May 2023
Health-related quality of life in long COVID-19 in context of symptom type
Mehmet Göktuğ Kılınçarslan 1, Özgül Ocak 2, Erkan Melih Şahin 1
1 Department of Family Medicine, 2 Department of Neurology, Faculty of Medicine, Çanakkale Onsekiz Mart University, Çanakkale, Turkey
DOI: 10.4328/ACAM.21508 Received: 2022-11-21 Accepted: 2023-01-13 Published Online: 2023-01-20 Printed: 2023-05-01 Ann Clin Anal Med 2023;14(5):379-383
Corresponding Author: Mehmet Göktuğ Kılınçarslan, Department of Family Medicine, Çanakkale Onsekiz Mart University, 17100, Merkez, Çanakkale, Turkey. E-mail: goktugmk@gmail.com P: +90 506 610 85 40 Corresponding Author ORCID ID: https://orcid.org/0000-0003-4197-1914
This study was approved by the Ethics Committee of Canakkale Onsekiz Mart University (Date: 2022-02-02, No: 2022-03)
Aim: Coronavirus disease 2019 (COVID-19) is complex multisystem disease. After 4 weeks of persistent symptoms, it is termed as Long COVID-19. Long COVID-19 causes a decrease in health-related quality of life (HRQoL). In this study, it was aimed to determine which symptoms were associated with lower HRQoL in Long COVID-19 in this study.
Material and Methods: This cross-sectional study was conducted in a tertiary research hospital. Patients who have positive RT-PCR results at least 28 days and at most 180 days ago were selected for the study. Online survey was applied to 266 patients who had positive PCR test results for COVID-19. The EuroQoL 5D-3L scale was used to measure the HRQoL as a dependent variable. Socio-demographic features and symptoms were assessed by the survey as independent variables. Due to heteroscedasticity, a robust standard error regression analysis was conducted to make inferences on the effects of persistent symptoms on HRQoL.
Results: Of the total 266 participants, 163 were females (63.3%). The mean age was 41.2 ± 11.8 years. One hundred forty-two patients (53.3%) did not report any ongoing symptom . Female gender and lower education level as socio-demographic variables, visual problems and myalgia as persistent symptoms were identified as risk factors for reduced HRQoL in Long COVID-19 patients.
Discussion: Long COVID-19 patients experience lower levels of HRQoL, especially those with visual problems and/or myalgia. Interventions to raise the HRQoL of Long COVID-19 patients should first target visual problems and myalgia.
Keywords: COVID-19, Long COVID, HRQOL, Symptom Assessment, Regression Analysis
Introduction
SARS-CoV-2 coronavirus (severe acute respiratory syndrome coronavirus 2), which is a pathogen of COVID-19 (coronavirus disease 2019), has infected over 535 million people and caused more than 6.5 million deaths globally, as of 17 June 2022 (available at: https://covid19.who.int/). Although it was seen as a respiratory disease at first, the complex multisystem nature of COVID-19 is well understood now [1]. COVID-19 can affect not only the lungs, but also the heart, coagulation system, kidney, brain and musculoskeletal system. Thus, it has various symptoms such as fatigue, headache, dizziness, anosmia, loss of taste etc.
Recently, while the rate of new cases of COVID-19 has declined sharply, Long COVID-19 is gaining more attention as a new phenomenon. Long COVID-19 is described as the occurrence of persistent symptoms after COVID-19 that cannot be explained better by another medical condition. In the presence of persistent symptoms, at least 4 weeks must pass from COVID-19 to accept that the patient has long COVID-19 [2]. But 4 weeks is not a definitive criterion according to the literature as even a period of more than 12 weeks after COVID-19 is also defined as Long COVID-19 in a report [3]. The pathophysiological basis of persistent symptoms after COVID-19 is not well understood, but it was shown that immunologic dysfunction plays a major role in this situation [4]. Progression from acute COVID-19 to Long COVID-19 is also independent of hospitalization needs at the acute COVID-19 stage [5]. The percentage of patients progressing to Long COVID-19 was determined as 2.3% to 60% [6,7]. The wide range between these presented percentages is probably due to the selection of patients with different durations after COVID-19.
Long COVID-19 causes a decrease in health-related quality of life (HRQoL) in the same way as COVID-19 [8,9]. Female gender and intensive care unit (ICU) admissions at the acute stage were determined as risk factors for reduction in HRQoL of patients who have Long COVID-19 [10,11]. But symptoms of Long COVID-19 were understudied in the context of lowering the effect on HRQoL. Fatigue has a significant effect on the lowering HRQoL, while dyspnea and anosmia have no effect on HRQoL according to a meta-analysis [11]. Hyposmia has also been shown to significantly reduce HRQoL in patients that suffer from Long COVID-19 [12]. Taboada at al. showed that dyspnea on exertion, myalgia, asthenia and arthralgia are associated with a decrease in HRQoL of Long COVID-19 patients, while insomnia, cough, anosmia and chest pain are not [13]. But these results depend on univariate statistics rather than multiple statistics (the type of statistics was not mentioned in the manuscript) that may lead to a raise in the type 1 error. Also, in the mentioned study, only patients who were admitted to ICU were sampled, so the generalizability of the study is limited.
Further research is needed to evaluate the HRQoL of Long COVID-19 patients by multiple statistics in the context of persistent symptoms. Thus, we aimed to determine which symptoms were associated with lower HRQoL in Long COVID-19.
Material and Methods
Study Design and Participants
This cross-sectional study was conducted in a tertiary research hospital in February 2022. Retrospective electronic health records of patients, who admitted to the outpatient clinic for COVID-19, were evaluated. People with positive reverse transcriptase polymerase chain reaction (RT-PCR) test results for COVID-19 were determined from a database of the hospital. Long COVID-19 has been described as ≥4 weeks after a positive RT-PCR [2]. Also due to the possible bias that may arise due to a novel phenomenon, patients with positive test results more than 180 days ago were not recruited in the study. To discriminate Long COVID-19 patients who have positive RT-PCR results at least 28 days and at most 180 days ago were selected as the study samples.
At first, 600 patients had positive RT-PCR for COVID-19. The number of patients who tested positive between ≥28 days and ≤180 days before was 320. We reached these 320 patients to obtain informed consent by telephone. Of these 320 patients, 24 did not give informed consent. Then, online links for the survey were sent to these 296 patients. However, 30 patients did not complete the survey. Thus, this study was conducted on 266 patients.
It was planned to use 22 independent variables for the multiple regression analysis for the study. When the minimum sample size was calculated according to the literature, it was shown that (20+5×22) 130 participants were sufficient [14]. Thus, in this study, more than double of the minimum number of patients were recruited.
Variables
HRQoL was defined as a continuous dependent variable. HRQoL of patients was measured by the EuroQoL 5D-3L scale [15]. The EQ-5D-3L1 is a widely used generic measure of health status consisting of two parts. The first part (the descriptive system) assesses health in five dimensions (Mobility, Self-care, Usual Activities, Pain/Discomfort, Anxiety/Depression), each of which has three levels of response (no problems, some problems, extreme problems/unable to). This part of the EQ-5D questionnaire provides a descriptive profile that can be used to generate a health state profile. For example, a patient with health status 11223 would have no problems in mobility and self-care, some problems with usual activities, moderate pain/discomfort, and extreme anxiety or depression. Each health state can potentially be assigned a summary index score based on societal preference weights for the health state. These weights, or utilities, are often used to compute Quality-adjusted life years (QALYs) for use in health economic analyses. Health state index scores generally range from less than 0 (where 0 is a health state equivalent to death; negative values are valued as worse than death) to 1 (perfect health), with higher scores indicating higher health utility, though health state preferences can differ between countries. The second part of the questionnaire consists of the Visual Analogue Scale (VAS), on which the patient rates his/her perceived health from 0 (the worst imaginable health) to 100 (the best imaginable health). The EQ-5D questionnaire is cognitively undemanding, taking only a few minutes to complete. Instructions to patients are included in the questionnaire. For calculating the index score of the scale for each patient, the value set for our country is needed. However, there is no value for our country. So, in this study we used the value set of the United Kingdom, published by Dolan [16] as suggested in EuroQoL user guide (available at: https://euroqol.org/wp-content/uploads/2018/12/EQ-5D-3L-User-Guide_version-6.0.pdf).
Turkish validity and reliability of the scale were performed by the EuroQol Group [17] and the scale was obtained with the permission of the EuroQol Group under the registration number 50370.
The independent variables were collected via a survey that consist of socio-demographic questions and symptoms that started at the acute stage of COVID-19 and continued until the time of completion of the questionnaire. Participants had choices of “never or ceased” “yes and I still suffer” for each question of symptoms. These symptoms were headache, fatigue, dyspnea, hyposmia, loss of taste, dizziness, numbness in extremities, asthenia, myalgia, visual problems, hearing loss, hypokinesia, tremor, insomnia, pre-syncope/syncope, amnesia, difficulty in concentrate, anxiety, and sense of worthlessness.
Statistical analysis
Categoric variables were represented as frequencies and continuous variables were represented as mean ± standard deviation. If a continuous variable was not normally distributed, it was represented as median (25th percentile – 75th percentile). The linear relationships between variables were controlled by scatter dot plots.
First, univariate analysis (t-test with “not assumed equal variances”) was conducted to see if patients who have specific symptom had a statistically significant difference in HRQoL compared to patients who did not have the symptom. Then Multiple linear regression was used as the main analysis to reduce Type 1 error. The Variance Inflation Factors (VIF) values for each independent variable were controlled, and if the VIF value was smaller than 10, then it was accepted as the absence of multicollinearity [18]. As most of our independent variables were categorical, it would be good to mention that it is appropriate to use dichotomous variables as independent variables in multiple linear regression [19]. After the multiple linear regression, the scatter plot of residuals vs predicted values was evaluated to see if the pre-test assumptions of the linear regression were satisfied. Heteroscedasticity was observed in the scatter-dot plot of the residuals. For dealing with the heteroscedasticity in regression analysis, “heteroscedasticity consistent standard errors” approach was needed, so, a general linear model was performed to reach HC3 version of the robust standard errors as suggested in the literature [20]. Reporting R-squared for robust regression is somehow controversial, but as it is not affected by heteroscedasticity [21], we chose to report the R-squared value obtained from multiple linear regression with the method of ordinary least squares to make a sense of percentage of explained variance of HRQoL by persistent symptoms. F statistic for the robust model was not reported because F statistics are biased by heteroscedasticity, and with robust standard error regression it no longer makes sense.
In the presence of missed variables, it was planned to exclude the missed case for concerning analysis. P-value lower than 0.05 was accepted as threshold for significance. All analyses were performed on IBM SPSS Statistics for Windows, Version 26.0. Armonk, NY: IBM Corp.
Ethical Approval and Informed Consent
The study was approved by Çanakkale Onsekiz Mart University’s Clinical Research Ethics Committee with ID of 2022-03. Verbal informed consent was taken from patients prior to the application of the online survey.
Results
Of a total of 266 participants, 163 were females (63.3%) and 103 (37.7%) were males. The mean age was 41.2 ± 11.8 years. The average duration elapsed from the positive RT-PCR test result was 103.9 ± 44.2 days. Of the participants, 12 (4.5%) did not need to take any medicine, 238 (89.5%) were treated at home, and 16 (6.0%) needed hospitalization at the acute stage of COVID-19. The number of participants who did not report any ongoing symptoms was 142 (53.3%). The most frequent symptoms were amnesia (20.7%) and fatigue (19.9%), respectively. The frequency of all persistent symptoms of the patients are shown in Table 1.
The EuroQoL 5D-3L index score ranged from 0.550 to 1.000, and its median was 1.000 (0.796 – 1.000). This High negative skewness of EuroQoL 5D-3L score occurred due to 182 (68.4%) participants reporting overall health state as 1.000. For the same reason, EuroQoL-VAS score of the patients was negatively skewed and its median was 100 (75-100).
Univariate analysis showed that all specified symptoms, except for the loss of taste and hearing loss, were associated with lower levels of HRQoL (Table 2). A robust standard error regression was calculated to make inferences about how various types of symptoms affect HRQoL in Long COVID-19. The dependent variable was HRQoL(EQ-5D-3L score), while socio-demographic (age, education level, gender) and various types of symptoms were independent variables (Adjusted R-squared: 0.488). Female gender and lower education level as socio-demographic variables, visual problems and myalgia as persistent symptoms were identified as risk factors for lower HRQoL in the robust standard error regression model. The robust standard error regression model is presented with details in Table 3.
Discussion
In this study, it was shown that for Long COVID-19 patients, female gender, lower educational level (socio-demographic factors) and visual problems, myalgia (as persistent symptoms) were associated with lower HRQoL, while headache, fatigue, dyspnea, hyposmia, loss of taste, dizziness, numbness on extremities, asthenia, hearing loss, hypokinesia, tremor, insomnia, pre-syncope/syncope, amnesia, difficulty in concentrating, anxiety and sense of worthlessness were not associated. Female gender has been s shown to be associated with lower levels of HRQoL in Long COVID-19 in a previous study [10] as in our study. Fatigue [11], hyposmia [12], dyspnea on exertion, myalgia, asthenia, and arthralgia [13] were also associated with lower levels of HRQoL in the literature. But fatigue, hyposmia, dyspnea were determined as not associated with HRQoL in this study. In the literature, specific symptoms were associated with lower HRQoL by univariate analysis. Univariate analysis causes inflated Type 1 error, so associations can be determined in contrast to reality. In this study multiple analysis was used, so, Type 1 errors were minimalized by removing the confounding effect of symptoms on each other. Even our univariate analysis showed that most of the symptoms were associated with lower levels of HRQoL (Table 2), while multiple analysis showed that only two of the symptoms (visual problems and myalgia) were associated with HRQoL (Table 3). Also, in the previous widest study, dyspnea on exertion, myalgia, asthenia, and arthralgia were associated with decrease in HRQoL of Long COVID-19 patients, but in the study, only patients who had been admitted to ICU were sampled [13]. Meanwhile, in our study, there were no patients requiring hospitalization in ICU. Thus, symptoms associated with HRQoL in different studies may be a result of different characteristics of samples (time from positive RT-PCR result, ICU admission rate, variant of pathogen).
