs. The ratio of women to men reporting the white code did not change significantly depending on the season (p=0.36). Table 3 reveals the assessment of the change in the distribution of gender, occupation, the area exposed violence, time, and season by years. The rate of WPV in 2018 was significantly higher in female gender (p<0.001), in doctors (p=0.002), in polyclinic room (p<0.001), time around 00:00-04:00 (p<0.001).
Figure 1 shows the periods (time) of WPV based on season and occupation. The best time was around 04:00-08:00 in all spring months for everybody but in the summer season,100% of WPV cases were against secretaries around 04:00-08:00. The worst time for doctors was between 08:00-12:00 hours in autumn. The worst time for nurses was in summer between 20:00 and 00:00 time o’clock. In the summer, 08:00 to 16:00 was the worst time for the security personnel. Figure 2 shows that in 2018, while the number of WPVs against doctors has increased in polyclinic room during the autumn, it decreased at the service floor after the pick in spring. Especially in all winter months, there was a large difference in WPV against doctors between polyclinic room (n=58 totally in winter) and service floor (n=8 totally in winter ) violence numbers. As seen in Figure 3, the first common reason of WPV against male HCPs was visitors’ problems, and secondly, technical/ physical problems, while among female HCPs, the most common reason was the waiting-line problem and secondly, opposition to a doctor’s directive by a patient. In 2018, patients or relatives with a psychological problems accounted for a higher percentage of violence against male healthcare workers but waiting-line problems had the highest rate in both genders.
Discussion
The results of this research show the importance of increased white code cases especially the percentage of doctors and female HCPs. The implications of this study are expected to provide feedback in describing increased WPV towards health workers. Institutions should train staff to handle violence, provide a therapeutic environment, simplify the reporting process, and encourage reporting of all types of violence.
Age and Gender
In some studies on WPV, the mean age of participants was 30.92 ± 7.94 years [9], 32.6 ± 5.1 years [10], 35.42 ± 7.89 years [11], or 36.4% were aged < 35 years [12] or it was significant for physicians aged between 31-40 years [11]. Bayram et al. observed that most participants were between 30 and 40 years of age and 60.1% were male in their WPV study. On the other hand, the rate of female gender was 59.6%, and the risk of violence was 2.4 times higher among younger people (≤ 29 years) in the study by Pınar et al. [5]. In our study, the mean age was 31 ± 6.8 years and 57% aged <30 years, similarly. In a systematic review emphasizing gender differences in physical violence, the researcher found that numerous studies showed that male health care professionals experienced more workplace physical violence than females [13]. A study showed that workplace violence and post violence effect on work efficiency is more prevalent in younger doctors [9]. In our study, age <30 years was significant in nurses and medical secretaries, but not for doctors or other occupations. The age parameter was not significant between genders. The female group had a bit higher percentage than the male group. Although the age variables were similar to the literature, we thought that differences in gender parameter may be the result of change in the working women rate based on some socio-cultural effects in different countries.
Evaluation of prevalence for white code
Among our white code cases, 63.3% were related to patient’s relatives or visitors. A total of 65 studies reported a one-year pooled 19.33% prevalence of WPV against HCPs, with prevalence estimates ranging from 2.75% to 88.31%. As a subgroup, WPV by patients or visitors was 26.38% in the European region, 14.53% in the western Pacific region, 20.71% in the African region, 17.07% in the eastern Mediterranean region, 23.61% in the Americas region, and 5.62% in the Southeast Asia region [8]. In our hospital, the prevalence of white code notifications seemed to be low (the highest value x %, yearly) for WPV literature rates, but it was just an iceberg because we could not learn the real percentage of unreported white code cases, all these were reported legal cases. It was an important problem related to most studies just like ours. For example, Niu et al. showed that only 4.9%–12% of the victims completed an incident or accident form [14]. Another rate of incidence was 33.3% in the study by Stanley et al. [15] and 41.6% of white code applications were submitted once or more, as well [11]. Distribution of WPV
The latest review based on the study by Mento et al. investigated the impact of WPV and found that major incidents of violence occur in emergency and psychiatric departments [16]. Most of the studies has assessed specifically workplace physical violence against nurses [8]. Even the proportion of WPV against nurses (22.99%) perpetrated by patients or visitors was significantly higher than against physicians (14.66%) in a meta- analysis [8]. In contrast to the literature, in our study, half of the white codes were doctors and a quarter were nurses. In the study by Li et al., WPV against male health care professionals (7.37%) perpetrated by patients or visitors was similar to that against female (8.40%) health care professionals [8]. In the study by Din et al., the prevalence of “verbal abuse” was found to be 76.29%, while that of “threat to assault” and “physical assault” was found to be 17.77% and 5.92%, respectively [9]. Chiawa et al. indicated that the prevalence of psychological violence among participants was 49.7%, and verbal abuse was the most common form of psychological violence, accounting for 40.8% of all [12]. In our study, insult + verbal threat (39.6%) was the most common type of WPV, and aggression, including any insult and/or verbal threat-totally was 67.4% , that is similar to the study by Hacer et al., in which they found that doctors who were exposed to violence at work were exposed to verbal and psychological violence more than physical violence [11].
In a study from America, the inclination to violence springs from the ghetto poor, the stigma of race, the fallout from rampant drug use, and drug trafficking, resulting in alienation and lack of hope for the future. Simply living in such an environment exposes young people to special risk of falling victim to aggressive behavior [17]. At the same time, an Indian study declared long working hours and poor work environment for government doctors, which makes them susceptible to making mistakes and prone to violence [1]. We thought that socio-economic factors would be related to WPV. The district of hospital location is the 32nd district (32nd/39) within the city according to the level of socio-economic development. In our clinical experience, some factors, such as living difficulties, drug use, etc, in this location, were higher than in other district locations.
Time differences (time, seasonality, variation among months, difference in years)
Working between 18:00 and 07:00 hours was an independent risk factor for WPV in the study by Pınar et al. [5]. According to a study by Al-Mascari et al., the majority of incidents took place during the afternoon (78.9%) or night shifts (93.1%) [10]. In our study, the most common time of violence occurrence was between 12:00 and 16:00 (%28.2) and between 08:00 and 12:00 (25.6%), similar to the study by Stanley et al., which showed that the time from 07:00 to 13:00 was the time of maximum violence occurrence (26.2%) [15].
Most Reported Reasons of WPV
In a study conducted in a university hospital, participants stated that the reason for the increase in violence against HCPs was related to lack of education of the patients and their relatives (73.2%) and was associated with longer waiting times in hospitals for examination (53.2%) [18]. A study from Israel suggested that waiting times may have a cultural element. While shortening waiting times and providing more information to patients and families could reduce the rate of violence, but a cultural change may need [2]. In our study, waiting line problems (such as long time waiting or mix waiting for line, etc.) were the most common reason (21.8%) reported with white code. Based on the years, especially the 2018 year was important because our hospital was damaged by a big fire and the health service was temporarily given in the additional service building. The additional service building was smaller than the main building, and all departments had to work together in very difficult conditions in polyclinics and emergency rooms. Thus, we thought that conditions like a long waiting-line or waiting time as a result of new working conditions might be a reason for increased WPV in 2018 compared to other years. Patients’ high expectations in tertiary hospitals could not be met exactly in extraordinary situations like fire, epidemics, earthquakes, etc. A bit of tolerance would help all of us.
Study Limitations
Victims of WPV did not report an incident or accident form, and the main reason was the belief that reporting such incidents was useless or unimportant as seen in different study samples [14]. As we started this study, our goal was to make a qualitative analysis of workplace violence against healthcare professionals and related factors based on open-ended, semi- structured interviews with HCPs, but we saw that victims had no belief in anything changing about violence and they did not want to reply questions in our pilot study. Thus, we had to make a quantitative study based on reported cases in the descriptive study of the retrospective design.
Conclusion
• Increased percentage of white code distribution especially towards doctors more than other Health Care professionals (HCPs) and towards females more than males in 2018 than in 2015, 2016, and 2017 years
• Waiting-line problems were the most common WPV reasons reported
• Nurses and medical secretaries aged under 30 years had significantly higher workplace violence (WPV) rates than aged over 30 years
• The only period without violence for all HCPs during four years was between 04:00-08:00 in the spring season every year
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.
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Mustafa Çalık, Melike Mercan Başpınar, Serpil Soyudoğru. Evaluation of “white code” notifications at the training and research hospital between 2015 and 2019. Ann Clin Anal Med 2021;12(6):626-632
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The effect of bilateral and unilateral knee arthroplasty under regional anesthesia on ischaemia-modified albumin and thiol/disulphide homeostasis
Seyda Efsun Ozgunay 1, Sermin Eminoglu 1, Nazan Cevik 2, Yasemin Ustundag 3, Mehmet Gamli 1, Zeynep Tabur 4, Umran Karaca 1, Derya Karasu 1, Canan Yilmaz 1, Ozcan Erel 5
1 Department of Anesthesiology and Reanimation, University of Health Sciences, Bursa Yuksek Ihtisas Training and Research Hospital, Bursa, 2 Department of Orthopedics and Traumatology, University of Health Sciences, Bursa Yuksek Ihtisas Training and Research Hospital, Bursa, 3 Department of Medical Biochemistry, University of Health Sciences, Bursa Yuksek Ihtisas Training and Research Hospital, Bursa, 4 Department of Anesthesiology and Reanimation, Bursa City Hospital, Bursa, 5 Department of Medical Biochemistry Laboratory, University of Health Sciences Ankara Yıldırım Beyazıt Research and Education Hospital, Ankara, Turkey
DOI: 10.4328/ACAM.20365 Received: 2020-10-06 Accepted: 2020-11-04 Published Online: 2021-02-09 Printed: 2021-06-01 Ann Clin Anal Med 2021;12(6):633-637
Corresponding Author: Seyda Efsun Ozgunay, Department of Anesthesiology and Reanimation, Bursa Yuksek Ihtisas Training and Education Hospital, Mimar Sinan Street Yildirim, 16290, Bursa, Turkey. E-mail: seyda-efsun@hotmail.com P: +90 5359723603 Corresponding Author ORCID ID: https://orcid.org/0000-0003-1501-9292
Aim: Tourniquet application in extremity surgery causes ischemia-reperfusion injury. An increase in ischemia-modified albumin level is an early indicator of ischemia. The aim of this study is to investigate the effect of bilateral and unilateral total knee arthroplasty on the oxidation parameters and ischemia- modified albumin level, and thiol/disulfide homeostasis.
Material and Methods: A total of 57 patients who underwent knee arthroplasty were included in the study. Patients were divided into two groups: group 1 with unilateral knee arthroplasty (n=33) and group 2 with bilateral knee arthroplasty (n=24). Sociodemographic features, ischemia-modified albumin levels, and thiol/disulphide homeostasis were evaluated.
Results: Ischemia-modified albumin levels at the 5th minute and 24th hour were significantly higher in the bilateral arthroplasty group compared to its pre- operative level (p=0.001 and p=0.01, respectively). In the unilateral group, ischemia-modified albumin was significantly higher only in postoperative 24th hour compared to preoperative levels (p=0.012). In the intergroup comparison, only the ischemia modified albumin value at 5 minutes was high in the bilateral group (p=0.002). The hospital stay in Group 2 was significantly longer than that of patients in Group 1 (p=0.035).
Discussion: In cases of bilateral knee arthroplasty with spinal-epidural anesthesia, preoperative thiol/disulfide homeostasis parameters and ischemia-modified albumin values did not differ at the postoperative 24th hour.
Keywords: Regional anesthesia; Knee arthroplasty; Bilaterally; Modified albumin; Thiol
Introduction
Osteoarthritis is a chronic degenerative disease with a high prevalence and costly treatment, especially involving load- bearing joints with pain, deformity, limited range of movement, and functional loss [1,2]. Most of the patients with osteoarthritis of the knee have symmetrical involvement, which requires bilateral surgery [3,4]. Total knee arthroplasty (TKA) is a frequent intervention in cases not responding to conservative treatment [5]. TKA can be performed on both knees simultaneously or in separate attempts [6-8]. Although simultaneous bilateral operation under a single anesthesia session has the advantages of lowering overall costs, shortening hospital stay, and better rehabilitation, the subject is under debate concerning the importance of patient selection [9,10].
Reperfusion after the ischemia incurred by TKA gives rise to protein fragmentation and changes in protein metabolism including protein synthesis inhibition [11]. Protein oxidation by the reactive derivatives, aromatic amino acids and thiol group oxidation can result in the transformation of protein products and some amino acid residues. The earliest sign of protein oxidation by free radicals is the oxidation of the -SH groups of amino acids. Thiols have interaction with most of the physiological oxidants and act as the essential antioxidant buffers [12]. Oxygen-free radicals cause lipid peroxidation in membranes, endothelial damage and can result in multiple organ failure. Another oxidation parameter that may be used as a perioperative ischemia marker is ischemia-modified albumin (IMA). Ischemia-reperfusion(I/R) injury, hypoxia, acidosis, and superoxide radical damage occur when the capacity of the albumin bind to metals by changing the structure of the N-terminal and IMA increases within minutes [13].
Surgery with anesthesia increases postoperative complications through endocrine, metabolic and immunological imbalance and increases morbidity and mortality incidences [14]. It is acknowledged that the tourniquet (TQ) application in extremity surgery causes I/R injury [9, 11, 15-18]. Despite the reduction in the operative time and intraoperative hemorrhage volume, incidences of local tissue and nerve damage as well as possibilities of venous stasis, endothelial dysfunction, and thromboembolism have been known [19]. There are investigations on anesthesia methods, I/R injury, stress hormones, and oxidation parameters in knee arthroplasty [12,15] but studies on the oxidative system in bilateral total knee arthroplasty (BTKA) are limited. Also, the occurrence of I/R injury and the preconditioning of ischemia in the first knee by TQ application in BTKA and its prevention in the second knee have been investigated [11, 20]. To the best of our knowledge, there has been no previous study on thiol homeostasis, which is a new biomarker of oxidative stress in bilateral knee arthroplasty.
In this study, we aimed to investigate the effect of TQ on ischemia- modified albumin (IMA) and thiol/disulfide homeostasis use in BTKA and unilateral total knee arthroplasty (UTKA) under combined spinal-epidural anesthesia (CSEA).
Material and Methods
The study protocol was approved by Uludag University School of Medicine’s Ethics Committee (52588837-000/392, 201711/37). Written informed consent was obtained from patients. The study was conducted in accordance with the principles of the Declaration of Helsinki. This prospective study was carried out in a single center. The physician who evaluated the laboratory results was blinded to the study.
Patients aged 50-75 years with physical status I-III of the American Society of Anesthesiologists (ASA) for undergoing elective TKA were included in the study. The exclusion criteria were communication difficulties, preoperative cerebrovascular disease, renal or liver insufficiency, inflammatory or rheumatic disease, systemic infection or infection at the application site, body mass index >35, use of corticosteroids and antioxidant agents, and the likelihood of redo surgery. Patients who required conversion to general anesthesia were also excluded from the study.
Initially, 108 patients were recruited for the study. However, 5 refused to participate, 4 required intraoperative conversion to general anesthesia, 9 had to undergo redo surgery, and 28 had other reasons for exclusion from the study. Three of the remaining 62 patients had haemolysed serum samples and 2 had inadequate serum samples so that a total of 57 patients were included in the study after assignment to the UTKA (Group 1, n=33) and BTKA (Group 2, n=24) groups. The demographic data of the patients were recorded.
Anesthesia management
Routine intraoperative monitoring was applied to all cases. Heart rate (HR), mean blood pressure (MBP), peripheral oxygen saturation (SpO2) were recorded pre-operatively, at 5, 10, 15, 45, 60, 90, and 120 minutes following the regional intervention and after deflating the TQ. The intraoperative routine sedation consisted of midazolam (starting dosage: 0.5-1mg and titrating up to the maximal dose of 5mg), which then was followed by CSEA (Spinal epidural combined set, Egemen®, Turkey) performed at the L3-4 interspace. The patients were then administered intrathecally 3 ml of 0.5% hyperbaric bupivacaine (Busacain Heavy, Haver®, Istanbul, Turkey), and 0.25% bupivacaine (10- 15ml) through an epidural catheter. The targeted hemodynamic values were defined as an increase or decrease in HR and MBP by more than 25% from baseline (16). After deflating the TQ, 3mg morphine HCl (Galen, Istanbul, Turkey) was administered through an epidural catheter for postoperative analgesia. Operative procedure
All bilateral TKAs were performed by three surgeons. Thigh tourniquets were inflated before skin incision and deflated after skin closure. In all cases, TKA was completed on the first side before starting on the contralateral side. A medial parapatellar approach and cemented TKA components were used in all patients. The patella was not resurfaced and surgical drains were used in all patients.
Oxidation-Antioxidant measurements
Blood samples obtained preoperatively at 0 time (T0), 5 minutes after TQ deflation (T1), and at the postoperative 24 hours (T2) were kept at -80 0C until analysis. Serum samples obtained after centrifugation of the blood samples at 3600 rpm for 10 minutes were analyzed in the same session for native thiol, total thiol, disulfide, disulfide/native thiol ratio (SSSH), disulfide/total thiol percent ratio (SS/Total SH), native thiol/ total thiol percent ratio (SH/Total SH), and IMA level.
A new spectrophotometric technique previously described by Erel et al. [12] for the measurement of thiol/disulfide homeostasis was used. The IMA was measured in absorption units (ABSU) using the spectrophotometric method described by Bar-Or et al [21].
Statistical Analysis
Statistical analyses of the data were performed using the Statistical Package for the Social Sciences (IBM SPSS Statistic Inc. version 21.0, Chicago, IL, USA). Continuous and ordinal variables were expressed as mean ± standard deviation, and nominal variables were expressed as frequency. The Kolmogorov-Smirnov test was used to determine the normality and homogeneity of the data distribution. Student’s t-test was used for continuous variables with normal distribution when comparing the two groups. The Pearson chi-square test was used to detect intergroup differences on the basis of the categorical variables. The Mann-Whitney U test was used to compare two groups for continuous variables without a normal distribution. To assess the relationship between measurements of the mean serum albumin, IMA, native-thiol, total thiol, disulfide, SSSH, SS total SH, and SH total SH levels at different times, the paired t-test and Wilcoxon signed rank test were used. A p-value of <0.05 was considered statistically significant.
Results
Data of the 57 patients included in the study were analyzed statistically (Figure 1). The two groups did not differ significantly in terms of demographic features (Table 1). Durations of anesthesia, total TQ application, and hospital stay were significantly prolonged in the Group 2 (p<0.001, p=0.006 and p=0.035, respectively) (Table 1).
When comparing the data of the two groups at T0, T1 and T2, no statistically significant differences were determined in the levels of native thiol, total thiol, disulphide, SSSH, SS/Total SH, SH/Total SH and serum albumin (p>0.05) (Table 2).
In both groups, intra-group comparisons of serum total thiol, disulfide, SSSH, SS/TOTAL SH, and SH/TOTAL SH levels at T0- T1 and T0-T2 showed no significant alteration. Only serum native thiol was significantly reduced at T0-T1 in the Group 1 (p=0.022) (Table 2).
The IMA levels at T0 and T2 did not differ significantly between the two groups. Inter-group comparison of IMA levels showed a statistical increase at T1 in the Group 2 (p=0.002) (Table 2). When the intragroup IMA levels were compared between the two groups, the T0-T2 level change in the Group 1 and the T0-T1 and T0-T2 level changes in the Group 2 increased significantly (p=0.012 and p=0.001, p=0.01, respectively) (Table2).
Serum albumin values did not differ between the two groups. When assessed within the group, the levels were significantly reduced in both groups in the T0-T1 and T0-T2 intervals (p=0.027, p=0.005 and p<0.001, p<0.001, respectively) (Table2). HR and MBP did not differ significantly between the two groups. In the Group 1, comparison of the HR and MBP at T0 and T1 showed a statistically significant change (respectively, p=0.009 and p<0.001). In the Group 2, HR did not change at T0 and T1, but at 5 minutes after the first and second TQ deflations, the MBP measurements were significantly reduced (p<0.002, p=0.005, respectively) (Table 3).
Discussion
Although research on lower extremity operations including BTKA has increased in recent years, investigations on the effect of TKA on the oxidative system are of limited scope. In our study investigated the effect of BTKA on IMA levels and thiol-disulphide homeostasis. In the Group 2, immediately after the second TQ deflation, IMA levels exceeded those observed in the Group 1. Whereas the native thiol value was low in the Group1, it showed no significant alteration in the Group 2 after the second TQ deflation. The duration of anaesthesia, TQ application and hospital stay were longer for the Group 2.
The use of a tourniquet in TKA causes tissue ischaemia distal to the cuff, and after TQ deflation, reperfusion injury occurs and affects the systemic circulation [11]. Safe timing and pressure limits in TQ use are subjects of debate. Prolongued TQ application results in I/R with severer metabolic, cellular and microvascular changes and the release of oxygen free radicals [11]. There are studies in the literature on metabolic and oxidative parameters such as lactic acid, phosphocreatine, glutathione and amino acid changes in knee surgery [11, 15, 16- 18, 20, 22]. Especially the effects of replacement therapies [11, 21] and anesthetic agents [16] on I/R are being investigated. There are limited clinical trials for reducing the I/R in TKA.
The thiol groups of proteins represent a diversified defense system against biochemical changes brought about by oxidative stress, with the thiols protected in the reduced state or as disulphides [23]. According to our knowledge, there has been no previous study on the thiol-disulphide homeostasis in TKA. The only study related to IMA was conducted by Kosucu et al. [16] in relation to I/R in arthroscopic knee surgery under inhalation, spinal and total intravenous anaesthesia (TIVA), when propofol intravenous anaesthesia was found to result in a lower level of I/R, and 1 and 6 hours after TQ deflation, the IMA levels were higher in patients under spinal anaesthesia. In our study, CSEA was used and IMA, which indicates acute ischaemia within minutes, was not distinctly affected at the 5th minute after TQ deflation in the UTKA group, but it was raised after 5 minutes in the BTKA group. There are differing recommendations in the literature for both the TQ and reperfusion intervals. However, most of the authors have recommended a duration of 1.5-2 hours [24,25]. The higher level of IMA in the Group 2 compared to the Group 1 may be related to the longer duration of TQ application.
Cheng et al. [15] investigated the reactive oxygen species (ROS) and lipid peroxidation in BTKA under spinal anaesthesia. At 5 and 20 minutes after the first TQ deflation and the resultant reperfusion, an increase in ROS production was observed, whereas 20 minutes after the second reperfusion, it returned to normality and no significant change was determined in lipid peroxidation. Lee et al. [20] reported that high doses of vitamin C helped prevent haemodynamic instability and ROS production in BTKA. Also, they observed in the control group that malondialdehyde levels were raised at 5t and the 20 minutes after TQ deflation as compared to the level after administration of anesthesia, but a significant change did not occur after the second TQ deflation. In both of these cited studies, by Cheng et al. [15] and Lee et al. [20], the oxidation parameters increased after the first TQ deflation, but did not change at the 20th minute after the second TQ deflation [15,20]. In BTKA cases, after intervention on the first knee, increased biochemical parameters of postoperative oxidative stress and muscle injury were detected along with increased levels of serum malondialdehyde, creatine kinase and lactic dehydrogenase compared to the second knee. In our study, native thiol level decreased at 5 minutes after the TQ deflation only in the UTKA patients, while the other values related to the thiol-disulfide homeostasis did not change. Although we did not determine serum parameters after the intervention on the first knee in the BTKA cases, native thiol values did not change after reperfusion in the second knee, which may be due to ischemic preconditioning effect. Ischemic preconditioning has shown that any injury occurring after an ischaemic event in another location in the body increases ischaemic tolerance of the tissue and reduces oxidative stress, inflammation, and apoptosis in the tissue [22, 25]. It is believed that a natural protective mechanism augmenting the tolerance to prolonged ischemia is activated in tissue after exposure to short-term ischemia and reperfusion.
Hemodynamically, in both Group 1 and Group 2, the MBP values differed significantly at the beginning and after the first TQ deflation, and this was also observed after the second TQ deflation. HR also changed significantly in Group 1, which may be due to the presence of more patients with ASA 2 and 3 classification in this group, although not statistically significant. The limitations of our study include being single centered, not investigating postoperative complications and the postoperative antioxidant status in the long term and also after the intervention on the first knee in the BTKA Group 2, and no cost analysis.
Conclusion:
Bilateral TKA under CSEA does not adversely affect thiol homeostasis and hemodynamics. Elevated IMA levels immediately after TQ deflation indicate that early-stage ischemia is more significant and critical. IMA and thiol homeostasis are similarly affected at the postoperative 24th hour. Although BTKA under a single anesthesia session is advantageous for patients with compatible general health, the durations of the operation and of hospital stay are extended. We believe that BTKA studies with a larger number of patients comparing different anesthesia methods and including cost analyses will be beneficial in the long 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.
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8. Stanley D, Stockley I, Getty CJM. Simultaneous or staged bilateral total knee replacements in rheumatoid arthritis. J Bone Joint Surg Br. 1990; 72(5): 772-4.
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11. Leurcharusmee P, Sawaddiruk P, Punjasawadwong Y, Chattipakorn N, Chattipakorn SC. The Possible Pathophysiological Outcomes and Mechanisms of Tourniquet-Induced Ischemia-Reperfusion Injury during Total Knee Arthroplasty. Oxidative medicine and cellular longevity. 2018;2018. DOI:10.1155/2018/8087598
12. Erel O, Neselioglu S. A novel and automated assay for thiol/Disulphide homeostasis. Clin Biochem. 2014; 47(18): 326-32.
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Seyda Efsun Ozgunay, Sermin Eminoglu, Nazan Cevik, Yasemin Ustundag, Mehmet Gamli, Zeynep Tabur, Umran Karaca, Derya Karasu, Canan Yilmaz, Ozcan Erel. The effect of bilateral and unilateral knee arthroplasty under regional anesthesia on ischaemia-modified albumin and thiol/disulphide homeostasis. Ann Clin Anal Med 2021;12(6):633-637
Citations in Google Scholar: Google Scholar
Investigation of the effect of smoking on depression and stress in healthcare workers during a pandemic
Öztürk Taşkın, Ufuk Demir, Veysel Garani Soylu
Department of Intensive Care Unıt, Kastamonu Training and Research Hospital, Kastamonu, Turkey
DOI: 10.4328/ACAM.20367 Received: 2020-10-09 Accepted: 2020-11-14 Published Online: 2020-11-25 Printed: 2021-06-01 Ann Clin Anal Med 2021;12(6):638-641
Corresponding Author: Öztürk Taşkın, Kastamonu Training and Research Hospital Intensive Care Unıt, Centrum, 37150, Kastamonu, Turkey. E-mail: drozturk275@hotmail.com P: +90 5076424188 Corresponding Author ORCID ID: https://orcid.org/0000-0001-7328-9579
Aim: In the COVID-19 pandemic, healthcare workers suffer from significant stress and anxiety disorders. The importance of smoking in the mortality and mor- bidity of COVID-19 disease is obvious. In this study, we aimed to investigate the effects of smoking on depression and perceived stress in healthcare workers who served at the forefront during the pandemic period.
Material and Methods: In our study, participants were asked questions on the Depression Severity Scale (PHQ-9), the Perceived Stress Scale (PSS 14), and the Fagerström Test for Nicotine Dependence (FTND) using aquestionnaire method, and the results were evaluated.
Results: Depression and stress symptoms were most often found in the healthcare workers included in our study. However, there was no statistically significant difference in depression and perceived stress scale between smoking and non-smoking groups.
Discussion: Previous studies have demonstrated that smokers are more affected by COVID-19 and that their morbidity rate is higher. Because of this informa- tion, smoking healthcare professionals are more symptomatic in terms of mental health disorders, but no statistical difference was reported between smokers and non-smokers in this study in terms of being symptomatic. Although smoking was revealed as a comorbidity for COVID-19, there was no significant differ- ence between smoking and non-smoking healthcare professionals in terms of mental health disorders.
Keywords: Smoker; COVID-19; Depression; Stress; Healthcare workers
Introduction
Coronavirus disease 2019 (COVID-19) was first identified in Wuhan, China, in December 2019 [1]. It first led to an epidemic in China and began to spread rapidly worldwide [2]. In March 2020, the World Health Organization declared the COVID-19 outbreak a global epidemic. The World Health Organization reported 36 000 000 cases worldwide on October 8, 2020. COVID-19 is basically a disease of the respiratory system, characterized by acute respiratory distress syndrome. COVID-19 is caused by a a variant of the SARS-CoV-2 coronavirus [3]. SARS-Cov-2 enters the body through mucosal tissues, i.e. the nose, mouth, upper respiratory tract, and less frequently, through the conjunctival mucosa. The S protein of SARS-CoV2 connects to the human body through the ACE 2 receptor [4]. The virus can rapidly manifest symptoms of acute respiratory distress syndrome (ARDS), acute respiratory failure, and other severe acute respiratory infections resulting in severe complications [5]. Exposure to tobacco products causes an inflammatory response and blockage in the lungs, increases mucosal inflammation, as well as the expression of inflammatory cytokines and tumor necrosis factor -alpha. It increases the permeability in epithelial cells, and the excessive increase of mucus decreases or impairs mucociliary clearance [6]. The number of ACE2 receptors increases among smokers. When comparing respiratory samples of smokers and non-smokers, an additional ACE 2 gene expression was reported among smokers [4]. It appears that smokers are more susceptive to SARS-CoV-2 [7].
It has been observed that healthcare professionals experience anxiety and stress disorders during the pandemic [8]. Smokers also face more severe complications during the course of COVID-19 [9]. Based on this information, the purpose of our study was to investigate the effects of smoking on depression and perceived stress among healthcare professionals working during the pandemic.
Material and Methods
This study was performed over the internet using a questionnaire survey after obtaining the consent of the participants. The identities of the participants were kept confidential. The survey items inquired their age, gender (male, female), profession (physician, nurse, anesthesia technician, estates staff), the department they were working at (operating rooms, the intensive care unit), a Patient Health Questionnaire-9 (PHQ- 9), the Fagerström test for nicotine dependence (FTND), and a perceived stress scale 14.
Our study adopted an epidemiological design and was approved by the Ethics Committee at Kastamonu University on September 15, 2020.
The study was planned as a monocenter study, and the participants were healthcare professionals at a pandemic hospital, aged 18–63, who provided complete answers to the research questions. Those who did not fully answer the questions were excluded.
The measurement instruments in the study were as follows:
1. The Patient Health Questionnaire-9 (PHQ-9, score range: 0-27) [10];
2. Overall scoring: normal (0-4), mild (5-9), moderate (10-14), and severe (15-27) depression;
3. The Perceived Stress Scale 14 (PSS 14, score range: 11-56) [11];
4. Overall scoring: low perceived stress (11-26), moderate perceived stress (27-41), high perceived stress (42-56);
5. The Fagerström Test for Nicotine Dependence (FBNT, score range: 0-10) [12];
6. Overall scoring: low addiction rate (0-4 points), moderate addiction rate (5-6 points), high addiction rate (7-10 points). The cutoff scores for the Patient Health Questionnaire-9 and the perceived stress scale were 10 and 27, respectively [11, 14]. The participants who scored above the cutoff threshold were accepted as having positive symptoms.
Results
One hundred seventy-four healthcare professionals between the ages of 18 and 63 participated in the study. Moreover, 118 (67.8%) participants were female and 56 (32.2%) were male. Almost 50% of the participants were nurses (nurse: 85 (48.9%), anesthesia technician: 25 (14.3%), estates staff: 27 (15.5%), physician: 37 (21.3%), n /%); 74 (42.5%) worked in the operating room, and the other 100 (57.5%) worked in the intensive care unit. Moreover, 68 (39%) of the 174 professionals in the study were active smokers. Among 68 smokers, ~50% (n = 32; 47%) experienced a change in their smoking habits during this period (quit, reduced, and increased). Furthermore, >50% of those who had a change in their smoking habits (n = 17; 53%) increased their amount of smoking during this period. The results of the Fagerström Test for Nicotine Dependence administered to active smokers during the pandemic suggested that 31 (50.8%) had a low addiction rate, 15 (24.6%) were moderately addicted and 15 (24.6%) were highly dependent (Figure 1).