Robust standard error multiple regression is the most precious strength of the study because it allows us to make an inference with minimal Type 1 error. Also, the sample size was almost twice the calculated size, so Type 2 error was expected to be minimal for the study. The results of the study should be generalized with caution because it was conducted in the tertiary hospital. None of the participants of this study required ICU admission, so this may limit inferences from this study for all Long COVID-19 patients. Further studies may be needed to reveal a better understanding of the association between persistent symptoms and lower levels of HRQoL. Also, investigating which interventions aim to redound HRQoL of Long COVID-19 patients, especially those with visual problems and/or myalgia, may be beneficial.
Conclusion
Long Covid-19 patients experience lower levels of HRQoL, especially those who have visual problems and/or myalgia. Interventions to raise the HRQoL of Long COVID-19 patients should first target visual problems and myalgia.
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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Mehmet Göktuğ Kılınçarslan, Özgül Ocak, Erkan Melih Şahin. Health-related quality of life in long COVID-19 in context of symptom type. Ann Clin Anal Med 2023;14(5):379-383
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The efficacy of pulmonary physiotherapy in bariatric surgery: A comparative study
Serdar Yormaz
Department of General Surgery, Faculty of Medicine, Selcuk University, Konya, Turkey
DOI: 10.4328/ACAM.21522 Received: 2022-11-28 Accepted: 2023-02-02 Published Online: 2023-02-11 Printed: 2023-05-01 Ann Clin Anal Med 2023;14(5):384-387
Corresponding Author: Serdar Yormaz, Department of General Surgery, Faculty of Medicine, Selcuk University, Konya, Turkey. E-mail: serdaryormaz@gmail.com P: +90 532 690 05 31 Corresponding Author ORCID ID: https://orcid.org/0000-0002-6273-3643
This study was approved by the Local Ethics Committee of Selcuk University (Date: 2020-04-22, No: 173)
Aim: In this study, we aimed to compare the pulmonary functions in patients who have undergone laparoscopic sleeve gastrectomy (LSG) with and without pulmonary physiotherapy (PP).
Material and Methods: Participants were randomized and separated into two groups of 61 patients each. In the first group, PP and mobilization were advised, and in the second group, ony mobilization was advised and pursued by medicians. The treatment protocol began on the postoperative first day and continued until the postoperative first week. The parameters assessed were pulmonary functions, a 6-minute walk test (6MWT) for lung capacity.
Results: The average age of the participants was 42 ± 3.16 years. The outcomes of the parameters were significantly different in patients who received PP compared with the control group. Significant healing was revealed, as well as an improvement in all the parameters of participants who underwent PP compared with the control group (p = 0.017*,0.012*,0.077,0.027).
Discussion: In patients with morbid obesity who have undergone sleeve gastrectomy, with the help of pulmonary physiotherapy, respiratory functions improved, oxygen saturation increased, functional capacity increased and they were discharged early.
Keywords: Obesity, Pulmonary, Sleeve
Introduction
Morbid obesity is a common disease in all developed countries, and the definitive solution is primarily surgery as the only option for patients who have not benefited from medical and supportive treatment. LSG, which has become almost the first step in bariatric surgery, also plays a significant role. After the bariatric surgery, patients lose weight, daily activities can be performed more effectively, and intra-abdominal pressure on the lung cavity decreases.
Pulmonary physiotherapy (PP) plays a significant role in the prevention of postoperative complications of bariatric surgery. Functional lung exercise decreased the length of stay in the hospital, and also possible complications such as atelectasis, pneumonia of pulmonary physiotherapy modalities were suggested [1].
Furthermore, pulmonary physiotherapy ensures adequate ventilation in the lungs, limited motion and increased muscle tone, and recommendations to contribute to good posture, and better rehabilitation program improve the patient’s quality of life [2-4]. In this study, we aimed to compare the pulmonary functions in patients who have undergone laparoscopic sleeve gastrectomy (LSG) with and without PP .
Material and Methods
Pulmonary outcomes of 122 patients who underwent LSG in a tertiary bariatric clinic were evaluated retrospectively. The Local Ethics Committee approved this retrospective research (2020/8–decision number 173). The necessary consultations (endocrinologist, psychiatrist, pulmonologist, nutritionist) were made for the patients who applied before the operation. BMI values of all patients were > 40 kg/m2. Bariatric procedures were also performed by an experienced bariatric surgeon team.
Study protocol
Trial Design
Pulmonary physiotherapy was performed on Group 1 patients who have undergone sleeve gastrectomy for 7 days. The therapy process began from the first day to the 7th day. All exercises were performed by a physiotherapist in the clinic until the discharge period.
In the preoperative and postoperative periods, the following parameters were evaluated: oxygen saturation, respiratory function test, a 6-min walk test for functional capacity. Pre- and post-test evaluations were performed by a physician in the field of the study. The physiotherapy protocol included postural drainage, breathing exercises, and coughing techniques. All pulmonary exercises were repeated twice a day for a total of 8 times.
Participants were mobilized as immediate as possible, they walked 45 minutes along the aisle on the second day,
Participants
One hundred twenty-two patients who have undergone LSG were separated into two groups of 61 patients each . The presence of chronic respiratory disease, alcohol, smoking, and drug dependence were added as exclusion criteria.
Pulmonary Functions
Lung capacities were assessed utilizing a spirometer (Model 2010, Medizintechnik AG, Zurich, Switzerland) according to the Thoracic Society guidelines. Vital capacity, forced vital capacity, and maximal voluntary ventilation performances were used . The highest values of forced vital capacity (FVC), (FEV1), FEV1/FVC ratio, peak exhaling flow (PEF), vital capacity (VC) were determined.
Minute Walk Test
Participants were asked to walk for 6 min along the clinic corridor. Standardized suggestions were given in every 60 minutes. The maximum distance, which was performed at the end of the application was recorded [5].
Statistical analysis
Data were analyzed using IBM SPSS Statistics 26 (SPSS, Inc., Chicago, IL, USA). Descriptive statistics were used to describe the basic characteristics. T-Tests were performed for indicating differences between the groups. P-value ≤ 0.05 was accepted as significant for all statistical levels.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
A total of 80 females and 42 males were included. The average age was 42.3 years, and body mass index (BMI) was 43.1 kg/m2, however there was no significant difference determined among the study groups. Each group included 61 patients (Table 1). Pulmonary functions of the participants after the procedure were assessed, and all values in the pulmonary physiotherapy group were found to be elevated, on the other hand, VC, TV, and FEV1/FVC outcomes were determined as statistically significant healing in pulmonary physiotherapy group (p < 0.05) (Table 1). The 6-minute walking test scores demonstrated a statistically significant increase after the physiotherapy process (p < 0.05). Furthermore, only 6-minute walking test was detected as significant elevation (Table 2).
Discussion
Morbid obesity disease is a common health problem all over the world, furthermore, this disease affects lung compliance worse than in the non-obese population. Bariatric Surgery is one of the most effective treatments for morbid obesity and has been demonstrated to positively affect pulmonary functions. Although there are some studies about pulmonary problems that may establish after a bariatric process, there are few studies about pulmonary physiotherapy enforcements for the early recovery time [4,6-8].
The aim of this research is to demonstrate that postoperative pulmonary physiotherapy resulted in increased respiratory function, saturated oxygen ratio, and functional capacity in participants after bariatric surgery. In addition, morbid obesity negatively affects lung function and decreases the contraction force of the pulmonary muscles.
Brovman et al. showed significant variation in TV in morbidly obese patients in the postoperative period. They also found significant improvement in pulmonary functions due to weight loss after the bariatric surgery and a reduction in pressure on the lung capacity. Pulmonary physiotherapy is a treatment modality especially in patients with morbid obesity. The real purpose of pulmonary physiotherapy is to rehabilitate the strength of exercise [9,10].
Lung capacity volumes were decreased after the surgical process, therefore, due to this process participants should force their bodies to walk as far as possible to prevent complications such as atelectasis, thromboembolism etc. In another study by Van Limmen et al., they found that FVC, FEV1 outcomes decreased after the laparotomy; besides, Borges-Santos et al. found a decline in pulmonary functions after the bariatric process on weight [11,12].
Because of this, pulmonary physiotherapy postoperatively is so important. Abdominal surgical process has demonstrated that expiratory reserve volume is reduced in morbidly obese patients compared to non-obese participants. The most common complication after the bariatric process is atelectasis, which is also determined in nearly 40% of the population. For this reason, pulmonary physiotherapy is the most significant therapeutic approach for the prevention of possible pulmonary complications [13,1]. Pouwels et al. showed that participants who have taken pulmonary treatment had elevated inspiratory muscle strength and maximal inspiratory pressure (MIP) on postoperative 3rd and 6 th months and achieved greater improvement than the control group [14].
Furthermore, a study by Umemura et al. found that patients who have undergone bariatric procedure supported with pulmonary physiotherapy experienced greater postoperative healing than those who have not undergone[15]. Tomich et al. reported that in obese women, breathing exercises are particularly effective with the volume-oriented device, and this leads to increased inspiration volume and reduced possible complications after bariatric surgery [16].
In the present study, it was shown that the participants who underwent pulmonary physiotherapy demonstrated an increase in pulmonary functions after the surgical process. Furthermore pulmonary rehabilitation aid to patients for decreasing the complications such as atelectasis and also pneumonia Besides that 6MWT is utilized for evaluating the differences in lung capacity after the pulmonary rehabilitation process. Desy Salvadego et al. reported that respiratory muscle endurance training (RMET) with body mass reduction program in obese participants resulted in a reduction in the O2 cost of cycling and perceived exertion during constant heavy-intensity exercise, and also this exercise program strengthened respiratory muscles. Furthermore, the meta-analysis by Li et al., have analyzed 11 RCTs and demonstrated an important improvement in the 6MWT post-intervention distance [18]. The 6MWT is widely utilized for evaluating walking capacity [19-23]. This is a convenient and safe process to evaluate the functional capacity of morbidly obese patients who have undergone the bariatric process [24, 25].
Present study outcomes have shown that participants who underwent pulmonary physiotherapy were determined as 51 % recovery in a 6-min walking distance. According to these outcomes, it has been found that the exercise volume of patients who have undergone surgery, particularly bariatric surgery, can be improved by pulmonary physiotherapy.
In the literature review, our study is one of the rare studies, which evaluate the lung capacity and exercise performance by applying the pulmonary physiotherapy.
There are also some limitations in the present research. First, the follow-up period is short and patients were not called again for follow-up in the first year, Secondly, high-resolution computed tomography was not utilized to show possible pulmonary complications.
Conclusion
As a conclusion of this research, pulmonary physiotherapy, which is performed on morbid obese participants in the postoperative period has improved lung functions, oxygen saturation and also functional capacity in those who have undergone bariatric surgery.
Acknowledgment
Special thanks to Associate Professor Kazım Körez for his help with the study statistics.
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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Serdar Yormaz. The efficacy of pulmonary physiotherapy in bariatric surgery: A comparative study. Ann Clin Anal Med 2023;14(5):384-387
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Postoperative pelvic irradiation and vaginal brachytherapy in stage II endometrial cancer
Necla Gurdal 1, Ozge Kandemir Gursel 1, Binnur Donmez Yilmaz 1, Nihal Dizdar 1, Bekir Eren 1, Mehmet Yalciner 1, Yakup Büyükpolat 1, Tanju Berber 1 Selvi Dincer 1, Halil Akboru 1, Hilal Irem Acan 1, Cakir Numanoglu 1, Yaren Ceran 1, Gizem Nur Can 1, Nurgul Yasar 2, Berna Akkus Yildirim 1
1 Department of Radiation Oncology, 2 Department of Medical Oncology, Prof. Dr. Cemil Tascioglu City Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.21529 Received: 2022-12-01 Accepted: 2023-01-13 Published Online: 2023-02-03 Printed: 2023-05-01 Ann Clin Anal Med 2023;14(5):388-393
Corresponding Author: Necla Gurdal, Department of Radiation Oncology, Prof. Dr. Cemil Tascioglu City Hospital, 34384, Şişli, Istanbul, Turkey. E-mail: gurdalnecla@hotmail.com P: +90 506 478 14 40 Corresponding Author ORCID ID: https://orcid.org/0000-0001-5627-3436
This study was approved by the Ethics Committee of Istanbul Prof. Dr. Cemil Tascioglu City Hospital (Date: 2022-10-17, No: E-48670771-514.99)
Aim: Stage 2 endometrial cancer is a heterogeneous disease and has a low incidence. The aim of this study is to examine the oncological results in patients with stage 2 endometrial cancer who received pelvic radiotherapy and vaginal brachytherapy (VBT).