The number of participants with positive symptoms on the PHQ 9 and PSS 14 scales was 77 (44.2%) and 102 (57.6%), respectively. There was no statistically significant difference between smokers and non-smokers on the Patient Health Questionnaire-9 (PHQ 9) and Perceived Stress Scale (PSS 14) in terms of showing symptoms (p = 0.73 for PHQ9; p = 0.30 for PSS 14) (Figure 2).
Among 174 professionals in the study, 77 (44.2%) showed symptoms on the Patient Health Questionnaire-9 (PHQ 9) and 112 (64.3%) on the Perceived Stress Scale (PSS 14); 29 (37.6%) of those showing symptoms based on the Patient Health Questionnaire-9 (PHQ 9) and 40 (35.7%) of those showing symptoms based on the Perceived Stress Scale were active smokers. There was a statistically significant difference between the smokers and non-smokers who were symptomatic on both scales regarding the severity of depression and perceived stress (p = .04 for PHQ9; p = .005 for PSS 14) (Figure 3).
Discussion
The harmful effects of smoking are well-known among community and healthcare professionals. However, smoking continues both among the community and among healthcare professionals. A study conducted by Krstev et al. reported that the smoking prevalence among healthcare professionals was 38%. Similarly, our study reported the smoking prevalence as 39% [14].
There are extensive epidemiological studies on the role of smoking in the emergence of viral infection. Blake et al. reported that the frequency of upper respiratory tract infections in 1230 soldiers in the US army was 22.7% among smokers and 16% among non-smokers, and that the relative risk was 1.5 times higher [15]. Cai et al. compared respiratory samples of smokers and non-smokers and reported higher ACE 2 gene expression among smokers [4]. Zhao et al. observed that the increase in ACE 2 gene expression increased viral reproduction and transmission. These results demonstrated that smokers are more susceptive to SARS-CoV-2 [7]. A recent study showed that the modified S protein of SARS-CoV-2 connects to the ACE2 receptor with an affinity 10–20 times higher than the first described SARS-CoV [18]. In a meta-analysis study on the COVID-19 pandemic, Patanavanich et al. stated that smoking is a risk factor for COVID-19 progression, and that COVID-19 is more likely to progress among smokers compared to non- smokers [17]. Because of these results, it is expected that smokers will have a fear of going through the disease process more severely if they are infected by COVID-19. Assuming that the awareness of this pathophysiological information is higher among healthcare professionals who are at the forefront of the fight against the pandemic, this fear and mental state may be more severe among them.
In a correlational study in the UK on the relationship between COVID-19 and anxiety, depression, and mental well-being symptoms, Smith et al. reported that the smokers in the community had lower levels of mental well-being [3]. In another study entitled ‘’Factors associated with mental health outcomes among healthcare workers exposed to coronavirus disease’’ 2019, Lai et al. reported that the overwhelming majority of healthcare professionals had low mental well-being levels [8]. In our study, about half of the participants were symptomatic on two scales.
Previous studies have demonstrated that smokers suffer from COVID-19 more severely and their morbidity rate is higher [18]. Because of this information, smoking healthcare professionals are more symptomatic in terms of mental health disorders, but no statistical difference was reported between smokers and non-smokers in this study in terms of being symptomatic. The reason for this might be that healthcare professionals do not have sufficient information or are unaware of the relationship between smoking and COVID-19. An earlier study revealed a positive effect of smoking on depression [19], which might be a reason for this result. Moreover, when the symptomatic cases on the depression severity and perceived stress scales were compared as smokers and non-smokers, we observed more severe symptoms among the non-smoking group.
Conclusions
COVID-19 has damaged the physical health of individuals and their mental health. The physiopathological link between smoking and COVID-19 has been documented in earlier studies. Although smoking was revealed as comorbidity for COVID-19, there was no significant difference between smoking and non- smoking healthcare professionals in terms of mental health disorders. We think that the current results may change as other studies with more participants appear or as more information is available on the relationship between smoking and COVID-19. Lımitations
There were certain limitations in the present study. First, the study used a cross-sectional design and investigated the mental state of participants during the six-month pandemic process. Since the pandemic process is still ongoing, it is difficult to comment on the mental state of the participants at the following stages. The second limitation was that it was not possible to determine the mental states of the participants before the pandemic. Some participants may have had mental health disorders prior to the pandemic.
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
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2. Emami A, Javanmardi F, Pirbonyeh N, Akbari A. Prevalence of Underlying Diseases in Hospitalized Patients with COVID-19: a Systematic Review and Meta-Analysis. Arch Acad Emerg Med. 2020;8(1):e35.
3. Smith L, Jacob L, Yakkundi A, McDermott D, Armstrong NC, Barnett Y, et al. Correlates of symptoms of anxiety and depression and mental wellbeing associated with COVID-19: a cross-sectional study of UK-based respondents. Psychiatry Res. 2020;291. DOI: 10.1016/j.psychres.2020.113138.
4. Guoshuai C. Bulk and single-cell transcriptomics identify tobacco-use disparity in lung gene expression of ACE2, the receptor of 2019-nCov. MedRxiv, 2020; DOI:10.1101/2020.02.05.20020107
5. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507-13. DOI: 10.1016/ S0140-6736(20)30211-7
6. Strzelak A, Ratajczak A, Adamiec A, Feleszko W. Tobacco Smoke Induces and Alters Immune Responses in the Lung Triggering Inflammation, Allergy, Asthma and Other Lung Diseases: A Mechanistic Review. Int J Environ Res Public Health. 2018;15(5):1033. DOI:10.3390/ijerph15051033
7. Zhao Y, Zhao Z, Wang Y, Zhou Y, Ma Y, Zuo W. Single-Cell RNA Expression Profiling of ACE2, the Receptor of SARS-CoV-2. Am J Respir Crit Care Med. 2020;202(5):756-9. DOI:10.1164/rccm.202001-0179LE
8. Lai J, Ma S, Wang Y, Cai Z, Hu J, Wei N, et al. Factors Associated With Mental Health Outcomes Among Health Care Workers Exposed to Coronavirus Disease 2019. JAMA Netw Open. 2020;3(3):e203976. DOI: 10.1001/ jamanetworkopen.2020.3976.
9. Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. China Medical Treatment Expert Group for Covid-19. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020;382(18):1708-20. DOI: 10.1056/NEJMoa2002032.
10. Zhang YL, Liang W, Chen ZM, Zhang HM, Zhang JH, Weng XQ, et al. Validity and reliability of Patient Health Questionnaire-9 and Patient Health Questionnaire-2 to screen for depression among college students in China. Asia Pac Psychiatry. 2013;5(4):268-75. DOI: 10.1111/appy.12103.
11. Zarghami A, Farjam M, Fakhraei B, Hashemzadeh K, Yazdanpanah MH. A Report of the Telepsychiatric Evaluation of SARS-CoV-2 Patients. Telemed J E Health. 2020; DOI:10.1089/tmj.2020.0125.
12. Bozkurt N, Bozkurt Ai. Assesment of the Fagerström test for nicotine dependence (FTND) used in the determination of nicotine dependence and developing a new test for the nicotine dependence. Pamukkale Medical Journal. (2016): 45-51.
13. Levis B, Benedetti A, Thombs BD. Depression Screening Data (DEPRESSD) Collaboration. Accuracy of Patient Health Questionnaire-9 (PHQ-9) for screening to detect major depression: individual participant data meta-analysis. BMJ. 2019;365:l1476. DOI:10.1136/bmj.l1476
14. Krstev S, Marinković J, Simić S, Jovićević A, Marković-Denić L. Determinants of smoking and smoking cessation among health professionals in Serbia: A cross- sectional study. Vojnosanit Pregl. 2014;71(5):481-90.
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19. Carroll AJ. Elucidating directionality between smoking and depression. J Psychosom Res. 2019;125:109790. DOI:10.1016/j.jpsychores.2019.109790
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Öztürk Taşkın, Ufuk Demir, Veysel Garani Soylu. Investigation of the effect of smoking on depression and stress in healthcare workers during a pandemic. Ann Clin Anal Med 2021;12(6):638-641
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Effectiveness of aflibercept treatment after dexamethasone in macular edema caused by branch retinal vein occlusion: Case series
Tayfun Şahin
Department of Ophthalmology, Hitit University Medicine Faculty, Corum, Turkey
DOI: 10.4328/ACAM.20371 Received: 2020-10-11 Accepted: 2020-11-18 Published Online: 2020-11-26 Printed: 2021-06-01 Ann Clin Anal Med 2021;12(6):642-646
Corresponding Author: Tayfun Şahin, Hitit University Medicine Faculty, Department Of Ophthalmology, 019030 Corum, Turkey. E-mail: drtayfunsahin82@gmail.com P: +90 506 328 4338 F: +90 364 713 0101 Corresponding Author ORCID ID: https://orcid.org/0000-0003-2319-0807
Aim: This study aims to assess the effectiveness of aflibercept in patients with macular edema caused by Branch Retinal Vein Occlusion following dexametha- sone implant treatment.
Material and Methods: This study included treatment-naive 20 eyes of 20 patients. At baseline and follow-ups, the patients’ Best Corrected Visual Acuity, the Central Macular Thickness and Central Macular Volume measures taken with Spectral-Domain Optical Coherence Tomography were recorded. The patients who had deterioration of visual acuity or macular thickness ≥ 300 were administered intraocular injection again. Recurrent cases following dexamethasone injection were administered aflibercept injection three times with an interval of one month.
Results: Compared to the baseline, the patients demonstrated an increase in visual acuity and a decrease in macular thickness and macular volume following the dexamethasone injection ( p=0.013, p=0.009, p=0.021, respectively). In an average of three and half months after the injection, there was a decrease in visual acuity (0.90 ± 0.44 logMAR), an increase in macular thickness (579 ± 107 μm) and macular volume (12.25 ± 1.55 mm3) (p>0.05 all). Three months after the the completion of three aflibercept injections, there was no deterioration in visual acuity (0.41 ± 0.23 logMAR) according to the recurrence time of macula edema (p=0.048). Macular thickness (288 ± 47 μm) and macular volume (8.59 ± 0.96 mm3) values demonstrated nonsignificant increases (p>0.05).
Discussion: Aflibercept treatment is effective in recurrence following the Dexamethasone treatment in macula edema caused by branch retinal vein occlusion.
Keywords: Aflibercept; Combination treatment; Dexamethasone; Macular edema; Vein occlusion
Introduction
Retinal venous occlusion (RVO) is the most common retinal vascular disease that causes vision loss after diabetic retinopathy [1]. The most common cause of RVO is the hemodynamic impairment in the veins associated with the compression caused by the atherosclerotic changes in the retinal artery [2]. Macular edema is the most common cause of vision loss in non-ischemic RVO [3]. Vascular permeability increases due to the increased mediators in the environment due to inflammation in RVO, which leads to macular edema [4]. The inhibition of the vascular endothelial growth factor (VEGF) in the RVO-associated macular edema could enable to decrease macular edema and increase vision [5]. Other inflammatory mediators and cytokines apart from VEGF also contribute to macular edema in RVO [6]. Targeting this increased cytokine and mediators in the treatment could yield more successful results in reducing macular edema. Corticosteroids inhibit the synthesis of other inflammatory cytokines and inflammatory cell migration. In addition, corticosteroids are known to cause cataract and increase intraocular pressure [7]. In cases with RVO-associated macular edema, the primary stage treatment generally includes anti-VEGF agents to avoid the potential side effects of corticosteroids.
In this study, we aimed to show the efficiency of the aflibercept treatment in cases with RVO-associated macular edema that developed recurrence following a dexamethasone implant treatment.
Material and Methods
This retrospective study was conducted from September 2017 to October 2018 and involved 20 eyes of 20 patients who applied to the ophthalmic clinic of our hospital due to macular edema caused by branch retinal vein occlusion (BRVO) and did not have any treatments before. Ethics committee approval was obtained (2019-31 decision number dated 10.07.2019) from the university, and the study followed the principles of the Declarations of Helsinki. A written informed consent form was obtained from the patients.
The patients underwent full ophthalmological examinations including baseline and follow-up best-corrected visual acuity (BCVA) measured with Snellen chart, biomicroscopic examination findings, intraocular pressure measurements (measured with Goldmann) and dilated fundus findings. Central macular thickness (CMT) and central macular volume (CMV) measurements were performed with Spectral-Domain Optical Coherence Tomography (SD-OCT; Heidelberg Engineering, Heidelberg, Germany). Visual acuity taken with Snellen was converted to logMAR. Fluorescein Fundus Angiography (FFA) of the patients was performed during the first application. Cases with suspected neovascularization in fundus during follow-ups received FFA again.
Intraocular injections were performed in an operating room environment. Topical anesthesia was administered with 0.5% proparacaine (Alcaine; Alcon Laboratories). The area around the eye was cleaned with 10% povidone-iodine. Povidone- iodine (5%) was administered intraocularly, and at least three minutes last while waiting for antisepsis. The area around the eye was covered with a sterile drape, and an eyelid speculum was placed. The patients’ intravitreal injections were done posterior to the superotemporal limbus (4 mm in phakic, 3.5 mm in pseudophakia).
In the beginning, the patients were administered 0.7 mg dexamethasone (Ozurdex; Allergan, Inc., Irvine, California, USA) implant injection. The patients’ follow-ups were performed in the second week, the fourth week, and then once a month after the dexamethasone injections. During their follow-ups, the patients who were found to have a one-level decrease in vision or a macular thickness of ≥ 300 μm were accepted to have developed recurrence. The patients who were accepted to have recurrence were administered intravitreal aflibercept (Eylea VEGF Trap-Eye; Regeneron Pharmaceuticals, Inc., Tarrytown, NY and Bayer Health-Care Pharmaceuticals, Berlin, Germany, 2.0 mg) injections three times with an interval of one month. After the three aflibercept injections, the patients were followed up once a month. The patients who were found to have a one-level decrease in vision or a macular thickness of ≥ 300 μm after the administration of three injections of aflibercept were applied aflibercept once as a maintenance treatment.
The patients who were administered an intravitreal injection, who received laser in the retina, who underwent vitrectomy surgery, who had a retina pathology apart from venous occlusion (diabetic retinopathy, choroidal neovascularization) and glaucoma were excluded from the study.
Statistical Method
Statistical analyses of the data were performed using SPSS (Version 22.0, SPSS Inc., Chicago, IL, USA, License). In line with the data distribution, descriptive statistics were reported as mean ± standard deviation or median (minimum-maximum). Descriptive statistics of the categorical data were presented as numbers and percentages (%). Normality distribution of the categorical data was presented as numbers and percentages (%). The normality distribution for the statistical test choice was evaluated with the Shapiro-Wilk Test. Repeated measure comparisons were performed using Repeated Measures ANOVA when the data were normally distributed and Friedman’s Test for the non-parametric data when the data were not normally distribute. AVONA and Friedman test and Bonferroni corrected posthoc multiple comparison tests were utilized to identify different measurements. Statistical significance was taken as p<0.05.
Results
This study involved 20 patients with BRVO-associated macular edema.
The demographic characteristics of the patients are demonstrated in Table 1.
BCVA was found to demonstrate an increase compared to the baseline (1.30 ± 0.59 logMAR) in the first month following the dexamethasone injection (0,79 ± 0,42 logMAR) (p=0.013). Follow-up examinations showed that recurrence occurred in four patients (20%) in the third month, 12 patients (60%) in the fourth month, and four patients (20%) in the fifth month. Although BCVA was better than baseline (0.90 ± 0.44 logMAR) when macular edema recurred, the difference was not statistically significant (p>0.05). Although CMT (579 ± 107 μm) and CMV (12.25 ± 1.55 mm3) values were also better than baseline, these values were not statistically significant (p>0.05). After the three aflibercept injections administered with an intervals of one month, there was an increase in BCVA (0.47 ± 0.36 logMAR), and a decrease in CMT (265 ± 43 μm) and CMV (8.35 ± 0.79 mm3) values (p=0.002, p=0.001, p=0.001, respectively). Compared to the time of recurrence three months after the last aflibercept injection, no worsening was reported in BCVA (0.41 ± 0.23 logMAR) (p=0.048), and CMT (288 ± 47 μm) and CMV (8.59 ± 0.96 mm3) were found to have non- significant increases (p>0.05).
It was considered that the patients did not need treatment (a one-level decrease in vision or a macular thickness of over 300 μm) up to six months after the third aflibercept injection. In the sixth month, four patients (20%) needed to be administered aflibercept infection. The other patients did not need treatment. Two months after the dexamethasone implantation, four patients (20%) had intraocular pressure (IOP) of over 21 mmHg. With a two-month topical antiglocomatose treatment, the IOP of these patients was taken under control. At the end of the first year, four patients were found to have cataract, and four patients (20%) were found to have neovascularization in the retina.
Discussion
To the best of our knowledge, the present study is the first study that assessed the efficiency of aflibercept after dexamethasone in cases with BRVO-associated macular edema.
After the dexamethasone injection, the increase in BCVA and the decrease in CMT and CMV were found to last throughout three-and-half months on average. At the end of this period, BCVA worsened and CMT and CMV values became close to baseline values.
In RVO, hypoxic pathophysiologic cascades associated with impaired hemodynamics are involved or a local inflammatory process starts. In vitreous, there is an increase in the number of inflammatory mediators and free radicals such as interleukin 6-8, monocyte chemotactic protein-1, angiotensin II, prostaglandins, and VEGF. The inner blood-retinal barrier connected to these mediators deteriorates and leakage occurs, which develops macular edema resulting in vision loss. Therefore, targeting other inflammatory mediators along with VEGF in the treatment of the RVO-associated macular edema is of importance in the treatment. Dexamethasone has been reported to decrease edema in the inflammatory response, fibrin accumulation, capillary leakage, inhibit phagocytic migration, and suppress inflammation. VEGF is a strong stimulus for vascular permeability. Corticosteroids have been shown to inhibit VEGF expression [6].
GENEVA study showed that dexamethasone implant was efficient in the treatment of cases that had RVO- associated macular edema. Patients who were administered dexamethasone injection were found to have increased visual acuity and decreased macular thickness compared to the patients who were administered a sham injection. The study reported that dexamethasone efficiency reached the maximum level in the second month, and it could continue up to 180 days [8]. Studies conducted later reported that the efficiency lasted three months on average and could degradedly continue up to six months [9, 10]. Joshi et al. treated patients who had RVO-associated macular edema and who developed recurrent macular edema after the dexamethasone implant treatment for the second time. They found that the duration of the efficiency was shortened in repeated dexamethasone injections [11]. In their study on the patients with RVO-associated macular edema, Yücel et al. reported that treatment with dexamethasone implant enabled an anatomic recovery rather than a functional recovery [12]. GENEVA study also evaluated the patients who were administered dexamethasone in terms of the side effects as well. The study showed that 16% of the patients had an IOP level of over 25mmHg, and 7.3% developed cataract [8].
In this study, the cases that developed recurrence after the dexamethasone treatment were given treatment by shifting to aflibercept. Such a shift was done as it is known that dexamethasone could cause cataracts, increase IOP, and shorten the duration of the efficiency of repeated injections [7, 11]. When macular edema developed recurrence, aflibercept, an anti-VEGF agent with combined effect, was utilized in the treatment. Aflibercept connects and deactivates the placental growth factor (PGF) that plays an important role in VEGF-A, VEGF-B, and vein permeability. After receiving three aflibercept injections, the patients in this study had no visual impairment three months later; however, CMT and CMV were found to have non-significant increases.
Due to the high affinity of aflibercept, it is known to have long- term effects at low concentrations [13]. The COPERNICUS and GALILEO studies have also reported that aflibercept was efficient in RVO-associated macular edema [14, 15]. VIBRANT evaluated whether aflibercept was more efficient compared to grid laser in BRVO-associated macular edema cases. It was reported that the eyes administered aflibercept showed significant recovery in their vision levels and a decrease in macular thickness in comparison to the eyes that were administered a grid laser [16]. It was reported that as aflibercept molecule regulated retinal microcirculation, it could provide an increase in vision [12].
Herbaut et al. reported that cases with diabetic macular edema with no response to dexamethasone or ranibizumab treatment were administered treatment by exchanging with aflibercept. After the treatment, 60% of the patients had a decrease in CMT and recovery of visual acuity [17]. Chiquet et al. continued treatment with dexamethasone in cases that had RVO-associated macular edema and who did not respond to bevacizumab treatment. In the first month, the patients were reported to have improved vision and decreased CMT (this effect worsened until the 12th month). In the same study, eight cases without any response to dexamethasone were administered bevacizumab treatment. In this group, no changes were reported in visual acuity, and the decrease in CMT was reported only in the first month [18]. The study conducted by Chiquet et al. was similar to the present study as they administered anti- VEGF (bevacizumab) following dexamethasone. The patients in this study were treated with aflibercept after dexamethasone. The patients were found to have improved vision and decreased CMT and CMV. After the third aflibercept injection, the efficiency of the treatment took about six months. After six months, four patients needed to be administered aflibercept injection once. The rest of the patients did not need any treatment.
Iu et al. reported that the combination of anti-VEGF and dexamethasone treatment was found to have better results compared to dexamethasone monotherapy in cases with RVO-associated macular edema [19]. We think that after the strong inhibition of mediators and cytokines released in the environment with dexamethasone in the beginning, regulation of retinal microcirculation leads to successful outcomes with aflibercept that deactivates VEGF-A, VEGF-B and PGF in patients with BRVO-associated macular edema. We believe that this combination could be an effective treatment option. This study has a number of limitations. Firstly, we did not have a control group. When we conducted this study, Social Security Institution recommended and paid the dexamethasone implant treatment in patients with RVO-associated macular edema. Therefore, we did not form a control group and started the treatment of the patients initially with the dexamethasone implant. The second limitation was that we had a limited number of patients. Most of the patients who applied to our clinic were patients who have previously been treated (intravitreal treatment/laser treatment). A higher number of patients and the formation of a control group (aflibercept monotherapy group) could be beneficial for future studies
Conclusion
The aflibercept combination treatment after dexamethasone gives anatomically and functionally positive results in BRVO- associated macular edema. We think that this treatment combination could decrease the total number of intravitreal injections to be administered to the patient. Future studies could shed more light on the issue.
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.
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Tayfun Şahin. Effectiveness of aflibercept treatment after dexamethasone in macular edema caused by branch retinal vein occlusion: Case series. Ann Clin Anal Med 2021;12(6):642-646
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Investigation of the effect of surgical menopause on physical, psychosocial and cognitive functions in women
Rabia Oz 1, Nesrin Yagcı 2
1 Fizyo Vital Physical Therapy and Wellness Counseling Center, 2 Pamukkale University School of Physical Therapy and Rehabilitation, Denizli, Turkey
DOI: 10.4328/ACAM.20372 Received: 2020-10-12 Accepted: 2020-11-26 Published Online: 2020-12-07 Printed: 2021-06-01 Ann Clin Anal Med 2021;12(6):647-652
Corresponding Author: Nesrin Yagci, Pamukkale University, School of Physical Therapy and Rehabilitation, Kinikli Campus, 20100 Denizli, Turkey. E-mail: nesrinyagci@yahoo.com P: +90 258 2964266 F: +90 258 2964494 Corresponding Author ORCID ID: https://orcid.org/0000-0002-5669-4932
Aim: This study was planned to examine the effects of surgical menopause on physical, psychosocial and cognitive functions.
Material and Methods: The study included 25 women aged 40-54 years. The participants consisted of healthy individuals who have not yet entered meno- pause, who have been diagnosed with surgical menopause and who were literate. Before surgical menopause, all participants were assessed using a form including demographic information for demographic data; 5 times sit to stand test, sit and reach test, half squat test, hand grip strength measurement test, Visual Analogue Scale for physical functions; Perceived Stress Scale, Center for Epidemiological Study Depression Scale, Hamilton Anxiety Rating Scale, Women’s Health Initiative Insomnia Scale for psychosocial functions; and Montreal Cognitive Assessment Scale for cognitive functions. All participants were reevaluated after 3 months of surgical menopause.
Results: The mean age of the participants was 45.96±4.26 years and the mean body mass index was 30.57±4.50 kg/cm2. In physical function tests, psychoso- cial functions, cognitive functions there was no statistically significant difference between the pre- and postoperative test results of the participants (p>0.05). The decrease in spinal pain intensity of the participants was statistically significant compared to the preoperative period (p<0.05). After surgery, the partici- pants’ scores on the CES-Depression Scale were decreased and the difference was statistically significant (p<0.05).
Discussion: After surgical menopause, participants’ depression levels and spinal pain improved. Surgical menopause did not affect the participants’ other physical, psychosocial and cognitive functions of.
Keywords: Pain, Cognitive dysfunction, Menopause
Introduction
Menopause is defined as the permanent cessation of the menstrual period and occurs after the cessation of ovarian function. The main change in menopause is a decrease in the level of estrogen, the female hormone secreted by the ovaries over time. This process can take 5 to 8 years if there is no radiotherapy, chemotherapy or surgical removal of the ovaries. Surgical removal of the ovaries is called bilateral oophorectomy. Bilateral oophorectomy is an operation for menopausal women who have not yet entered menopause. Surgeons usually opt for bilateral oophorectomy during a hysterectomy (surgical removal of the uterus). Surgical menopause; is applied for reasons such as abnormal bleeding, chronic pelvic pain or symptomatic leiomyoma or ovarian cancer [1].
In this process, a woman experiences hormonal changes, loses her fertility and begins to age. During this period, due to hormonal changes, many mental (concentration difficulties, irritability and depression), physical (sexual problems, genitourinary atrophy, vasomotor symptoms, insomnia, cardiovascular system problems and osteoporosis) and cognitive problems arise [2]. While hormones such as estrogen and progesterone are beneficial for muscle performance, changes in the levels of hormones can affect the decline in physical function [3]. Additional factors related to surgical menopause can affect physical function. For example, events and conditions that lead to surgical menopause, physical recovery after surgery, or sudden or early changes in hormone levels may result in lower levels of physical function among women who have undergone surgical menopause compared to women entering natural menopause [4]. The biological link between menopause and moodfocusesonhowlowestrogenlevelsareassociatedwitha negative mood. In this case, as the ovarian estrogen production is very low and stable in post menopause, it is expected to be associated with increased psychological symptoms. A study investigating depression in middle-aged women concluded that these symptoms are not associated with natural menopause, but with stress, family problems, other menopausal symptoms, or a previous history of depression [5]. In the literature, it is thought that a decrease in estrogen levels is the cause of are responsible for cognitive and physical dysfunction in this period of life. However, the findings of studies investigating the effect of estrogen replacement therapy on cognitive function are contradictory [6]. For this reason, the problem is thought to be more complex than just estrogen deficiency.
Studies have addressed one or more of these problems, but their effects on physical, psychosocial, and cognitive functions before and after surgical menopause have not been examined from such a wide perspective. It is of great importance for women to identify the relevant problems during this period and to help the healthcare personnel to solve the problems. Therefore, this study was planned to examine the effects of surgical menopause on physical, psychosocial and cognitive functions in women.
Material and Methods
Participants
This study was conducted with a total of 70 healthy participants from XXX Hospital, XXX Hospital and XXX Private Health
Obstetrics and Gynecology Polyclinics between January 2017 and September 2017. The participants received a surgical indication for menopause (total abdominal hysterectomy and bilateral-salpingo oophorectomy) by a specialist. The population of the study was accepted as the sample. It was approved at the board meeting of XXX University Non-Interventional Clinical Research Ethics Committee dated 03.08.2016 and numbered 60116787-020 / 47564 that there was no ethical obstacle in conducting the study. The research was conducted according to the Helsinki Declaration and written informed consent was obtained from all participants before the study.
Forty-five participants who met the inclusion criteria were included in the study. Fifteen participants who did not wish to participate in the study were excluded and the study was started with 30 participants. The study was completed with 25 participants, excluding 5 participants who did not come to the second evaluation 3 months after the surgical operation (Figure 1). Inclusion criteria were as follows: age range of 40-54,notyetinmenopause,beingdiagnosedwithsurgical menopause and being literate. Those with diabetes mellitus, stroke and physical disabilities, pace maker users, MI history, cardiovascular surgery history, breast cancer, etc., those who use drugs for reasons such as cooperative organizations and those with advanced psychiatric problems were excluded from the study. Age, height, weight, body mass index, education, marital status, disease, smoking, drug use, employment status were assessed among the groups.
Spinal pain areas of the participants were determined by marking them on the body chart. Pain intensity was evaluated with the Visual Analogue Scale (VAS).
Cardiovascular endurance and functional mobility of the participants were evaluated with 5 sit-and-go tests. The participants were asked to stand up and sit down again as quickly as possible without any support while sitting on a chair with back support. The time they repeat this movement 5 times measured with a stopwatch and the result was recorded in seconds.
The sit and reach test was used to evaluate trunk flexion and hamstring muscle group flexibility. Participants were asked to lean forward on the test bench and were told to stop for at least 2 seconds at the last point reached. The distance that can be reached is recorded in cm. The test was repeated 3 times and the best score was recorded.
Muscular endurance of the lower extremities was evaluated by the semi-squat test. In this test, participants were asked to kneel and stand up halfway on a hard surface without shoes. The test began with the “start” command from the physiotherapist, and the crouching movements of the participants in 1 minute were counted. During the test, the participants were asked to squat so that the knee would not pass in front of the foot, not to lift their heels from the ground, and to keep their torso upright. Upper extremity muscular endurance was evaluated with the Hand Grip Strength Measurement Test (HGSMT). The gripping strength was measured with a JAMAR brand hydraulic hand dynamometer. Measurements were made by the same physiotherapist as recommended by the American Hand Therapists Association, while the participants were in the unsupported sitting position, the dominant upper extremity was flexed, the forearm was supported by the body in the middle position, and the average value was recorded as kg / F [7].
The Perceived Stress Inventory (PSI), whose Turkish validity and reliability study was conducted by Bilge et al., was used to determine the stress levels of the participants. Feelings and thoughts experienced by the participants in the last month were evaluated. The total score ranges from 0 to -32 points on the scale. The scale was evaluated on the basis of the total score and subscale scores (perceived stress and perceived coping). Higher total scores and scores from subscales indicate that perceived stress level is high [8].
The Hamilton Anxiety Rating Scale (HAR-S) was used to determine the anxiety levels of the participants. This scale, developed by Hamilton [9] in 1959, was prepared to determine the level of anxiety and symptom distribution in individuals, and to measure the change in severity. It consists of 14 items that question mental and physical symptoms. Validity and reliability studies in our country were carried out by Yazıcı et al. [10].
The CES-Depression Scale was used to determine the depressive symptoms of the participants. The CES Depression Scale was developed by the American National Institute of Public Health. The CES-Depression Scale is used in epidemiological studies not to diagnose, but to detect the presence of depression [11]. The scale consists of 20 items. The scale is evaluated by four responses that the participants felt during the last week. The total score range is between 0 and 60. In this study, the scale, whose Turkish validity and reliability study was conducted by Tatar et al. was used [12].
The Women’s Health Initiative Insomnia Scale (WHIIS) was used to evaluate the insomnia levels that could affect the emotional states of the participants. The Turkish validity and reliability study of this scale was conducted by Timur and Şahin in 2009 [13]. It is a valid and reliable scale that can be used to evaluate insomnia especially during menopause [14]. The highest score on the scale shows the greatest degree of insomnia symptoms. The lowest score that can be obtained on the scale is 0, the highest score is 20.
The Montreal Cognitive Assessment Scale (MBRS) was used to evaluate the cognitive functions of the participants. Montreal Cognitive Assessment Scale is a screening scale developed by Nasreddine et al. to distinguish healthy individuals from individuals with mild cognitive impairment [15]. In this study, the scale, whose Turkish validity and reliability study was conducted by Özdilek and Kenangil [16] in 2014, was used. In the Montreal Cognitive Assessment Scale, there are items that evaluate the dimensions of attention and concentration, executive functions, memory, language, visual-spatial skills, abstract thinking, calculation and orientation. The lowest score that can be obtained on the scale is 0, the highest score is 30. As a result of the standardization study conducted in our country, the cut-off score for distinguishing healthy individuals from individuals with mild cognitive impairment was determined as 21 [17].
Statistical analysis
The data were analyzed using the program SPSS 20.0 (IBM SPSS Statistics 20 software (Armonk, NY: IBM Corp.)). Continuous variables are given as mean ± standard deviation and categorical variables as numbers and percentages. The
Shapiro Wilk test was used for the normal distribution of the evaluation data of all participants. In the dependent group comparisons, the significance test of the difference between the two spouses was used because parametric test assumptions were provided for comparing the physical, psychosocial and cognitive functions of the participants before and after surgery since the parametric test assumptions were not provided in the data obtained from the Perceived Stress Scale, Wilcoxon two-sample paired tests were used. P <0.05 was considered statistically significant in all analyzes.
Results
The mean age of the participants was 45.96 ± 4.26 years, and their mean body mass index was 30.57 ± 4.50 kg / cm2. Twelve participants were housewives (48%), 22 were married (88%), 23 (92%) gave birth. While 76% of the participants had spine pain, they reported that they had the most back pain (47.40%) (Figure 1). In physical function tests, there was no statistically significant difference between the pre- and postoperative test results of the participants (p> 0.05). The decrease in spinal pain severity of the participants after surgery compared to the pre-surgery was found to be statistically significant (p <0.05) (Table 1). In physical function tests, there was no statistically significant difference between the pre- and postoperative test results of the participants (p> 0.05). The decrease in spinal pain severity of the participants after surgery compared to the pre-surgery was found to be statistically significant (p <0.05) (Table 2). No statistically significant difference was found in the psychosocial functions of the participants before and after surgical menopause in Hamilton Anxiety Rating Scale, Women’s Health Initiative Insomnia Scale, Perceived Stress Scale and its sub-parameters (p> 0.05). After surgery, a decrease in the scores of the participants on the CES-Depression Scale was detected, and the difference was found to be statistically significant (p <0.05) (Table 3). No significant difference was found in the cognitive functions of the participants before and after surgery (p> 0.05) (Table 3).
Discussion
The aim of this study is to examine the effects of surgical menopause on physical, psychosocial and cognitive functions in women. After surgical menopause, it was concluded that women’s spinal pain and depression mood improved compared to pre-surgical menopause.
Surgical menopause is a condition that affects women in all aspects. The gradual decreases in estrogen and androgen levels during the natural transition process is responsible for most of the initial problems with menopause. Although the timing of menopause is relatively constant, the nature and severity of symptoms can vary greatly among women from different ethnicities and geographic locations for reasons not well understood [18]. Most women approaching menopause require medical assistance for vasomotor problems, urogenital atrophy, sexual dysfunction, psychological and somatic disorders, or a combination of these. In a study that examined menopausal complaints and hormonal status after menopausal surgery, the effects of surgery was high immediately after the operation (10 days), while it decreased to the premenopausal level 5-6 weeks after surgery [19]. Although there was no change in vasomotor symptoms and sleep disturbance 5-6 weeks after the operation, an improvement was observed in anxiety, depression, somatic problems and muscular and skeletal system pain. In our study, a decrease in depressive symptoms and improvement in spinal pain severity were found after surgical menopause.
In the study conducted by Rodriguez et al., the relationship between both quality of life and climacteric symptoms with physical performance was investigated. The intensity of menopausal symptoms and worsening of quality of life have been associated with poor physical performance [1]. In our study, we evaluated physical functions with the sit-to-go test, sit-lie test, semi-squat test and hand grip strength test 5 times, and we could not find a statistically significant difference 3 months after surgery. We think that the lack of change in physical functions is related to the participants’ sedentary lifestyle and the unchanged environmental factors.
Depression symptoms differ in everyone and can occur in every period of our lives. According to Borkoles et al., depressive symptoms are more common in the perimenopause than in the postmenopausal period [20]. In another study, it was stated that surgical menopause affects the depression levels of the participants [21]. In this study, no statistically significant difference was found between the psychosocial functions of the participants between the Perceived Stress Scale and its sub-parameters before surgical menopause and the scores after surgical menopause on the Hamilton Anxiety Rating Scale (p> 0.05). We think that this result is due to the fact that the participants consisted of healthy individuals and that depression tendencies were not detected before surgery.
The results of the studies investigating the effects of surgical menopause on mood are contradictory; Gibson et al. observed in their 10-year study that the symptoms of depression were high during the premenopause period, they started to decrease during the perimenopause and continued to decrease during the postmenopausal period [22]. In our study, it was found that depressive symptoms of the participants before surgical menopause decreased 3 months after surgery. We think that this situation is related to the reasons for the surgery (such as abnormal bleeding, benign and malignant causes) and postoperative uncertainty.
There are studies in the literature arguing that a decrease in estrogen levels is responsible for cognitive and physical dysfunctions in this period of life [8]. Santoro et al. [23] argue that changes in cognitive functions are related to age, not hormones. A study investigating the effects of surgical menopause on cognitive functions found that the year of surgery was associated with cognitive functions, whereas surgery performed after natural menopause had no effect on cognitive functions [24]. Our study predicted that women’s cognitive functions would be affected by surgery for menopause, but there was no change in the cognitive functions of the participants after surgery. The reason for this is that the factors affecting cognitive functions are not only related to hormones, but the patient’s family life, economic status, education level, genetic factors and general health status may also affect cognitive functions.
Our study has some limitations. The absence of a control group to compare women with natural menopause makes us not fully understand the physical and psychosocial effects of surgical menopause on women. The small number of participants and the lack of long-term follow-up of the participants led us to evaluate the effects of surgical menopause only in the short term. We believe that further studies would reveal more precise and striking results by evaluating these limitations.
In conclusion, this study, found that the psychosocial functions of women before surgical menopause only affected their depressive moods, and this situation improved after surgery. It was found that women before surgical menopause mostly complained of low back pain, and after surgical menopause, the severity of pain in the waist region decreased. According to our study, surgical menopause did not effect the physical and cognitive functions of women.
As a result of this study, we think that it is important to plan treatments with a multidisciplinary approach by healthcare professionals before menopause surgery. In this way, the health problems experienced by women specific to this period can be minimized and the menopause period can be passed more easily.
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.
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8. Bilge A, Öğce F, Genç RE, Oran NT. Algılanan stres ölçeği (ASÖ)’nin türkçe versiyonunun psikometrik uygunluğu. Ege Üniversitesi Hemşirelik Yüksekokulu Dergisi. 2009;2(25):61-72.
9. Hamilton M. The assessment of anxiety states by rating. Br J Med Psychol. 1959;32(1):50-5. DOI:10.1111/j.2044-8341.1959.tb00467.x
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Rabia Oz, Nesrin Yagcı. Investigation of the effect of surgical menopause on physical, psychosocial and cognitive functions in women. Ann Clin Anal Med 2021;12(6):647-652.
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Results of surgical treatment with proximal femur nail in adult femur pertrochanteric fractures
Emre Ergen 1, Mustafa Karakaplan 1, Bünyamin Arı 2, Okan Aslantürk 3, Özgür Yılmaz 3, Erkay Nacar 4
1 Department of Orthopaedics and Traumatology, Inonu University Medical School, Malatya, 2 Department of Orthopaedics and Traumatology, Ankara Yenimahalle Training and Research Hospital, Ankara, 3 Department of Orthopaedics and Traumatology, Malatya Training and Research Hospital, Malatya, 4 Department of Public Health, Karabuk Provincial Directorate of Health, Karabük, Turkey
DOI: 10.4328/ACAM.20373 Received: 2020-10-15 Accepted: 2020-11-14 Published Online: 2020-11-24 Printed: 2021-06-01 Ann Clin Anal Med 2021;12(6):653-657
Corresponding Author: Emre Ergen, Inonu University Medical School, Orthopaedics and Traumatology Department, Malatya, Turkey. E-mail: emreergen99@hotmail.com P: +90 537 764 71 68 Corresponding Author ORCID ID: https://orcid.org/0000-0002-6452-2401
Aim: Proximal femoral nails are widely used in the treatment of pertrochanteric fractures, as they can be applied in a shorter time and with less bleeding, with their more stable biomechanical properties during axial loading. In this retrospective study, conducted in our institution, we aimed to determine the effective- ness of PFN, especially in various osteoporotic conditions, mental health conditions, anesthesia risk, functional outcomes and mortality
Material and Methods: Functional and radiologic results of 109 consecutive patients with intertrochanteric femur fractures, who have undergone osteosynthe- sis with proximal femoral nail between October 2009 and January 2015, were examined retrospectively. In addition to demographic characteristics, the type of fracture, comorbidities, type of trauma, duration from the moment of fracture to surgery, surgery duration and complications, presence of union and position of the implant were evaluated clinically and radiologically. The American Society of Anesthesiologists (ASA) scale was used for surgical risk assessment. The Harris Hip Scoring System was used for functional evaluation.
Results: Fifty-nine patients were male and 50 were female. The mean age was 77,69 (17 -102) years. The mean follow-up time was 32,9 (12-61) months. The etiology was as follows: a simple fall in %89.9 of cases, a fall from height in %7,3 of cases and motor vehicle accidents in %1,8. Operative procedures were performed within an average of 3,54 days after admission to our hospital (range 0-17 days). The average length of hospital stay was 7,76 days (range 2-56 days). Nine patients had complications related to the fracture. The mean score on the Harris scale at the last follow-up was 79,6 (48-100). The mortality rate in the first year was %29,6. A high ASA score and age over 80 years were found to generate a statistically significant increase in the risk of mortality and poor functional outcome.
Discussion: Pertrochanteric fractures are usually diagnosed in elderly patients due to low energy traumas. The first choice of treatment must be surgical for an early return to pre-fracture activity levels. The proximal femoral nail is a reliable, safe and effective treatment method for pertrochanteric fractures due to its advantages such as application with closed reduction, providing anatomic and biological fixation, short surgical time, low blood loss and complication rate, and the possibility of early weight-bearing.
Keywords: Intertrochanteric fractures; Proximal femoral nail; Harris hip score
Introduction
Classically, fractures occurring in the region between the large trochanter and the small trochanter are called intertrochanteric femur fractures. Proximal femoral fractures involve some unique challenges in elderly patients with increased comorbidities and predisposition factors and conditions such as osteoporosis [1- 4]. In the whole world, the incidence of these fractures increases due to the prolonged life expectancy [5]. In the United States, there are approximately 200000 hip fractures per year, and this number is expected to increase to 500000 per year in 2040 [6]. In a study investigating the incidence of hip fracture in Turkey, in the year 2010, 17800 hip fractures are expected to rise to 50,000 in 2035 increasing by about three times [7].
The purpose of the treatment of intertrochanteric fractures is to minimize the medical complications and technical errors that may arise, and to give the patient ability to move safely again, reaching the patient’s pre-fracture activity level.
Proximal femoral nails are widely used in the treatment of these fractures as they can be applied in a shorter time and with less bleeding, with their more stable biomechanical properties during axial loading. In this retrospective study conducted at our institution, we aimed to determine the effectiveness of PFN, especially in a variety of osteoporotic conditions, mental conditions, anesthesia risk, functional outcomes, and mortality [8, 9].
Material and Methods
Informed consent was obtained from all patients and ethics committee approval was obtained from our institution for the study. Between October 2009 and January 2015, 109 patients who underwent osteosynthesis with Veronail® proximal femur nail due to pertrochanteric femur fracture were retrospectively evaluated. Patients with extracapsular, pertrochanteric fractures evaluated as AO Type 31-A1, Type 31-A2 and Type 31-A3 and subgroups were included in the study.
Patients who did not have the ability to walk before the fracture, patients with pathological fractures, or previous surgical history of the ipsilateral femur and hip, and fractures extending more than 5 centimeters distal to the trochanter minor were not included in the study.
The demographic data, the nature of trauma, the type of fracture, and concomitant systemic diseases accompanying other fractures were recorded. The preoperative health status was evaluated by obtaining a history of any comorbid disease and medication, and by determining the physical health status according to the American Society of Anesthesiologists (ASA). Electrocardiogram, electrolytes, liver and kidney function tests, complete blood count, bleeding time and serology tests were performed for surgery preparation. At the time of admission, both hip anteroposterior, femoral anteriorposterior and lateral including the broken side of the hip were taken.
The duration of the operation, the type of anesthesia, and the number of blood transfusions needed were recorded. The duration of hospitalization before and after the surgery was evaluated.
Surgical Technique
Veronail® proximal femoral nail, which allows compression in the double-axis with double compressive locked telescopic
cephalic screws, was used for stabilization. After the patients were anesthetized, they were placed on the fracture table in the supine position. Closed reduction was performed under fluoroscopy. After nail insertion, telescopic screws were used for AO 31.A1 and AO 31, and A2 fractures for proximal fixation. In cases of AO 31.A3 fractures, fixed screws were used in the convergence configuration. Nail distal locking was performed statically and dynamically.
Postoperative course
Infection prophylaxis with second-generation cephalosporins and deep vein thrombosis prophylaxis with low molecular weight heparin were applied to all patients until the first month. Patients with stable trochanteric fractures were mobilized with the aid of a walker by loading as much as they could tolerate on the first postoperative day. Reinforcement rehabilitation of the knee and hip circumference muscles was started. Patients with unstable trochanteric fractures were applied partial weight- bearing with a walker during the first 6 weeks after surgery, and weight-bearing ratio were increased after 6 weeks. The patients were called to the outpatient clinic controls for suture removal in the second week after surgery. The functional status assessment was performed in conjunction with radiological evaluation in patients who were invited to the control visits at the 6th week, 6th month, and 12th month, and then once a year. Radiological evaluation
We took into account the union in the fracture, the position of the implant, the degree of secondary varus, calcification at the tip of the trochanter major, and the penetration into the hip joint of proximal screws.
Functional Evaluation
According to the Harris Hip Scoring system in functional evaluation, 90-100 points: excellent, 80-89 points: good, 70-79 points: moderate and <70 points: evaluated as bad results. The evaluation in the first year after the operation was taken into consideration. Patients who died in the first year were excluded from functional evaluation.
Statistical Analyses
SPSS 22.0 version package program was used in the statistical analysis of the data in our study. Categorical measurements were summarized as numbers and percentages, while numerical measurements were summed as mean and standard deviation, median and minimum-maximum. Shapiro Wilk and Kolmogorov-Smirnov tests were used for normal compatibility tests. Student-T Test and One-Way ANOVA were used for numerical data that conformed to normal, and Mann-Whitney U and Kruskal-Wallis Tests were used for non-normal data. In the categorical data, Pearson Chi-Square and Yates Chi- Square were compared, and in comparing the two numerical data, Pearson’s Correlation Test was used for the data that conformed to the norm, and Spearmen Correlation was used for non-normal data. A p-value of less than 0.05 was considered statistically significant.
Results
The demographic characteristics of the patients, ASA classification, causes of injury and the results of the patients whose Harris hip score was calculated in the study are summarized in Table 1. Twenty-three of 109 patients died within 3 months after surgery, 2 within 3-6 months and 4 within 6-12 months. Patients followed up for less than 12 months were excluded from the functional results. The remaining 80 patients were followed up for an average of 32.9 months, with a minimum of 12 and a maximum of 61 months. Patients were evaluated with the Harris Hip Score (HHS) for fracture union and functional results.
In our study, the average of HHS in 80 patients with a follow- up period of at least one year was 79.6 (48-100). There was no statistically significant difference between HHS and age. In the statistical evaluations performed by dividing the patients into groups under the age of 70, between the ages of 70 and 80, and above the age of 80, it was observed that the HHS values of the patients showed a significant decrease with the advancing age (p <0.001). When we tested homogeneity between groups in post hoc analysis, it was found that variance homogeneity was different (p <0.001). In the T-mean Post Hoc test performed on groups with different variance homogenity, the statistical difference was significant when comparing the group of patients over 80 years old with other groups. Concomitant diseases are shown in Table 2. Most common concomitant disorders were hypertension, diabetes mellitus and chronic obstructive pulmonary disease. The patients were operated on an average of 3.54 days (0-17 days). Patients with a mean hospital stay of 3.32 days (1-50 days) after surgery were found to have a mean hospital stay of 7.76 days, with a pre-operative waiting period. No statistically significant difference was found between the length of preop hospital stay and the mortality rate (p = 0.817). The average number of transfusions was calculated as 0.9 units. A statistical difference was found between transfusion and mortality risk (p = 0.012). Also we observed that the type of anesthesia had no effect on mortality.
The distribution of fractures according to the AO classification system is shown in Table 3. When the patients were compared according to death risks associated with subtypes of AO classification, there was no statistically significant difference between fracture stability and risk of death within one year (p = 0.267). There was no statistically significant difference regarding the effect of fracture stability on HHS (p = 0.246). It was found that age below 70 and above in A3.3 fractures caused a statistically significant difference in HHS (p = 0.029) Nine patients had complications related to the fracture. There were two proximal screws cut-out with secondary varus malposition, one nonunion and implant failure (Figure 1), and one femoral shaft fracture at the level of the distal screw after a simple fall. Also, one patient with non-union was revised using plate screw osteosynthesis and an iliac crest autograft. We encountered pulmonary embolism in three patients and surgical site infection in one patient. Unfortunately, all patients with pulmonary embolism died within one week of surgery. No patients had an iatrogenic femoral shaft fracture during surgery. Patients with a secondary varus and proximal screw cut out did not accept secondary surgery.
In the one-year follow-up, the mortality rate was calculated as 29.6%. The one-year death rate in patients over 80 years of age was found to be 42.6%. When the patients were divided into groups under the age of 70, between 70 and 80 and above 80, a statistically significant difference was found (p <0.001), and the risk of death was higher in patients over 80 years of age. In the statistical evaluation made using Pearson chi-square test, it was observed that there was an increase in ASA classification and an increased risk of death (p = 0.029).
Discussion
Although hip fractures are the most common traumatic injury in the older age population, they are also one of the most important causes of morbidity and mortality despite current medical advances and current approaches in preoperative and postoperative follow-up. Management of these patients becomes more complicated due to accompanying health problems. Mortality rates can be up to 10% within 30 days after surgery, but this rate varies between 20% and 30% at the end of the first year [10-12]. In our study, the mortality rate was found to be 26% over a period of one year, and the result was found to be consistent with the literature.
In their study, Hue and colleagues stated that advanced age, male gender, limited ability to walk preoperatively, difficulty in performing daily life activities, high ASA score, low mental capacity, weak cognitive functions, dementia, diabetes, cancer and heart disease are early mortality risk factors after hip fracture [13]. Elderly patients with comorbid diseases have an increased risk of mortality in the postoperative period. The risk of mortality increases in patients with impaired homeostasis, anemia, dehydration, and prolonged preoperative preparation period [11, 14-16]. In our study, although the one- year mortality rate was 35% in patients with more than five days of preoperative preparation period, we found that this increased time did not cause a statistically significant increase in mortality risk.
The Veronail® implant, which we used in our study, does not require medullar reaming, it is thin, its tip is blunt, it has two screws that can be sent to the femoral neck proximally, and distal screws can be locked both statically and dynamically [17, 18]. Since the proximal screws are locked into the nail, Z effect is not observed, and compression is provided by the telescopic screw structure. The proximal screw sent to the neck can be sent as a convergent. This feature can reduce the incidence of screw peeling by allowing more bone stock to remain proximal to the screw.
During the surgery, it was shown that after reaming the nail entry point, loss of reduction can occur while attaching the nail. Xu and colleagues reported that during intertrochanteric fracture surgery, there may be reduction losses during the proximal femoral nail applications due to improper nail insertion, inadequate imaging with scopy, excessive traction and removal of auxiliary reduction tools prior to complete stabilization. Also, it was stated that lag screws or helical blades may promote reduction loss as the twisting forces will cause rotational deformation at the proximal fragment [19]. The proximal fracture fragment is more resistant to rotational forces due to the presence of two screws in the Veronail®. Unlike similar systems (PFN-A®, Synthes 17 mm) (InterTan®, Smith and Nephew 17mm), in Veronail®, the proximal nail diameter is smaller (15 mm). This feature benefits the preservation of bone stock. In addition to tolerating minor errors during proximal reaming, it also prevents reduction loss while attaching the nail. It is evident that nail design has great importance in reducing the complication rate after fracture treatment. When patients who underwent osteosynthesis due to intertrochanteric femur fracture were examined, it was reported that the need for secondary surgery was 3% in the intramedullary hip screw, 6% in slide screw plating and 4-12% in PFN® [20]. In a study conducted by Liu et al., they reported that 20.5% of 223 patients developed mechanical complications [21]. In our study, three of 109 patients underwent secondary surgery. Since two patients with lag screw cut-out did not want to be operated, revision surgery was not performed. The reoperation requirement ratio was calculated as 6.42%. As a result, complication rates with Veronail in our study are lower than using other intramedullary implants reported in the literature [22-24].
Conclusions
Although the efficiency of proximal femur nails in the treatment of intertrochanteric fractures is obvious, the absence of Z-effect in the implant we use is the advantage of such systems. The low mechanical complication rates of the implant are remarkable.
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.
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Download attachments: 10.4328_ACAM.20373
Emre Ergen, Mustafa Karakaplan, Bünyamin Arı, Okan Aslantürk, Özgür Yılmaz, Erkay Nacar. Results of surgical treatment with proximal femur nail in adult femur pertrochanteric fractures. Ann Clin Anal Med 2021;12(6):653-657
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Investigation of factors affecting musculoskeletal pain and quality of life in university students
Fatih Tekin, Feride Yarar
School of Physical Therapy and Rehabilitation, Pamukkale University, Denizli, Turkey
DOI: 10.4328/ACAM.20374 Received: 2020-10-15 Accepted: 2020-11-14 Published Online: 2020-11-26 Printed: 2021-06-01 Ann Clin Anal Med 2021;12(6):658-662
Corresponding Author: Fatih Tekin, Pamukkale University, School Of Physical Therapy And Rehabilitation, Denizli, Turkey. E-mail: fzt.ftekin@hotmail.com P: +90 258 296 4264 Corresponding Author ORCID ID: https://orcid.org/0000-0001-7829-7957
Aim: In this study, we aimed to examine the factors affecting musculoskeletal pain and quality of life in university students experiencing musculoskeletal pain.
Material and Methods: Two hundred-eighteen (F:120; M:98) (X=21.22±1.9) university students studying at Pamukkale University School of Physical Therapy and Rehabilitation were included in the study. Due to the Covid-19 pandemic, the study was conducted over the phone and online. The correlation between the Cornell Musculoskeletal Discomfort Scale and the Nottingham Health Profile with gender, age, BMI, smoking habit, exercise habit, and time spent in front of a desk-computer-TV was examined.
Results: Age parameter was correlated with back musculoskeletal pain in the trunk region (p<0.05). Body Mass Index parameter was correlated with back, lower back and shoulder musculoskeletal pain (p<0.05). Smoking habit was found to be correlated with musculoskeletal pain in the right hand and wrist (p<0.05). Exercise habits were found to be correlated with musculoskeletal pain in all regions except both hands and wrists and both lower legs (p<0.05). There was a correlation between time spent sitting at the desk-computer-TV and musculoskeletal system pains in the neck, back, low back, shoulder and hip (p<0.05). Qual- ity of life was moderately correlated with smoking habits (p<0.05) and was positively correlated with exercise habits (p<0.05). Significant correlations were found between the duration of sitting at the desk-computer-TV and the quality of life parameters (p<0.05).
Discussion: University students suffer from musculoskeletal pain due to a relatively intense training program based on practice and some harmful habits, and their quality of life is negatively affected by this situation. Students should take precautions to protect their musculoskeletal systems and gain regular exercise habits.
Keywords: College students; Musculoskeletal pain; Quality of life
Introduction
Musculoskeletal system disorders are defined as disturbances or diseases in the musculoskeletal system and arising from work, according to the International Occupational Health and Safety Commission. The term “arising from work” is used by the World Health Organization to describe the scientific cause of a multi- factor disease that starts with the effect of two factors such as job performance and work environment [1]. Musculoskeletal disorders in working and education life occur due to repetitive physical movements such as bending, stretching, grasping, holding, turning, compression, and stretching that cause damage to tendons, muscles, nerves and other soft tissues [2]. These common movements in the usual activities of daily life are actually not harmful. What makes these movements harmful is the continuous repetition, speed, and lack of time between two movements for recovery [3].
Health-related quality of life refers to the ability of health to fulfill the functions of individuals and the physical, mental and social space that individuals perceive in their lives. Health-related quality of life criteria are widely used in health programs, evaluation of the effectiveness of treatment and economic evaluation studies [4]. Today, it is aimed not only to eliminate diseases but also to increase the quality of life of people. Therefore, an increasing efforts are being made to measure well-being and quality of life [5].
Musculoskeletal pain that occurs in young adults may be due to any organic pathology of neoplastic, inflammatory or infectious origin, and the majority of cases develop due to factors such as posture and working conditions. In various studies on the subject, in the formation of musculoskeletal system pain in the early period, it has been determined that gender, class of study, computer use, the burden of students, sitting time, time after school, academic stress and exercise habits are effective [6]. The aim of this study is to examine the factors affecting musculoskeletal pain and quality of life in university students experiencing musculoskeletal pain.
Material and Methods
The study was conducted in September-October 2020. Two hundred-eighteen (F:120; M:98) (X±SD = 21.22±1.9) university students studying at Pamukkale University School of Physical Therapy and Rehabilitation were included in the study. The inclusion criteria were being between the ages of 18-30 and having idiopathic musculoskeletal pain in at least one part of the body, while the exclusion criteria were to have any diagnosis that would cause pain in the musculoskeletal system and to have undergone a surgical operation within the last 6 months. Participation in the study was voluntary. The questionnaires used were filled in by phone and various online methods due to the Covid-19 pandemic.
It was decided by Pamukkale University Non-Interventional Research Medical Ethics Committee with the number of 60116787-020/37898 that the study was ethically appropriate. Informed approval was obtained from every participant in the study.
Demographic Data Form
The data of the participants such as gender, age, height, weight, exercise habits, daily sitting time at a desk, daily computer use, daily television watching time and smoking habit were recorded in demographic data forms. For the exercise habit, it is required to exercise regularly for at least 3 days a week in the last 6 months and to have been smoking for at least the last 6 months for the smoking habit.
Cornell Musculoskeletal Discomfort Questionnaire
The Cornell Musculoskeletal Discomfort Questionnaire (CMDQ) takes into account the severity and frequency of pain in the body, taking into account body postures, gender and the way the work is done. Turkish adaptation study has been done. The questionnaire has separate evaluations for female/male and sitting time/standing jobs. In the questionnaire, 18 different body regions are presented in the form of options to what extent and how often they cause discomfort in the last week, and people are asked to choose the one that suits them. From the 3 groups of questions presented in the questionnaire, the answers given for each of the 18 body regions and the risk score for each region are calculated. Values corresponding to the answers given in the CMDQ risk score calculation are multiplied with each other. The Turkish validity and reliability study was performed by Erdinç et al. [7].
Nottingham Health Profile
The Nottingham Health Profile (NHP) is a general health questionnaire developed to measure the physical, emotional and social effects of diseases on a person. It contains a total of 38 questions in six parts: pain, physical activity, energy, sleep, social isolation and emotional reaction. Questions are answered as yes or no. Each section is scored between 0-100. Zero (0) indicates the best health status, 100 the worst health status [8]. The adaptation of NSP to Turkish and its psychometric properties were made by Kucukdeveci et al. [9].
Statistical Analysis
In the power analysis made in line with the information obtained from the literature, assuming that the effect size of the correlation between the variables to be examined could be moderate (r=0.4), it was calculated that 90% power could be obtained at a 95% confidence level when at least 184 people were included in the study [10]. Considering the possible data loss, it was planned to include at least 200 participants in the beginning of the study.
The data were analyzed with SPSS 25 (IBM SPSS Statistics 25 software (Armonk, NY: IBM Corp.)) package program. Continuous variables are given as mean ± standard deviation. Since the correlations between continuous variables are suitable for normal distribution, they were analyzed using Pearson correlation analysis.
Results
The gender parameter was not found to correlate with musculoskeletal pain in any part of the body (Tables 1 and 2) (p>0.05).
Age parameter was correlated with back musculoskeletal pain in the trunk region (p<0.05), but not with neck and low back pain (Table 1) (p>0.05). Age parameter was not correlated with musculoskeletal pain in the extremities (Tables 2 and 3) (p>0.05).
While the BMI parameter was correlated with musculoskeletal pain in the back, lower back and shoulder (p<0.05), it was not correlated with pain in other regions (Tables 1 and 2) (p>0.05). Smoking habit was found to be correlated with musculoskeletal pain in the right hand and wrist (Table 2) (p<0.05). Apart from these, it was not correlated with pain in any other region (Tables 1 and 2) (p>0.05).
Exercise habits were found to be correlated with musculoskeletal pain in all regions except both hands and wrists and both lower legs (Tables 1 and 2) (p<0.05).
While there was a correlation between time of sitting at the desk-computer-TV and neck, back, low back, shoulder and hip musculoskeletal system pains (p<0.05), no correlation with pain in other regions was found (Tables 1 and 2) (p>0.05). According to Table 3, while quality of life was moderately correlated with smoking habits (p<0.05), it was positively correlated with exercise habits (p<0.05). Significant correlations were found between the duration of sitting at the desk- computer-TV and the quality of life parameters (p<0.05).
Discussion
The results of this study showed that physiotherapy and rehabilitation students suffer from musculoskeletal pain in various parts of their bodies due to reasons such as prolonged sitting in front of a table-computer-television, smoking habit, high BMI and insufficient physical activity. Gender and age factors do not have a significant effect on this situation.
It has been shown that musculoskeletal pain, especially low back pain, is a reality for many physiotherapy and rehabilitation students [11]. Moreover, these students are from the young population, as in our study.
In the current literature, physiotherapy and rehabilitation students also suffer from musculoskeletal pain during education, as in various health departments such as medicine, nursing, dentistry, occupational therapist and health technician. Physiotherapy and rehabilitation students are at higher risk compared to other departments [12].
In the current literature, there are conflicting findings that the musculoskeletal pain experienced by students of various health sciences varies by gender. Some studies state that male gender is a risk factor, while others state that female [13-15]. In our study, it was found that the musculoskeletal pain in the university students did not depend on gender.
In our study, the age criterion did not make a significant difference. The reason for this situation is possibly the young population and the narrow age range. The literature has also reported that the risk of musculoskeletal pain increases as it progresses, especially by age 65 [16].
According to the results of our study, as BMI increases, the level of musculoskeletal pain felt by the students in the shoulder, low back and back region increases significantly. As the BMI increases, the loads on the vertebral column increase and consequently, despite the young age, pain is felt in the back and low back regions. In the current literature, there are studies supporting these findings [17, 18]. On the other hand, according to the results of our study, BMI does not have a significant effect on musculoskeletal pain in other body parts.
A possible reason of the significant correlation between smoking habits and musculoskeletal pain felt in the right hand and wrist region was the badly affected circulatory system in the upper extremity [19].