Material and Methods: Between 2000-2020, all operated eighty patients with stage 2 endometrial cancer were included in the study. Patients were analyzed in terms of baseline characteristics, adjuvant radiation (RT) planning modality, intracavitary VBT, chemotherapy (CT), local relapse, distant failure, overall survival (OS), and disease-free survival (DFS).
Results: At the end of a median follow-up of 82 months, none of the patients who underwent pelvic external RT and VBT had vaginal/pelvic failure. It was observed that there was a 13-fold increase in the risk of mortality in patients aged 60 years and older (HR=13,2 ; 95% CI=1.89–92.07, p=0.09 ). The 5- and 10-year OS rates were 92% and 86%, 5 and 10-year DFS rates were 94% and 91%, respectively.
Discussion: In the presence of poor prognostic factors in stage 2 endometrial cancer, pelvic external RT and VBT is an effective adjuvant treatment methods with excellent oncological results.
Keywords: Stage II Endometrial Cancer, Radiotherapy, Brachytherapy
Introduction
Endometrial cancer is one of the most common cancers in women worldwide. At the time of diagnosis, endometrial cancer that confined to the uterus is seen in approximately 67%, which is associated with higher survival rates [1]. The most important prognostic factors are old age, stage, grade, depth of myometrial invasion, lymph node involvement, tumor size, lymphovascular space invasion (LVSI) and poor histology [2, 3] .
The surgical staging system, developed in 1988 by the International Federation of Gynecology and Obstetrics was updated in 2009. Formerly both endocervical glandular invasion and stromal invasion were included in stage II. With the revision in 2009, the definition of Stage 2 disease was defined as the presence of only cervical stromal involvement (both microscopically and macroscopically) without extending beyond the uterus and lymph node involvement [4].
Among all endometrial cancers, stage 2 disease is thought to be approximately 5-8% [5,6]. Cervical stromal involvement is important as it is associated with an increased risk of LVSI and lymphatic metastases [7,8].
According to some recurrence prediction models, cervical stromal invasion was also observed to be among the risk factors [9]. Although its incidence is low in all stages, it is a very heterogeneous group in terms of histological grade, depth of myometrial invasion, LVSI status, extent of cervical invasion, molecular subtype, presence of serous/ clear cells [10]. Which of these subgroups has an indication for external pelvic RT, in whom vaginal brachytherapy (VBT) alone is sufficient, who should receive systemic treatment, or how chemotherapy (CT) and RT should be combined, etc., questions await answers.
Our knowledge of stage 2 disease to date is generally based on subgroup analyzes of large-scale clinical trials [3, 11, 12]. In this study, our goal is to report the treatment approaches and results of the patients with cervical stromal invasion limited to the uterus, which has a narrow area among all endometrial cancer patients. In addition, another aim is to examine in detail postoperative external pelvic RT and brachytherapy applications in this group of patients in terms of dose, technique and disease control.
Material and Methods
Study Population
Between 2000-2020, patients who applied to our center with the diagnosis of endometrial cancer were evaluated retrospectively. According to the guidelines of the International Federation of Gynecology and Obstetrics (FIGO 2009), postsurgical eighty patients with stage 2 were included in the study [4]. All patients were analyzed in terms of age at diagnosis, comorbidity, type of surgery, histology, grade, tumor size, depth of myometrial invasion, stage, LVSI, type of lymphadenectomy, number of dissected pelvic/paraaortic lymph nodes, adjuvant radiation (RT) planning modality, intracavitary VBT, chemotherapy (CT), local relapse, distant failure, overall survival, and progression-free survival. The study protocol was approved by the Ethics Committee of Istanbul Prof. Dr. Cemil Tascioglu City Hospital.
Postoperative Pelvic External Beam Radiation Therapy (EBRT)
Before 2008, RT planning was applied to patients as a 2-dimensional (2-D) anterior-posterior pelvic region. In the 2008-2012 period patients were treated as 3D conformal box technique with a belly board in order to reduce the intestinal dose. Since 2012, the volumetric modulated arc therapy technique (VMAT) has been used for patients.
Simulation
All patients underwent computed tomography simulation with a Philips Brilliance (Amsterdam, Switzerland) scanner. In order to better protect the surrounding tissues at risk such as the rectum, bladder and bowel, both before the simulation and before each treatment, the patients were made to drink 1-1.5 liters of water to adjust the bladder fullness, and bowels were emptied using anti-constipation medication. The patients were immobilized in the supine position and the pelvic region between L1 and the upper 1/2 of the femur was imaged with axial 3mm sections. These computed tomography simulation images were transferred to the Varian Eclipse TPS station (Varian Medical Systems, Palo Alto, CA) for target volume delineation.
Volume Definition
Clinical target volumes (CTV) were delineated according to the Radiation Therapy Oncology Group (RTOG) contouring guidelines. The entire vaginal stump, paravaginal-parametrial tissues, common iliac (up to L4-L5 interspace)- external-internal iliac nodal regions, presacral lymph node regions were included in the treatment area with a safety margin of 7-15 mm. Also, bladder, rectum, bowel and femoral heads were delineated as the organs at risk (OAR).
Radiotherapy Planning
Plans were designed with volumetric arc technique (dual-spring) according to healthy tissue tolerance dose limits. Treatment was delivered on a Rapidarc – Trilogy linear accelerator using two arcs that rotate 360° in opposite directions (179° clockwise and 181° counterclockwise). The collimator angle was set to 30°/330°. Planning was done with Eclipse version 10.0 using 6MV high energy photon energy. The suitability of the radiotherapy plans was checked by examining the isodose curves and dose-volume histograms (DVH). The daily treatment time was approximately 5 to 8 minutes. Weekly cone-beam computed tomography (CBCT) and daily kilovoltage (KV) imaging were taken to monitor the RT field in the patients.
Brachytherapy
Brachytherapy was performed as 2-D before 2013, and the dose was defined to point A. As of 2013, 3-D brachytherapy applications have been started. The treatments were administered in 3-5 fractions, usually every other day, with a cylinder applicator suitable for the patient’s vagina anatomy. Before each treatment, the patients were given a diet program and treatment preparation was made by bowel cleansing with enemas at night and in the morning. HDR Nucletron device with iridium 192 source was used for the treatment. Before the cylinder application, the bladder was emptied by inserting a Foley catheter. After the application, the patient was immobilized in accordance with the treatment position and computed tomography simulation images were obtained. These images were transferred to the Nucletron Oncentra Brachy treatment planning system for intracavitary brachytherapy planning.
Target volumes were delineated in accordance with the recommendation of the American Brachytherapy Society (ABS). The treatment doses were defined to the upper 1/3 vaginal surface and the full length of the vagina for serous and clear cell histologies. Bladder, rectum, sigmoid, urethra, and small intestine were delineated as the organs at risk (OAR). OAR dose tolerance limits were taken into consideration according to ABS guideline recommendations (Figure 1).
Statistical Analysis
The descriptive statistics of the numerical variables obtained in the study are given as the median (range) value. The descriptive statistics of the categorical variables are given as numerical values and percentages. Data distribution was assessed by the Kolmogorov–Smirnov test. In consideration of the sample size, the non-normal distribution of variables was assumed, and nonparametric tests were used for between-group comparisons. Thus, categorical and numerical variables were compared using the chi-square test and the Mann–Whitney U-test, respectively. Endpoint definitions: local failure (time to any locoregional event related to EC), distant progression (time to any non-regional event related to EC), OS (time to any death), and disease-free survival (time to any event related to EC). The follow-up time for the patients were measured from the date of surgery. Kaplan–Meier curves were generated for overall survival (OS) and disease-free survival (DFS) and significance was assessed using the log-rank test. Frequency tables and statistics were performed using SPSS 25 software (SPSS Inc., Chicago, IL, USA). The probability value of p<0.05 was considered significant.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
Patient Characteristics
The median age of the patients was 57,5 (range, 35-86). Median follow-up was 82 (range, 9-273) months. 54% of the patients had an additional comorbid disease. 83,8 % of the cases had endometrioid tip adenocancer (IDC) histology. The baseline characteristics of the patients are presented in Table 1. All patients underwent TAH+BSO. The median tumor size was 4,5 cm (range: 1-13). Lymphadenectomy was applied to 66% of the patients. 21 % of the patients received adjuvant chemotherapy and the regimen was carboplatin paclitaxel. Considering the statistical analysis, it was observed that the depth of myometrial invasion and LVSI were higher in patients aged 60 years and older (p=0.006, p=0.001, respectively). Also, an increase in the incidence of positive LVSI, deep myometrial invasion and high grade histology was observed in patients with a tumor size of 2 cm or more (p=0.034, p=0.041, p=0.008 respectively) (Table 2).
Adjuvant Radiotherapy Details
All patients underwent postoperative pelvic external RT and VBT. The median dose of RT administered was 46 Gy (45-50 Gy) and the median dose of VBT was 18 Gy (15-28,5 Gy). The prescribed pelvic RT doses were 50,4 Gy/28fr (27 % pts), 50 Gy/25fr (20% pts), 48 Gy/24fr (2% pts), 46 Gy/23fr (25% pts), 45 Gy/25fr (26% pts). The prescribed VBT doses were 27,5 Gy/5fr (12,5 % pts) , 25 Gy/5fr (7,5 % pts), 24Gy/3fr (11% pts), 20 Gy/4fr (6 % pts), 18 Gy/3fr (33 % pts), 15 Gy/3fr (30 % pts). Treatment Details are presented in Table 3.
Oncological Results
After a median follow-up of 82 months, no local recurrence was observed in any patient. Only one patient died due to disease. Ten patients died due to non-disease reasons. Distant metastasis was encountered in five of the patients. The sites of metastasis were the peritoneum, paraaortic area, abdominal lymphatic, mediastinum, supraclavicular area, femoral lymphatic area. The median time to metastasis were 23 months (7-122 months).
As salvage treatment, one patient received metastasectomy followed by CT, and the other patients received CT. There was no difference in local control, distant metastasis, or overall survival between patients who received and did not receive CT. While the rate of metastasis was 3% in patients with dissected pelvic lymph nodes 10 or more, it was 8.5% in patients with less than 10, but this difference did not reach statistical significance. When the factors affecting survival were examined, it was observed that only age was significant in both univariate and multivariate analyzes. It was observed that there was a 13-fold increase in the risk of mortality in patients aged 60 and over (HR=13,2; 95% CI=1.89–92.07, p=0.09 ). The 5 and 10 year OS rates were 92% and 86%, the 5 and 10 year DFS rates were 94% and 91%, respectively (Figure 2-3 ).
Discussion
When the patients in the present study were evaluated in terms of prognostic factors, 10% of the patients had unfavorable histology, 40% of the patients were 60 years and older, 58.8% of the patients had deep myometrial invasion, and 48.8% were LVSI positive. The rate of patients who did not undergo any pelvic sampling was 33.75%. With these features, it was observed that none of the patients who received pelvic external RT and VBT had vaginal/pelvic failure.
Vetter et al. analyzed 9.690 patients with stage 2 endometrial cancer using the national cancer database. When the treatment modalities were examined, EBRT alone, VBT alone and EBRT+ VBT were applied to 16.1%, 27.5%, and 24.4% of the patients, respectively. CT was applied to 14.3% of the patients. When the oncological results were examined, a decrease in the risk of death was observed in patients who received RT alone and RT combined with chemotherapy. When compared to the RT alone group, they found that the risk of death was lower in the RT combined with CT group [5].
Harkenrider et al. retrospectively analyzed the data of 106 patients who received VBT alone for stage 2 endometrial cancer in a multicenter study. Only patients with endometrioid type histology were included in the study. 88.6% of patients were grade 1 or 2, 98.1% had microscopic cervical stromal invasion, 89.6% had pelvic lymph node dissection. With the median 39-month follow-up, the five-year rate of pelvic recurrence, distant metastasis, and DFS were 4.2, % 7.2% and 74%, respectively. In conclusion, it was emphasized that only VBT could be an option only in a selected group of patients with low risk [13].
Lee et al. examined patients with stage 2 according to FIGO 2009 in their national cancer database and reviewed the results of 2261 postsurgery patients with endometrioid-type histology. Advanced age, African-American race, inadequate lymph node sampling, and high histological grade were found to be independent poor prognostic factors for stage 2 disease. When they compared the patient groups with EBRT, EBRT + VBT and VBT alone, no difference was observed between the three modalities in patients who did not undergo lymphatic dissection. But they observed that the overall survival results were better in the VBT alone group in patients who underwent lymphatic dissection. These results were explained by the fact that the VBT alone group consisted of patients with lower grade, higher lymph node sampling rate and negative LVSI [14].
Chen et al. reported a median 64.6-month single-center results of 110 patients from 1990 to 2013. According to their analysis, 70.9 % of the patients received EBRT+VBT, 13.6% received EBRT alone and 13.6% received VBT alone. CT was applied to 19.1% of the patients. In the study, locoregional recurrence was observed in 5 patients . The time to recurrence was observed as 17.5 months. Distant metastasis was observed in 17 patients, and 14 of these patients were in the EBRT +/- VBT group. The absence of pelvic lymph node dissection and the use of VBT alone, although on the border of statistical significance, were observed as predictive factors for locoregional recurrence. In the survival analysis, the 5-year overall survival rate in patients with grade 3 or poor histology was 65.8% for the EBRT ± VBT group and 33.3% for the VBT alone group (p = 0.020) [6].