There are conflicting findings in the literature regarding the correlation between smoking and musculoskeletal pain. There are studies [20] stating that smoking affects pain in the musculoskeletal system in university students, as well as studies stating that it has no effect [21].
Individuals with exercise habits have lower musculoskeletal pain in almost all neck, back, low back, upper extremity and lower extremity regions. In light of the findings from this study, we can make the comment that correct and regular exercise prevents and/or relieves musculoskeletal pain in university students aged 18-30. From another perspective, we could say that the reduced physical activity will cause musculoskeletal disorders in university students [12]. Contrary to our findings, in a study conducted with medical faculty students, it was observed that students with regular exercise habits experienced 4 times more musculoskeletal pain in the back area compared to students who did not [13]. We thought that the reason for this situation was that the medical faculty students in the study in question did not perform the exercises correctly, and the physiotherapy and rehabilitation department students were trained about the correct exercise from the first period of their education, so they did the exercises correctly.
According to the results of this study, time spent sitting at a desk, computer or television has been associated with musculoskeletal pain in the neck, back, low back, shoulder and hip regions. Sitting at a desk for a long time to study, sitting at the computer for activities such as study or games, and sitting at the computer watching television cause long-term immobilization in students, so all muscles, especially pivot areas such as the neck, back, low back and shoulder-hip caused pain in the skeletal system.
In the current literature, there are studies showing that sitting at a desk or computer for a long time negatively affects the entire musculoskeletal system, in support of these findings [13, 21]. In addition, there are studies showing that sitting at the computer for a long time causes upper arm pain, especially in university students [13], as well as studies showing that it causes more shoulder and neck pain [21].
According to the results of our study, factors such as, gender, age and BMI were not significantly correlated with the quality of life of the studied student population. The facts that the students are in a social environment in the university and their age is not yet advanced are considered as the reasons for this situation. On the other hand, in the current literature, it has been shown that female gender [22] and older age [23] have a negative effect on the quality of life of university students. Smoking habit negatively affects the quality of life based on energy level, pain, social isolation, sleep and physical activity and consequently decreases the quality of life. There are studies supporting these findings in the current literature [24, 25]. Sitting time for long periods of time at a desk, computer and TV creates social isolation, disrupts sleep patterns, reduces physical activities and causes musculoskeletal pain. As a result, even if it is a young and social population, the quality of life of university students aged 18-30. Supporting these findings, there are studies showing that sedentary life and long-term immobilization negatively affect the quality of life of university students [22, 23].
The strength of our study is that, contrary to the existing studies in the literature, it is not aimed to investigate the presence of musculoskeletal pain in university students in a certain department, but to investigate the causes of these pains and the quality of life of students who already have musculoskeletal pain. In addition, it emphasizes the positive effects of regular exercise habits on the musculoskeletal system and quality of life, and the negative effects of smoking habits and immobilization time, which increases with technology in today’s youth. The limitation of our study is that participants from only one university and one department were included in the study. University students suffer from musculoskeletal pain due to intense education program and some harmful habits, and their quality of life is negatively affected by this situation. Students should take precautions to protect their musculoskeletal systems and gain regular exercise habits.
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.
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Fatih Tekin, Feride Yarar. Investigation of factors affecting musculoskeletal pain and quality of life in university students. Ann Clin Anal Med 2021;12(6):658-662
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The effects of intravitreally injected dexamethasone implant and anti-VEGF on macular edema due to retinal vein occlusion
Aydin Yıldız, Sedat Arıkan
Department of Ophthalmology, Onsekiz Mart University, Canakkale, Turkey
DOI: 10.4328/ACAM.20378 Received: 2020-10-23 Accepted: 2020-11-23 Published Online: 2020-12-01 Printed: 2021-06-01 Ann Clin Anal Med 2021;12(6):663-666
Corresponding Author: Aydin Yildiz, Department of Ophthalmology, School of Medicine, Canakkale Onsekiz Mart University, Barbaros Street, 17100, Canakkale, Turkey. E-mail: sedatozcan78@gmail.com P: +90 533 559 5252 Corresponding Author ORCID ID: https://orcid.org/0000-0003-0396-5900
Aim: In this study, we aimed to investigate the efficacy of intravitreal treatment modalities for macular edema secondary to central retinal vein occlusion (CRVO) and branchial retinal vein occlusion (BRVO).
Material and Methods: A total 58 patients with macular edema secondary to CRVO and BRVO were included in this retrospective study. The patients followed up between 2012 and 2018 were subjected to either intravitreal dexamethasone (DEX) implant injection (Group 1), or intravitreal anti-vascular endothelial growth factor (anti-VEGF) containing ranibizumab injection (Group 2). Additionally, the patients who received the combination of intravitreal DEX and anti- VEGF treatment (Group 3) were also assessed in this study. The degree of central macular thickness (CMT) using optical coherence tomography, and best -corrected visual acuity (BCVA) levels were evaluated in all groups before and after treatment.
Results: CRVO and BRVO were present in 12 and 46 patients, respectively, and the mean follow- up time was 38 months. The mean CMT values measured in pretreatment vs. posttreatment period in Group 1, Group 2 and Group 3 were 448±41.3μm vs.217.7±15.9μm (p<0.05), 492±38.5μm vs.249.3±13.8μm (p<0.05), and 562.5±85.7μm vs.330.3±55.9μm (p<0.05), respectively. Regarding the comparison of BCVA levels measured in the pretreatment vs. postreatment period, there was a statistically significant increase in all groups as follows: 0.8±0.08 logMAR vs. 0.4±0.08 logMAR (p<0.05) in Group 1, 0.9±0.1 logMAR vs. 0.3±0.05 logMAR ( p<0.05) in Group 2, and 1.6±0.3 logMAR vs. 0.5±0.1 logMAR( p<0.05) in Group 3.
Discussion: The intravitreal injection treatments with either dexamethasone implant or anti-VEGFs can have a potential effects on the resolution of macular edema secondary to BRVO. Moreover, their combination can be beneficial for the persistent macular edema arising from CRVO.
Keywords: Retinal vein occlusion; Intravitreal injections; Dexamethasone implant; Aflibercept; Ranibizumab
Introduction
Retinal vein occlusion, leading to a varying degree of painless visual loss is one of the most commonly encountered retinal vascular diseases in ophthalmic practice. The clinical severity of this disorder usually depends on the degree of retinal venous insufficiency, namely, the visual prognosis is often poor in case of central retinal vein occlusion (CRVO), whereas it may be good if the retinal vein is partially occluded that is branchial retinal vein occlusion (BRVO). Moreover, the ischemic type of CRVO can cause profound painful visual loss owing to neovascular glaucoma. This condition is frequently seen in the retinal artery- vein crossing areas, where they share the same adventitial sheath [1, 2].
There are many systemic and visual causes for the obstruction etiology. Systemic causes include hypertension, diabetes mellitus, and atherosclerosis, while eye-related causes include glaucoma and hyperopia [3, 4].
The increased pressure in the retinal capillaries leads to changes in the serum part of the blood. The fluid enters the retinal layers in the macula and forms a pathology called macular edema. The tight connections between endothelial cells in the inner wall of retinal capillaries are disrupted, and vascular endothelial growth factor (VEGF) secreted from these endothelial cells increases macular edema by increasing permeability of these vessels. Macular edema is the most common cause of decreased vision in retinal vein occlusion [5].
The most commonly used treatment methods are laser photocoagulation, intravitreal steroid injection, and intravitreal anti-VEGF injection [6]. The intravitreal depot form as a dexamethasone (DEX) implant has been developed for more effective treatment in retinal vein occlusions [7]. It has not been determined exactly which treatment is more effective.
In this study, it was aimed to evaluate the effectiveness of the treatment modalities and response to these treatments in patients with CRVO and BRVO, both on visual acuity and macular thickness.
Material and Methods
This study was conducted on patients admitted to Canakkale Onsekiz Mart University Ophthalmology Clinic between the years 2012 and 2018. The study was approved by the local ethics committee.
The study was carried out retrospectively with the review of the medical records of the patients with retinal vein occlusion. Inclusion criteria were: central retinal vein occlusion, branch retinal vein occlusion, and macular edema. Patients with prior ocular surgery, retinal arterial occlusion, dense cataracts obscuring retinal images, central corneal opacity, age-related macular degeneration, central serous chorioretinopathy, and posterior uveitis were excluded.
All patients underwent a detailed ophthalmological examination. Systemic diseases were questioned. The diagnosis of vein occlusion was established both by fundoscopic examination and by fluorescein angiography imaging. Optical coherence tomography OCT (Zeiss Cirrus, Zeiss Meditec. Inc, Germany) was performed to detect macular edema in all patients. The first and last visual examinations were recorded as the best- corrected visual acuity according to the Early Treatment
Diabetic Retinopathy Study (ETDRS) chart.
These patients have been followed up between the years 2012 and 2018 and were subjected to either intravitreal anti-vascular endothelial growth factor (anti-VEGF) containing ranibizumab injection (Group 1) or intravitreal dexamethasone (DEX) implant injection (Group 2). Additionaly, the patients who received the combination of intravitreal DEX and anti-VEGF treatment (Group 3) were also assessed in this study. All patients had unilateral involvement.
All intravitreal injections were performed in the operating room under aseptic conditions with an order of topical anesthetic, 10 % povidone iodine instillation, sterile draping, injection of dexamethasone implant or anti-VEGF with a 30G needle from the superonasal or superotemporal pars plana, topical antibiotic instillation, and eye patching.
The preference for an intravitreally injected agent was primarily made according to the presence of subretinal fluid, intraretinal cystic changes, and hyperreflective dots in the retinal layers. Phacoemulsification surgery was performed in patients who developed cataracts. Trabeculectomy was performed in case of no response to medical therapy for glaucoma.
Statistical Analysis
The Wilcoxon test, available in the SPSS 20.0 software, was performed for comparison of CMT before and after treatment of the same patients. The p-value of less than 0.05 was considered significant (Table 1).
Results
The right eye was affected in 27 patients and the left eye in 31 patients. The patients were followed up for an average of 38.1 months (min: 14, max: 89). CRVO and BRVO were detected in 12 (20.7%) and 46 (79.3%) patients, respectively. The mean follow-up time was 38 months.
The mean age of the patients was 66.9 ± 10.5 (min: 46, max: 88) years. The study included 28 women (48.3%) and 30 men (51.7%). The most commonly seen systemic disease was hypertension in 27 patients (46.5%), while no systemic disease was detected in eighteen patients (31%). Other systemic diseases are shown in Table 2.
Ranibizumab was intravitreally injected to 22 patients with a varying number of injections. Central macular edema was decreased in 19 patients. The average central macular thickness (CMT) before treatment was 448±41.3μm and after treatment it decreased to 217.7±15.9μm (p <0.05). While the mean pre- injection visual acuity was 0.8±0.08 logMAR, it was found to be 0.4±0.08 logMAR after treatment (p <0.05). Intravitreal DEX-implant was done in 24 patients with varying numbers of injections. The mean CMT before treatment was 492±38.5μm and after treatment it decreased to 249.3±13.8μm (p <0.05). The mean visual acuity was 0.9±0.1 logMAR before treatment and 0.3±0.05 logMAR after treatment (p <0.05). Twelve patients received ranibizumab injections and DEX-implants at different times as change therapy. In this group, the mean CMT before the injections was 562.5±85.7μm and the vision was 1.6±0.3 logMAR, while the macular thickness after treatment was 330.3±55.9μm and the vision was 0.5±0.1 logMAR. The changes in both visual acuity and macular thickness were statistically significant (p <0.05).
In CRVO patients, the injections were the form of a DEX-implant in three (25%), anti-VEGF in three (25%), and a combination in the remaining six (50%) patients. Among BRVO patients, 21 (45.7%) were treated with DEX-implant, 18 (39.1%) were treated with anti-VEGF, and seven (15.2%) were treated with mixed treatments.
The average number of injections was 2.6, 1.3, and 7.2 in Group 1, Group 2, and Group 3, respectively. Out of 58 patients, an increase in visual acuity was detected in 53 (91.4%). In two patients, visual acuity decreased compared to their first visit. In three patients, visual acuity did not change. Only in one eye, the visual acuity fell to the level of hand motion, and in the other eye, visual acuity remained at the level of hand motion. There was no loss of light perception in any eye.
Two patients had glaucoma at the time of the diagnosis. During follow-up, four patients developed glaucoma: two patients in Group 1 and two patients in Group 2. Two patients who developed glaucoma following DEX-implant and did not respond to medical treatment underwent trabeculectomy. Glaucoma was kept under control without medication after trabeculectomy in both patients. Cataract surgery was performed in nine patients. While eight of these patients were in Group 2, only one case was in Group 1.
Discussion
In the treatment of retinal diseases, intravitreal injections have frequently been used as a first-line treatment. The most commonly used injections are anti-VEGF agents and DEX- implant.
In their study with anti-VEGF, Ayyildiz et al. injected a single dose of anti-VEGF to the patients with BRVO or CRVO who developed macular edema. They observed a decrease in CMT in both groups. The decrease in BRVO was significant, while in CRVO was not [8]. Shiono et al. reported a significant decrease in CMT and an increase in visual acuity after anti-VEGF injection in patients with macular edema due to BRVO [8]. In similar studies, Fukami et al., and Sarikaya et al. also reported significant decrease in CMT [9, 10].
In our study, similar to the literature, a significant reduction in CMT was also observed in 86.4% of the patients with anti-VEGF injection. The average CMT was decreased from 448 microns to 217 microns after the treatment. This decrease was also associated with an increase in visual acuity.
Macular edema related to vein occlusion may persist despite anti-VEGF treatment leading to the search for alternative treatments such as DEX-implant, slow-release and long-acting steroid implant [11,12]. Kanra et al., reported a significant decrease in patients with retinal vein occlusion [13]. In our study, we also found significant decrease in CMT with the DEX- implant. The mean CMT was decreased from 492 microns to 249 microns after the treatment with an associated increase in visual acuity.
The studies related to DEX-implant show the effectiveness of the treatment. Unsal et al., reported a decrease in CMT in the first three months then it maintained following three months [22]. Eter et al. reported improvement in both visual acuity and macular edema in a multi-center study [23]. Donati et al. reported a significant increase in visual acuity with better retinal functions in the early period [14].
Development of cataract and glaucoma has been seen more than other treatments in DEX-implant [15]. In our study, while eight of 34 (23.5%) patients developed cataract impairing visual acuity, and two (5.9%) patients required trabeculectomy after DEX-implant. Rajesh et al. reported the rate of cataract and glaucoma surgery as 32% and 0.5%, respectively [16]. The lower rate of glaucoma surgery than in our study may be attributed to the higher rate of diabetic macular edema in their study instead of vein occlusion. In another study similar to our rates, Hemarata et al. reported that 4.6% of patients required glaucoma surgery [17].
In our study, the average reduction in CMT was 217 microns in the anti-VEGF group, and 242 microns in the DEX-implant, with no statistical significance between the groups (p>0,05). Gu et al. compared the two treatment methods and reported no difference between them. The only difference was the increase in intraocular pressure in the steroid group [18]. Ji et al. also found no difference between the two methods in a meta- analysis study [19].
If there was no response to one of the treatment regimens, another option was used. Manousaridis et al. reported the decrease in CMT after DEX-implant in retinal vein occlusion patients with no response to anti-VEGF treatment [20].
In our study, in one fifth of the patients, changes were done between DEX-implant and anti-VEGF injections. The changes were done from anti-VEGF to dexamethasone implant in ten patients, and reverse in two with a response rate of 91.7% . Balal et al reported that anti-VEGF treatment could be done after DEX-implant in case of persistant macular edema [21].
In conclusion, the intravitreal injection treatments with either dexamethasone implant or anti-VEGFs can have a potential effects on the resolution of macular edema secondary to BRVO. Moreover, their combination can be beneficial for the persistent macular edema arising from CRVO.
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.
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6.Hu Q, Li H, Xu W, Du Y, Ma C, He J. Comparison between Ozurdex and intravitreal anti-vascular endothelial growth factor treatment for retinal vein occlusion- related macular edema: A systematic review and meta-analysis of randomized controlled trials. Indian J Ophthalmol. 2019;67(11):1800-9.
7.Ayyıldız T, Oral A, Calli U, Salkaci O, Kandemir B, Ozerturk Y. Short-term results after single-dose intravitreal bevacizumab treatment for macular edema secondary to central and branch retinal vein occlusions. South Clin Ist Euras. 2017; 28(3):184-9.
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12.Haller JA, Bandello F, Belfort R Jr, Blumenkranz MS, Gillies M, Heier J, et al. Randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with macular edema due to retinal vein occlusion. Ophthalmology. 2010;117(6):1134-46.
13.Kanra AY, Ardagil Akcakaya A, Ari Yaylali S, Altinel MG, Sevimli N. The efficacy and safety of intravitreal dexamethasone implant for the treatment of macular edema related to retinal vein occlusion: real-life data and prognostic factors in a Turkish population. Turk J Ophthalmol. 2017;47(6):331-7.
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17. Hemarat K, Kemmer JD, Porco TC, Eaton AM, Khurana RN, Stewart JM. Secondary Ocular Hypertension and the Risk of Glaucoma Surgery After Dexamethasone Intravitreal Implant in Routine Clinical Practice. Ophthalmic Surg Lasers Imaging Retina. 2018;49(9):680-5.
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Aydin Yıldız, Sedat Arıkan. The effects of intravitreally injected dexamethasone implant and anti-VEGF on macular edema due to retinal vein occlusion. Ann Clin Anal Med 2021;12(6):663-666
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Imatinib Mesylate induces apoptosis in chronic myeloid leukemia cells by triggering nitric oxide production
Aynur Karadağ Gürel 1, Tülin Özkan 2, Buket Altınok Güneş 3, Asuman Sunguroğlu 2, Fügen Aktan 4
1 Department of Medical Biology, School of Medicine, Usak University, Usak, 2 Department of Medical Biology, School of Medicine, Ankara University, Ankara, 3 Medical Laboratory Techniques, Vocational School of Health Services, Ankara University, Ankara, 4 Department of Biochemistry, Faculty of Pharmacy, Ankara University, Ankara, Turkey
DOI: 10.4328/ACAM.20379 Received: 2020-11-02 Accepted: 2020-11-30 Published Online: 2020-12-12 Printed: 2021-06-01 Ann Clin Anal Med 2021;12(6):667-671
Corresponding Author: Aynur Karadağ Gürel, Usak University, Faculty of Medicine Dean’s Office 4th Floor, 64200, Usak, Turkey. E-mail: aynur.karadag@usak.edu.tr P: +90 276 221 21 21-6240 GSM: +90 5326821113 F:+90 276 221 22 34 Corresponding Author ORCID ID: https://orcid.org/0000-0002-5499-5168
Aim: Chronic Myeloid Leukemia (CML) is a myeloproliferative disease characterized by abnormal clonal proliferation of hematopoietic stem cells. The over- production of nitric oxide (NO) causes reactive oxygen species and subsequent oxidative stress to cell toxicity. The production of factors such as nitric oxide (NO) and reactive oxygen species (ROS) in the cell and/or tissue environment affects the behavior of normal cells and cancer cells. In this study, we aimed to investigate the effects of nitric oxide formed as a result of Imatinib Mesylate (STI571, Gleevec®) metabolism on cell death.
Material and Methods: 32D (Control) and 32DP210 Cells were treated with 10um of Imatinib Mesylate for 24, 48 and 72 hours. Methyl tetrazolium assay (MTT) was used for cell viability. Griess assay and capillary electrophoresis were used to measure Imatinib Mesylate -mediated NO production. The number of cells leading to apoptosis was calculated by counting 1000 cells and compared with the amount of NO. Statistical analysis of the obtained data was done with SPSS for Windows statistical package program.
Results: The presence of NO is important for increased cell death in the cell culture medium. Imatinib mesylate concentrations administered to healthy and CML groups increased intra cell NO levels by a significant amount in Bcr-Abl+ CML cell lines. The production of NO per apoptotic body is decreased during the apoptosis, and analysis of NO production using CE in these cells has rapid and efficient separation ability.
Discussion: As a result, knowing the molecules and effects regulating NO activity better appears to be a target point to remove many irregularities of these molecules. Sensitive detection of these metabolic products is important as variations in NO levels in many diseases provide information about development of diseases and treatment.
Keywords: Chronic myeloid leukemia; Imatinib mesylate (STI571, Gleevec); Nitric oxide; Capillary electrophoresis; Apoptosis
Introduction
Chronic myeloid leukemia (CML) is a clonal hemopoietic stem cell disease, characterized by the presence of Bcr-Abl oncoprotein and mutual translocations between the chromosome 9 (ch9) and 22 (ch22) long arms [1]. Imatinib mesylate, known as STI571 or Gleevec, is a successful tyrosine kinase inhibitor (TKI) commonly used for CML treatment. The development of TKI significantly increased the survival of CML patients [2]. Imatinib mesylate suppresses these tyrosine kinase receptors by blocking the ATP binding site and is accepted as the first- stage treatment of CML and gastrointestinal stromal tumors [3]. Reactive oxygen species (ROS) are important for tumor cell apoptosis, mitochondrial stability and chemotherapeutic effects. Additionally, ROS may act like mitogens stimulating the proliferation and migration of tumor cells [4]. ROS can damage DNA directly or through intermediates, and plays an important role in genome integrity as increased ROS production is associated with Bcr-Abl activity. [5].
Cell toxicity may cause organ function disorder and serious health problems. Recent studies have revealed that many toxic materials, overproduction of nitric oxide, reactive oxygen species and later occurring oxidative stress may cause cell toxicity [6]. At low concentrations, intracellular oxidants act like signal transducers, inducing growth factors, hypoxia and other receptor-ligand systems [7, 8]. Additionally, these oxidants may damage lipids, proteins, RNA and DNA at concentrations above threshold levels; thus, they trigger cell death through apoptosis and/or necrosis pathways [9, 10]. ROS, like oxygen ions and peroxides, comprise natural by-products of normal oxygen metabolism and they are reactive molecules containing oxygen that play an important roles in cell signals and homeostasis [11]. The biological functions of ROS and their potential role in cancer development and disease progression have been researched in recent years. ROS mediates cancer cell apoptosis induced by a variety of anticancer agents and other stimulants. Additionally, several studies have shown that anticancer agents reduced ROS production and increased malignant cell apoptosis [12, 13]. Bcr-Abl stimulates the production of ROS. ROS induces abl kinase activation. Since ROS activates Abl kinase, the Bcr-Abl kinase inhibitor imatinib is thought to have an effect opposite to the endogenous ROS induced by Bcr-Abl [5, 14-16]. In this very complicated network of biological processes, certain molecules may have binary roles linked to activity as a part of the content and on complicated intracellular and intercellular communication paths. Some, like reactive species, play a role in protecting the regular physiological environment; however, they may become pathogenic vectors for cell injury and destruction under pathophysiological conditions and contribute to disease development [16-18]. NO is believed to play a dual role in damaging or protecting cell functions. Nitric oxide may induce both apoptosis and necrosis in a variety of cells. Additionally, the NO-dependent effect mechanism of Imatinib Mesylate has not yet been determined; however, many studies have shown that apoptosis is closely related to changes in NO levels [18]. In this study, we aimed to understand the developed cytotoxicity mechanism caused by Imatinib Mesylate derived NO in CML and Control cell lines, nitrite levels were assessed before and after imatinib administration and cell death was monitored.
Material and Methods
Cell Culture and Reagents
Murine IL-3-dependent myeloblastic cell lines 32D (normal) and 32Dp210 (CML lines) were purchased from ATCC (American Type Culture Collection). 32Dp210 were maintained in RPMI1640 supplemented with FBS (10%), 100 U/ml penicillin, and 100 mg/ml Penicillin/streptomycin at 37°C, in a humidified atmosphere of 5% CO2. The cells were plated in 96-well plates, covered with collagen (Sigma) at the density of 2x 105 /cm2. 32D cell lines were grown in RPMI supplemented with 10% fetal calf serum (FCS), glutamine, penicillin, streptomycin, and 10% conditioned medium from the WEHI-3B cell line, as a source of IL-3. WEHI-3B cells produce high levels of IL-3 and used WEHI- 3B-conditioned medium as a source of IL-3. The cells were passaged every 3 days, and the supernatant was centrifuged in 2500 rpm and collected for IL3.
Imatinib Mesylate (Novartis, Basel, Switzerland) was prepared by dissolving the stock solution in Dimethyl Sulfoxide (DMSO) (Applichem, A2940) at a concentration of 2mg/ml and stored at -20°C. A dose of 10μM Imatinib Mesylate was used for this assay because we showed that 10μM was required to induce apoptosis at 24 hours.
Cell Viability
The MTT assay, reduction of 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide to a purple formazan product, was used to estimate cell viability and growth. Cells were plated in triplicate in 96-well plates at a density of 5×106 cells/ well, and the next day the media was replaced with media containing Imatinib Mesylate. Cells were treated with the previously mentioned concentrations for 24, 48 and 72 hours. After 24, 48 and 72 hours, the media was replaced with MTT containing media (0.5mg/ml). The cells were incubated at 37°C for 4 hours, an equal volume of solubilization solution was added and incubated at 37°C overnight to solubilize formazan crystals. Then the absorbance at 540 nm was read using a spectrophotometric microplate reader. The viability of cells was calculated as viability percentage in comparison to non-treated cells.
Determination of Nitrite/Nitrate in Supernatans using Griess Reaction and Capillary Electrophoresis
Griess assay: Nitric oxide production was determined by measuring nitrite, the stable end product, using the Griess reagent according to the manufacturer’s protocol. On a 96- well plate, 500 μl of supernatant was added, followed by 500 μl of sulfanilamide and 500 μl of N-1-naphthylethylenediamine dihydrochloride (NED). Absorbance was read at 540 nm with nitrite concentrations determined using a standard nitrite curve. Capillary Electrophoresis: At determined times, samples taken from the cell culture were placed in 15 mL Falcon tubes, centrifuged for 10 min at 900 rpm, and then the supernatant portions were taken and samples were stored at -20 °C. Immediately before measurements, samples were thawed, diluted 1:5 with water and then samples were prepared for measurement with 0.5:1 IS and centrifuged for 5 min at 4000 rpm and measurements were performed.
Morphological Assay for Apoptotic Cells
Typical apoptotic cells, under a light microscope, show small, highly condensed chromatin bodies. Each apoptotic body has a fragmented piece of nucleus surrounded by a viable cell membrane. In addition, for confirmation of morphological assessments of apoptosis, smears were stained with Wright- Giemsa stain. The cells were centrifuged and the pellets were resuspended in minimum volumes of PBS. The cells were fixed and stained with 1 ml per slide of Wright-Giemsa stain for 1 min. After 4 min, the slides were rinsed with water and air- dried.
Statistical Analysis
The cells were studied in triplicates; each replication three times foreachassay.Statisticalanalysisofthegroupsaccordingto the initial value of the control cells was performed according to the one-way ANOVA test. Statistical analysis of the obtained data was done with the statistical package program software SPSS for Windows version 22.0. Results were given as mean ± standard deviation and p < 0.05 was considered significant.
Results
Determination of Live Cell Amounts with the MTT Method in Cells with Imatinib Mesylate Administered
The number of viable cells was determined with the MTT method in the presence and absence of 10μM concentration of Imatinib Mesylate at hours 0, 4, 6, 8, 10, 12, 24, 48 and 72. According to our results, in the presence and absence of Imatinib Mesylate from the 24th hour, the number of 32D viable cells increased; however, there appeared to be no variation in the number of viable cells in the 24 hour period. However, 32D cells with Imatinib Mesylate administered were identified to have slower proliferation compared to the rates for controls. Contrary to this, for the 32Dp210 cell lines, Imatinib Mesylate caused cell death from the 24th hour, with an increase in the cell numbers for control cells in this series from the 24th hour (Figure 1). Apoptotic Index of Cells Administered with Imatinib Mesylate Following Imatinib Mesylate administration, preparations of 32D and 32Dp210 cells were observed under a microscope and apoptotic cell counts per 1000 cells were determined. Control and Imatinib Mesylate-administered 32D cells were observed to have a reduction in ‰ apoptotic cell counts from the 12th hour, and this reduction was statistically significant (p<0.05). There was no significant change observed for apoptotic cell amounts in control 32Dp210 cells. However, 32Dp210 cells with Imatinib Mesylate administered were observed to have a significant increase in apoptotic cell amounts from the 24th hour (p<0.05) (Figure 2). In conclusion, Imatinib Mesylate induced cell death in 32Dp210 cells, and suppressed proliferation. The microscopic appearance of apoptotic cells is shown in Figure 3. Determination of Nitrite in Supernatans by Simple Griess Reaction
Under physiological conditions, NO is oxidized to nitrite and nitrate in a ratio of about 3:2. The conversion of nitrite to nitrate in oxygenated solutions is quite slow. According to the standard chart drawn, the amount of nitrite/nitrate taken from the cell media at different times was calculated by the Griess method. The value of nitrate concentrates per apoptotic cell ratio (%o) was evaluated according to the baseline data. According to our results, there was a significant increase in nitrate concentration per apoptotic cell at 72 hours at 32D control cells in the absence of Imatinib Mesylate.
Determination of Nitrite/Nitrate in Supernatans using Capillary Electrophoresis
Capillary electrophoresis for nitrite and nitrate estimation was performed according to a method proposed Tuncel et al. [19]. Electropherograms were drawn for samples under standardized conditions, peak areas were calculated and the nitrate concentrations for both cell lines were identified. According to the calculated concentrations, no significant increase or decrease in nitrate concentrations was observed in both cell lines.
Nitrate Concentration (with the capillary electrophoresis method)/Apoptotic Cells
Assessment of nitrate levels, identified with the capillary electrophoresis method as a marker of NO release, was assessed linked to the presence of apoptotic cells in the medium before and after Imatinib Mesylate administration. The nitrate concentrations per ‰ apoptotic cell proportion were assessed between the groups. 32D cells without Imatinib Mesylate administration had a statistically significant increase in nitrate concentration/‰ apoptotic cell ratio after 24 hours, while this ratio significantly increased at the 72nd hour for 32D cells with Imatinib Mesylate administered (p<0.05). For 32Dp210 cells without Imatinib Mesylate administration, no significant change was observed for 72 hours, while in the presence of Imatinib Mesylate, the ratio of nitrate concentration to ‰ apoptotic cells decreased significantly from the 24th hour. Nitrite Concentration (with Griess method)/‰ Apoptotic Cells Results
Cell counts cannot be standardized after the 24th hour, so assessment of nitrite levels with the Griess method, as a marker of NO release, was performed linked to the presence of apoptotic cells in the medium before and after Imatinib Mesylate administration. According to our results, 32D control cells had a significant increase in nitrate concentration per ‰ apoptotic cells in the 72nd hour in the absence of Imatinib Mesylate. The ratio of nitrite concentration (μM) to ‰ apoptotic cell amount identified with the Griess method, as marker of NO release, and the ratio of nitrate (μM) to ‰ apoptotic cell proportion, identified with the capillary electrophoresis method were compared.
Discussion
Chronic myeloid leukemia is a hematopoietic system disease characterized by the presence of Bcr-Abl. In recent years, signal transduction inhibitors were used for leukemic cell treatment. Especially Imatinib Mesylate is a selective Bcr-Abl tyrosine kinase inhibitor affecting P210 Bcr-Abl. Some anticancer drugs display antitumor effects on cancer cells by inducing apoptosis, and targeting apoptosis has become an important point in current cancer treatments. In this study, the apoptotic effects of NO released into the cell culture medium during cell death induced by imatinib mesylate on 32D and 32Dp210 myeloid cells were investigated. In this study, Imatinib Mesylate used for CML treatment induced apoptotic cell death and nitric oxide amount, a significant parameter for apoptosis, was measured with the rapid and sensitive method of capillary electrophoresis and the Griess method.