Paulson et al. obtained stage 2 endometrial cancer patient’s surveillance and reporting records from the cancer registry data. Two hundred sixty four patients who had received adjuvant RT were examined in terms of oncological outcomes according to whether they received mini-pelvic field + VBT , full-pelvic field RT + VBT and VBT alone. It was stated that recurrence-free survival did not differ between these three groups. In addition, when all subgroups were examined, it was observed that CT increased recurrence-free survival and that the mini-pelvic field + VBT group provided disease control similar to the fullc group. In conclusion, they emphasized that mini-pelvic field + VBT can be applied in patients with negative LVSI and no lymph node involvement, full-pelvic field RT +/- VBT can be applied in patients who have not undergone pelvic lymphatic dissection, and VBT alone can be applied in low-risk stage II patients [15].
In the ESGO/ESTRO/ESP guidelines, EBRT is recommended for stage 2 endometrial cancer, and it is reported that only VBT can be considered for stage 2 grade 1, LVSI negative patients [16].
In the NCCN guidelines, EBRT and/or VBT is recommended for the adjuvant treatment of Stage 2 disease. There is a category 2B level recommendation for CT. In addition, it is emphasized that only VBT may be an option in patients with grade I-II myometrial invasion depth below 50%, LVSI negative and cervical stromal invasion at microscopic level.
Conclusion
Stage 2 endometrial cancer is a highly heterogeneous group. Larger series and prospective randomized studies are needed in terms of which RT modality will be appropriate in which subgroup. When treatment planning, prognostic factors should be considered and current guidelines should be followed. However, DFS and OS results are excellent with appropriate treatment selection on a patient basis.
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.21529
Necla Gurdal, Ozge Kandemir Gursel, Binnur Donmez Yilmaz, Nihal Dizdar, Bekir Eren, Mehmet Yalciner, Yakup Büyükpolat, Tanju Berber, Selvi Dincer, Halil Akboru, Hilal Irem Acan, Cakir Numanoglu, Yaren Ceran, Gizem Nur Can, Nurgul Yasar, Berna Akkus Yildirim. Postoperative pelvic irradiation and vaginal brachytherapy in stage ii endometrial cancer. Ann Clin Anal Med 2023;14(5):388-393
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Incidence of emergency surgery in anterior abdominal wall hernias
Turgay Karatas 1, Engin Burak Selcuk 2, Mehmet Karatas 3, Atilla Yildirim 4, Ibrahim Nuvit Tahtali 5, Ahmet Kadir Arslan 6
1 Department of Anatomy, Inonu University, 2 Department of Family Medicine, Inonu University, 3 Department of Medical History and Ethics, Inonu University, 4 Department of General Surgery, Malatya Training and Research Hospital, 5 Department of Urology, Malatya Training and Research Hospital, 6 Department of Biostatistics and Medical Informatics, Inonu University, Malatya, Turkey
DOI: 10.4328/ACAM.21531 Received: 2022-12-02 Accepted: 2023-01-13 Published Online: 2023-02-03 Printed: 2023-05-01 Ann Clin Anal Med 2023;14(5):394-398
Corresponding Author: Turgay Karataş, Department of Anatomy, Faculty of Medical, Inonu University, 44050, Battalgazi, Malatya, Turkey. E-mail: drkaratas44@hotmail.com P: +90 422 341 07 45 F: +90 422 341 00 36 Corresponding Author ORCID ID: https://orcid.org/0000-0002-1480-606X
This study was approved by the Clinical Research Ethics Committee of Inonu University (Date: 2018-10-23, No: 2018/161)
Aim: This prospective study was conducted to analyze the incidence of emergency surgery in anterior abdominal wall hernias (AWH).
Material and Methods: A total of 659 patients with anterior AWH were examined. Patients with anterior AWH who underwent elective or emergency surgery were included in the study. In this study, groin and non-groin hernias constitute anterior AWHs. Gender, age, anesthesia and repair methods, elective and emergency surgery, hernia types, side of groin hernias, recurrent or primary hernias were determined and recorded. Emergency surgery incidences of hernias were evaluated in terms of gender, age, hernia types, groin hernia sides, primary or recurrent hernias.
Results: Emergency surgery was performed in 64 patients (9.7%). The incidence of emergency surgery was found to be higher in females. In anterior AWHs, the emergency surgery incidence was found to be higher in non-groin hernias than in groin hernias (P<0.001). The emergency surgery incidence was highest in femoral hernias among groin hernias and incisional hernias in non-groin hernias. In terms of primary and recurrent cases, the emergency surgery incidence was significantly higher in recurrent cases (P<0.001). However, when the emergency surgical incidence of all anterior AWHs such as inguinal, femoral, incisional, umbilical and epigastric hernias in the study were compared, no significant difference was found among them.
Discussion: Emergency surgery incidence was found to be higher in females and in recurrent cases. However, there was no significant difference in the incidence of emergency surgery among all anterior AWH types.
Keywords: Abdominal Wall Hernia, Groin Hernia, Inguinal Hernia, Incarceration, Emergency Surgery
Introduction
A hernia is a condition in which abdominal tissues or organs, surrounded by the peritoneum, protrude from the abdominal wall through a defect in the abdominal wall. Abdominal wall hernia (AWH) is common in the community with a prevalence of 1.7%. Inguinal hernia constitutes most of the AWHs (75%) [1]. Every year, approximately 20 million people in the world are operated for inguinal hernia. In the United States of America and Germany, 350,000 and 100,000 abdominal hernia operations are performed each year, respectively [2]. Over time, the incidence of abdominal hernias has increased and the surgical techniques used have also improved. For this reason, operations of AWH have increased the interest of many surgeons on this subject [3].
Incarceration is the inability to push the contents of the hernial sac back into the abdomen. In the case of strangulation, the blood circulation of the structures in the hernia sac is disturbed and this situation is quite serious [4]. Incarcerated AWHs, a common surgical emergency, constitute 5-15% of AWHs. The most of incarcerated abdominal hernias are incarcerated groin hernias (IGH) [5].
We conducted this prospective study to analyze the incidence of AWHs that are incarcerated and require emergency surgery.
Material and Methods
Our prospectively designed study was initiated after approval by the ethics committee. The study protocol was approved by the Inonu University Malatya Clinical Research Ethics Committee (No. 2018/161). This study was started in December 2018 and finished in December 2021. After obtaining ethical approval for the study, informed consent was obtained from each subject. The period in which this study was conducted also includes the period when the SARS-COV 2 epidemic in Turkey was severe. Patients who were admitted to the hospital due to anterior AWH and were operated on as an elective or emergency were included in the study. In this study, groin and non-groin hernias constitute anterior AWHs. Anatomically, hernias in regions other than the anterior abdominal wall were excluded. Gender and age of the patients, anesthesia and repair methods, patients undergoing elective and emergency surgery, hernia types, side of groin hernias, recurrence, or primary hernias were determined and recorded.
The incidence of hernias requiring emergency surgery was evaluated in terms of gender, age, hernia types, groin hernia sides, primary or recurrent hernias.
Statistical Analysis
The normality of the continuous data was evaluated by the Shapiro-Wilk test and the independent samples t-test was used for comparisons. Categorical data were represented by numbers and percentage. Comparisons due to these variables were performed by Pearson’s chi-square test or continuity-corrected chi-square test, where appropriate. In all analyses, a two-tailed significance level was considered as 0.05. Statistical analysis was performed using IBM SPSS Statistics for Windows version 22.0 (New York, USA).
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
A total of 659 patients with anterior AWHs who underwent elective and emergency surgery in the hospital were included in the study. Four hundred seventy-four (72%) patients were male and 185 (28%) were female. The age range of the patients was 15-102 years, and the mean age was 50±12.2 years. The age range of male patients was 15-102 (50.4±13.2 ) and female patients was 17-82 (49±10.5 ).
Of the patients, 135 (20.5 %) were operated with general anesthesia and 524 (79.5%) were operated with regional anesthesia. Mesh herniorrhaphy was applied to 625 patients (94.8%), and the remaining 34 patients (5.2%) underwent primary herniorrhaphy.
Elective surgery was performed in 595 patients (90.3%), and emergency surgery was performed in 64 patients (9.7%) due to incarceration. Thirty-four male and 30 female patients underwent emergency surgery.
Groin hernia count was 575. Groin hernias consisted of 540 inguinal (indirect, direct and pantaloon hernias) and 35 femoral hernias. The number of non-groin hernias was 84 in total.
Non-groin hernias consisted of incisional hernias (21 median, 8 Pfannen-stiel, 4 right paramedian, 3 suprapubic, 2 Mc Burney, 2 sub-umbilical trocar, 2 right subcostal and 1 left subcostal incision), umbilical hernias and epigastric hernias. The number and percentage of hernia types were shown in Table 1.
The number of right groin hernias was 287 (44.6%), left 167 (29%), and bilateral 121 (21%). There were 559 primary hernias (84.8%), and 100 recurrent hernias (15.2%). The age range of the patients who underwent emergency surgery was between 28 and 102 years. The mean age was 59.4±16.1 years. 45.3% of these patients were over 65 years of age, and 54.7% were under 65 years of age. The age range of emergency surgery was 35 – 102 years in males, 28- 82 years in females. The mean age was 68.2±12.4 years in males, 59±15 years in females.
Tissue resection was performed in 47 of 64 patients. The tissue resections of 34 omentum, 9 resections of the small bowel, 3 resections of omentum and small bowel, and 1 resection of omentum and appendix vermiformis were performed.
In groin hernia, the number of emergency surgery was 44, and the number of elective cases was 531. Tissue resection was performed in 28 patients with groin hernias (21 omentum resections, 4 small bowel resections, 2 omentum and small bowel resections, 1 omentum and appendix vermiformis resection). While the rate of small bowel resection was 1% in groin hernias, this rate was 13.6% in incarcerated groin hernias (IGH).
In non-groin hernias, the number of emergency surgery was 20, and the number of elective surgery was 64. Tissue resection was performed in 19 patients with non-groin hernias (13 omentum resections, 5 small bowel resections, 1 omentum and small bowel resection). The rate of small bowel resection was 7.1% in non-groin hernias, this rate was 30% in incarcerated non-groin hernias.
The number and percentage of elective and emergency surgery in groin hernias (inguinal, indirect inguinal, direct inguinal, pantaloon, femoral), non-groin hernia (incisional, umbilical, epigastric hernias), sides of hernia, primer, and recurrent hernias are shown in Table 2.
Tissue resection was performed in twenty patients with inguinal hernias (14 partial omentectomy, 3 small bowel resection, 2 partial omentectomy and small bowel resection, 1 partial omentectomy and appendix vermiformis resection). In thirteen patients, the hernia contents were reduced into the abdomen because there was no necrosis. Small bowel resection rate was 0.9 % in inguinal hernias, this rate was 15.1% in incarcerated inguinal hernias.
An emergency operation was performed for the femoral hernias, seven of them underwent partial omentectomy and 1 small bowel resection. The rate of small bowel resection was 2.8% in femoral hernias, this rate was 9% in incarcerated femoral hernias.
We detected incisional hernias in 21 median, 8 Pfannenstiel, 4 right paramedian, 3 suprapubic, 3 Mc Burney, 2 sub-umbilical, 2 right subcostal and 1 left subcostal incisions. Incisional hernias that underwent emergency surgery were 8 median, 2 Pfannenstiel, 2 right paramedian and 2 Mc Burney incisions. Partial omentectomy was performed in eight of them and small bowel resection in four of them. Small bowel resection rate was 9% in incisional hernias, this rate was 28.5% in incarcerated incisional hernias.
In umbilical hernias, 2 partial omentectomy, 1 small bowel resection, and 1 omentum and small bowel resection were performed due to necrosis. The rate of small bowel resection was 6% in umbilical hernias, this rate was 33.3% in incarcerated umbilical hernias.
The rate of emergency surgery in femoral and incisional hernias was found to be significantly higher than in inguinal hernias (P<0.05). Emergency surgery rates were compared in indirect inguinal, direct inguinal, and femoral hernias, and a significant difference was found among them (P<0.001).
Gender, age, hernia types (groin, non-groin, femoral, incisional, inguinal, direct, indirect), hernia sides, primary and recurrent emergency surgery rates are compared in Table 3.
In addition, the emergency surgery incidences of inguinal, femoral, incisional, umbilical and epigastric hernias, which are the anterior AWHs included in our study, were compared, and no statistically significant difference was found between them.
Discussion
Abdominal wall hernias (AWH) are the most common surgical diseases in the general surgery department [6]. AWH operations are generally performed in middle-aged patients and mostly in the male gender (53.5%) [7]. The mean age of our patients was 50±12.2 years and most of them were male patients (72%).
It has been reported that 5-13% of incarceration will be seen in anterior AWH and emergency surgery will be performed [8]. Bowel necrosis may develop in 10-15% of incarcerated patients and bowel resection can be performed urgently [9]. We performed emergency surgery for incarceration in 9.7% of anterior AWHs. Small bowel resection was performed in 18.7% of incarcerated cases, and this value was higher than the literature values.
According to the literature, emergency surgical procedures for incarcerated AWH were mostly applied to males. Eyvaz et al. reported that most of the emergency hernia cases (53%) were male [10]. In the study by Derici et al., 62.6% of the patients who underwent emergency surgery due to incarcerated AWH were males and 37.4% were females [11]. In our case, 53.1% of the patients who underwent emergency surgery were males and 46.8% were females. In addition, we found that the incidence of emergency surgery on the anterior AWHs was significantly higher in females (16.2%) than in males (7.2%) (P<0.001).
Emergency surgeries of the anterior AWH are usually performed on the elderly. Harissis et al reported that the mean age of their patients who underwent emergency surgery for AWHs was 66.5 years (range 25-95) [12]. Venara et al. found the mean age of emergency surgery to be 74 (range: 18-109) [13]. The mean age of our patients who underwent emergency surgery was below the literature values of 59.4 ±16.1 years.
Most incarcerated abdominal hernias (50-80%) are incarcerated groin hernias (IGH). Bowel resection is performed in approximately 15% of IGH patients due to necrosis [5]. The annual risk of strangulation in groin hernia is approximately 1-3% [14]. On the other hand, Chen et al. found that the rate of bowel resection in incarcerated groin hernias was 21%, and they performed most of the resections in the elderly and females [15]. We encountered that IGH constituted 68.7% of incarcerated AWHs and the small bowel resection rate was 13.6% in IGH. Small bowel resection rate in IGH was lower than the literature value. IGH surgeries account for 5% to 15% of groin hernia surgeries [13]. Emergency surgery due to incarceration rate was found to be 7.7% in groin hernias and 23.8% in non-groin hernias in this study. Emergency surgery incidence in non-groin hernias was significantly higher than in groin hernias (P<0.001).
10% of patients with inguinal hernia undergo emergency surgery due to incarceration. It is stated that the risk of strangulation in inguinal hernias is between 0.29% and 2.9% [16]. We found that the rate of emergency surgery due to incarceration in inguinal hernias was 6.1%, and small bowel resection was performed due to strangulation in 0.9% of inguinal hernias. Indirect inguinal hernias constitute the majority of incarcerated inguinal hernias (89%) [4]. Likewise, we encountered that incarceration was most common in indirect hernias (81.8%). Also, the incidence of emergency surgery in indirect hernias was significantly higher than in direct hernias (P=0.004).
Femoral hernias are not common and constitute a small portion (3-4%) of all hernias. It has been observed that strangulation develops in more than one-third of femoral hernias. In addition, it was reported that the rate of emergency surgical intervention in femoral hernias is higher than in other hernias [17]. In the study by Alimoglu et al. involving 83 patients with femoral hernia, 71.2% of the patients were females. They performed emergency surgery in 36 patients (40%) and resectioned 17 of these patients [18]. In addition, Chen et al. reported that the risk of emergency surgery and bowel resection is higher in femoral hernias than in other hernias [19]. In our study, femoral hernias accounted for 5.3% of all AWHs. Females constituted 77.1% of patients with femoral hernia. In femoral hernias, both the rate of emergency surgery (31.4%) and the rate of small bowel resection (2.8%) were lower than the literature values.
The incidence of incisional hernia worldwide is not known exactly [20]. Incarceration is encountered in 6-15% of incisional hernias [21]. Dietz et al. performed emergency surgery on 26 patients (6.5%) in a series of 401 incisional hernias. They performed bowel resection in seven patients (24.2%) who were operated on urgently [20]. In incisional hernias, our rate of emergency surgery (31.8%) was higher than the values found in the literature. At the same time, our rate of small bowel resection (9%) in incisional hernias was lower than in the literature.
Kulah et al. reported that they performed emergency surgery for 188 right-sided and 103 left-sided incarcerated inguinal hernias in their hernia series [22]. We performed emergency surgery for 27 incarcerated inguinal hernias on the right side and 13 on the left side. In our case, the rate of emergency surgery on the right side was 9.5% and on the left side was 7.6%. There was no significant difference between the right and left sides in terms of emergency surgery incidences (P=0.613).
In the study conducted by Bessa et al., eighteen (21.25%) of 80 patients who underwent emergency surgery for ventral incarceration had recurrent hernias [23]. Recurrent hernia was present in 27 (42.2%) of 64 patients who we performed emergency surgery for incarceration, and this result was higher than the literature value. Also, the rate of emergency surgery in patients with a recurrent hernia (27%) was significantly higher than in patients with a primary hernia (6.6%) (P<0.001) in this study.
In the light of literature findings, it is seen that femoral hernia is the most common anterior AWH in which emergency surgical intervention and bowel resection are performed [17-19]. However, we found that there was no statistically significant difference in the incidence of emergency surgery for all anterior AWH types in this study. This result we obtained contradicts the findings of the literature.
As stated in our study, many other results we obtained were also different from the literature values. We strongly believe that the difference between the results we obtained and the classical literature data may be due to the fact that this study was conducted during the SARS- COV 2 epidemic period and this epidemic affected the results.
The limitations of this study were that it was conducted during the SARS COV 2 epidemic, it was single-centered, and pediatric patients were not included in the study. Due to the prospective nature of the study, the fact that all the findings of the patients were obtained accurately and completely and this situation positively affected the results of the study constitutes the strength of the study.
Conclusion
The incidence of emergency surgery in anterior AWHs was found to be higher in females and in recurrent cases. Surgical emergencies incidence in non-groin hernias was significantly higher than in groin hernias. The femoral hernia had the highest incidence of emergency surgery in groin hernias and incisional hernia in non-groin hernias. There was no significant difference between the incidence of emergency surgery for all types of anterior AWHs.
In addition, according to our findings, it was concluded that the surgical priorities of inguinal, femoral, incisional, umbilical and epigastric hernias in the anterior abdominal wall are equal in elective conditions.
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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Turgay Karatas, Engin Burak Selcuk, Mehmet Karatas, Atilla Yildirim, Ibrahim Nuvit Tahtali, Ahmet Kadir Arslan. Incidence of emergency surgery in anterior abdominal wall hernias. Ann Clin Anal Med 2023;14(5):394-398
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Do body composition, hemogram and lipids differ between obese women with and without gonarthrosis?
Gökhan Peker 1, Dila Mete Peker 2, Rahman Köseoğlu 3, Orkun Gül 4
1 Department of Orthopaedics And Traumatology, University of Health Sciences, Trabzon Kanuni Education and Research Hospital, 2 Department of Internal Medicine, Trabzon Kanuni Education and Research Hospital, 3 Department of Internal Medicine, Trabzon Yıldızlı Medicalpark Hospital, 4 Department of Orthopaedics And Traumatology, Trabzon Yıldızlı Medicalpark Hospital, Trabzon, Turkey
DOI: 10.4328/ACAM.21540 Received: 2022-12-06 Accepted: 2023-01-20 Published Online: 2023-02-04 Printed: 2023-05-01 Ann Clin Anal Med 2023;14(5):399-403
Corresponding Author: Gökhan Peker, Department Of Orthopaedics And Traumatology, Trabzon Kanuni Education and Research Hospital, 61250, Yomra, Trabzon, Turkey. E-mail: drgokhanpeker@gmail.com P: +90 532 588 70 51 Corresponding Author ORCID ID: https://orcid.org/0000-0002-6211-6645
This study was approved by the Ethics Committee of University of Health Sciences, Trabzon Kanuni Education and Research Hospital (Date: 2020-12-23, No: 2020/84)
Aim: Knee osteoarthritis (KOA) is due to fat mass (FM) rather than lean mass (LM) in the body. In this study, we aimed to investigate differences in body composition in obese women with and without gonarthrosis; we also aimed to investigate serum inflammatory and lipid values between the groups.
Material and Methods: Ninety-six women were separated into gonarthrosis and control groups and retrospectively analyzed. Body composition analysis was performed by the TANITA device. The neutrophil/lymphocyte (NLR) and monocyte/lymphocyte (MLR) ratios, low-density (LDL-C) and high-density lipoprotein cholesterol (HDL-C) values, triglyceride (TG) values, and TG/HDL-C ratio of the two groups were compared.
Results: Body mass index, body and leg fat ratio, body fat mass (BFM) to body lean mass (BLM) ratio, leg fat mass (LFM) to leg lean mass (LLM) ratio were higher in the gonarthrosis group (p<0.001). BLM and LLM percent was higher in the control group (p<0.001). There was no significant difference in serum inflammatory and lipid values except for HDL-C.
Discussion: Both groups consisted of obese women. It was observed that while the rate of BFM and LFM was high in people with gonarthrosis, the rate of LM was low. This is the first study comparing the body composition of obese patients with and without gonarthrosis. The primary implication in this study is that weight reduction in individuals with obesity and gonarthrosis should primarily target adipose tissue.
Keywords: Gonarthrosis, Body Composition, Obesity, Women, Bioelectrical Impedance Analysis
Introduction
Although the incidence and treatment costs of knee osteoarthritis (KOA) are so high, however, ideal treatment methods for gonarthrosis have not been found yet [1]. Therefore, it is important to prevent causative factors. Age, gender, body weight, impaired lipid metabolism, adipose tissue inflammation and joint trauma may all play a role [2, 3].
The human body is composed of fatty mass (FM) and lean mass (LM) that includes muscle and bone, which can not be determined using body mass index (BMI) [3].
In the pathogenesis of KOA, the immune system is activated [4]. Neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR) may reflect the balance of the immune response [4].
We posited that persons with obesity and KOA may have dyslipidemia, higher inflammatory values like MLR and NLR, higher percentage of body fat mass (BFM) and higher leg fat mass (LFM), not lean mass (LM), than individuals without KOA. This study tested this hypothesis by identifying significant differences in body composition, serum lipid values, and complete blood count parameters comparing obese women with and without gonarthrosis.
Material and Methods
The study was a retrospective case-control study and was approved by the local Ethics Committee of the authors’ institution. Two hundred thirty-five patients admitted to the obesity center of the hospital between 2019 and 2020 were retrospectively investigated for the study. Informed consent was obtained from all participants.
Hemogram and lipid tests were routinely performed at the time of admission. Patients were classified according to the World Health Organization classification for obesity (Table 1).
Body composition parameters, including FM (kg) and LM (kg), were measured by the TANITA MC 780 MA segmental body composition analyzer, consisting of a weighing platform that performs bioelectrical impedance analysis (BIA) of a bare-footed standing person. Body composition differs by gender, with men having more LM and women having more FM [5]; thus the study included only women to eliminate gender differences. Ninety-six of 235 patients who had sufficient data on retrospective examination were included in the study. The body composition analyzer calculated body fat mass (BFM), leg fat mass (LFM), body lean mass (BLM), leg lean mass (LLM), body skeletal muscle mass (BSM), leg skeletal muscle mass (LSM) and percentages of FM and LM. These results were proportioned according to the load-capacity model to obtain BFM/BLM and LFM/LLM results [6]. Percentages (%) of BFM, LFM, BLM, LLM, LFM/BFM and LSM/BSM were calculated. The leg muscle mass index (LMMI) was established to measure relative muscle mass relative to body size by dividing leg muscle mass (kg) by the square of body length (m2) [7].
Patients with systemic pathology, including any inflammatory joint disease, infection, any chronic renal failure, a history of musculoskeletal trauma or surgery, and those who received corticosteroids, anti-inflammatory and lipid-lowering drugs were excluded from the study.
Patients were divided into two groups. Forty-eight obese patients who had stage 2 and higher osteoarthritis were included in the gonarthrosis group. Forty-eight patients with obesity without joint pain complaints and normal knee radiographs were included in the control group. In determining the stage of osteoarthritis, the Kellgren-Lawrence classification, which is the WHO standard for epidemiological studies, was used [8]. Patient radiographs were separately evaluated by two different orthopedists, each unaware of the other. In cases of conflict, a third was consulted.
Based on laboratory tests, the NLR, MLR, LDL-C, HDL-C, triglyceride (TG), TG/ HDL-C values were compared between the two groups.
The mean differences between the control (n = 48) and gonarthrosis (n = 48) groups were compared for the variables of interest. Before the comparison, the normality of groups was assessed with the Shapiro-Wilk test, and an independent sample t-test was used to compare the means for variables that were determined to be normally distributed (p<0.05, for Shapiro-Wilk). Afterward, the remaining variables (p>0.05, for Shapiro-Wilk) were tested with a non-parametric Mann-Whitney U test. Different stages of gonarthrosis, which are classified as control group (n=48), stage 2 (n=16), stage 3 (n=12), and stage 4 (n=20) were also compared for the same interested variables. Due to the small stage 3 sample size, these comparisons were used with the Kruskal-Wallis test. Finally, Dunn’s post hoc procedure was used for the pairwise comparison of each gonarthrosis stage using adjusted p-values. P-values less than 0.05 were considered statistically significant. The analysis was conducted in SPSS version 26.0, and figures were produced in an R package ggplot2.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
One hundred ninety-two legs of 96 patients were examined. In the gonarthrosis group, there were 16 patients with stage 2, 12 patients with stage 3 and 20 patients with stage 4 gonarthrosis patients. Gonarthrosis was bilateral in all patients. There was no difference in composition between the two legs in any of the patients. Each patient’s leg was randomly selected for composition analysis. The average age in the control group (42.65 ± 9.19) was less than in the gonarthrosis group (53.57 ± 8.60). The correlation between age (48.05 ± 10.42) and fat mass ratio (39.90 ± 4.58) was evaluated for all gonarthrosis and control group subjects. Pearson’s correlation test identified a weak relationship between variables (r = 0.216, p-value = 0.036). A strong relationship is not seen in the scatter plot (Figure 1).
BFM%, LFM%, BFM/BLM and LFM/LLM were significantly higher in the gonarthrosis group (p<0.001), while BLM% and LLM% were higher in the control group (p<0.001).