The first member of signal transduction inhibitors and causing effect by binding to the ATP binding region of the kinase domain, Imatinib Mesylate is selectively effective on Bcr-Abl positive cells. At minimal doses, Imatinib Mesylate (0.1μM) is effective on Bcr-Abl positive cells; however, at high doses (10μM), apoptotic cell death is triggered in the majority of cells and proliferation is known to be inhibited [20]. In this study, the dose inducing maximum apoptosis of 10 μM Imatinib Mesylate was administered to 32D and 32Dp210 cells and cell death was observed for 72 hours, and a rapid increase in apoptotic cells numbers was observed in 32Dp210 cells at 24 hours and longer. Increasing apoptotic cells counts are in parallel with the reduction in the amounts of viable cells. Oetzel et al. took the duration of 48 hours in an apoptosis model induced with 10 μM Imatinib Mesylate on Bcr-Abl cells [20]. Contrary to this, our study observed that for 32D cells, there was a reduction in viable cell amounts after 24 hours and longer and a reduction in apoptotic cell levels in this period in the presence and absence of Imatinib Mesylate in the medium. 32Dp210 cells without Imatinib Mesylate administered had an increase in the number of viable cells, though there was no significant change observed in apoptotic cell levels [21]. As a result, the presence of NO is important for increased cell death in the cell culture medium. Imatinib concentrations administered to healthy and CML groups significantly increased intracell NO levels in Bcr-Abl+ CML cell lines.
Capillary electrophoresis has many superior aspects like high selectivity, rapid detection, requiring low amounts of sample and reactives, and detection levels that can be lowered to very low levels and is used for differentiation and detection of chemical compounds. It is very difficult to detect the amount of NO with very short half-life and this structure rapidly metabolizes to nitrite (NO2-) and nitrate (NO3-). As a result, the aim of the research was to measure nitrites (NO2-) and nitrates (NO3-), stable end products of NO metabolism, used as markers of NO release. In our study, samples taken at different times from 32D and 32Dp210 cell media had nitrate levels identified with capillary electrophoresis as NO release marker [19].
After administration of Imatinib Mesylate to both cell lines, there was no significant increase or reduction in nitrate levels measured with the capillary electrophoresis method. To date, no studies have been found on NO release with Imatinib Mesylate, and the information about this topic is not sufficient. For structures with anticancerogenic effect, important parameters are reducing cell proliferation and increasing apoptosis. Studies have explained that structures with anticancerogenic effect also cause iNOS inhibition. Imatinib Mesylate inhibits the JAK2 tyrosine kinase enzyme activated in 32Dp210 cells and c-Myc RNA expression [22]. In this situation, it is clear that Imatinib Mesylate with anticancerogenic and proapoptotic effect both prevents cell proliferation and causes iNOS inhibition.
In order to emphasize the relationship of NO with apoptotic cells, the proportion of NO release to apoptotic body formation was calculated. In this situation, when the nitrate concentration detected with capillary electrophoresis to ‰ apoptotic cell ratio is assessed, 32D control cells had an increase in the of amount nitrate per apoptotic cell at 24 hours and later. Linked to the increasing apoptotic bodies after Imatinib Mesylate administration to cells, the rate of this increase slowed. However, while the nitrate amounts in 32Dp210 control cells did not change, there was a rapid increase in apoptotic body levels at 24 hours and later after Imatinib Mesylate administration and linked to this, a rapid reduction in this ratio. In this situation Imatinib Mesylate slowed the proliferation of 32D cells, increased apoptosis in 32Dp210 myeloid cells, and caused a rapid reduction in nitrate levels. Results were parallel to the values for NO release determined with capillary electrophoresis; however, due to the large standard deviation related to the method, reductions were not identified to have statistical significance. As the ‰ apoptotic cell rates were very low for 32D control cells without Imatinib Mesylate administered, the nitrite concentration to ‰ apoptotic cell rates calculated at 72 hours was found to be statistically significant compared to initial values (p<0.005). When we compare data obtained with the Griess method and capillary electrophoresis method, we did not identify a very good linear correlation between these values. The increase in NO synthesized from L-arginine in cancer and many pathological situations shows that NO is used as a signal molecule by apoptotic signal metabolisms. However, the response to varying signals in cells may be to stop apoptosis, just as it may inversely be to initiate apoptosis. As a result, knowing the molecules and effects regulating NO activity better appears to be a target point to remove many irregularities of these molecules. Sensitive detection of these metabolic products is important as variations in NO levels in many diseases provide information about development of diseases 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.
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Aynur Karadağ Gürel, Tülin Özkan, Buket Altınok Güneş, Asuman Sunguroğlu, Fügen Aktan. Imatinib Mesylate induces apoptosis in chronic myeloid leukemia cells by triggering nitric oxide production. Ann Clin Anal Med 2021;12(6):667-671
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Evaluation of the effect of COVID-19 disease on ventricular density using computer tomography
Pinar Gundogan Bozdag 1, Gulden Eser Karlıdag 2
1 Clinic of Radiology, Fethi Sekin City Hospital, 2 Clinic of Infectious Diseases and Clinical Microbiology, University of Health Sciences, Fethi Sekin City Hospital, Elazig, Turkey
DOI: 10.4328/ACAM.20381 Received: 2020-10-24 Accepted: 2020-11-23 Published Online: 2020-12-03 Printed: 2021-06-01 Ann Clin Anal Med 2021;12(6):672-675
Corresponding Author: Pınar Gundogan Bozdag, Fethi Sekin City Hospital, Clinic of Radiology, Elazig,Turkey. E-mail: Pbozdag23@gmail.com P: +90 532 137 7622 Corresponding Author ORCID ID: https://orcid.org/0000-0002-7303-5832
Aim: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a novel coronavirus identified at the end of 2019. Radiological examinations, espe- cially thorax Computed Tomography (CT), play an important role in the fight against this infectious disease. In this study, we aimed to analyze the effect of COVID-19 disease on the cardiac ventricles by measuring density on CT.
Materials and Methods: Patients who underwent thorax CT with a pre-diagnosis of COVID-19 and whose Polymerase Chain Reaction (PCR) test was positive, and patients who underwent CT for any reason were included in the study. Among 270 patients included in the study, 147 were men, 123 were women, and the mean age was 45.5 (29.2-62) years. The patients with a positive PCR test were divided into three groups. The control group and the three groups were compared with each other in terms of age, gender, CTR, right and left ventricular density.
Results: In both studies, a significant difference was found between the groups in terms of age (p<0.005). There was no significant difference between Group 1 and Group 3 in terms of age, right and left ventricular density, and CTR (p>0.005).
Discussion: In patients with COVID-19, cardiovascular comorbidities are common. Therefore, early diagnosis will boost the effectiveness of treatment. Consid- ering the severity of the disease and the primary focus on managing infection and respiratory failure, not all patients have complete cardiac data and imaging results are not available. Ventricular density and CTR measurements on CT did not yield significant results in COVID-19 patients. However, we think that more patients and appropriate imaging will yield important results, as previous studies have shown the impact of COVID-19 disease on the cardiovascular system.
Keywords: COVID19; Tomography; Cardiomyopathies; Cardiac ventricles
Introduction
Coronavirus disease (COVID-19) has emerged as a global pandemic. A significant aspect of reducing the spread of this virus is its early and accurate diagnosis and effective quarantine for those infected [1]. In the fight against this infectious disease, radiological examinations, especially thin- slice thoracic computed tomography (CT), play an important role. Although the results of the polymerase chain reaction (PCR) test are negative, CT can identify individuals people suspected of having COVID-19 [2]. Radiological examinations are greatly important in the early diagnosis and treatment of COVID-19. Since a chest radiograph has a lower resolution and may be normal in the early stage of infection, it is not recommended as a first-line imaging technique for COVID-19 [3]. Physicians have recently recorded an increase in stress cardiomyopathy during the COVID-19 outbreak worldwide, with an unknown mechanism behind it [4].
In our study, we aimed to show the effect of COVID-19 disease on the cardiac ventricles by measuring ventricular density on CT.
Material and Methods
Permissions for this study were obtained from the …University Non-Invasive Research Ethics Committee and the Ministry of Health. Since the study was retrospective and no risk was noted for patients, informed consent was waived.
Without intravenous contrast agent administration, all images were taken on a single scanner (Philips Healthcare, Ingenuity Elite Netherland) with the patient in supine position and inspiration. The CT protocol was as follows: 120 kV, auto tube current 100–200 mA, 128 mm detector, and slice thickness 2–5 mm. Image analysis was performed using an institutional digital database system.
Medical records and images of patients who had thoracic CT between April and July 2020 with a preliminary diagnosis of COVID-19 and who had a positive PCR test, as well as records and images of patients who had thoracic CT between April and July 2019 as a control group for any reason were scanned retrospectively. The study was conducted in a single center in … State Hospital.
In our first study, patients were divided into two groups: pre- and post-COVID-19 periods. The first group was divided into patients with a negative PCR test and no CT pathology and the second group into patients with a positive PCR test and who ignored CT involvement.
Among 270 patients included in the study, 147 (54.4%) were male and 123 (45.6%) were male. The average age of all patients was 45.5 (29.2-62) years.
In our second study, the same patients in Group 2 were divided into two different sub-groups. Patients with a negative PCR test and normal CT were assigned to Group 1; patients with a positive PCR test and normal CT were assigned to Group 3; patients with a positive PCR and involvement on CT were assigned to Group 4.
In the cardiothoracic ratio (CTR), the right and left ventricular densities in all patients were measured by a single expert radiologist with 8 years of experience with the hospital imaging system on the axial slice of unenhanced thoracic CTs.
Statistics
All statistical analyses were performed using SPSS version 20.0 (SPSS Inc, Chicago, IL). Continuous variables were expressed as mean ± standard deviation or median values and ranges, whereas categorical variables were expressed as absolute numbers. The Kruskal–Wallis one-way analysis of variance tests was used for intergroup comparisons; while the Bonferroni test was used for post hoc analysis (p-value < 0.05 was considered statistically significant). Also, the Student’s t-test and the Mann–Whitney U test were used for intergroup comparisons (p-value < 0.05 was considered statistically significant).
Results
A total of 270 patients, 69 before COVID-19 between April and July 2019 and 201 during the period of COVID-19 between April and July 2020 were included in the study. They were first divided into two groups based on their PCR and CT results. Group 1 included patients with a negative PCR test and normal CT findings (Figure 1), while Group 2 included patients with a positive PCR test and CT (whose CT findings were ignored). Both groups were compared with each other in terms of age, gender, CTR, and right and left ventricular densities.
There was a significant difference in the mean age between the two groups (pre-COVID-19 period, 41.8 ± 12.7 [29.1–54.5] years, and COVID-19 period, 46.9 ± 17.4 [29.5–64.3]) (p = 0.01) (Table 1), which may be due to the extreme course of COVID-19 disease in the elderly, requiring further imaging and hospitalization. The total mean age was 45.6 ± 16.4 [29.2–62] years. One hundred forty-seven (54.4%) of the patients included in the study were male and 123 (45.6%) female. In Group 1, 27 (39.1%) of the 69 patients were female and 42 (60.8%) were male. In Group 2, 96 (47.7%) of the 201 patients were female and 105 (52.2%) were male. There was no significant difference between the groups in terms of gender (p = 0.214), right ventricular and left ventricular densities, and CTR (Table 1).
Group 2 was later divided into two additional groups based on the presence of CT involvement: Groups 3 and 4. Group 3 included patients with a positive PCR test and normal CT findings, while Group 4 included patients with a positive PCR test and CT findings (Figure 2). Groups 1, 3, and 4 were compared in terms of age, gender, CTR, and right and left ventricular densities.
In Group 3, 32 (45.7%) of the 70 patients were female and 38 (54.2%) were male. In Group 4, 64 (48.8%) of the 131 patients were female and 67 (51.1%) were male. There was no significant difference in terms of gender between the groups (p = 0.779). The mean age in total was 45.6 ± 16.4 [29.2–62] years. A significant difference between the groups in terms of age was also observed (p < 0.001). In post hoc analysis, there was a significant difference between Groups 1 and 4 (p < 0.001) and Groups 3 and 4 in terms of age (p = 0.001).
We suppose that this difference is due to the severe course of COVID-19 disease in the elderly, requiring additional imaging and hospitalization, whereas there was no significant difference between Groups 1 and 3 (p = 0.970). In terms of right ventricular and left ventricular densities and CTR (Table 2), no significant difference was found between the groups.
Discussion
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel coronavirus first identified in Wuhan, China, at the end of 2019. It has caused more than 1,700,000 confirmed COVID-19 cases and nearly 110,000 deaths worldwide. It is responsible for respiratory syndrome, ranging from mild flu-like symptoms to severe respiratory failure (due to acute respiratory distress syndrome), shock, multi-organ failure, and death [5].
In patients with COVID-19, cardiovascular comorbidities are common, and these patients are at a greater risk of morbidity and mortality [6]. Therefore, early diagnosis will boost the effectiveness of treatment.
Myocardial inflammation accompanied by regional scarring and pericardial enhancement was the most common pathology found in 60 patients who had recently recovered from COVID-19 [7].
Evidence from animal models and human studies suggests that viral infections can cause severe damage to cardiomyocytes through direct virus-mediated and secondary immune reactions, eventually leading to chronic myocarditis and dilated cardiomyopathy [8].
Autopsy data on infection provided by SARS-CoV in 2003 and MERS-CoV in 2012 will help better understand the function of the cardiovascular system. ACE2 is the putative receptor for SARS viruses, found mainly in epithelial cells of the upper respiratory region, pulmonary endothelium, and pulmonary alveolar pneumocytes and in other cell types in different organs as well, including the heart and kidneys. In the literature, a case of cardiac tamponade in a 47-year-old man infected with SARS-CoV-2 was identified as a complication of myocarditis and pericarditis [9]. The rates of heart damage and mortality are significantly associated with COVID-19 patients [10]. Myocardial damage associated with COVID-19 may represent myocarditis in some patients with or without pre-existing cardiovascular disease. Acute myocarditis following a COVID- 19-associated respiratory tract infection in a 53-year-old Italian woman who had no prior heart disease has also been documented by Inciardi et al. and supports this hypothesis. Considering the severity of the disease and the primary focus on managing infection and respiratory failure, not all patients have complete cardiac data, including electrocardiography, and their echocardiography, coronary angiography, and magnetic resonance imaging results are not available [11].
Conclusion
The above studies have shown the effect of COVID-19 disease on the cardiovascular system. We aimed to display the myocardial damage by measuring density on CT. We believe that due to myocardial inflammation, COVID-19 infection may decrease the ventricular density on unenhanced CT in relation to inflammation and increase ventricular density during the scar formation period. The fact that our study’s results was not significant may be due to a lack of understanding of other comorbidities in patients in the control and PCR-positive groups in detail, the age mismatch between the groups, the unenhanced tomography images, and the small number of our patients. We hope that if the contrast-enhanced images are taken with appropriate point and the patients’ history is questioned in depth and the number of patients is increased, significant outcomes can be achieved in the future.
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. Guo L, Ren L, Yang S, Xiao M , Chang D , Yang F et al. Profiling Early Humoral Response to Diagnose Novel Coronavirus Disease (COVID-19). Clin Infect Dis. 2020;71(15):778-85. DOI: 10.1093/cid/ciaa310.
2. Zhao W, ZhongZ, Xie X, Yu Q, Liu J. Relation Between Chest CT Findings and Clinical Conditions of Coronavirus Disease (COVID-19) Pneumonia: A Multicenter Study. Am J Roentgenol. 2020;214(5):1072-7. Doi: 10.2214/AJR.20.22976.
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4. Jabri A, Kalra A, Kumar A, Alameh A , Adroja S , Bashir H, et al. Incidence of Stress Cardiomyopathy During the Coronavirus Disease 2019 Pandemic. JAMA Netw Open. 2020;3(7):e2014780. DOI:10.1001/jamanetworkopen.2020.14780.
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11. Bonow RO, Fonarow GC, O’Gara PT, Yancy CW. Association of Coronavirus Disease 2019 (COVID-19) With Myocardial Injury and Mortality. JAMA Cardiol. 2020;5(7):751-3. DOI: 10.1001/jamacardio.2020.0934.
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Pinar Gundogan Bozdag, Gulden Eser Karlıdag. Evaluation of the effect of COVID-19 disease on ventricular density using computer tomography. Ann Clin Anal Med 2021;12(6):672-675
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Reasons for transition to open surgery in laparoscopic cholecystectomy
Mustafa Şentürk, Murat Çakır, Mehmet Biçer, Mehmet Aykut Yıldırım
Department of General Surgery, Necmettin Erbakan University Meram faculty of medicine, Konya, Turkey
DOI: 10.4328/ACAM.20382 Received: 2020-10-24 Accepted: 2020-11-25 Published Online: 2020-12-07 Printed: 2021-06-01 Ann Clin Anal Med 2021;12(6):676-679
Corresponding Author: Mustafa Şentürk, Department of General Surgery, Necmettin Erbakan University Meram Medicine Faculty, Konya, Turkey. E-mail: m-sntrk@hotmail.com P: +90 5362029499 Corresponding Author ORCID ID: https://orcid.org/0000-0002-3230-1743
Aim: Laparoscopic cholecystectomy is a minimally invasive surgical technique that has become widespread since the 1980s. Many factors are effective in the conversion to open surgery. This study aimed to investigate the rates and reasons for the conversion to open in laparoscopic cholecystectomy surgeries in our hospital.
Material and Methods: This study aimed to examine 3263 cholecystectomy cases with the conversion to open during surgery between June 2014 and June 2019. Patients were examined in terms of age, sex, comorbidities, acute cholecystitis attack status, previous surgery, adhesion, gallbladder wall thickness, revealing surgical anatomical structure, surgical complications, length of hospital stay, and mortality. The results were evaluated statistically.
Results: Data of 70 patients, who were performed laparoscopic cholecystectomy with the conversion to open surgery during the procedure, were reviewed. The conversion rate was 2.3%. Among the patients, 28 were female and 42 were male. Sixty-two of the patients had an episode of acute cholecystitis. The most common reason for the conversion was that the anatomy could not be revealed.
Discussion: It should be kept in mind that laparoscopic cholecystectomy surgery, which is interpreted as a simple surgical procedure, can always be converted to an open surgery and there may be vital complications.
Keywords: Laparoscopic cholecystectomy; Complication; Conversion to open
Introduction
Laparoscopic cholecystectomy is a minimally invasive surgical technique that has become widespread since the 1980s. Today, it is one of the most commonly used intraabdominal laparoscopic surgeries [1]. Ninety percent of cholecystectomies are performed by the laparoscopic technique. Laparoscopic cholecystectomy is superior to open cholecystectomy in benign symptomatic gallbladder diseases due to less postoperative pain, shorter hospital stay, shorter recovery, and better cosmetic results [2]. The aim of the conversion from laparoscopic to open surgery is to eliminate, or at least reduce, surgical complications. Laparoscopic cholecystectomy has a higher complication rate than open cholecystectomy [3,4]. However, recently, open cholecystectomy complications have been increasing due to the decrease in open cholecystectomy experience and complicated cases that are not performed by the open method [5-7]. The conversion rate to the open method is 9.5% [5]. Many factors affect the conversion to open surgery. These include age, gender, emergency surgery and previous surgery-related adhesions [6]. This study aimed to investigate the rates and reasons for the conversion to open in laparoscopic surgery in our hospital, in the light of the literature.
Material and Methods
We investigated the results of cases with the conversion to open surgery in laparoscopic cholecystectomies in our hospital. The study was designed retrospectively. Local ethics committee approval was received for the study. Patients who underwent cholecystectomy for symptomatic benign gallbladder diseases other than malignant diseases were included in the study. Patients were examined in terms of age, sex, obesity, comorbidities, acute cholecystitis attack status, adhesion, gallbladder wall thickness, endoscopic biliary tract interventions, previous surgery, revealing surgical anatomical structure, surgical complications, length of hospital stay and mortality. Patients with a gallbladder wall thickness of 4 mm or more, increased white blood cell count and right upper quadrant tenderness were evaluated as acute cholecystitis. The study was conducted according to the Declaration of Helsinki. Informed consent was obtained from all individual participants included in the study.
Statistical Analysis
Social Science Statistical Package (SPSS Inc., Chicago, IL, USA) software was used for bio-statistical analysis. When data were presented as mean values, the standard deviation values were given, and when they were presented as mean values, the minimum (min) -maximum (max) values were indicated.
Results
The records of 3263 patients who underwent cholecystectomy were reviewed retrospectively, and 263 patients who underwent open surgery were identified. The rate of open cholecystectomy was 8%. Seventy (26.6%) of the open cholecystectomies were started laparoscopically. The study was conducted on 70 patients. The rate of conversion from laparoscopy to open surgery was 2.3%. Twenty-eight (40%) of the patients were female and 42 (60%) were male. The mean age was 55 (18-82) years for males and 42 (18-84) years for females. The body mass index (BMI) was 30.1 in men and 32.2 in women (Table 1). Among the cases with chronic diseases, Diabetes Mellitus was present in 14 (20%), hypertension in 29 (41.4%), chronic liver disease in 8 (11.4%), chronic lung disease in 4 (5.7%) and neurological disorders in 4 (5.7%) patients. Sixty-two patients (88.6%) had a previous episode of acute cholecystitis attack and were hospitalized. The mean interval between operation and first acute attack was 3.5 (1-18) months. Seventeen (24.3%) of the cases, underwent lower abdominal surgery and 15 (21.1%) underwent upper abdominal surgery. Grade 1-2 adhesions were observed in patients who underwent lower abdominal surgery, whereas grade 2-3 adhesions were observed in those who underwent upper abdominal surgery (8). In pericholecystic adhesion cases, 56 (80%) patients were observed to have omentum and peripheral organ adhesions. Seven patients had only omental adhesions.
The endoscopic biliary intervention was performed in 50 patients (71.4%) before surgery. Among the reasons for convertion, the anatomy could not be revealed in 46 (65.7%) while 11 (15.7%) had Mirizzi syndrome, 4 (5.7%) were with bleeding, 4 (5.7%) had a cholecystoenteric fistula, 3 (4.3%) were with suspected malignancy, and bile was coming from the gallbladder bed in 2 (2.9%) (Table 2). The mean hospital stay was 8.6 (3-31) days. Mortality was seen in 2 (2.9%) cases due to respiratory failure on postoperative 4th and 20th days.
In 49 (70%) patients, chronic cholecystitis was present histopathologically. In 59 (84.3%) cases, gallbladder wall thickening observed during surgery was confirmed histopathologically.
Discussion
Laparoscopic cholecystectomy is currently the gold standard method in gallbladder surgery. This common surgical procedure has its specific complications. When a problem is encountered during a laparoscopic cholecystectomy, it is necessary to proceed to a safer open procedure [2]. The rate of conversion to the open procedure is between 6.3-9.5% [5, 9]. As the surgical experience increases, the complication of laparoscopic surgery [10] and biliary injury decreases. Our ratio is much lower than this value and is 2.3%. We think that this is due to an experienced surgical team and surgical equipment with good- quality. Another reason for this is that we perform surgery in all acute cholecystitis cases before the 48th hour in men and before 72nd hour in women. We give priority medical treatment to patients who apply late.
In laparoscopic cholecystectomy, many factors are effective in the conversion to open. The most important of these factors is the lack of anatomical structure reveal [11]. The most important factors that disrupt the anatomical structure are adhesions due to previous surgery and acute and chronic cholecystitis. Surgery is more difficult in patients who underwent endoscopic retrograde cholangiopancreatography [12]. The reason for this is not fully enlightened. Endoscopic intervention cases are complicated cases. Previous endoscopic interventions increase pericholecystic fibrosis and possibly disrupt the anatomical structure. Adhesions formed in the calot triangle make surgical dissection difficult [13]. Bleeding in this area makes dissection more complicated. In our experience, the most important reason for the conversion is when the anatomical structure cannot be revealed; when the distinction between the cystic duct and the common bile duct cannot be made completely. The idea of injury to the biliary tract is important in the conversion to open. Fibrosis in the dissection area during surgery makes the surgery and the differentiation of anatomical structures more difficult. Adhesions resulting from previous surgery make laparoscopic surgery more difficult. This causes problems during the trocar entry. This leads to prolonged surgery and damage to organs other than the gallbladder. Male gender and advanced age were found to be effective in the conversion to open [11]. It was stated that estrogen is effective in this situation [14]. Difference in terms of anatomical structures, dietary habits, and response to inflammation between the two sexes have been reported to be effective. According to our data, it was determined that there was a greater conversion rate in the male gender. However, we did not obtain any data on advanced age. It is known that previous surgeries can cause a conversion to open surgery. However, it is known that this complicates the whole laparoscopic surgery and is not only specific to gall bladder surgery. In particular, this makes it difficult to reach the gallbladder region in upper abdominal surgery.
The surgical experience is effective in the conversion to open. After the first 200 cases, there is a serious decrease in the conversion to open [15]. The learning curve of laparoscopic cholecystectomy is between 10 and 50 [16]. Experienced surgeons perform more complicated laparoscopic surgeries with fewer complications. Since the operations performed by experienced surgeons were examined in our study, the rate of conversion to open surgery was much lower than in the literature. Many complications during operation are overcome by laparoscopic surgery.
Biliary system injuries during surgery are seen at a rate of 0.4% to 0.6% [17]. This ratio is higher than with open cholecystectomy. Injury may be noticed during laparoscopic cholecystectomy or in the postoperative period. Another complication seen during the operation is vascular and intestinal injuries. The injury rate is between 0.14% and 0.25%. Intestinal injuries are usually caused due to adhesion and can be repaired laparoscopically. However, in cases in which anatomy cannot be revealed, the injury is large and intraabdominal contamination is present, the conversion to open surgery is safer. In our cases, there was no conversion to open surgery due to intestinal injury. However, due to a cholecystoenteric fistula, 4 patients required conversion to open. The patient was switched to open surgery due to severe bleeding. Hepatic artery injury occurred in 1 of these cases and repaired with open surgery. Other bleedings occurred in the gallbladder bed. None of the bleedings resulted in death. Conclusion
It should be kept in mind that laparoscopic cholecystectomy surgery, which is interpreted as a simple surgical procedure, can always be a conversion to open surgery, and there may be vital complications. The rate of conversion to open in laparoscopic surgery depends on the surgical experience. For inexperienced centers, this rate is very low, but can never be completely zeroized.
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.
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17. McPartland KJ, Pomposelli JJ. Iatrogenic biliary injuries: classification, identification, and management. Surg Clin North Am. 2008;88(6):1329–43.
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Mustafa Şentürk, Murat Çakır, Mehmet Biçer, Mehmet Aykut Yıldırım. Reasons for transition to open surgery in laparoscopic cholecystectomy. Ann Clin Anal Med 2021;12(6):676-679
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The effect of body composition on prognosis in critically ill COVID-19 patients
Ismail Beypinar 1, Murat Bayav 2, Anil Ucan 3, Serdar Efe 4
1 Department of Medical Oncology, Eskişehir City Hospital, 2 Department of Radiology, Eskişehir City Hospital, 3 Department of Internal Medicine, Eskişehir City Hospital, 4 Department of Intensive Care, Eskişehir City Hospital, Eskişehir, Turkey
DOI: 10.4328/ACAM.20383 Received: 2020-10-25 Accepted: 2020-11-24 Published Online: 2020-12-05 Printed: 2021-06-01 Ann Clin Anal Med 2021;12(6):680-684
Corresponding Author: Murat Bayav, Eskişehir City Hospital, Department of Radiology, Eskişehir, 26080, Turkey. E-mail: muratbayav@hotmail.com P: +90 5356171747 Corresponding Author ORCID ID: https://orcid.org/0000-0002-8210-4182
Aim: Although limited risk factors were observed with the accumulated evidence during the SARS-CoV-2 (COVID-19) pandemic, there is still a lack of evidence for markers distinguishing asymptomatic-mild disease from severe disease. In this study, we aimed to evaluate the prognostic impact of sarcopenia and vis- ceral adipose tissue in ICU patients treated for COVID-19.
Material and Methods: The study designed as a retrospective cross-sectional study for evaluating the effect of prognostic radiologic features in COVID-19 infected patients. The patient characteristics, intubation status and dates, transfer to ICU, and last control or death dates were recorded. Axial CT images, including all abdominal muscles, total skeletal muscle area, were calculated. The total and psoas sarcopenia index (PSI) was calculated by dividing the square of the patient’s height by the square meter (cm2/m2). Also, axial CT images of the body fat subcutaneous adipose and visceral adipose tissue distribution areas were calculated in cm2 using threshold values of -30 to -190 for adipose tissue.
Results: In the study population, there were nine deaths that occurred among male patients. In univariate analysis, chronic obstructive pulmonary disease and PSI were found to be related to prognosis. The median survival was 14 days in PSI low group. The prognostic effect of the PSI was still valid in the male population. Other factors had no relationship with survival in univariate analysis. In multivariate analysis, the prognostic effect of TSI and PSI was related to prognosis, while COPD lost its prognostic effect.
Discussion: In this study, we found a new prognostic factor in critically ill COVID-19 patients, which may be a new area of interest. In contrast to other studies, we found no effect of BMI and visceral adipose tissue on mortality in COVID-19 patients treated in ICU. This feasible method needs further evaluation and validation with prospective studies in a large patient population.
Keywords: COVID-19; Mortality; Sarcopenia; Visceral adipose tissue; Prognosis; Critically ill patients
Introduction
SARS-CoV-2 (COVID-19) is a single-stranded RNA spherical virus which has glycoprotein spikes [1]. Multiple subtypes of coronaviruses have the capability of infecting humans. The major subgroups which have severe infection capacity are COVID-19, MERS, and SARS-CoV-1 [2]. The primary target of the COVID-19 is angiotensin-converting enzyme-2 (ACE-2) located on the alveolus and ciliated bronchial epithelium. Air- borne droplets were shown to be the direct dissemination way of the viral particles [3]. Cough, fever, and shortness of breath are the most frequent symptoms of the disease. It has been reported that myocardial damage, respiratory and renal failure are the leading reasons for death in COVID-19 patients [4]. Approximately 200.000 deaths, confirmed by the World Health Organization, occurred related to COVID-19 till April 25, 2020 worldwide [5].
According to the literature, the groups most affected by COVID-19 were immunocompromised and older adults. High rates of respiratory failure during the disease are the major problem in COVID-19 infection [6]. Although limited risk factors with the accumulated evidence were observed during the pandemic, there is still a lack of evidence for markers distinguishing asymptomatic-mild disease from severe disease [7].
Catabolism of the main skeletal muscle proteins is a frequent phenomenon for chronic conditions such as cancer and chronic obstructive lung disease [8]. Also, cachexia is known to be related to increased mortality in cancer patients [9]. Differences in body composition between males and females have been observed in previous studies in both healthy subjects, patients with cirrhosis, or cancer. Muscle tissue was enlarged in males, while females had enlarged adipose tissue [10]. Sarcopenia is one of the new areas of interest in cancer patients in relation to a clinical marker [11]. Obesity, according to body mass index (BMI), is associated with a decreased treatment response in breast cancer patients [12]. Obese patients are not uniform; some patients remain metabolically stable, which is called the ‘obesity paradox’ [13]. In addition, sarcopenia can be masked by increased BMI, which leads to the phenomenon of sarcopenic obesity [14]. For these reasons, BMI is not a reliable marker for estimating body composition and disease prognosis.
A new study reported that increased BMI might be related to increased mortality in patients hospitalized for COVID-19 [15]. Computed tomography (CT) is a reliable method to evaluate the muscle quality and adipose tissue [16].
To our knowledge, there are no studies investigating the prognostic effect of sarcopenia in critically ill patients hospitalized for COVID-19. In this study, we try to evaluate the prognostic impact of sarcopenia and visceral adipose tissue in ICU patients treated for COVID-19.