The Shapiro-Wilk test determined that groups of TG and TG/HDL variables were not normally distributed (p<0.01 for each group). Thus, the Mann-Whitney U test was applied to these two variables, and no significant difference was found for these variables (p=0.228 and p=0.970, respectively).
Comparison of disease stages
In Table 2, median values for each stage and p-values for the Kruskal-Wallis test are shown.
A significant difference was observed between the 4th stage gonarthrosis and control groups in terms of BFM% (p<0.01) and BLM% (p<0.01). A significant difference was observed between the 4th- stage and 2nd- stage gonarthrosis groups in terms of BFM% (p=0.028) and BLM% (p<0.01). A significant difference in terms of LLM% was determined between the 4th- stage group and all other groups (p<0.01 for all three). There was a significant difference in HDL cholesterol between the control group and the gonarthrosis group (p<0.01). Similarly, by examining the box graphs given in Figure 2, it can be observed that the difference generally occurs in the 4th stage (excluding HDL -C). No significant difference was found between the two groups in terms of serum LDL-C, TG values, NLR, MLR and TG-HDL-C ratio values (p>0.05), (Table 3).
Figure 2 presents comparisons between disease stages for the remaining variables.
Discussion
This is the first study to show a difference in body composition between obese women with and without gonarthrosis. Although most previous analyses have relied on data from studies with dual-energy X-ray absorptiometry (DEXA), this study differs in collecting data obtained by BIA and using a control group consisting of women with obesity. There are many studies showing that OA patients have higher weight and BMI than those without OA, with no clear information on whether this difference is due to FM or LM. The reason of this difference may shed light on methods of reducing excess weight, which is a cause of gonarthrosis. This study demonstrates that KOA is associated with high BFM and LFM ratio in women with obesity and determines the ratio of BLM and LLM to be higher in patients with obesity without gonarthrosis (Table 3). As the stage of osteoarthritis increased, a significant increase was observed in the ratio of body and leg fat.
It has been reported that individuals of the same age, height and weight may differ in body shape, composition and energy needs. It is recognized that body composition can independently affect health [9]. One classification of abnormal body composition phenotype as a load-capacity model [load being FM (fat mass) and capacity LM (lean mass)] was calculated as the ratio of FM/LM [6]. The load capacity model is also a method of determining the excess fat mass (FM) as well as low lean soft tissue (LST) in people with class II/III obesity [10]. In our study, according to the load capacity model, it was observed that women with gonarthrosis had greater metabolic load than the control group (p<0.001). According to this result, gonarthrosis adds a burden to the already increased metabolic load in obesity.
There are several body composition measurement methods exist, including BIA, quantitative magnetic resonance, air displacement plethysmography, DEXA, MRI, MR spectroscopy, PET/computed tomography, and PET/MRI [9]. Our study used a BIA. BIA devices are commonly used in clinical practice and research studies [9]. Compared to MRI and DXA, BIA is fast, cheap and there is no risk of radiation exposure. Recent developments in BIA technologies involve systems that incorporate multiple frequencies (MF-BIA) and multiple body segments. The TANITA BIA system achieves a valid measurement of body fat percentage in older adults and is convenient and practical for use in public health settings [11].
A study utilizing DXA whole-body scan (Hologic QDR-4500) found that women with KOA have a greater FM than non-OA individuals. Thus, the association between BMI and OA is mainly mediated by FM [3]. Lee et al. studied the ratio of leg to whole-body muscle mass and leg to whole-body fat mass and found them to be lower and higher, respectively, in the knee OA group. They used DXA to measure leg muscle mass and found a significant association with knee pain in people with radiographic KOA (rKOA). They reported that low leg muscle mass is a useful clinical indicator of symptomatic KOA, and that DXA is a potentially excellent tool for quickly assessing leg mass in patients with KOA [12]. Abbate et al. conducted a comparative study with DXA between female patients with rKOA and those without and found significantly higher mean BMI, weight, FM, percent FM, LM in women with rKOA. Compared with women without rKOA, women with rKOA had significantly lower mean percent LM [13]. Utilizing BIA, Sowers et al. found FM, LM and straight muscle mass (SMM) to be greater in women with KOA at rates of 41%, 11.5%, 10%. Women with KOA had lower SMM to FM ratios. Mean BMI was 24% greater in women with KOA. FM and SMM were associated with K&L KOA score [14]. Our study found no significant difference between the study and control groups in terms of the leg-to-body muscle mass and leg-to-body fat mass ratios. Our study did not include clinical findings such as pain and stiffness and our study’s measurements were made by the BIA method. As the ratio of BFM was high, the ratio of LM, including muscle mass, was low in osteoarthritis. Body fat was statistically significant in proportion to the stage of the disease, and an inverse relationship was found regarding the percentage of LM. While the BMI in the gonarthrosis group was significantly higher than in the control group, our study observed that it increased in parallel with the gonarthrosis stage (Table 2).
A high BMI has been associated with increased odds ratios of KOA (2.81) and hand OA (2.59), but not hip (1.11)[15]. These findings suggest that OA is not just caused by overload. Recent studies have suggested that adipose tissue inflammation and lipid metabolism disruption play important roles in obesity-related OA [16, 17]. Dyslipidemia in obesity is characterized by high plasma levels of TGs and free fatty acids (FFAs), low levels of HDL-C with HDL dysfunction, and normal or slightly increased levels of LDL-C [18]. Disturbances in HDL metabolism, together with a different factor, can cause problems in cartilage homeostasis [16]. HDL-C has different effects, such as inhibiting inflammation in the absence of an acute phase response (APR), but increasing inflammation in the presence of an APR [19]. Although it has been reported that HDL-C values mostly decrease with inflammation and gonarthrosis, there are also publications showing the opposite [20-22]. We found HDL-C values to be higher in gonarthrosis patients in our study (p<0.05).
Adipose tissue inflammation is also seen as a characteristic feature in obesity, as cytokines, which are secreted from adipocytes and immune cells cause low-grade inflammation. In addition to systemic cytokine production, the infrapatellar fat pad produces cytokines [15]. MLR and NLR were also studied in KOA patients, who exhibited a significant increase compared to the control group. It has been reported that MLR has a high diagnostic value [4]. We also analyzed these values in our study but found no significant difference between the two groups.
Conclusion
Our BIA-based body composition analysis of patients with obesity and knee osteoarthritis included only female patients, yielding a simpler comparison opportunity in our study. When comparing two obese groups, patients with gonarthrosis were found to have a higher percentage of BFM and LFM and lower LM. There was no significant difference between the two groups in serum inflammatory and lipid values except HDL-C. The primary implication in this study is that weight reduction in individuals with obesity and gonarthrosis should primarily target adipose tissue. Our study is the first to include persons with obesity as a control group in the investigation of body composition in osteoarthritis and we believe it will shed light on new studies. Prospective studies with larger sample sizes 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.
References
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2. Godziuk K, Prado CM, Woodhouse LJ, Forhan M. The impact of sarcopenic obesity on knee and hip osteoarthritis: a scoping review. BMC Musculoskelet Disord. 2018; 19(1):271.
3. Ho-Pham LT, Lai TQ, Mai LD, Doan MC, Nguyen TV. Body Composition in Individuals with Asymptomatic Osteoarthritis of the Knee. Calcif Tissue Int. 2016; 98:165-71.
4. Gao K, Zhu W, Liu W, Ma D, Li H, Yu W, et al. Diagnostic value of the blood monocyte-lymphocyte ratio in knee osteoarthritis. J Int Med Res. 2019; 47(9):4413-21.
5. Bredella MA. Sex Differences in Body Composition. Adv Exp Med Biol. 2017; 1043:9-27.
6. Siervo M, Prado CM, Mire E, Broyles S, Wells JC, Heymsfield S, et al. Body composition indices of a load-capacity model: gender- and BMI-specific reference curves. Public Health Nutr. 2015; 18(7):1245-54.
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10. Johnson Stoklossa CA, Sharma AM, Forhan M, Siervo M, Padwal RS, Prado CM. Prevalence of Sarcopenic Obesity in Adults with Class II/III Obesity Using Different Diagnostic Criteria. J Nutr Metab. 2017; 2017:7307618.
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15. Grotle M, Hagen KB, Natvig B, Dahl FA, Kvien TK: Obesity and osteoarthritis in knee, hip and/or hand: an epidemiological study in the general population with 10 years follow-up. BMC Musculoskelet Disord. 2008; 9:132.
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22. Welty FK: How do elevated triglycerides and low HDL-cholesterol affect inflammation and atherothrombosis? Curr Cardiol Rep. 2013; 15(9):400.
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Gökhan Peker, Dila Mete Peker, Rahman Köseoğlu, Orkun Gül. Do body composition, hemogram and lipids differ between obese women with and without gonarthrosis? Ann Clin Anal Med 2023;14(5):399-403
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Texture analysis of pharynx in chronic phase Epstein-Barr virus infection
Murat Baykara, Okan Yaman
Department of Radiology, Faculty of Medicine, Fırat University, Elazığ, Turkey
DOI: 10.4328/ACAM.21551 Received: 2022-12-14 Accepted: 2023-03-20 Published Online: 2023-03-27 Printed: 2023-05-01 Ann Clin Anal Med 2023;14(5):404-408
Corresponding Author: Murat Baykara, Department of Radiology, Faculty of Medicine, Fırat University, 23119, Elazığ, Turkey. E-mail: muratbaykara@hotmail.com P: +90 532 771 20 88 Corresponding Author ORCID ID: https://orcid.org/0000-0003-2588-9013
This study was approved by the Non-Interventional Research Ethics Committee of Firat University (Date: 2021-11-18, No: 2021/12-03)
Aim: Epstein-Barr virus (EBV) is a human herpes virus that can be found worldwide and causes latent infections. EBV is responsible for the etiology of infectious mononucleosis, Burkitt’s lymphoma, and nasopharyngeal carcinoma (NPC) through the transformation of infected cells. In this study, it was aimed to investigate nasopharyngeal soft tissue differentiation by texture analysis in neck computed tomography (CT) images of EBV-positive individuals.
Material and Methods: EBV-positive and negative healthy individuals of the same age and gender were selected consecutively from HIS and their neck CT images were evaluated with texture analysis.
Results: While there was no significant difference between the groups in any of the same tissue parameters investigated for the largest lymph node in the neck, it was observed that only a small fraction of the 224 tissue parameters analyzed for each of the largest lymph node at the right neck IIA level, pharynx, and nasopharynx were statistically significant.
Discussion: Despite some limitations, texture changes on CT in chronic EBV infection may lead to the identification of imaging markers that predict individuals at high risk of NPC.
Keywords: Human Herpesvirus 4, Epstein-Barr Virus Infections, Computerized Tomography, Computer-Assisted Image Processing, Nasopharyngeal Carcinoma
Introduction
Epstein-Barr virus (EBV) is a human herpes virus that can be found worldwide, causing lytic and latent infections and transformation of infected cells [1]. Serological and nucleic acid hybridization methods have shown that EBV is responsible for the etiology of infectious mononucleosis (IM), Burkitt’s lymphoma (BL), and nasopharyngeal carcinoma (NPC). The virus has two target cell types, these are B lymphocytes and epithelial cells. The virus replicates in vivo in the lymphoid and nasopharyngeal tissue epithelium [2-4]. EBV, which can be found in the saliva of 10-20% of normal people, is transmitted by close contact (kissing disease) and enters the body through the oropharyngeal mucosa. EBV first infects the epithelial cells of the oropharynx and salivary glands, and then the lymphoid tissues of the larynx. Heterophile antibodies to EBV infection, usually subclinical, are found in 90% of people over the age of four, regardless of gender. IM is common worldwide and usually occurs in the 15-20 age group, while BL is more common in children from Central Africa and New Guinea, and NPC is more common in males living in South East Asia. Serology and virus isolation can be used for diagnosis. There is no specific treatment for EBV infection [5-7].
The contents of the pharyngeal soft tissue include the mucosa of the nasopharynx and oropharynx, as well as the submucosal structures surrounding Waldeyer’s ring, minor salivary glands (MSG), pharyngeal constrictor and levator veli palatini muscles, and the torus tubarius. The Waldeyer ring includes the adenoids, palatine, and lingual tonsils, and the ring-like configuration of lymphoid tissue can be considered as a mechanism that protects the body from inhaled and ingested antigens. Tonsil crypts lined with deep mucosa cause a characteristic striated appearance on contrast imaging and may obscure small primary tumors [8-10]. Squamous cell carcinoma originating from the mucosa represents the most common malignant neoplasm in pharyngeal cavity. Tumors originating from Waldeyer ring lymphoid tissue and MSG are extremely rare. Inflammatory disease of the oropharynx represents a spectrum from non-focal tonsillitis to tonsilar or peritonsillar abscess. Congenital lesions include nasopharyngeal Tornwaldt cysts and those related to the embryological thyroglossal duct, including cysts and lingual thyroid [8, 11-13].
Texture analysis, which is frequently used to identify various biomarkers and characterize tumors and can distinguish between normal and abnormal structures, requires calculating the intensities in the region of interest (ROI) from all pixels using a full statistical analysis [14-17].
In this study, it was aimed to investigate whether the pharyngeal soft tissue differentiates by texture analysis of the neck computerized tomography (CT) images of EBV-positive (case) and negative (control) healthy individuals.
Material and Methods
The entire study was performed in accordance with the 1983 revised version of the 1975 Declaration of Helsinki. Local Ethics Committee approval was obtained (Session Date: 18 November 2021, Issue: 2021/12-03).
Study population
Cases who underwent serological EBV test in the last five years from the University Hospital Information System (HIS) were scanned and 50 cases with neck CT images in the Hospital Picture Archiving and Communication System (PACS) were included in the study. EBV- positive (case group) and negative (control group) healthy individuals of the same age and gender were selected consecutively using HIS and PACS. The cases whose CT image quality was found to be visually low by a 20-year-experienced radiologist (M.B.) were excluded from the study.
Data acquisition and analysis
Real-time polymerase chain reaction (RT-PCR), high sensitivity optimized for diagnostic use, and highly specific QIAGEN artus EBV PCR developed for use with QIAsymphony® SP/AS and Rotor-Gene® Q (QIAGEN GmbH, Hilden, Germany) instruments kits (QS-RGQ Kit) were administered to the subjects using the methods described in the literature [18].
Computerized tomography images were obtained from the 128-slice GE Revolution HD system (General Electric, Milwaukee, WI, USA) installed in the hospital radiology department. Images were transferred from the PACS to a separate storage medium in DICOM (Digital Imaging and Communications in Medicine) image format. Then the images were transferred to a Windows 10 (Microsoft Corporation, Seattle, WA, USA) based computer and processed to obtain the final data. The entire analysis algorithm applied to all selected images was done with an in-house software coded in MATLAB (version R2021b; MathWorks, Natick, MA, USA).
All regions of the pharynx, nasopharynx, and largest in neck and largest in right level IIA lymph nodes were selected individually in the axial images that best represent the anatomy, without exceeding their borders, with an ROI determined by a senior radiologist (M.B.).
Histogram, co-occurrence matrix with all neighbor levels from one to five and run-length matrix values obtained from ROIs have been previously described in the literature [14, 19-21].
Statistical analysis
Data were presented as mean ± standard deviation. The statistical analyses were conducted with IBM SPSS (for Windows version 26, IBM Corporation, Armonk, New York, USA) statistics software. The normality of the distribution of the data was analyzed with the Kolmogorov–Smirnov test. Based on the test findings, Student’s t-test and Mann-Whitney U test were used to compare the groups. p<0.05 was accepted as statistically significant.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
There was no statistically significant difference in terms of gender (p=0.614) and age (p=0.878) between the groups consisting of eight EBV-positive case groups of four people of each gender (mean age, 53.75±16.98 years) and the control group consisting of five females and three males (mean age, 52.88±14.36 years).
It was observed that only a small portion of the 224 texture parameters analyzed for each of the pharynx, nasopharynx, and the largest lymph node at the right neck IIA level were statistically significant (p<0.05) (Table 1-3). There was no significant difference between groups in any of the same texture parameters investigated for the largest lymph node in the neck (p>0.05).
Discussion
Most nasopharyngeal carcinomas (NPC) detected in endemic areas of the world such as southern China, as well as in many non-endemic regions of the world, are undifferentiated carcinomas due to EBV infection. EBV-based markers can be found in blood as well as histological samples of NPC and are used to screen patients. Despite the high EBV-DNA specificity of the population, most patients referred for endoscopic examinations do not have NPC [22, 23].
While plasma EBV-DNA levels remain consistently high in chronic/occult infections, it has been reported that they return to normal after approximately 200 days at the latest in acute EBV-related diseases. The putative potential link between EBV infection and NPC development may provide an imaging marker for the future when CT texture analysis is used [24, 25].
In this study, all eight participants in the case group were still positive for plasma EBV-DNA 2 years after initial infection. It is interesting that EBV-DNA positive participants have different texture characteristics on CT examination than normal ones. Although it is an expected finding to see that EBV infection affects tissue with nasopharyngeal soft tissue involvement, it can be said that the inhomogeneity caused by complex anatomical structures that prevent more tissue parameters from forming differently cannot be excluded with CT. In addition, although the level 2A lymph node shows EBV-related tissue differences, the largest lymph node in the neck does not show this relationship. It can be said that EBV infection takes place in the adjacent lymphatic system in addition to nasopharyngeal soft tissue involvement and is limited. In this context, since latent EBV infection plays a role in NPC oncogenesis, texture analysis findings may be a biomarker to pre-identify individuals at risk of developing NPC.
Limitations
The present study had a few limitations. First, the number of cases is very small in order to provide sufficient evidence. Then, other potential factors such as air pollutants and other irritant infections that may be important in the heterogeneity of soft tissues were not analyzed. Third, the pharynx and nasopharynx consist of a large number of tissues that are indistinguishable on CT, making it difficult to obtain a homogeneous texture. Finally, the absence of similar previous studies eliminated the possibility of any comparison.
Conclusion
In the presence of positive plasma EBV-DNA, the presence of texture difference on CT may be an independent predictive factor for NPC. However, these are only preliminary results, this potential link between EBV infection and texture on CT deserves further investigation as it may lead to the identification of imaging markers that predict individuals at high risk of NPC.
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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5. Edwards RH, Raab-Traub N. Major Role for Cellular MicroRNAs, Long Noncoding RNAs (lncRNAs), and the Epstein-Barr Virus-Encoded BART lncRNA during Tumor Growth In Vivo. mBio. 2022; 13(3): e0065522.
6. Stanjek-Cichoracka A, Laszewska A, Wozniak-Grygiel E, Necki M, Latos M, Zawadzki F, et al. Assessment of the Serologic Status in Epstein-Barr Virus in Patients Qualified for Lung Transplantation in the First Half of 2021. Transplant Proc. 2022;54(4):1124-6.
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Murat Baykara, Okan Yaman. Texture analysis of pharynx in chronic phase epstein-barr virus infection. Ann Clin Anal Med 2023;14(5):404-408
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Is COVID-19 a risk for postoperative delirium and death in elderly patients after emergency surgery?
Fadime Çınar
Department of Nursing, Faculty of Health Sciences, Nişantaşı University, Istanbul, Turkey
DOI: 10.4328/ACAM.21552 Received: 2022-12-15 Accepted: 2023-02-21 Published Online: 2023-02-27 Printed: 2023-05-01 Ann Clin Anal Med 2023;14(5):409-413
Corresponding Author: Fadime Çınar, Department of Nursing, Nişantaşı University, Istanbul, Turkey. E-mail: fadime.cinar@nisantasi.edu.tr P: +90 542 392 99 03 Corresponding Author ORCID ID: https://orcid.org/0000-0002-9017-4105
This study was approved by the Ethics Committee of Foundation University (Date: 11-01-2021, No: E-20292139-050.01.04-424)
Aim: While recent evidence describes atypical outcomes of coronavirus disease 2019 (COVID-19) in elderly patients, the frequency of delirium and associated outcomes in elderly patients with COVID-19 (coronavirus disease 2019) infection undergoing emergency surgery are not well defined. This study aims to determine the effect of COVID-19 on postoperative delirium and postoperative death in elderly patients undergoing emergency surgery.
Material and Methods: This descriptive and cross-sectional study was conducted in general surgery, orthopedics, and cardiovascular surgery clinics of a public hospital, including 30 days of follow-up between April 1 and May 1, 2021. All patients who were admitted to these clinics for emergency surgery intervention on these dates constituted the study population, while a total of 140 patients aged ≥65 years, who met the study criteria, formed the sample of the study. Descriptive Characteristics Form and Nursing Delirium Screening Scale (Nu-DESC) were used as data collection tools in the study. SPSS 25.0 statistical program was used for data analysis.
Results: Thirty (42.85%) of the SARS-CoV-2 positive (n=70) patients developed delirium in the study. 12.9% (n=18) of the patients died within 30 days of follow-up after surgery. There were 30 (69.8) of 70 SARS-CoV-2 positive patients who developed delirium, and 12 patients (25.5) died after testing positive for COVID-19, with a mean of 8.08Ŧ1.56 days within 30 days of admission.
Discussion: These findings may lead to a poor clinical prognosis for COVID-19 infection delirium and postoperative death in patients over 65 years of age undergoing emergency surgery.
Keywords: COVID-19 Pandemic, Postoperative Delirium, Old Age, Risk Factors
Introduction
While the most common and life-threatening complication of coronavirus disease 2019 (COVID-19) is a respiratory complication, there are increasing reports of neurological and psychiatric involvement [1]. Delirium may be a symptom of many diseases, especially in frail and elderly patients, and is considered an independent risk factor for mortality [2]. The overall prevalence of delirium in the hospital setting is approximately 14-24%; it is approximately 30% higher in emergency room surgeries or medical services [3]. To date, clinical manifestations of delirium in elderly patients with COVID-19 have rarely been described; however, few studies have analyzed the clinical aspects of delirium in COVID-19. Some studies have focused on epidemiological data and outcomes [4]. Delirium is one of the most common neurological disorders, and if it is not recognized and treated when surgical intervention is required, it increases morbidity and mortality [5].
COVID-19 contributes to delirium through several brain pathways [6]. Significant contributors include cytokine storms and immune dysregulation accompanying COVID-19, which trigger neuroinflammation (in the brain and meninges) and hypercoagulability. The hypercoagulable state contributes to cerebral infarction in 1% to 3% of hospitalized patients with COVID-19, more often from large than small-vessel involvement [7]. This study involving 214 patients diagnosed with COVID-19 showed that 45% of conscious patients had neurological symptoms, and some of them had some symptoms indicating impaired consciousness [8]. In patients with COVID-19, delirium may develop due to factors such as direct central nervous system (CNS) involvement, induction of CNS inflammatory mediators, the secondary effect of other organ system failure, the effect of sedative strategies, prolonged mechanical ventilation time, or social isolation [6]. Notably, delirium occurring during COVID-19 may also be a sign of prodromal infection or hypoxia associated with severe respiratory failure [9]. Acute infections, respiratory diseases, pneumonia, acute lung disease, and surgical interventions are factors that cause delirium in the elderly, and cognitive changes may develop in these patients. Delirium after surgical intervention is an independent predictor of higher mortality, higher treatment costs, and more extended treatment and hospitalization [10]. After surgical intervention, the systemic inflammatory process is activated leading to the release of cytokines and neurotransmitters. Cytokines initiate microglial activation, increasing the permeability of the blood-brain barrier to neurotoxins and leading to cognitive impairment [11].
Understanding the epidemiological features of delirium and COVID-19 is an urgent research priority, especially in older people, where age increases the risk of developing delirium and COVID-19-related death. Recently, the volume of published literature on delirium in patients with COVID-19 has increased. Therefore, a comprehensive synthesis of existing evidence investigating the prevalence, incidence, and mortality of delirium in COVID-19 patients is necessary to inform clinical care and public health policies. In this study, we aimed to identify mortality differences between COVID-19 patients with and without delirium.
Material and Methods
This study was initiated after obtaining permission from the Ethics Committee of a Foundation University (Decision no:11-01-2021/E-20292139-050.01.04-424) and the head physician of the public hospital, where the research was conducted in terms of the feasibility of the research. This descriptive study was conducted at the Orthopedics, Cardiovascular, and General Surgery Clinics of a Public Hospital in Istanbul between April and May 2021. In this study, patients were evaluated for delirium for an average of 3 days after emergency surgery. In this study, patients who continued to be treated in the hospital for at least seven days after surgical intervention were evaluated for delirium for three days. The study population consisted of patients aged ≥ 65 years who were hospitalized for emergency surgical intervention at the institution where the study was conducted, who voluntarily agreed to participate in the study, and whose verbal and written consent was obtained. While some of these patients had a positive preoperative COVID-19 test, others had a positive post-intervention COVID-19 test. This study included 140 patients who met the inclusion criteria without selecting a sample. To eliminate the effect of confounding factors, 70 patients over 65 years of age who underwent emergency surgery and had a negative test were included in the study as the control group, and 70 patients with a positive test (Figure 1). Four patients were excluded from the study because they were transferred to the preoperative intensive care unit due to respiratory problems.
In this study, the “Descriptive Characteristics Form” and “Nursing Delirium Screening Scale (Nu-DESC)” were used as data collection tools. The Nursing Delirium Screening Scale (NU-DESC) was used to screen for post-surgical delirium. This scale was described by Gaudreau et al. (2005) and consists of five items: disorientation, inappropriate behavior, inappropriate communication, illusion-hallucination, and psychomotor slowing [12]. Patients were identified as COVID-19 positive if presented positive swab test confirming SARS-CoV-2 infection. To determine post-surgical delirium, the “Nurse Delirium Screening Scale” was performed 1-3 days after surgery, and delirium screening was performed three times a day between 08-16, 16-24, 24-08 hours. According to the symptoms appearing at these time intervals, a neurologist’s consultation was requested to diagnose delirium, which was recorded. Clinical physicians and nurses were informed about the initiation of necessary interventions for patients diagnosed with delirium. Delirium was indicated by a total of ≥2 points.