Material and Methods
Study Participants
The archive records of patients, who were diagnosed with COVID-19 between 11th March 2020 and 15th June 2020 at the Eskişehir City Hospital Intensive Care Unit, were retrospectively analyzed. Patients with COVID-19 were diagnosed using PCR. Oropharyngeal and nasal swabs were obtained in PCR samples.
Patients who do not have PCR testing or have inadequate diagnosis were excluded. Patient characteristics, height, weight, comorbidities such as diabetes mellitus (DM), hypertension (HT), chronic obstructive pulmonary disease (COPD) and coronary artery disease (CAD), smoking status, diagnosis, intubation status and dates, transfer to ICU, and last control or death dates were recorded. The exclusion criteria were lack of adequate diagnosis, CT images, and follow-up.
Ethics
The study was approved by the Turkish Ministry of Health and the Ethics Committee of the Faculty of Medicine at Eskişehir Osmangazi University (approval number 2020/277) and was carried out in accordance with the Declaration of Helsinki principles and all applicable regulations.
Statistical analysis
Statistical analysis of the study was performed using SPSS software (Statistical Package for the Social Sciences, version 22.0, SPSS Inc, Chicago, IL). Descriptive data were presented as either means or median for continuous variables, frequencies and percentages were reported for categorical variables. ROC analysis was performed to determine the optimal cut-off value, but if an optimal cut-off value cannot be determined, the median values will be used in the statistical analysis. Pearson’s X2 test was used to assess the associations in categorical variables. OS curves were estimated by the Kaplan-Meier product- limit method. Life tables were established to determine the proportional survival analysis.
Body composition assessment and CT analysis
The first CT images obtained in the emergency room or in the patient’s clinic were used in the study to avoid calculating COVID-19 induced sarcopenia. On axial CT images, including all abdominal muscles (psoas, erector spinae, quadratus lumborum, external and internal oblique, and rectus abdominis), total skeletal muscle area (SMA) was calculated from the third lumbar vertebrate (Figure 1). The total and psoas sarcopenia index (TSI-PSI) was calculated by dividing the square of the patient’s height by the square meter (cm2/m2). Also, axial CT images of the body fat subcutaneous adipose and visceral adipose tissue distribution (VAT, SAT) areas were calculated in cm2 using threshold values of -30 to -190 for adipose tissue (Figure 2).
Results
Thirty-six patients were included in the study. Four patients were excluded due to a lack of adequate imaging procedures. The counts of male and female patients in the study were 28 and 8, respectively. The median age of the study population was 68 years. The median weight, height, and BMI of the study population were 80 kilograms, 1.7 meters, and 26,8 kg/m2, respectively. The demographic features of the study population are described in Table 1.
In the study population, there were nine deaths that occurred among male patients. No death was observed in female patients. In univariate analysis, COPD and PSI were found to be related to prognosis (p=0,001, p=0,010). Although median survival was not reached in the high PSI group, PSI had a relationship with prognosis (Figure 3). The median survival was 14 days in the low PSI group. The prognostic effect of the PSI was still valid in the male population. (p=0,007) Gender, DM, HT, CAD, TSI, VAT, BMI (categorized for both 25 and 30 kg/m2) had no relationship with survival in univariate analysis (Table 2). In multivariate analysis, the prognostic effect of TSI and PSI was related to prognosis, while COPD lost its prognostic effect (p=0,044; p=0,035; p=0,33).
Discussion
To our knowledge, this is the first study that evaluates the prognostic effect of sarcopenia in ICU patients. In our research, TSI and PSI were found to be an independent risk factor in COVID-19 infected ICU patients.
COVID-19 is known to have high mortality in the geriatric population. Conditions such as sarcopenia and frailty are frequently seen in the elderly [17]. Sarcopenia is defined as the loss of a prominent muscle tissue that is related to increased vulnerability to stressors [18]. Previous studies have shown a relationship between sarcopenia and ICU mortality [19]. Interestingly, COVID-19 infection was found to induce weight loss in animal models via interferon-gamma and tumor necrosis factor-alpha. This effect disappeared after the treatment [20]. Regulations, including social isolation during the pandemic, were strictly applied, especially to the elder population, which may accelerate muscle loss in a short period. Also, chronic conditions such as DM and COPD are responsible for sarcopenia in this group [21]. Although some new reports have been published, which have shown a relationship between high BMI and poor outcome in COVID-19 infection, no literature is available investigating sarcopenia in this condition. The death rates were higher in countries with a high prevalence of obesity, such as the United States of America (USA), Canada, the United Kingdom, and Mexico. This phenomenon was speculated to be related to sarcopenia, DM, CAD, increased function of the renin-angiotensin-aldosterone system (RAAS), obstructive sleep apnea, and deficiency of vitamin D. In the USA, a single- center experience showed that obesity and male gender are independent risk factors for COVID-19 infection [15]. In addition, a study investigating patient outcomes in China reported more symptoms and a severe disease course with increasing BMI [23]. In contrast to this literature, we did not found a significant relationship between BMI and COVID-19 infection, which might be related with sarcopenic obesity phenomenon. This result was supported by increased BMI but low mortality in female patients in the study population. Also, increased visceral adipose tissue was speculated to be a reservoir to the virus, which might induce an abnormal cytokine release and cause a poor outcome [24]. In our study, we found no relationship between visceral adipose tissue and increased mortality in critically ill patients. Although obstructive sleep apnea might be related to increased mortality due to obesity, no data were available in our study [25].
The limitations of this study were the small sample size, and the retrospective nature of the study made it hard to evaluate the outcomes. Although the first images were used to assess sarcopenia on CT images, the early period of the disease might affect the body composition. No deaths were observed in female patients, which might inflict the strong prognostic effect of sarcopenia in this patient group.
Conclusion
In this study, we found a new prognostic factor in critically ill COVID-19 patients, which may be a new area of interest. In contrast to other studies, we found no effect of BMI and visceral adipose tissue on mortality in COVID-19 patients treated in ICU. This comfortable and applicable method needs further evaluation and validation with prospective studies in a large patient population.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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Ismail Beypinar, Murat Bayav, Anil Ucan, Serdar Efe. The effect of body composition on prognosis in critically ill COVID-19 patients. Ann Clin Anal Med 2021;12(6):680-684
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Angiogenic factors and evaluation of vascular status in preeclampsia
Şerif Aksin 1, Numan Çim 2, Hanım Güler Şahin 3, Deniz Balsak 4
1 Department of Obstetrics and Gynecology, Siirt University Faculty of Medicine, Siirt, 2 Department of Obstetrics and Gynecology, Istanbul Bilim University Faculty of Medicine, Istanbul, 3 Department of Obstetrics and Gynecology, Yuzuncu Yıl University Faculty of Medicine, Van, 4 Department of Obstetrics and Gynecology, Batı Hospital, Diyarbakır, Turkey
DOI: 10.4328/ACAM.20577 Received: 2021-03-09 Accepted: 2021-05-12 Published Online:2021-05-27 Printed: 2021-06-01 Ann Clin Anal Med 2021;12(6):685-689
Corresponding Author: Şerif Aksin, Department of Obstetrics and Gynecology, Siirt University Faculty of Medicine, Siirt, Turkey. E-mail: serifaksin1@gmail.com P: +90 5052774937 Corresponding Author ORCID ID: https://orcid.org/0000-0002-1301-2508
Aim: The aim of this study was to measure serum levels of the angiogenic factors nitric oxide (NO), soluble endoglin (s Eng), soluble fms-like tyrosine kinase-1 (s Flt-1), placental-derived growth factor (PIGF) and vascular endothelial growth factor (VEGF) and to measure uterine and umbilical arterial blood flow using Doppler ultrasonography to investigate the physiopathology of preeclampsia and endovascular dysfunction by comparing brachial artery dilatation and the thickness of the carotid artery with normal pregnant women.
Material and Methods: Forty pregnant women with preeclampsia and 40 healthy pregnant women (control group) were recruited for the study in April 2011 and October 2011 at Van Yuzuncu Yil University. Systolic and diastolic blood pressure, urinary protein in spot urine samples, complete blood counts, aspartate transaminase (AST), alanine aminotransferase (ALT) levels of sEng, sFlt-1, VEGF, PIGF and NO, and APGAR scores at one and five minutes after birth were recorded and compared in all patients. Intima-media thickness of the carotid artery, brachial artery dilatation and umbilical artery Doppler parameters of all pregnant women were assessed and recorded.
Results: When compared to the control group, systolic and diastolic blood pressures urinary protein in spot and 24-hour urine collection, levels of AST, ALT and sFlt-1, and uterine artery Doppler parameters were significantly higher, whereas VEGF, platelet count and APGAR scores at one and five minutes after birth were lower in the preeclampsia group (p<0.001). Brachial artery dilatation before obstruction was found to be insignificant in both groups, while post- obstructive dilatation was found to be significantly higher in the control group.
Discussion: Uterine artery Doppler evaluation, assessment of brachial artery dilatation and measurement of VEGF and sFlt-1 levels seem to be useful in pre- eclampsia.
Keywords: Angiogenic; Preeclampsia; Vascular; Brachial Artery; Nitric Oxide
Introduction
Despite significant developments in obstetric diagnosis and treatment services, preeclampsia is one of the leading causes of maternal and fetal morbidity and mortality in developed countries [1]. Diagnosing preeclampsia before the clinical picture emerges will undoubtedly provide an important advantage for the physician. In case of early diagnosis, there will be options to protect the patient from this entity or delay the onset of the clinical picture, and this will have positive effects in terms of maternal and neonatal results [2].
The pathophysiological development of preeclampsia is multifaceted, and it is known that it develops as a result of insufficient invasion of maternal spiral arteries by endovascular cytotrophoblasts. Following this event, spiral arteries cannot sufficiently convert from low-capacity high-resistance vessels to high-capacity low-resistance uteroplacental vessels. Since the migration of endovascular trophoblasts occurs in the early period of pregnancy, it can be stated that preeclampsia starts long before the clinical picture emerges.
Impairment in the uterine artery Doppler is among the indications of this [3]. In addition, impairment in brachial artery dilatation in preeclampsia, where endothelial damage plays a part, may be associated with NO secretion and endothelial damage [4].
VEGF, PlGF, sFlt-1, sEng, NO and what their receptors produce have been revealed, and the role of angiogenic factors in the pathophysiology of the disease has been emphasized. These factors can initiate the activation of endothelial cells, which is a well-defined event in preeclampsia. Among these factors, the balance between VEGF and sFlt-1, which is its natural antagonist, and the changes they show in preeclamptic pregnant women, have attracted the attention of many researchers; it has been emphasized that they can be useful in revealing the etiopathogenesis of preeclampsia, which is a public health problem [5].
We also aimed to reveal the relationship that may be important in terms of preeclampsia pathophysiology by examining these parameters in our preeclamptic patient group, normal pregnant group and postpartum group.
Material and Methods
This study was conducted between April 2011 and October 2011 at Van Yuzuncu Yil University. The study has been approved by the Van Yuzuncu Yıl Üniversity Ethics Committee. The female participants, who were included in the study, were informed about the study and their verbal and written consents were obtained. Between January and April 2011, 40 patients were included in the study group according to their last menstrual period or if they did not remember their last menstrual periods, it was examined whether they were diagnosed with preeclampsia according to ultrasonographic fetal biometric measurements and ACOG 2015 Preeclampsia criteria. Similarly, 40 healthy pregnant women of the same age and in the same week who applied for pregnancy control were included in the study. The pregnant women included in the study group postpartum were invited and reevaluated at 6 weeks postpartum. Preeclampsia diagnosis was established in the presence of 140/90 mmHg and higher blood pressure (in two measurements performed every other six hours) and proteinuria (at least 300 mg or higher in 24-hour urine) developing after the 20th week of pregnancy in the pregnant woman who had been previously normotensive. In the healthy pregnant group included in the study, it was ensured that the age and gestational week were similar to the patient group. Exclusion criteria were as follows: maternal diabetes, renal disease, multiple pregnancy, fetal anomaly, cardiovascular disease, IUEF (Intrauterine ex fetus).
Information of the patients in the study and control groups were recorded in research forms, which had been prepared previously. These forms included patients’ age, gravida, parity, pregnancy week, systolic-diastolic blood pressure, protein in spot urine, hemoglobin (Hgb), platelet count, urea, creatinine, liver function tests, Aspartate aminotransferase, Alanine aminotransferase, NO, s Eng, sFlt-1, PlGF, VEGF values in pregnancy and postpartum period, carotid artery intima thickness, brachial artery width and dilatation value, uterine artery RI-PI-S/D value, uterine artery notch, umbilical artery RI-PI-S/D values, 1st- and 5th-minute APGAR score of the infant.
Ultrasonographic evaluations of the preeclamptic (n=40) and healthy pregnant (n=40) groups were conducted during pregnancy and postpartum period using a General Electric Medical Systems Voluson 730 Expert 3-dimensional color Doppler device. The Carotid artery intima thickness was measured using transabdominal 2.5-7.5 mHz convex probe. Uterine artery doppler was performed to measure RI-PI-S/D, uterine artery notch and umbilical artery RI-PI-S/D values. Arterial and venous flow was stopped for 5 minutes after the arm was inflated with a blood pressure cuff to measure the dilatation due to brachial artery flow. Then, the brachial artery dilatation was measured after the flow returned to normal. The blood samples taken from antecubital veins of the patients were centrifuged at 4000 rpm/10 min (Nüve NF 800R, Ankara, Turkey), placed in Eppendorf tubes, and kept at –80 °C in an unlighted environment. In serum samples prepared after the collection of the samples of all groups, the NO, sEng, sFlt-1, PlGF, VEGF levels were examined through the quantitative sandwich enzyme immunoassay. The measurements were performed in the Farmasina medical laboratory.
Statistical analysis
After the patient data were transferred to the SPSS 16.0 for Windows package program in a computer environment, statistical analysis was carried out. While descriptive statistics for continuous variables were expressed as mean, standard deviation, minimum and maximum values, the categorical variables were stated as number and percentage. Student’s t-test was used to compare the mean scores of the groups in terms of continuous variables. In order to determine the relationship among these variables, Pearson’s correlation coefficients were calculated. In addition, the Chi-square test was performed to determine the relationship between the groups and categorical variables. In the calculations, the level of statistical significance was determined as <0.05 – <0.01
Results
A total of 80 pregnant women diagnosed with preeclampsia in the third trimester (n=40) and at a similar age (n=40) were included in the study population. The cases were invited and reevaluated in the 6th week postpartum. Values were given as mean ± standard deviation. Clinical and biochemical values of preeclampsia and normal pregnant patient groups are given in Table 1. There was no statistical difference between age, parity and gravida in both groups (p>0.05). The difference in platelet, AST, ALT, 1. minute APGAR, 5. minute APGAR values between the preeclampsia group and the normal pregnant group was statistically significant (p< 0.001).
The mean serum level of NO in the preeclamptic pregnant group was detected as 19.60±10.08, while it was 18.53±12.39 in the healthy pregnant group, and the difference was not found to be statistically significant (p=0.376). The mean serum level of sENG in the preeclamptic pregnant group was detected as 8.74±2.51 ng/ml, while it was 8.77±2.07 ng/ml in the healthy pregnant group, and the difference was not found to be statistically significant (p=0.504). The mean serum level of sFlt-1 in the preeclamptic pregnant group was detected as 12.9±10.5 pg/ml, while it was 8.34±10.2 pg/ml in the healthy pregnant group, and the difference was found as statistically significant (p < 0.001). The mean serum level of PlGF in the preeclamptic pregnant group was detected as 303.71±21.83, while it was detected as 349±212.56 in the healthy pregnant group, and the difference was not found to be statistically significant (p=0.498). The mean serum level of VEGF in the preeclamptic pregnant group was detected as 156.3±11.20 pg/ml, it was determined as 212.40±12.65 pg/ml in the healthy group, and the difference was found to be statistically significant (p < 0.001) (Table 2). Serum NO, sEng, sFlt-1, PlGF, values of preeclamptic and healthy pregnant groups in the postpartum period were compared, and no statistical difference was found (p>0.05).
The mean serum level of NO in the preeclamptic pregnant group was detected as 9.22 ±2.19, while it was 8.64 ±4.04 in the healthy pregnant group, and the difference was not found to be statistically significant (p= 0.320). The mean serum level of sENG in the preeclamptic pregnant group was detected as 5.99±3.34 ng/ml, while it was 5.42±2.13 ng/ml in the healthy pregnant group, and the difference was not found to be statistically significant (p=0.634).
The mean serum level of sFlt-1 in the preeclamptic pregnant group was detected as 5.6 ±1.69 pg/ml, while it was 5.65 ±3.68 pg/ml in the healthy pregnant group and the difference was found as statistically significant (p= 0.840). The mean serum level of PlGF in the preeclamptic pregnant group was detected as 300.39 ±30.03, while it was detected as 311.30 ±124.65 in the healthy pregnant group, and the difference was not found to be statistically significant (p=0.283). The mean serum level of VEGF in the preeclamptic pregnant group was detected as 212.40±122 pg/ml, it was determined as 291.16±166 pg/ ml in the healthy group, and the difference was found to be statistically significant (p=0.014).
While the carotid artery intima thickness of preeclamptic pregnant women was determined as 0.53±0.04 mm, this value was 0.54±0.04 mm in the healthy pregnant women, and the difference among them was not statistically significant (p=0.807). While the preobstruction brachial artery width of the preeclamptic pregnant women was found as 3.76±0.46 mm, it was determined as 3.75±0.44 mm in the healthy pregnant women, and the difference among them was not statistically significant (p=0.957). While the postobstruction brachial artery width of the preeclamptic pregnant women was determined as 3.97±0.63 mm, it was determined as 4.60±0.56 in the healthy pregnant women and the difference was found as statistically significant (p < 0.001). Comparison of the uterine artery doppler of the preeclamptic pregnant women and healthy pregnant women was found to be statistically significant (p < 0.001). While the rate of notch in the uterine artery was 66% in the preeclamptic pregnant women, it was 6% in healthy pregnant women (Table 3).
Discussion
Despite developments in the field of obstetrics, preeclampsia is still the second most common cause of maternal and fetal morbidity and mortality after embolism. The classic diagnosis triad is hypertension, proteinuria and edema observed following the 20th week of pregnancy [6]. Our study tries to understand the relationship between vascular structures and endovascular dysfunction in preeclampsia based on soluble endoglin (sEng), soluble fms-like tyrosine kinase 1 (sFlt-1), vascular endothelial growth factor (VEGF), PIGF and NO measurements and doppler USG analysis. Defining the circulating two anti-angiogenic proteins (s Eng and s Flt-1) will help us understand the connection between abnormal placentation and endothelial dysfunction. The increase in the production of these two anti- angiogenic proteins is stated to induce endothelial dysfunction by inhibiting PlGF, VEGF circulating proangiogenic factors [7]. In our study, the mean sEng level was determined as 8:47±2:51 ng/ml in the preeclamptic pregnant group, while in the healthy pregnant group, it was detected as 8.77±2:07 ng/ml, and the difference between them was not statistically significant (p>0.05). Levine et al. in their study, in which they investigated sEng level, examined a total of 552 pregnant women with 72 preterm preeclampsia (<37 weeks), 120 term preeclampsia (≥37 weeks), 120 gestational hypertension, 120 normotensive SGA and 120 non-normotensive SGA. In this study, it was revealed that the circulating sEng level increased significantly 2-3 months before the onset of preeclampsia [8]. Lubis et al. in the study, in which they predicted early-onset preeclampsia, uterine artery circulation and PIGF levels were effective in predicting preeclampsia, and no change in s Eng levels was observed [9]. In our study, it was determined that the mean sFlt-1 level of the preeclamptic pregnant group was 12.90±10.5, while it was 8.34±10.2 in the healthy pregnant group, and the difference between them was statistically significant (p < 0.001). The receptor sFlt-1 associated with maternal endothelial dysfunction is a component of preeclampsia pathogenesis [10]. Levine et al. put forward the increased expression of sFlt-1 and decreased expression of VEGF. More importantly, it was revealed that the administration of exogenous sFlt-1 on rats caused preeclampsia-like disease alone [11].
In our study, the serum level of VEGF of the preeclamptic pregnant group was determined as 156.3±112.0, while it was detected as 212.40±112.65 in the healthy pregnant group, and the difference was found to be statistically significant (p<0.001). VEGF is known to stimulate vasodilation and angiogenesis. Although this isoform is up-regulated in preeclampsia, its metabolic activities can be blocked by other proteins that bind to VEGF and inhibit its functions. Both sFlt-1 and sEng bind to VEGF and inhibit its functions [12]. In the study conducted by Tang, the increased expression of sFlt-1 and decreased expression of VEGF in preeclampsia were revealed [13]. Circulating free PlGF levels decrease in preeclampsia [14]. Binding to circulating sFlt-1, which is found at higher levels, was shown as the reason for this. In our study, when the mean serum level of PlGF in the preeclamptic pregnant group was compared with the normal pregnant group, the difference was not found to be statistically significant (p>0.05).
In our study, when the serum level of NO in preeclampsia pregnant group was compared with the serum level of NO in the healthy pregnant group, the difference was not found to be statistically significant (p>0.05). Noorbakhsh M et al. determined that serum nitric oxide levels were significantly higher in preeclamptic women compared to the normotensive pregnant women, and found that there was a (+) correlation between nitric oxide levels [15]. Valeria C et al. determined that the levels of plasma NO metabolites decreased in preeclamptic patients [16]. In a study conducted by Silver et al., it was reported that there was no difference between preeclampsia and the pregnant group, which is consistent with our study [17]. The brachial artery dilatation test is accepted as an in vivo marker of vascular “function”, and IMK measurement of carotid arteries is a “structural” marker of the vascular damage degree [18]. In our study, no significant difference was found when the carotid artery intima–media thickness and umbilical artery dopplers were compared in preeclampsia pregnant group and normal pregnant group. In our study, the mean value of carotid artery intima–media thickness of our patient population was below the pathological lower limit of 0.53 mm. Akhter et al. stated that there is a relationship between carotid artery intima thickness and pre-eclampsia t and cardiovascular diseases, and this non-invasive method should be used [19]. In a study by Blaauw et al., they excluded all risk factors of 22 nulliparous preeclampsia and 22 normal pregnant women, and it was observed that carotid artery intima media thickness increased in nulliparous preeclampsia patients [20]. After 4 years, Blaauw et al, who examined the same preeclampsia and normal pregnant patient group, did not increase carotid artery intima thickness in preeclampsia cases and reported that this may be a temporary adaptive condition in preeclampsia [21]. In our study, it was found that the expected dilatation was not observed after the test in the preeclampsia pregnant group in the brachial artery dilatation test, performed on the preeclampsia pregnant group; however, the posttest brachial artery dilatation was at a sufficient level in the normal pregnant group. Dilatation due to the increased flow in peripheral arteries was shown to be largely provided by NO secreted from the endothelium. Dilatation due to reactive response occurring after ischemia is known to be an endothelium- dependent phenomenon. This a repeatable and non-invasive method, which patients can easily tolerate and is applied to determine endothelial function, is widely used in clinical studies. A dilatation of 10 percent is generally accepted as the lower limit value [22]. In our study, the brachial artery width, which was 3.7 mm in the preeclampsia pregnant group before the test, was found as 3.9 mm after the test, and the dilatation difference, which was 2 mm in average, was observed below the dilatation limit of 10% in line with the literature. In a study conducted by Filho et al., it was reported that brachial artery dilatation test values were lower in the preeclampsia pregnant group compared to normal pregnant women, and doppler values were higher in uterine artery compared to the control group, while there was no difference in carotid artery intima-media thickness [23]. Malhotra AS et al, suggested that FMD be used as a noninvasive marker to predict preeclampsia development [24]. On the other hand, Praciano De Sousa et al. reported that the brachial artery FMD as independent parameters did not have a good predictive value for hypertensive disorders in the second trimester [25].
Conclusion
We think that uterine artery Doppler, assessment of brachial artery dilation and measuring VEGF, sFlt – 1 levels are helpful in predicting preeclampsia. It can be concluded that brachial artery dilation test can be effective in predicting hypertension in patients in parallel with the endovascular dysfunction developing as a result of NO dysfunction.
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.
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2. Staff AC. The two-stage placental model of preeclampsia. J Reprod Immunol. 2019; 134–135:1-10.
3. Običan SG, Odibo L, Tuuli MG Rodriguez A, Odibo OA. Third trimester uterine artery Doppler indices as predictors of preeclampsia and neonatal small for gestational age. J Matern Fetal Neonatal Med. 2020; 33(20):3484-9.
4. Weissgerber TL, Milic NM, Milin-Lazovic JS, Garovic VD. Impaired Flow- Mediated Dilation Before, During, and After Preeclampsia: A Systematic Review and Meta-Analysis. Hypertension. 2016;67(2):415-23
5. Eddy AC, Bidwell GL, George EM. Pro-angiogenic therapeutics for preeclampsia. Biol Sex Differ. 2018;9(1):36.
6. ACOG Practice Bulletin No. 202: Gestational Hypertension and Preeclampsia. Obstet Gynecol. 2019;133(1):1. DOI: 10.1097/AOG.0000000000003018.
7. Kar M. Role of biomarkers in early detection of preeclampsia. J Clin Diagn Res. 2014;8(4):BE01-4.
8. Levine RJ, Lam C, Qian C, Yu KF, Maynard SE, Sachs BP, et al. Soluble Endoglin and Other Circulating Antiangiogenic Factors in Preeclampsia. N Engl J Med. 2006;355(10):992-1005.
9. Lubis MP, Hariman H, Lumbanraja SN, Bachtiar A. The role of placental growth factor, soluble endoglin, and uterine artery diastolic notch to predict the early onset of preeclampsia. Open Access Maced J Med Sci. 2019;7(7):1153-9.
10. Veisani Y, Jenabi E, Delpisheh A, Khazaei S. Angiogenic factors and the risk of preeclampsia: A systematic review and meta-analysis. Int J Reprod Biomed. 2019;17(1):1-10.
11. Levine RJ, Maynard SE, Qian C, Lim K-H, England LJ, Yu KF, et al. Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med. 2004; 350(7):672- 83.
12. Liberis A, Stanulov G, Ali EC, Hassan A, Pagalos A, Kontomanolis EN. Pre- eclampsia and the vascular endothelial growth factor: a new aspect. Clin Exp Obstet Gynecol. 2016;43(1):9-13.
13. Tang Y, Ye W, Liu X, Lv Y, Yao C, Wei J. VEGF and sFLT-1 in serum of PIH patients and effects on the foetus. Exp Ther Med. 2019;17(3):2123-8.
14. Agrawal S, Shinar S, Cerdeira AS, Redman C, Vatish M. Predictive Performance of PlGF (Placental Growth Factor) for Screening Preeclampsia in Asymptomatic Women: A Systematic Review and Meta-Analysis. Hypertension. 2019;74(5):1124-35.
15. Noorbakhsh M, Kianpour M, Nematbakhsh M. Serum levels of asymmetric dimethylarginine, vascular endothelial growth factor and nitric oxide metabolite levels in preeclampsia patients. ISRN Obstet Gynecol. 2013;2013:104213
16. Valeria C, Sandrim ACT, Gomes VA , Cavalli RC , Tanus-Santos JE. Nitric Oxide Formation Is Inversely Related to Serum Levels of Antiangiogenic Factors Soluble Fms-Like Tyrosine Kinase-1 and Soluble Endogline in Preeclampsia. Hypertension. 2008;52(2):402-7.
17. Silver RK, Kupferminc MJ, Russell TL, Adler L, Mullen TA, Caplan MS. Evaluation of nitric oxide as a mediator of severe preeclampsia. Am J Obstet Gynecol. 1996;175(4 Pt 1):1013-17.
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19. Akhter T, Wikström AK, Larsson M, Naessen T. Individual common carotid artery wall layer dimensions, but not carotid intima-media thickness, indicate increased cardiovascular risk in women with preeclampsia: an investigation using noninvasive high-frequency ultrasound. Circ Cardiovasc Imaging. 2013;6(5):762- 8.
20. Blaauw J, Van Pampus MG, Van Doormaal JJ, Fokkema MR, Fidler V, Smit AJ, et al. Increased intima-media thickness after early-onset preeclampsia. Obstet Gynecol. 2006;107(6):1345-51.
21. Blaauw J, Souwer ET, Coffeng SM, Smit AJ, van Doormaal JJ, Faas MM, et al. Follow up of intima-media thickness after severe early-onset preeclampsia. Acta Obstet Gynecol Scand. 2014;93(12):1309-16
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25. Praciano De Sousa PC, Gurgel Alves JA, Bezerra Maia E Holanda Moura S Araujo Júnior E, Martins WP, Da Silva Costa F. Brachial artery flow mediated dilation and pulsatility index change as independent predictors for hypertensive disorders in the second trimester of pregnancy. Eur J Obstet Gynecol Reprod Biol. 2016;200:94-7.
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Şerif Aksin, Numan Çim, Hanım Güler Şahin, Deniz Balsak. Angiogenic factors and evaluation of vascular status in preeclampsia. Ann Clin Anal Med 2021;12(6):685- 689
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Beta-catenin or Pax 2. Which one is more useful in endometrial cancer?
Devrim Kahraman
Department of Pathology, TOBB Economics and Technology University School Of Medicine, Ankara, Turkey
DOI: 10.4328/ACAM.20691 Received: 2021-05-05 Accepted: 2021-05-27 Published Online: 2021-05-31 Printed: 2021-06-01 Ann Clin Anal Med 2021;12(6):690-693
Corresponding Author: Devrim Kahraman, TOBB economics and technology university school of medicine, Department of Pathology, TOBB Hospital Ankara Yasam caddesi no:5 pk:06510 Söğutozu/Ankara, Turkey. E-mail: dr.devrimsonmez@gmail.com P: +90 5055250295 Corresponding Author ORCID ID: https://orcid.org/0000-0001-9858-9252
Aim : Pax 2 is a nuclear transcription factor. It is essential for the embryonic development of Müllerian organs and is suppressed through at later stages of embryonic development, but is reactivated during carcinogenesis. Beta- catenin is a protein that is translocated from membrane to cytoplasm and nucleus in WNT activation as a signaling pathway. Endometrioid carcinoma is associated with beta- catenin mutations. This study aimed to evaluate PAX2 and Beta- catenin expressions in benign and precancerous endometrial hyperplasias.
Material and Methods: The study was performed on 40 endometrial curettage materials, including benign endometrial hyperplasia (n: 20), precancerous en- dometrial hyperplasia (n: 10), and endometrioid carcinoma (n: 20) as study groups. For immunohistochemical evaluation, one representative paraffin block for each case was selected.
Results: Pax 2 nuclear staining was detected in all endometrial tissues. The mean percentage was % 70 in benign hyperplasia and % 90 in precancerous endo- metrial hyperplasia and endometrioid carcinoma. Beta- catenin membranous-cytoplasmic staining was detected in only precancerous endometrial hyperplasia with a percentage of % 80 and endometrioid carcinoma with a percentage of % 90.
Discussion: Pax 2 is expressed in benign endometrial hyperplastic, precancerous endometrial hyperplasia and carcinoma, but beta catenin is expressed in only precancerous endometrial hyperplasia and carcinoma. These findings suggest that both the WNT signaling pathway and PAX 2 transcription factor may contribute to the development of endometrial cancer.
Keywords: Cancer Precursor; Endometrial Hyperplasia; Endometrioid Carcinoma; Cancer Biomarkers
Introduction
Endometrial cancer is the most common gynecological malignancy, which is responsible for approximately %4 of all cancers in women worldwide [1]. Endometrial hyperplasia is an irregular proliferation of endometrial glands with an increased gland stromal ratio and a benign process . When it is combined with atypia, the WHO classification system categorises it as “atypical endometrial hyperplasia [EH]” or “endometrial intraepithelial neoplasia [EIN]” (ESGO – European Society of Gynaecological Oncology. Pocket Guidlines _ Endometrial Cancer; 2017). The categorization is based on histomorphological criteria [2,3], and histological examination is the standard between benign and premalignant EH. It may cause additional problems, especially in poor inter- and intra- observer evaluations.
PAX 2 is a member of the paired box gene family. There are nine members from PAX1 to PAX9. PAX 2 is expressed during embryonic development and organogenesis [4]. Also, PAX proteins play a critical role in various types of malignancy [5,6]. In the literature, the immunohistochemical evaluation of PAX2 has been recommended to distinguish premalignant lesions in endometrial hyperplasia [7]; but this can also be seen in benign endometrial hyperplasia. Therefore, we need support for a definitive differential diagnosis.
Beta-catenin plays a role in WNT activation as a signaling pathway. Aberrant activation of the WNT/Beta- catenin pathway has been reported in patients with endometrial cancer [8]. Beta- catenin can be a good sporter for distinguishing precancerous lesions and focal malign areas.
In this study, we aimed to evaluate PAX2 and Beta- catenin expressions in precancerous endometrial tissues and malignant focal areas in hyperplastic endometrial fragments.
Material and Methods
Case selection:
In this study, we used paraffin blocks of curettage materials of 60 endometrial tissues. We evaluated them in three diagnostic categories as follows: 20 benign endometrial hyperplasias, 20 precancerous endometrial hyperplasias, and 20 endometrial carcinomas. The samples were particularly chosen from the population of reproductive age and postmenopausal period. Histological classification of benign and precancerous endometrial hyperplasia was based on the World Health Organization criteria (ESGO – European Society of Gynaecological Oncology. Pocket Guidlines _ Endometrial Cancer; 2017). The tumors were staged according to the 2009 Federation Internationale de Gynecologie et d’Obstetrique (FIGO) staging system [9]. The histological grading was also based on the FIGO system.
Immunohistochemical analysis:
With the examination on hemotoxylin and eosin (H&E) stained slides of the samples, one representative block for each case was selected for immunohistochemical evaluation. Sections with 3 μm thickness were cut from the blocks and incubated with PAX2 rabbit anti-human polyclonal [pSer393] antibody [isotype: IgG, catalog ID/Lot ID: LS-B2450/27017, Lifespan Biosciences, Seattle, USA] at a dilution of 1:100 for 35 min, in an automatic immunostainer (BenchMark XT Staining Module, Ventana
Medical Systems Inc; Tucson, AZ, USA) using the streptavidin Biotin complex immunodetection system. Antigen retrieval was achieved with CC2 (citrate, pH:6) solutions (Ventana) and protein blockage was applied. Diaminobenzidine was used for chromogen, followed by hematoxylin counterstaining. Fetal kidney tissue was used as a positive control. In the examination, only the specific nuclear staining was considered positive. In all cases, nuclear staining was detected in various (of moderate or strong intensity) percentages. The percentage of positive nuclei was achieved by counting 1000 epithelial endometrial cells. An alternative scoring system was also applied with reference to Monte et al [10].
Results
All endometrial tissues showed moderate to strong staining in endometrial epithelial cells with PAX2. All precancerous endometrial hyperplasia and endometrial carcinoma samples showed moderate to strong staining with Beta-catenin. Immunoreactivity was only nuclear in PAX2 and membranous- cytoplasmic in Beta- catenin. Non-specific staining was not observed in both biomarkers.
PAX2 expressions varied in quantity in benign endometrial hyperplasia, it was diffuse and strong in precancerous endometrial hyperplasia and endometrial carcinoma (Figure2). Beta-catenin expressions were not seen in benign endometrial hyperplasia, it was diffuse and strong in precancerous endometrial hyperplasia (Figure 2) and endometrial carcinoma (Figure 3).
Differences among subgroups were marked. The positivity rate with PAX2 was increased in the sequence of benign endometrial hyperplasia, precancerous endometrial hyperplasia, and endometrioid carcinoma. Whereas beta-catenin positivity was seen only in precancerous endometrial hyperplasia in endometrioid carcinoma.
Discussion
The present study revealed the role of Beta-catenin expressions in precancerous endometrial hyperplasia and endometrial carcinoma. When used with PAX2, the degree of neoplasia can be demonstrated with more supportive findings. We found that all of the endometrial samples (benign endometrial hyperplasia, precancerous endometrial hyperplasia and endometrioid carcinoma) showed moderate to strong nuclear immunoreactivity to PAX2. Staining reactivity was strongest in endometrial carcinoma. It was lowest in benign endometrial hyperplasia. These findings are in accordance with the other studies showing that PAX2 plays a role in endometrial carcinogenesis [11-16]. Staining with Betacatenin provided a significant benefit in the differential diagnosis of carcinoma from benign tissues. Whereas beta-catenin positivity is seen only in precancerous endometrial hyperplasia and in endometrioid carcinoma, the role of beta-catenin in colon carcinogenesis has been known for a long time [14]. However, the effect of beta-cetanin on endometrial cancer has only just been revealed. It is reportedly implicated in endometrial and ovarian carcinogenesis [17]. Dysfunction in the activation of the WNT/Beta-catenin pathway can promote cancer development [18]. Jun-Jiang et all. reported abnormal WNT/Betacatenin signaling in endometrial cancer. They found a significant correlation between multi-drug resistance protein 4 with betacatenin mRNA levels in endometrial cancers, in particular at stages I and IV. Also, Coopes A et al. showed aberrant activation of WNT/Beta-catenin in endometrial cancer [8]. The level of beta-catenin inside the cell is a key to the canonical Wnt/Betacatenin signaling [14]. In 2009, Jeong JW et al. found that beta-catenin mediates glandular formation. They also showed that dysregulation of beta-catenin induces hyperplasia formation in the murine uterus [15]. Several prior studies found different results about the relationship between Beta-catenin mutations and recurrence and its effect on prognosis. Myers A et al. found nine times higher odds of Betacatenin mutation in tumors of those patients who recurred compared to those who did not [16]. In 2012, Byron et al. evaluated disease- free survival in stage I or II endometrial cancer and could not find any difference based on Beta-catenin status [17]. In 2017, Katherine C. et al considered all stages of endometrial carcinomas, and as a result, they found that Beta-catenin mutant tumors were associated with higher rates of grade 1-2 disease. They found low rates of Beta-catenin in deep myometrial invasion and in lymphatic/vascular space invasion [18]. Thus many previously published studies have indicated the importance of beta-catenin in carcinogenesis [19-24]. In this study, we studied the comparison of beta-catenin and PAX2 in endometrial carcinogenesis for the first time with benign, precancerous and malign tissues. Thus, we can say that Beta- catenin mutation is an indicator of cancer, but the effect on prognosis is still controversial in the literature.
Scientific Responsibility Statement
Theauthorsdeclarethattheyareresponsibleforthearticle’sscientificcontent 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
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2. Kurman R, Carcangiu M, Herrington C, Young R. World Health Organization Classification of Tumors of Female Reproductive Organs, 4th edn. Lyon: International Agency for Research on Cancer (IARC) Press; 2014.
3. Sanderson PA, Critchley HOD, Williams ARW, Arends MJ, Saunders PTK. New concepts for an old problem: the diagnosis of endometrial hyperplasia. Hum Reprod Update. 2017; 23(2):232-54.
4. Baak JP, Mutter GL. EIN and WHO94. J Clin Pathol. 2005; 58(1):1-6.
5. Hueber PA, Iglesias D, Chu LL, Eccles M, Goodyer P. In vivo validation of PAX2 as a target for renal cancer therapy. Cancer Lett. 2008; 265(1):148-55.
6. Muratovska A, Zhou C, He S, Goodyer P, Eccles MR. Paired box genes are frequently expressed in cancer and often required for cancer cell survival. Oncogene. 2003; 22(39):7989-97.
7. Rabson EJ, He SJ, Eccles MR. A PANorama of PAX genes in cancer and development. Nat Rev Cancer.2006; 6(1):52-62.
8. Coopes A, Henry Ce, Llamosas E, Ford CE. An update of Wnt signaling in endometrial cancer and its potential as a therapuetic target. Endocr Relat Cancer. 2018; DOI: 10.1530/ERC-18-0112.
9. Pecorelli S. Revised FIGO staging for carcinoma of the vulva, cervix and endometrium. Int J Gynaecol Obstet. 2009; 105(2):103-4.
10. Monte NM, Webster KA, Neuberg D, Dressler GR, Mutter GL. Joint loss of PAX2 and PTEN expression in endometrial precancers and cancers. Cancer Res. 2010; 70(15):6225-32.
11. Wu H, Chen Y, Liang J, Shi B, Wu G, Zhang Y, et al. Hypomethylation linked activation of PAX2 mediates tamoxifen stimulated endometrial carcinogenesis. Nature. 2005; 438(7070):981-7.
12. Zhang LP, Shi XY, Zhao CY, Liu Y-Z, Cheng P. RNA interference of PAX2 inhibits growth of transplanted human endometrial cancer cells in nüde mice. Chin J Cancer. 2011; 30(6): 400-6.
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15. Jeong JW, Lee HS, Franco HL, Broaddus RR, Taketo MM, Tsai SY, et al. Betacetanin mediates glandular formation and dysregulation of beta-catenin induces hyperplasia formation in the murine uterus. Oncogene. 2009; 28:31-40.
16. Andrea M, William T B, Michelle S H, Ursula M, Larissa L. β-Catenin mutations in recurrent FIGO IA grade I endometrioid endometrial cancers. Gynecol Oncol. 2014;134(2):426-7.
17. Byron SA, et al. FGFR2 Point Mutations in 466 Endometrioid Endometrial Tumors: Relationship with MSI, KRAS, PIK3CA, CTNNB1 Mutations and Clinicopathological Features. PLoS One. 2012;7(2):e30801
18. Kurnit KC, Kim GN, Fellman BM, Urbauer DL, Mills GB, Zhang W, et al. CTNNB1 [beta-catenin] mutation identifies low grade, early stage endometrial cancer patients at increased risk of recurrence. Mod Pathol. 30(7):1032-41. DOI: 10.1038/modpathol.2017.15.
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Devrim Kahraman. Beta-catenin or Pax 2. Which one is more useful in endometrial cancer? Ann Clin Anal Med 2021;12(6):690-693
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The association between dietary protein intake and depression among university students
Gokce Cakmak Kafadar, Selma Fırat, Suheyla Tekın, Selin Esen
Department of Nutrition and Dietetics, Kırklareli University School of Health, Kırklareli, Turkey
DOI: 10.4328/ACAM.20704 Received: 2021-05-12 Accepted: 2021-05-24 Published Online: 2021-06-02 Printed: 2021-06-01 Ann Clin Anal Med 2021;12(6):694-698
Corresponding Author: Gokce Cakmak Kafadar, Kırklareli University School of Health, Department of Nutrition and Dietetics, 39060, Kırklareli / Turkey. E-mail: gokceckmk@gmail.com P: +90 288-214-55-47 F: +90 288- 214-70-86 Corresponding Author ORCID ID: https://orcid.org/0000-0002-0364-1546
Aim: Depression, a chronic disease, affects approximately 322 million people worldwide. The results of studies examining the relationship between depression and consumption of milk and dairy products and protein are unclear. The aim of this study was to examine the relationship between healthy university students’ milk and milk products and protein intake and depression.
Material and Methods: This cross-sectional study was conducted with 1444 healthy university students aged 18-39 in Kırklareli in 2019. The data consisting of the Food Frequency Questionnaire (FFQ), Beck Depression Inventory, and anthropometric measurements were collected by dietitians.
Results: According to the results of the study, the daily dietary protein intake (g) and the energy from protein (%) differed significantly between participants with and without symptoms of depression (p <0.01). Depression scores and protein intake of participants, and energy from dietary protein (%) are inversely correlated (p<0.05, p<0.001, respectively). According to the regression analysis results, a negative association was found between the Beck depression score and the dietary protein percentage (p <0.001).
Discussion: In our study, it was concluded that increasing the amount of protein in the diet can reduce the risk of depression in healthy university students. It is necessary to pay attention to the energy of the diet from protein in places that provide food service systems (canteen, university cafeteria, dormitory cafeteria, etc.) where university students eat.
Keywords: Depression; Dietary Intake; Protein; Milk; Dairy Products
Introduction
Depression affects approximately 322 million people worldwide (WHO. Depression and other common mental disorders global health estimates. World Health Organisation. Geneva, Switzerland, 2017) . It is suggested that inflammation, oxidative stress, and intestinal microbiota all play a key role in the etiology of depression [1]. Nutrition is an effective factor in the prevention and management of depressive disorders [1]. There are many studies on the relation of milk and dairy products with depression [2-9]. In a systematic review, it was shown that the relationship between dairy consumption and depressive symptoms is contradictory and inconsistent [2]. While there are studies showing that there is no relationship between milk consumption and depressive symptoms, there are also studies that have found a significant relationship between consumption of milk and dairy products and depressive symptoms [3-7]. One study found that high yogurt consumption in women was associated with a lower risk of depression [8]. In a study evaluating the relationship between calcium intake and depression in university students, low calcium consumption was associated with insomnia and depression [9].
The results of studies on the relationship between dietary protein and depression are not clear. While some studies show that dietary protein intake is inversely related to the risk of depression, other studies have reported that this relationship is not significant [6, 10-12]. Another study showed that total protein intake and protein intake from milk and dairy products can reduce the risk of depressive symptoms in adults living in the USA [13].
Controversial results have been obtained in studies examining the relationship between depression and milk and dairy products and protein consumption. In this study, it was aimed to contribute to the literature on this subject by evaluating the relationship between the consumption of milk and dairy products and the total protein intake of university students with the risk of depression.
Material and Methods
Setting and Sample
All registered undergraduate students studying at Kırklareli University, Kırklareli central district campuses, formed the universe of the study (N = 18065). The minimum sample size was determined to be 970 with a 95% confidence interval, 50% unknown expected prevalence, 5% margin of error (α = 0.05), 3% deviation (d = 0.03), which is the method of calculating the sample size of the study in proportions. Considering possible data loss, the sample size was increased by 70% and it was targeted to reach 1650 people. The proportionate stratified sampling method was used in the study. The three campuses in the central district were stratified and the number of people from each campus to be included in the study was determined according to the population sampling rate. Considering that it may affect the findings, 9 out of 1650 students who are > 39 years old were excluded from the study. Unmarried students were included, and 23 married students were excluded. Finally, 174 individuals with any health problems among the students were excluded from the study. The study sample consists of 1444 individuals.
Ethical approval
Ethical approval was obtained from Kırklareli University Institute of Health Sciences Ethics Committee (in 2019, protocol code: P0120R00). Before participating in the study, the participants were informed about the study and their consent was obtained. Food Frequency Questionnaire
In this survey, the frequency and amount of food consumed were questioned. The food frequency questionnaire including 5 groups of foods (milk and dairy products, meat-egg-legume, vegetable and fruit, bread and cereal, oil-sugar-sweet and drinks) was applied to participants to remember their consumption of the last month. The consumption frequency consists of 8 frequencies. The daily amount of food consumption was calculated by multiplying the total amount with the coefficients of these frequencies: each meal (3), every day (1), 1-2 times a week (0.215), 5-6 times a week (0.7855), 1 time in 15 days (0.067), 1 time per month (0.033) and never (0). The energy and nutrient intake of the individuals were calculated by entering daily food intake in the BEBIS 8.0 software (Nutrition Information System).
Depression Status
The Beck Depression Inventory (BDI), which was developed by Beck et al. and whose validity and reliability study was conducted by Tegin and Hisli, was applied to the participants. A high total score indicates that the severity of the depression is high (Tegin B. Cognitive Disorders in Depression: A review according to the Beck model. PhD thesis, Ankara, Hacettepe University Social Sciences Institute, 1980). [14, 15]. In addition, the BDI has cut-off points. According to the scores obtained, ≤9 points mean no depression and ≥10 points are classified as having depression (10-16: mild, 17-29: moderate, ≥30: severe). Anthropometric Measurements
Body weight and height, of the individuals were taken and recorded in the questionnaire form using electronic scales sensitive to 100 grams of body weight, without shoes and thin clothes. The height was measured with a portable stadiometer without shoes and against the wall.
The BMI (kg/m2) of the individuals was calculated and classified. WHO classification was used in this process. Thirty and over are classified as obese, 25-29.9 slightly obese, 18.5-24.9 normal and <18.5 underweight [16].
Study Analysis
Analyzes were made in IBM SPSS software 24th version. Data are given as frequency (%), mean ± SD or median (33th-67th percentiles). The normality of the distribution was checked with the Kolmogorov-Smirnov test. Student’s t-test, a parametric test, and the Mann-Whitney-U test, a nonparametric test were used in comparing the differences between averages. Pearson’s Chi-Square Test was used to compare the differences between ratios. The relationship between continuous variables was checked with Spearman’s rho correlation tests. The amount of milk consumption, yogurt consumption, cheese consumption, dairy-based dessert consumption and the predictors of depression were determined using multiple linear regression analysis. All p- values were two- tailed and were considered statistically significant at <0.05.
Results
A total of 1444 participants (52.6% men and 47.4% women) were recruited. BMI status of the participants (64.9% normal, 9.3% underweight, 25.8% overweight and obese) was determined.
It was observed that the participants with a non-depressive score and a depressive score did not differ in terms of total daily energy (kcal), meeting energy requirement (%), daily carbohydrate intake (g), energy from dietary carbohydrate (%), daily fat intake (g), energy from dietary fat (%), daily calcium intake (mg) and meeting calcium requirement (%). However, lower protein intake (g, P=0.002) and energy from dietary protein (%, p<0.001) was seen in participants with a depressive score. The rate of meeting the calcium requirement was 86.16% (Table 1).
There was no correlation between daily consumption of milk and dairy products, calcium intake and the Beck depression score (p> 0.05). There are correlations between the protein intake (p = 0.013, r = -0.065) and dietary protein percentage (p <0.001, r = -0.092) with Beck’s depression score (Table 2). In Table 3, the association between the Beck depression score and the percentage of dietary energy from protein was evaluated using linear regression analysis. In the sex-adjusted model, a statistically significant negative association was found between dietary energy from protein (% kcal) and Beck Depression score (B: -0.148, 95% CI: -0.248; -0.047).
Discussion
In our study, it was observed that there was no statistical difference between the participants who showed and did not show symptoms of depression according to the Beck depression score in terms of dietary energy intake (kcal), energy requirement percentage (%), dietary carbohydrate intake (g), dietary carbohydrate percentage (%), dietary fat intake (g), dietary fat percentage (%), and dietary calcium intake (mg). However, the dietary protein intake (g) and dietary protein percentage (%) were found to be statistically lower in individuals with depression symptoms than in those without depression symptoms. In this study, a negative correlation was found between Beck’s depression score and dietary protein amount (g) and dietary energy from protein percentage. In addition, there was no significant correlation between Beck’s depression score and daily milk and dairy consumption and dietary calcium. According to the sex-adjusted regression model, a negative association was found between the Beck depression score and the dietary energy from protein.
As a result of the literature review, it is seen that the relationships between depression and milk and dairy products and calcium are not clear, and there are conflicting and inconsistent results. For example, a systematic review found that the relationship between dairy consumption and depressive symptoms was contradictory and inconsistent [2], while a study on 1319 women in Japan found that more milk consumption during pregnancy reduced postpartum depressive symptoms [3].
In a study examining the factors affecting the prevalence of depressive symptoms during pregnancy, it was concluded that yogurt and calcium intake may be associated with low depressive symptoms during pregnancy [5]. In a study conducted with 887 elderly individuals in Japan, it was observed that consumption of dairy products reduces depressive symptoms regardless of gender [4]. In a cross-sectional study involving 1000 university students in Jordan, it was found that participants with moderate to severe insomnia had lower milk and calcium consumption and higher anxiety and depression scores compared to participants without insomnia [9]. In another study, milk and dairy products, vegetable protein and calcium intake were found to be significantly lower in Korean women with polycystic ovary syndrome (PCOS) with symptoms of depression [17]. In a cohort study, high yogurt consumption was found to be associated with a lower risk of depression in women [8]. In another study, consumption of milk-based desserts in adults was found to be negatively associated with depressive symptoms [18]. A cross- sectional study of 19,596 adults to investigate the relationship between yogurt consumption and depressive symptoms in China suggested that there was no significant relation between normal yogurt consumption level and depressive symptoms, however the relatively high frequency of yogurt consumption in a small subset of subjects (twice / day) has been associated with increased depressive symptoms [7]. In our study, the positive relationship found between the consumption of milk- based desserts and depression was not significant, but in a study conducted with Type 1 diabetics in Finland, an increase in the “dessert” score was reported to be positively associated with depressive symptoms [19].
There are studies in the literature that find an inverse relationship between dietary protein and depression scores, as in our study [10, 11, 13, 19-21]. In a study involving 17,845 adults living in the USA, using data from 2007-2014, it was concluded that protein intake could reduce the risk of depression [13]. In two cross-sectional studies conducted separately in Japanese male workers [10] and Spanish children [11], an inverse relationship was found between protein intake and depression. A cross-sectional study of 976 adults with Type 1 diabetes in Finland concluded that a preference for protein over carbohydrates and fats was associated with lower levels of depressive symptoms [19]. In the Villanueva Elderly Health Study, a negative relationship was observed between protein and depression [20]. In a study of 1947 men and 2909 women between the ages of 25-74, it was concluded that while increasing protein intake created a protective effect in men, there was a positive relationship between protein intake and severe depressive mood in women [6]. Unlike the results of our study, there are also studies that have not found a positive or any relationship between protein and depression. In a cross- sectional study conducted in Israel with 112 elderly individuals [21], it was observed that there was no difference in protein intake between depressive and non-depressive groups. In a cross-sectional study conducted in Poland [12], it was found that the relationship between protein intake and depressive symptoms was not significant. In another study, on Korean women diagnosed with PCOS, those with depression symptoms were found to have significantly higher energy intake from protein [17].
Various studies indicate that tryptophan, tyrosine, and calcium may prevent or reduce depression [18, 22, 23]. It has been confirmed that serotonin deficiency is associated with depressive symptoms [22]. Milk is a good source of tryptophan, an essential amino acid. 5-hydroxy tryptophan formed as a result of the hydroxylation of tryptophan is the precursor compound of serotonin [18, 22]. Therefore, intake of tryptophan can reduce depressive symptoms by increasing the level of serotonin in the brain [22]. In addition, milk and dairy products are a good source of tyrosine, and tyrosine has been found to affect mood as it is a precursor of dopamine [22]. Torres et al. [23] found that the decrease in extracellular Ca2+ concentration that occurs during excitatory transmission is detected by neighboring astrocytes, and adenosine triphosphate (ATP) released from astrocytic Cx43 hemi channels enhances inhibitory transmission by activating P2Y1 receptors on neurons. Higher calcium intake can attenuate extracellular Ca2+ fluctuations and hinder inhibitory transmission. This may be effective in decreasing depressive symptoms [23]. Calcium also participates in the synthesis of serotonin by activating tryptophan hydroxylase, which may reduce depressive symptoms [18].
Conclusion
In our study, it was concluded that increasing the amount of protein in the diet can reduce the risk of depression in healthy university students. However, no significant relationship was found between milk and dairy consumption and depression. Experimental studies are needed to overcome the inconsistencies in the literature.
Study Strengths
Our study was carried out on a large sample, and this increases the reliability of our study. In addition, since our study was conducted before the COVID-19 pandemic, all participants were interviewed face-to-face. Food consumption records were taken by nutrition and dietetics experts.
Study limitation
Since the food frequency questionnaire was used in our study, some mistakes may be made in the specified amounts of consumption due to incorrect recall. In order to minimize these mistakes, food consumption records were applied through a large sample by nutrition and dietetics specialists. In addition, due to the survey not only of milk and dairy products, but also all food groups, dairy products with different compositions (semi-fat, non-fat) could not be evaluated.
Since the Beck Depression Inventory is an individual self- administered scale to identify individuals with depressive symptoms, there may be inconsistencies in the results. Individuals with a disease statement were excluded from the study. It is a study limitation because it is based on an individual statement. Also, this may have reduced the number of patients diagnosed with severe depression in our study. Finally, since our study was not an experimental study, the food consumption of individuals was not intervened. This situation prevents the establishment of a full and distinct cause-effect relationship in the correlation between food consumption and depression.
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.
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Gokce Cakmak Kafadar, Selma Fırat, Suheyla Tekın, Selin Esen. The association between dietary protein intake and depression among university students. Ann Clin Anal Med 2021;12(6):694-698
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Comparison of the clinical results of closed intramedullary nailing in femoral shaft fractures between 1997-1999 and 2015-2019
Bedrettin Akar, Mucahid Osman Yücel
Department of Orthopedics and Traumatology, Sakarya Yenikent State Hospital, Kocaeli, Turkey
DOI: 10.4328/ACAM.20712 Received: 2021-05-22 Accepted: 2021-05-27 Published Online: 2021-06-02 Printed: 2021-06-01 Ann Clin Anal Med 2021;12(6):699-703
Corresponding Author: Bedrettin Akar, Department of Orthopedics and Traumatology, Sakarya Yenikent State Hospital, 41000, Yenidoğan, İzmit Kocaeli, Turkey. E-mail: drbedrettin@gmail.com P: +90 532 2089652 Corresponding Author ORCID ID: https://orcid.org/0000-0001-7461-1777
Aim: In this study, we aimed to show the changes in treatment principles and factors affecting healing by comparing the previous clinical results of the ante- grade closed intramedullary nail (AСIMN) application with the current clinical results in the treatment of Femoral Shaft Fractures (FSF).
Material and Methods: Patients who underwent AСIMN due to FSF were named Group A (years 1997-1999) and Group B (years 2015-2019). Group A consisted of 25 patients, with a mean age of 41 years, and a mean follow-up of 29.1 months. Group B consisted of 17 patients, with a mean age of 51 years, and a mean follow-up of 22.3 months. Patients with pathological fractures, polio sequelae, cerebral palsy and pelvic fractures were excluded from the study. The clinical length of stay and operation processes of the groups were followed. Evaluations were made according to Thoresen criteria.
Results: In Group A, it was observed that union was sufficient in the clinical and radiological examinations of 17 patients who came for control. In Group B, of the 15 patients, 13 had complete union and 2 patients had delayed union. The mean between operation and trauma (days) in Group A was found to be significantly higher than in Group B (p = 0.0001). The mean operation time (min) in Group A was found to be significantly lower than Group B (p = 0.0001). No significant difference was observed between the Thoresen criteria distributions of both groups (p = 0.52).
Discussion: The AСIMN technique continues to be the preferred method in FSF. While there were no significant changes in etiology, frequency and treatment principles, improvements were observed in the structure, design and locking methods of implant materials. Significant improvements were observed in the preoperative waiting periods and operation times of the patients. We can attribute these developments to improved clinical conditions and increased surgical experience. Despite all the developments, there was no significant difference in the basic principles of the surgical technique and clinical results. We think that more comprehensive studies using different treatment modalities and more patient numbers are needed in the future.
Keywords: Femoral Fractures; Nailing; Intramedullary Nailing; Osteosynthesis
Introduction
FSF, which constitutes 8% of all fractures, occurs with high-energy trauma (traffic accident, falling from height) [1,3,6,7,12,15]. It is a cause of high mortality and morbidity as it causes fat embolism and Acute Respiratory Distress syndrome [10].
The first IMN application started with Küntcher in 1940 and in the following years different researchers developed their own nails (Klemm –Shellman 1972, Grosse –Kemps 1978, Hucksetp 1979) [2,5,9,14]. It has been reported that a force of 280 newton meters is required to fracture the femur, and forces above this value spread to soft tissues [8,11].
The currently accepted classification of femoral fractures is the AO classification, and a coding system is used to describe the type of fracture that results in 27 different models [24]. (3 = femur, 2 = diaphysis). In our study, the fracture types of the patients were 3.2.A and 3.2.B.
These fractures have a high potential for union and a low rate of pseudoarthrosis [3,7,11,14,22,25]. The aim of treatment is to achieve union by providing anatomic length and axis with early mobilization [7,12]. Rapid union after closed intramedullary nailing is due to excessive collateral circulation around the femoral shaft. High rates of union and low infection rates have been reported with the use of closed nailing techniques [4,7,11]. Static locking should be used in segmental fractures to prevent shortening and rotation. Since static locking will delay fracture union, it should be dynamized 8 to 12 weeks after the operation [2,5,8,13,17,21].
Reamerization increases the stability of the fracture line by providing a larger contact surface between the bone and nail, so a larger diameter stronger nail can be placed. Additionally, endosteal blood flow is stimulated, which activates factors that accelerate union at the fracture site [1,6,13]. Although those who support reamerization of the medulla are in the majority, some researchers consider reamerization unnecessary [4,9,23].
Material and Methods
In Group A, ACIMN technique was applied to 25 patients between 1997-1999 in Istanbul Training and Research Hospital. Seventeen patients came for control. In Group A, the mean age was 41 years, 16 patients were male, 9 were female; 14 left, 11 right, 14 static and 11 dynamic locking nails of different brands (Orthofix-italy, Russel Tailor -USA, Ünku type 1-Turkey) were applied (Figure 1).
The average follow-up time was 29.1 months. In addition to FSF, 7 patients had different types of fractures (wrist fracture, Humerus fracture, forearm fracture, tibia fracture, clavicle fracture, etc.). In our study, the fracture types of the patients were 3.2.A and 3.2.B, according to AO classification (Table 1). Etiological reasons were as follows: 13 patients had a traffic accident; 11 patients had fallen from height and 1 patient had fractures as a result of a fall of a heavy object. In Group A, according to the AO classification, 18 patients had 32-A and 7 patients had 32-B type fractures. The average nail thickness was 10.7 mm, and the average nail length was 36.9 cm. Nails of the thickest possible diameter were used, taking as the beginning the piriform fossa entrance and reamerizing the medulla. Locking was done with proximal and distal locking screws placed externally, but difficulties caused by the instrument set during locking caused both prolongation of time and excessive damage to the tissues. The patients who were mobilized on a postoperative day 2 were invited to the control visits at 1, 3, 6 and 12 months and followed up clinically and radiologically. In Group B, ACIMN technique was applied to 17 patients with nails of different brands (Titan-USA, TST-Turkey Tıpmed- Turkey, Discotech, Polmed-Turkey) between 2015-2019 in Sakarya Yenikent State Hospital. Fifteen patients came for control visits. The mean age was 51 years, 10 patients were men, 7 were women, in 12 patients on the right, in 5 patients on the left, static locking was applied to 11 patients and dynamic locking was applied to 6 patients, the average follow-up period was 22.3 months. In addition to FSF, 4 patients had different fracture types (tibia fracture, wrist fracture, patella fracture, etc.). The etiological reasons were a fall from a height in 7 patients and a road traffic accident in 10 patients. According to the AO classification, 13 patients had 32-A and 4 patients had 32-B type fractures. The patients were operated with ACIMN technique with scopi on the traction table. In 2 patients who had difficulty in reduction, the fracture was reduced by opening the fracture site with a 5 cm minimal incision. The locking mechanisms of the nails contain mechanisms, which are different from each other.
Instead of the classical locking screw from the outside, the Discotech nail is inflated with a solution to lock the nail, while rigid fixation is provided by using internal locking nails in TST and Polmed nails. In practice, the medulla was reamerized with reference to the entrance to the piriform fossa. The patients were regularly called for follow-up visits at the postoperative 1, 3, 6, and 12th months, and their radiological and clinical examinations were performed. The nail thickness used is on average 10.8 mm and the nail length is on average 36.9 cm. The patients were mobilized on the post-op 2nd day and quadriceps and hamstring exercises were started.
Statistical Analysis
Statistical analyzes in this study were performed using the NCSS (Number Cruncher Statistical System) 2007 Statistical Software (Utah, USA) package program. In the evaluation of the data, in addition to descriptive statistical methods (mean, standard deviation), the distribution of variables was examined with the Shapiro-Wilk normality test, the independent t-test was used for the comparison of the normally distributed variables in binary groups, and the chi-square test was used for the comparison of qualitative data. The results were evaluated at the significance level of p <0.05.
Results
Thoresen’s classification was used to evaluate the results. According to this table, the results were divided into 4 categories according to the fracture axis, ipsilateral knee motion arc, pain, and the presence of edema and classified as excellent, good, moderate and poor [16]. In Group A, union was observed in all of our 17 patients. Limited range of motion was found in 2 patients. As the callus formation was sufficient in the radiological controls of 14 patients who underwent static locking, it was dynamized at the end of 12- 14 weeks. According to the Thoresen criteria, 14 patients were evaluated as excellent, 1 patient was evaluated as good due to tuberositas pain, 1 patient as moderate due to 5-degree valgus deformity developed post-op, and 1 patient as bad due to post- op infection. In one of our patients, purulent discharge occurred from the incision site after the operation.
The infection in the patient was treated by applying specific antibiotherapy. One patient was revised due to a near-distal fracture and a 20-degree valgus deformity due to the fact that the distal fragment could not be controlled during the operation. In the 2-year follow-up of this patient, it was observed that the fracture was fully welded, the hip and knee movements were complete, and a 5-degree valgus deformity sequela remained in the radiological examination.
Group B had complete union in 13 patients and delayed union in 2 patients. On clinical examination, hip and knee range of motion was found to be complete, except for 2 patients. Static locking patients were dynamized on average at 13 weeks. Complete union was observed in the 6th week after dynamization. Two patients, who were hospitalized in the intensive care for a long time due to multiple trauma, developed limitation of movements in the hip and knee joints. There were no signs of infection in the patients. Edema developed due to deep vein thrombosis in 2 patients and necrosis due to compression in the wound area in 1 patient. Circulation problem was treated with DVT treatment and wound problem by debriding necrotic tissues and applying wet dressing. According to Thoresen criteria, 13 patients in Group B were evaluated as excellent, 1 patient as good, and 1 patient as fair. In Group A, the period between hospitalization and surgery was quite long, such as 10-15 days, in the past, due to the inadequacy of health facilities and the problems in the supply of hospitals. Skeletal traction was applied to the patients during this period. The long waiting time before the operation created some difficulties due to the contraction of the muscles and tissues during the operation. In group B, all patients were operated on the traction table. The time between hospitalization and operation was approximately 3-4 days (Table 2). The increase in the number of health institutions and the diversity of the supply of materials in recent years has enabled patients to be operated in a short time.
The mean time between operation and trauma (days) in Group A was found to be statistically significantly higher than in Group B (p = 0.0001). The average operation time (minutes) in Group A was found to be statistically significantly lower than in Group B (p = 0.0001) (Figure 2). The mean follow- up time (months) in Group A was found to be statistically significantly higher than in Group B (p = 0.006). Statistical clinical results of the groups are shown in Figure 3.
Discussion
The AKIMN technique has an advantage over other techniques in FSF’s union and clinical recovery [2,3,6,9,13,16,22]. In this technique, since the fracture line is not opened and the fracture hematoma is not evacuated, fracture healing and union time are much more advantageous than the open IMN technique [1,4,11]. At the entrance, the piriform fossa or trochhanter type is referenced [1,2,6,7,9,13,15,17]. FSF is usually seen in young people aged 20-40. Hans Decker in a series of 1003 cases, found an average age of 31.3 years; Goran Denckward and Lilliestron found an average age of 32.4 years in 45 cases, and Kalenderer, in 71 cases, determined the average age of 35 years [6,9,20]. In this study, the average age in Group A was 41.5 years, and the average age in Group B was 51.3 years. Among the etiological reasons, Brumback stated that traffic accidents accounted for 84% and 16% were other causes in etiology, Kalenderer explained the etiological reasons with 66.1% of traffic accidents, 33.9% other factors and Enson explained the etiological reasons with 68.6% traffic accidents [14,15,20]. In this study, the main etiological cause in Group A was traffic accident with 52%, while in Group B, it was traffic accident with 58.7%. There is no consensus on the timing of the IMN in the FSF. In their meta-analytical study, Ayman El-Menyar et al. reported that there was no significant difference in the timing of early versus late IM nailing, indicating that it accelerates the joining and healing of such fractures.
In FSF, reamerization techniques of the medullary canal provide both mechanical and biological support for intramedullary nailing. Local formations accumulated at the fracture site by reamerization support union by functioning like a bone graft containing osteoprogenitor cells and inductive molecules. Reamerization increases the joining rate 4 times. While the union is 98.5% in reamerized intramedullar nails (RIN), this rate is 84% in unreamerized nails (URIN) [1,4,9,16,23]. A-Bing Li et al showed in their study that RIN improved the rate of union of fractures, shortened the time to union, and decreased the incidence of nonunion or delayed union [1]. Reamerization can damage the blood flow of the internal cortical bone, but as a reaction, the periosteal blood flow may increase 6-fold, which can stimulate fracture healing, and it has been stated that RIN can provide greater stability and reduce the risk of implant replacement [3,5,7,11,17,23]. Clatworthy et al concluded that fracture stability is an important determinant of rapid union [25]. A wider nail can be inserted into the medullary canal after reamerization to improve cortical contact and provide greater stability. Grundnes et al reported that a tight-fitting nail increases the periosteal reaction [17]. Tornetta in a series of 81 patients, applied reamerized IMN to 42 patients and unreamerized IMN to 39 patients [12]. The bone healing rate is much higher in the RIN group. The blood loss may be greater, but it will never be at the level that requires a blood transfusion [4]. Thorosen et al. applied RIN to 48 patients and reported very good results [16]. In our study, we applied RIN to all patients in both groups. As a result, complete union was achieved in all our patients. It is clearly seen that the RIN technique in IMN application has significant advantages over the URIN technique in terms of both stability and joining time. Nader Helmy et al evaluated the functional results of FSF treated with anterograde IMN by performing 2 different objective measurements (KinCom muscle test and Gait analysis) [11]. Isokinetic muscle testing was performed on hip abductors, hip extensors, and knee extensors using a KinCom muscle testing machine. In addition, walking laboratory analysis was performed on the patients. As a result, they stated that in IMN techniques with anterograde entry, it caused a slight lack of muscle strength in the hip abductors and extensors, which returned to normal in the later periods, and that it did not cause any change in the gait model in gait analysis [11]. Brumback and Virkus explained that IMN techniques may cause embolization by causing a slight decrease in endosteal blood flow and an increase in intramedullary pressure, but this effect is temporary; however, this complication is slightly more pronounced in URIN compared to RIN [14].
In the AKIMN method, there are different opinions about whether the locking should be static or dynamic. Those who argue that static locking should be made to prevent shortening and rotation are in the majority. Thorosen et al. applied 35 dynamic and 13 static locking to 48 patients. As a result, they stated that static locking is appropriate in cases where there is doubt about the stability of the fracture [16]. Enson et al. performed static locking in 8 of 12 patients and dynamic locking in 4 and achieved union in a mean of 17.1 weeks [15]. Akbaş performed 9 unlocking, 39 dynamic and 16 static locking [7]. In our study, in Group A, static locking was performed in 14 patients and dynamic locking in 11 patients. In Group B, static locking was applied to 11 patients and dynamic locking was applied to 6 patients. In conclusion, static locking should be preferred in the treatment of comminuted and unstable femoral fractures because it prevents shortening and rotation deformities.25StaticIMNcarriesweight,controlsshortening and rotation, but osteoporosis develops in the bone when stress is reduced. Dynamic locked system, on the other hand, is a system that shares the load, so it allows early load delivery, and there is no screw breakage problem. However, it has less control over shortening and rotation.
Dabezies et al. stated that while maintaining the length and rotation in the fracture line with static locking, micro movement is limited [19]. In the literature, it has been reported in many studies that delayed union or nonunion is more common in static locking than dynamic locking. There have been many studies in the literature regarding when dynamization will occur after static locking. In order to accelerate the healing of the fracture in patients, dynamization should be started as of 12-16 weeks when sufficient callus formation is seen. Tornetta started to dynamize on average in 10-12 weeks, Akbaş in 12 weeks, Brumback in 14-16 weeks and Kalenderer in 9 weeks [7,12,14,20]. After dynamization, the load placed on the implant before will cause stress on the bone, this stimulates the formation of callus and increases the hardness of the existing callus [1,2,5,8,11,16,22]. In our study, we applied dynamization as of the 12th week in cases where we performed locking statically. As a result, dynamization is a method that accelerates fracture healing and increases the hardness of the callus. Since a long time ago, closed anterograde IMN technique has been the first method preferred by orthopedists in FSF. While there were no significant changes in the etiological causes, frequency and treatment principles over time in both groups, improvements were observed in the structure, design and locking methods of the implant materials applied. In both groups, past and current treatment principles are not different, and success in such fractures is high with appropriate indication and correct application technique. Static locking should be used to prevent shortening and rotation in fractures with segmental fragments. The medulla must always be reamerized. When mobilizing patients on the first day after surgery, hip and knee rehabilitation should be started earlier. Although we investigated the effectiveness of current treatments in our study, we think that studies using new techniques and new treatment modalities with larger numbers of patients are needed in the future.
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.
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2. Hamahashi K , Uchiyama Y , Kobayashi Y , Ebihara G , Ukai T, Watanabe M. Clinical outcomes of intramedullary nailing of femoral shaft fractures with third fragments: a retrospective analysis of risk factors for delayed union. Trauma Surg Acute Care Open. 2019; 4(1): e000203. DOI: 10.1136/tsaco-2018 -000203.
3. Ricci WM, Gallagher B, Haidukewych GJ. Intramedullary nailing of femoral shaft fractures: Current Concept. J Am Acad Orthop Surg. 2009;17(5):296-305. DOI: 10.5435/00124635-200905000-00004.
4. Angadi DS, Stepherd D E T, Vadivelu R. Rigid intramedullary nail fixation of femoral fracturesin adolescents: what evidence is available? J Orthopaed Traumatol. 2014; 15:147-53. DOI : 10.1007/ s10195-013-0270-y
5. El-Menyar A, Muneer M, Samson D, Al-Thani H, Alobaidi A, Mussleman P, et al. Early versus late intramedullary nailing for traumatic femur fracture management: meta- analysis. J Orthop Surg Res. 2018;13(1):182. DOI: 10.1186/ s13018-018-0884-0.
6. Gabarre S, Alberada J, Gracia L, Puertolas S, Ibarz E, Herrera A. Influenza of gap size, screw configuration, and nail materials in the stability of anterograde reamed intramedullary nail in femoral transverse fractures. Injury. 2017; 48(Suppl. 6): S40-6. DOI :10.1016/S0020-1383(17)30793-3
7. Akbaş A, Kunt M, Ünsaldı T, Bulut O. Erişkin FSF nın tedavisi ve bu tedavide IMN nin yeri (The treatment of adult FSF and the role of IMN in this treatment). Acta Orthop Traumatol Turc. 1994; 28:161-7.
8. Herrera A, Rosell J, Ibarz E, Albareda J, Gabarre S, Mateo J, et al. Biomechanical analysis of the stability of antergrade reamed intramedullary nails in femoral spiral fractures. Injury. 2020;51 (Suppl. 1): S74-9. DOI: 10.1016/j. injury.2020.02.034.
9. Gänsslen A, Gösling T, Hildebrand F, Pape HC, Oestern HJ. Femoral shaft fractures in adults: treatment options and controversies. Acta Chir Orthop Traumatol Cech. 2014;81(2):108-17.
10. Denisiuk M, Afşari A, editors. Femoral Shaft Fractures. Treasure Island (FL): Stat Pearls Publishing; 2020; p.84-96
11. Helmy N, Jando VT, Lu T, Chan H, O’Brien PJ. Muscle function and functional outcome following standart anterograde reamed intramedullary nailing of isolated femoral shaft fractures. J Orthop Trauma. 2008; 22 (1):10-5. DOI :10.1097/BOT.0b013e31815f5357.
12. Tornetta P 3rd , Tiburzi D. The treatment of femoral shaft fractures using intramedullary interlocked nails with and without intramedullary reaming: a preliminary report. J Orthop Trauma. 1997; 11 (2):89-92. DOI: 10.1097/00005131- 199702000-00003
13. Jiang M, Li C, Yi C, Tang S. Early intramedullary nailing of femoral shaft fracture on outcomes in patients with severe chest injury. A meta-analysis. Sci Rep. 2016; 26; 6:30566. DOI: 10.1038/srep30566
14. Brumback R J, Virkus WW. Intramedullary nailing of the femur: reamed versus nonreamed. J Am Acad Orthop Surg. 2000; 8(2):83-90. DOI: 10.5435/00124635- 200003000-00002.
15. Enson C, Ozbaydar M.U, Çalbıyık M, Yurdoğlu C. The use of interlocking intramedullary nailing in the management of adult femoral shaft fractures. Acta Orthop Traumatol Turc. 1996; 30 (2):139-43.
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Bedrettin Akar, Mucahid Osman Yücel. Comparison of the clinical results of closed intramedullary nailing in femoral shaft fractures between 1997-1999 and 2015-2019. Ann Clin Anal Med 2021;12(6):699-703
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Spontaneous extensor pollicis longus (EPL) tendon rupture after ironing
Serdar Karaman 1, Muhammed Köroğlu 2, Zeynep Maraş Özdemir 3, Kadir Ertem 1
1 Department of Orthopedics and Traumatology, Medicine Faculty of İnönü University, Malatya, 2 Kilis State Hospital, Kilis, 3 Department of Radiology, Medicine Faculty of İnönü University, Malatya, Turkey
DOI: 10.4328/ACAM.20386 Received: 2020-10-29 Accepted: 2020-12-01 Published Online: 2020-12-11 Printed: 2021-06-01 Ann Clin Anal Med 2021;12(6):704-707
Corresponding Author: Serdar Karaman, Department of Orthopedics and Traumatology, Medicine Faculty of İnönü University, 44280, Battalgazi, Malatya, Turkey. E-mail: drserdarkaraman@gmail.com P: +90 5373040091 Corresponding Author ORCID ID: https://orcid.org/0000-0002-5546-3649
Spontaneous tendon ruptures can occur rarely. Distal radius fractures, steroid applications and systemic diseases are mostly attributed to its etiology. In the treatment of spontaneous tendon ruptures, primary repair is not possible and tendon transfer is often required. The EPL tendon is the main extensor of the thumb. This muscle originates from the interosseous membrane, especially the dorsal part of the ulna. The EPL passes from the third dorsal extensor compart- ment ulnar to the Lister’s tubercle before returning to the thumb. Since spontaneous tendon ruptures often occur due to degeneration, the defect is large in the area of the rupture. Therefore, spontaneous tendon ruptures are treated with tendon transfer rather than end-to-end repair. In this case report, we aimed to present a case of extensor indicis proprius (EIP) tendon transfer to our 64-year-old female housewife who was admitted to our clinic with a spontaneous rupture of the EPL tendon a resulting from excessive ironing in a short term. As a result of the examination and radiological evaluation of the patient who ap- plied to our clinic with the complaint of inability to extend the thumb extension, a spontaneous EPL tendon rupture was diagnosed and surgical treatment was decided. While making a diagnosis of spontaneous tendon rupture, it was learned that the patient had no trauma and rheumatologic disease in her anamnesis. Ultrasound and magnetic resonance imaging (MRI) were used to confirm the diagnosis radiologically. The spontaneous EPL tendon rupture treatment was successfully provided by the transfer of the extensor indicis proprius (EIP) tendon. At the six month of follow-up after the surgical treatment, it was observed that the finger regained its former function. In elderly patients, repetitive, forceful finger movements for a long time may cause spontaneous tendon rupture. Long-term coercive thumb movement is a risk factor for EPL spontaneous tendon rupture.
Keywords: Spontaneous tendon rupture; Extensor pollicis longus (EPL); Tendon transfer
Introduction
EPL tendon rupture is known to occur spontaneously after frac- tures, as a result of drug applications such as steroids, repeti- tive and excessive abnormal motion of the wrist joint, rheuma- toid arthritis and atypical etiology that are also mentioned in the literature. [1]
Extensor pollicis longus (EPL) is a skeletal muscle that follows a complex anatomical course in human hands. The EPL is respon- sible for the extension of the terminal phalanx of the thumb and adds the first metacarpal. This muscle originates from the interosseous membrane, especially the dorsal part of the ulna. The EPL passes from the third dorsal extensor compartment ulnar to the Lister’s tubercle before returning to the thumb. The anterior interosseous artery supplies the first part of the EPL tendon before the synovial sheath. The radial artery supplies the tendon after the synovial sheath. The vascularity of the ten- don in the third compartment of the Lister tubercle is weak or avascular. [2] The tendon of a watershed area with limited blood flow is at risk of ischemia and consequent tendon degen- eration. As a matter of fact, we shared the case of spontaneous EPL rupture due to repetitive motion after degeneration, which is an atypical etiology. It is known that end-to-end repair can- not be performed in spontaneous ruptures, thus it is treated with tendon transfer. Clinical examination is very significant in diagnosing a tendon rupture, and ultrasound and magnetic resonance (MR) can confirm the diagnosis.
Case Report
A 64-year-old female patient was admitted to our clinic with complaints of inability to use her thump. When diagnosis of spontaneous tendon rupture was made, it was learned that the patient had no history of trauma or rheumatologic disease. The situation that is meaningful in the story; we’ve learned that for the past ten days she has been ironing every day and using her thumb to release the steam boosting from the iron. It was learned that while using her thumb, she suddenly had a sense of detachment at the wrist level and could not lift her thumb.
In the examination, the patient was unable to actively extend her thumb, and the flexion action was complete. The patient had no known systemic disease other than hypertension and obesity. In the patient’s medical history, there was endoscopic median nerve decompression due to the bilateral carpal tunnel four years ago, and high tibia osteotomy for both knees due to medial gonarthrosis 10 years ago. The patient who had no rheumatologic disease had a sedimentation rate of 18mm / h (normal value 0-20), c-reactive protein value of 0.41mm / dl (normal value 0-0.35) and a rheumatoid factor of 22.8 (normal value 0-20). Although the rheumatoid factor value was positive, there were no clinical findings. There is no osseous pathology in X-ray imaging. After examination with ultrasound and magnetic resonance (MR) of the wrist, the extensor pollicis longus tendon was found to have a full-thickness rupture in the 3rd extensor compartment and there was a 3 cm gap at the level of the Lister’s tubercle and distally (Figure 1).
After a sterile environment suitable for surgical operation un- der axillary-block anesthesia, a slightly oblique dorsal incision over the third extensor compartment was performed and a full- thickness rupture of the EPL tendon and the fibrotic thickening were observed, the fibrotic part was excised and sent to the pathology. Then the EIP tendon was detected by entering the wrist through the dorsal extensor crisis. The EIP tendon was ex- cised by cutting the dorsal second metacarpophalangeal (MCP) joint level. Then, the EIP tendon was transferred to the EPL ten- don with Pulvertaft method, and the thumb extension tone was maintained with sufficient tension. The incisions were closed in a standart fashion (Figure 2a, 2b, 2c, 2d).
A short arm thumb splint was applied at the appropriate exten- sion level. The pathology report was evaluated as fibrosis and a chronic inflammatory event. The splint was preserved for 6 weeks, after which the rehabilitation procedure was started. At the 6th month of the postoperative period, the patient had ac- tive extension of up to forty degrees on the 1st finger (Figure 2e, 2f).
Discussion
Etiology of spontaneous tendon rupture: plaque and fixator applied to the radius, systemic diseases and steroid injection should be kept in mind in the spontaneous degenerative pro- cess. In our case, there was no history of trauma, no steroid injection, no systemic disease. Among the rare causes of EPL tendon rupture, dorsal ulna dislocation, madelung deformity, and necrotic scaphoid fracture have been previously reported in the literature. [3] A case of spontaneous EPL rupture due to cal- cific tendinitis was reported. [4] In Kannus’ study, 97% of spon- taneous tendon ruptures were found to be degenerative, and in our case, this pathology was supported. [5] The treatment of spontaneous EPL rupture was reviewed, and surgical options tried included direct repair, tendon transfer, and tendon graft- ing. Direct end-to-end repair is difficult because rupture tip is often fragile and thin. After removing the unhealthy part, there is always a gap between the proximal and distal end. Tendon transfer or tendon graft has become the standard procedure. When it comes to tendon transfer, EIP transfer is the standard technique for spontaneous EPL rupture. If the EIP tendon can- not be used, the palmaris longus (PL) tendon can be used as a graft [6]. In our case, the EIP transfer was done and the satis- faction was provided. Jun and his colleagues in the case report also worked as a seamstress and repeated the same movement for a long time in a patient who was referred to the EPL rup- ture and tendon transfer [1]. Our patient was a housewife, but in the last period she had been ironing for a long time. One cadaveric study suggested that a direct crush injury to the EPL can occur as a result of contact between the Lister tubercle and the base of the third metacarpal bone in a simulated fall onto an outstretched hand [7]. In a retrospective study on eight pa- tients with EPL tendon rupture, 4 patients were found to have an EPL tendon rupture without bone fracture. These 4 patients had a history of falling on the wrist [6]. Due to the anatomical structure of the EPL tendon and its nutrition at the wrist level, spontaneous rupture is more common than other tendons [2, 7].
Our patient had no history of falling on the wrist. Zviac at al. ob- served spontaneous rupture of the EPL tendon in patients with- out severe trauma or inflammatory diseases, Lister tubercle abnormalities, synovitis and tenosynovitis, and concluded that EPL tendon rupture can occur without trauma due to abrasion of the tendon around the Lister tubercle, regardless of age [8]. Our patient tested positive for rheumatoid factor, but the pa- tient had no symptoms of rheumatoid arthritis such as morning stiffness, did not meet the diagnostic standard, and synovitis was not observed during the operation. The patient had ironed at home for a long time in recent days. However, this patient was a housewife and became the first patient to spontaneously rupture the extensor due to repetitive movements while long time ironing.
Conclusion
In elderly patients, repetitive forceful finger movements for a long time may cause spontaneous tendon rupture. Long-term coercive thumb movement is a risk factor for EPL spontaneous tendon rupture. Spontaneous tendon rupture is not rare and has nearly complete function with appropriate surgical treatment. Clinical messages
Spontaneous tendon ruptures should be in our mind in any situ- ation limiting movement without trauma. While questioning the etiology, it should be kept in mind that tendon rupture can be caused by atypical causes.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical stan- dards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Conflict of interest
None of the authors received any type of financial support that could be consid- ered potential conflict of interest regarding the manuscript or its submission.
References
1. Choi JC, Kim WS, Na HY, Lee YS, Song WS, Kim DH, et al. Yae Hoon Park. Spontaneus rupture of the extensor pollicis longus tendon in a tailor. Clin Orthop Surg. 2011; 3(2):167-9.
2. Hirasawa Y, Katsumi Y, Akiyoshi T, Tamai K, Tokioka T. Clinical and microan- giographic studies on rupture of the E.P.L. tendon after distal radial fractures. J Hand Surg Br. 1990; 15(1):51-7.
3. Harvey FJ, HArvey PM. Three rare causes of extensor tendon rupture. J Hand Surg Am. 1989; 14(6):957-62.
4. Ertem K, Özdemir ZM, Görmeli G, Köroğlu M. Attritional rupture of the exten- sor pollicis longus tendon due to calcified extensor carpi radialis tendon group: a case report. Joint Diseases and Related Surgery. 2017; 28(1):59-61.
5. Kannus P, Jozsa L. Histopathological changes preceding spontaneous rupture of a tendon. A controlled study of 891 patients. J Bone Joint Surg Am. 1991; 73(10):1507-25.
6. Hu C-H, Fufa D, Hsu C-C, Lin Y-T, Lin C-H. Revisiting spontaneous rupture of the extensor pollicis longus tendon: eight cases without identifiable predisposing factor. Hand (N Y). 2015; 10(4): 726–31.
7. Ferreres A, Llusá M, García-Elías M, Lluch A. A possible mechanism of direct injury to the EPL tendon at Lister’s tubercle during falls with the wrist fully ex- tended. J Hand Surg Eur Vol. 2008; 33(2):149-51.
8. Zvijac JE, Janecki CJ, Supple KM. Non-traumatic spontaneous rupture of the extensor pollicis longus tendon. Orthopedics. 1993; 16(12):1347-50.
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Serdar Karaman, Muhammed Köroğlu, Zeynep Maraş Özdemir, Kadir Ertem. Spontaneous extensor pollicis longus (EPL) tendon rupture after ironing for a long time: A case report. Ann Clin Anal Med 2021;12(6):704-707
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Endoscopically detected multicentric squamous cell carcinoma of the esophagus; Case presentation and literature review
Serkan Yalaki 1, Hüseyin Pülat 2, Oktay Karaköse 3, Serdar Şenol 4
1 Department of Gastroenterology, Mersin City Training and Research Hospital Mersin, 2 Department of Surgical Oncology, Mersin City Training and Research Hospital Mersin, 3 Department of Surgical Oncology, Samsun Training and Research Hospital Samsun, 4 Department of Gastroenterological Surgery, Samsun Training and Research Hospital Samsun, Turkey
DOI: 10.4328/ACAM.20387 Received: 2020-10-29 Accepted: 2020-12-14 Published Online: 2020-12-23 Printed: 2021-06-01 Ann Clin Anal Med 2021;12(6):708-710
Corresponding Author: Oktay Karaköse, Surgical Oncology Department of Samsun Training and Research Hospital Samsun, Turkey. E-mail: oktaykarakose@gmail.com P: +90 5065348909 Corresponding Author ORCID ID: https://orcid.org/0000-0002-2429-3915
Esophageal cancer is the 8th most common cancer worldwide and the 6th most common cause of cancer-related deaths. In general, the majority of esopha- geal cancer cases are more common in underdeveloped regions and are more common in males than females. Esophageal squamous cell carcinoma (ESCC) tends to occur in the proximal and middle esophagus and is the dominant sub-type worldwide, accounting for approximately 90% of all esophageal cancers. In a single patient, the simultaneous detection of an esophageal tumor endoscopically at multiple sites is very rare. Here, we aimed to discuss the case and literature in which endoscopic examination revealed all foci to be ESCC on biopsy.
Keywords: Endoscopy; Carcinoma; Squamous cell
Introduction
Esophageal cancer is the 8th most common cancer worldwide and the 6th most common cause of cancer-related deaths. Its incidence shows differences according to countries and even regions in the same country. In general, the majority of esophageal cancer cases are more common in underdeveloped areas and are more common in males than females [1]. In our country, it is most commonly seen in Eastern Anatolian and Eastern Black Sea regions [2,3]. The incidence is reported to be 5-10 / 100.000 in the general population.
Esophageal cancer has two primary subtypes; esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are the most common subtypes and are seen more commonly in the 7th and 8th decades of life. ESCC tends to occur in the proximal and middle esophagus and is the dominant sub-type worldwide, accounting for approximately 90% of all esophageal cancers in regions with the highest incidence of esophageal cancer worldwide, especially from Northern Iran to the Northern-Central China and Russia [4]. Although the formation of more than one independent SCC is described in 14-31% of cases; these cases could be determined by examining surgical preparates. These secondary cancers are mostly in situ carcinomas and superficial ESCCs [5-8]. In a single patient, the simultaneous detection of an esophageal tumor endoscopically at multiple sites is very rare. Here, we aimed to discuss the case and literature in which endoscopic examination revealed all foci to be ESCC on biopsy.
Case Report
A 52-year-old female patient applied with pain complaint during swallowing. It was known from her medical history that she had been suffering from diabetes for 15 years and had been on hemodialysis program for 5 years due to chronic renal failure. As the result of the upper gastrointestinal endoscopy, between esophageal 30th-35nd centimeters a malignant looking ulcerovegetative mass which narrowed the lumen was detected (Figure 1A,B); 4-8 mm diameter nodular lesions independent of each other with swollen surfaces were observed between esophageal 28th-22nd centimeters (Figure 1C); and finally a vegetative mass narrowing the lumen between the esophageal 20th-17th centimeters was observed (Figure 1D).
Tumoral lesions with dark-colored, oval and distinct nuclei, containing widespread mitosis and showing single-cell keratinization within nests on the desmoplastic stromal floor were observed on biopsies taken from all the lesions separately. It was detected with PanCK, P40 and P53 stainings in the immunohistochemical examination. It was reported as ESCC. PET-CT showed a significant increase in the involvement of the esophagus segment approximately 50 mm in length, extending at the level of T1-T3 vertebrae, which caused wall thickening in the proximal esophagus and completely covering the passage in some areas (SUVmax: 13,2). Esophageal wall thickening and prominent involvement were observed at the level of the T5-T9 vertebrae, approximately 91 mm in length from the subcarinal area to the distal esophagus (SUVmax: 15.9).
Discussion
Esophageal cancers constitute 1.5-2% of all cancers worldwide and 5-7% of gastrointestinal cancers and 1.8% of all cancer- related deaths are related to esophageal cancer [1,2]. Squamous cell carcinoma and adenocarcinomas are the most common types of esophageal cancers. In regions where esophageal malignancies are common in the world, histologically it has been found that 90% of these malignancies are ESCC [2]. Although there is no definite incidence in our country, it is mostly observed in the regions of Eastern Anatolia and the Eastern Black Sea regions [3].
The incidence of esophageal cancer increases with age and peaks during the 7th and 8th decades of life, and it is more common in men than women [4-6]. The fact that our patient was young female is not compatible with the literature.
SCC typically occurs in the middle and lower third of the esophagus, with only 10%-15% occurring in the upper one- third segment [7]. Endoscopically, they are usually identified as single, ulcerated or ulcerovegetative lesions. Malignant lesions with similar characteristics were observed in the upper and lower esophagus [6,7].
Two theories have been described to explain the appearance of multiple carcinomas. The theory of monoclonal neoplasia predicts that a strain from a single transformed cell can spread to produce multiple tumors. In some cases, individual tumor nodules are seen in the esophagus or stomach wall. By examining the resected oesophageal specimens, this situation called intramural metastasis may be detected in about 11- 16% of cases. These metastases are thought to be caused by intramural lymphatic spread [8]. In our case, in accordance with this information, metastatic nodular formations, which were thought to be caused by an ulcerovegal malignancy in the lower segment of the esophagus, were detected.
In the field-effect model, it is predicted that independent tumors develop as a result of genotoxic effects of carcinogens. It is thought that viral infections, nutritional deficiencies and dietary habits play a role in the carcinogenicity process and that the mucosa becomes sensitive to the development of multiple tumors as a result of this. According to the field carcinogenesis theory, atypical epithelial hyperplasia, metaplasia, pre-invasive carcinoma (in situ) and fully developed carcinoma areas can be found in various regions in the upper aerodigestive canal [8]. In 20.2% of patients with esophageal carcinoma, synchronous or metachronous carcinoma was detected in another region. Patients with upper aerodigestive system tumors are at greater risk for developing of second primary cancers in the same region [7,8].
In conclusion, it should be kept in mind that multicentric malignancies as well as intramural metastatic lesions, may frequently occur in individuals with esophageal carcinoma. Therefore, careful evaluation should be done to prevent another lesion from being missed during endoscopic examinations.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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Serkan Yalaki, Hüseyin Pülat, Oktay Karaköse, Serdar Şenol. Endoscopically detected multicentric squamous cell carcinoma of the esophagus; Case presentation and literature review. Ann Clin Anal Med 2021;12(6):708-710
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