Data analysis
The data were analyzed using the Statistical Package for Social Sciences version 25.0 software for Windows. The Kolmogorov-Smirnov and Shapiro-Wilk tests, Fisher’s precision test, the Mann-Whitney-U test, and Student’s t-test for independent groups were used in the analysis. The Kaplan-Meier analysis was used to calculate the probability of survival. Statistical significance was set at p ≤ 0.001 and p ≤ 0.05, respectively.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
A total of 140 patients, 84 (60 %) men and 56 (40 %) women were included in the study. While delirium developed in 33.6% of the patients (n=47), it did not develop in 66.4% (n=93). Thirty (42.85%) of the SARS-CoV-2-positive (n=70) patients developed delirium. There were 140 patients who got tested, and 70 (50%) were positive for SARS-CoV-2 and 13 (5 9.3) of these patients were positive before surgery. They died within 30 days of follow-up after surgery, which accounted for 12.85% of the patients (n=18). There were 30 (69.8%) of 70 SARS-CoV-2-positive patients who developed delirium, and 12 patients (25.5%) died after testing positive for COVID-19, with a mean of 8.08Ŧ1.56 days within 30 days of admission. Peri-operative risk factors were compared according to the development of delirium in the patients included in the study (Table 1). There was a significant difference (p<0.05) between patients with and without delirium. Baseline characteristics and comparison of perioperative risk factors in COVID-19 patients with and without delirium are presented in Table 1.
There was a significant difference (p<0.05) between patients with and without delirium. Comparison of perioperative risk factors in COVID-19 patients with and without delirium is presented in Table 2.
The results of the logistic regression analysis are presented in Table 3.
A survival probability assessment in delirious and non-delirious
COVID-19 patients was performed using the Kaplan-Meier curve (Figure 2). There was a statistically significant difference in the 30-day survival between the two groups, which was in favor of patients without delirium (p <0.001).
Discussion
In this study, 30 (69.8%) of the SARS-CoV-2 positive (n=70) patients developed delirium, and 12 (25.5%) of these patients developed death with a mean of 8.08±1.56 days within 30 days of admission. Patients who were SARS-CoV-2 positive before or after surgery and who developed delirium had a significantly lower survival rate than those without a proven infection. In addition, in COVID-19 patients, delirium was three times higher (95% CI: 1.52-7.07) when the patients were COVID-19 positive.
Postoperative death was 4.9 times (95% CI: 1.73-14.28%) higher than in those without delirium. In the meta-analysis study, the prevalence, incidence, and mortality from delirium in COVID-19 patients were 24.3% (95% CI: 19.4-29.6%), 32.4% (95% CI: 20.8-45.2%), and 44.5% (95% CI: 36.1-53.0%), respectively. In addition, mortality in COVID-19 patients with delirium increased 3-fold than in those without delirium [5]. Mounting evidence supports the high occurrence of delirium and other neuropsychiatric manifestations of COVID-19 [13,14]. A recent study reported delirium as a common presenting symptom in older adults without any other typical COVID 19 symptoms [15]. The literature supports the results of this study. In our study, in COVID-19 patients with delirium, mortality was 4.9 times higher than in those without delirium. The pathophysiology of this excess mortality in COVID-19 patients with delirium is likely to be multifactorial, but it is suggested that brain involvement in COVID-19, rather than worsening of pre-existing comorbidities, is responsible [16].
According to the results of multivariate logistic regression analysis, it was determined that delirium developed 3.2 times more in those with positive COVID-19 status, which was the starting point of the study, compared to those with negative COVID-19 status. The odds of mortality in COVID-19 patients presenting with delirium at any point of hospitalization was 17 times higher [17]. This study determined that chronic diseases
were risk factors for the development of both COVID-19 and delirium and contribute to the development of delirium, which is consistent with the literature. Older people usually also have other co-morbidities that induce chronic inflammatory states, such as hypertension, obesity, and diabetes mellitus, which contribute to the development of severe COVID-19 by activating RAS, which then activates the angiotensin II type 1 receptor and produces pro-inflammatory cytokines, vasoconstriction, fibrosis, thrombosis, and reactive oxygen species (ROS). Moreover, older patients have a reduced expression of ACE2 and therefore a reduced capacity to produce vasodilators, anti-inflammatory, anti-fibrosis, anti-thrombosis, and ROS neutralizer [18]. These conditions likely contribute to the development of poor outcomes from COVID-19 in older patients who present with delirium symptoms. It should also be noted that delirium occurring during COVID-19 may be a manifestation of a prodromal infection or hypoxia associated with severe respiratory failure [11]. The results of this study were similar to those reported in the literature.
Conclusion
In elderly patients undergoing emergency surgery for severe SARS-CoV-2 infection, delirium is an early sign of deterioration of homeostasis; therefore, it should be monitored and prevented to avoid increased mortality. Elderly people are the most vulnerable to severe COVID-19 infection and mortality rates. The current diagnostic guideline for COVID, does not routinely exclude delirium, leading to an under-detection of COVID-19. The addition of delirium as a common symptom of COVID-19 would avoid missing important cases and allow earlier identification and management of vulnerable patients at a high risk for poor outcomes. Identifying risk factors in seeing, recognizing, and monitoring the process can guide preventive interventions. Therefore, it is recommended to focus on delirium-prone patients based on these risk factors when designing future delirium prevention strategies or etiological studies.
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. Leonardi M, Padovani A, McArthur JC. Neurological manifestations associated with COVID-19: a review and a call for action. J Neurol. 2020;267(6):1573-76.
2. Persico I, Cesari M, Morandi A. Frailty and Delirium in Older Adults: A Systematic Review and Meta-Analysis of the Literature. J Am Geriatr Soc. 2018;66(10):2022-30.
3. Morandi A, Di Santo SG, Zambon A, Mazzone A, Cherubini A, Mossello E, et al. Delirium, dementia, and in-hospital mortality: the results from the Italian Delirium Day 2016 a national multicenter study. The Journals of Gerontology: Series A. 2019; 74(6):910-16.
4. Alkeridy WA, Almaghlouth I, Alrashed R. A. Unique Presentation of Delirium in a Patient with Otherwise, Asymptomatic COVID-19. J Am Geriatr Soc.2020;68(7):1382-84.
5. Shao SC, Lai CC, Chen YH, Chen YC, Hung MJ, Liao SC. Prevalence, incidence and mortality of delirium in patients with COVID-19: a systematic review and meta-analysis. Age Ageing. 2021; 50(5):1445-53.
6. Kotfis K, Roberson SW, Wilson JE. COVID-19: ICU delirium management during SARS-CoV-2 pandemic. Crit Care. 2020;24(1):176.
7. Inouye SK. The Importance of Delirium and Delirium Prevention in Older Adults During Lockdowns. JAMA. 2021;325(17):1779-80.
8. Mao L, Jin H, Wang M, Hu Y, Chen S, He Q, Hu B. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol. 2020;77(6): 683-90.
9. Girard TD, Thompson JL, Pandharipande PP, Brummel NE, Jackson JC, Patel M. B, et al.
Clinical phenotypes of delirium during critical illness and severity of subsequent long-term cognitive impairment: a prospective cohort study. The Lancet Respiratory Medicine. 2018;6(3):213-22.
10. Ahmad I, Rathore FA. Neurological manifestations and complications of COVID-19: A literature review. JOCN. 2020;77: 8-12.
11. Hayhurst CJ, Patel MB, McNeil JB, Girard TD, Brummel NE, Thompson JL, et a. Association of neuronal repair biomarkers with delirium among survivors of critical illness. J Crit Care. 2020; 56: 94-99.
12. Çınar F, Aslan, FE. Evaluation of postoperative delirium: validity and reliability of the nursing delirium screening scale in the Turkish language. Dement Geriatr Cogn Disord Extra. 2019; 9(3):362-73.
13. Helms J, Kremer S, Merdji H, Clere-Jehl R, Schenck M, Kummerlen C, et al. Neurologic features in severe SARS-CoV-2 infection. New England Journal of Medicine. 2020;382(23): 2268-70.
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16. Mcloughlin BC, Miles A, Webb TE, Knopp P, Eyres C, Fabbri A, et al. Functional and cognitive outcomes after COVID-19 delirium. Eur Geriatr Med. 2020; 11(5): 857-62.
17. Kotfis K, Witkiewicz W, Szylińska A, Witkiewicz K, Nalewajska M, Feret W, et al. Delirium Severely Worsens Outcome in Patients with COVID-19—A Retrospective Cohort Study from Temporary Critical Care Hospitals. J Clin Med. 2021;10(13): 2974.
18. Czick M, Shapter C, Shapter R. COVID’s Razor: RAS Imbalance, the Common Denominator Across Disparate, Unexpected Aspects of COVID-19. Diabetes Metab Syndr Obes. 2020; 13: 3169.
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Fadime Çınar. Is COVID-19 a risk for postoperative delirium and death in elderly patients after emergency surgery? Ann Clin Anal Med 2023;14(5):409-413
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Turkey-based COVID-19 publications in pediatrics: A bibliographic analysis
Fatma Sargın
Department of Pediatrics, Konya Beyhekim Training and Research Hospital, Konya, Turkey
DOI: 10.4328/ACAM.21555 Received: 2022-12-19 Accepted: 2023-02-02 Published Online: 2023-02-09 Printed: 2023-05-01 Ann Clin Anal Med 2023;14(5):414-417
Corresponding Author: Fatma Sargın, Department of Pediatrics, Konya Beyhekim Training and Research Hospital, Konya, Turkey. E-mail: fatmasargin@yahoo.com.tr P: +90 533 726 32 29 Corresponding Author ORCID ID: https://orcid.org/0000-0002-4514-1857
Aim: The aim of this research is to analyze the pediatric COVID-19 literature published in Turkey and to guide future research.
Material and Methods: Between 11.03.2010 and 11.12.2022, the Web of Science (WoS) All Databases collection was searched for publications related to COVID-19 and pediatric patients. The keywords used during this search were coronavirus-19, COVID-19, SARS-CoV-2, novel coronavirus, 2019-nCoV, pandemic, and/or pediatric, pediatric, children, child. After this search, the selected publications were scanned one by one to determine whether they were suitable for the present study. Authors, organizations, journals, document types, distribution of publications by years (months), most used keywords were obtained from the Web of Science (WoS) All Databases collection. Descriptive analyzes were made from all these obtained data.
Results: The number of COVID-19 publications originating from Turkey in the field of pediatrics was determined as 375. 48.2% of all publications were published in 2022. These 375 publications were published in 167 different journals. In these publications, the most active author, journal and organization were Yasemin Ozsurekci, Turkish Archives of Pediatrics and University of Health Sciences, Turkey, respectively. The most commonly used keywords were ‘’child, patient, pandemic, SARS-CoV and vaccine. The most active document types were research articles (295 (78.6%)), editorial materials (15 (4.0%)), letters (43 (11.5%)) and review articles (22 (5.9%)).
Discussion: We analyzed all articles about COVID-19 from Turkey in the field of pediatrics published so far in the WoS Databases collection. It is obvious that a large literature has emerged in our country on pediatric patients, although not as much as in adults. The long-term adverse effects of the pandemic on pediatric practice and especially on children will need to be evaluated in more detail in future research.
Keywords: COVID-19, Pediatric, Turkey
Introduction
On December 30, 2019, a series of pneumonia cases of unknown origin were reported in Wuhan, Hubei province of China [1]. The virus isolated on January 7, 2020 was found to be the new coronavirus (2019-nCoV / SARS-CoV-2) [2]. On March 11, 2020, the World Health Organization (WHO) declared COVID-19 a pandemic (available at: https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200311-sitrep-51-covid-19.pdf?sfvrsn=1ba62e57_10). The detection of the first COVID-19 case in Turkey coincided with March 11, 2020. With 144,099,374 confirmed cases and 3,061,912 deaths worldwide, COVID-19 affected 223 countries (available at: https://www.who.int/emergencies/diseases/novel-coronavirus-2019).
Children are less likely to be infected with SARS-CoV-2 than adults, and most pediatric cases are asymptomatic or clinically mild [3]. In children with COVID-19, supportive treatment is usually sufficient and hospitalization is often not required [6]. In pediatric patients, COVID-19 typically presents with mild symptoms such as cough, fever, sore throat and diarrhea. However, severe clinical symptoms such as hyperinflammatory syndrome, increased severity of childhood-onset type 1 diabetes, and multisystem inflammatory syndrome can be seen in some children, especially those with underlying diseases [5-8]. Although COVID-19 vaccines have been determined to be safe for adults, trials are ongoing to determine whether they are safe for children.
This pandemic has sparked a flood of medical literature on various aspects of COVID-19. There are more than 100,000 articles on PubMed about COVID-19. As in all categories, new articles continue to be published every day in all areas of pediatrics. In the present study, we aimed to analyze publications related to pediatric COVID-19 originating from Turkey with a bibliometric perspective and for guiding future research.
Material and Methods
The present study is a bibliometric citation analysis study. The WoS All Databases collection (Philadelphia, Pennsylvania, USA) was used in this bibliometric citation study. Between 11.03.2010 and 11.12.2022, the Web of Science (WoS) All Databases collection was searched for publications related to COVID-19 and pediatric patients. The keywords used during this search were coronavirus-19, COVID-19, SARS-CoV-2, novel coronavirus, 2019-nCoV, pandemic, and/or paediatric, pediatric, children, child. These keywords were scanned in the title, abstract and keywords in the Web of Science (WoS) All Databases collection in order to identify relevant publications. After this search, the selected publications were scanned one by one to determine whether they were suitable for the present study. Publications not related to pediatric COVID-19 were excluded from the study. Articles co-authored by Turkish and non-Turkish authors were included in the present study if the responsible author was from Turkey. In addition, we excluded publications that did not include a pediatrician in the list of authors. The authors, organizations, journals, document types, distribution of publications by years (months), the most used keywords were obtained from the Web of Science (WoS) All Databases collection. Graphical mapping of the keywords via VOSviewer software was done to assess the current research focus during the pandemic. Also, MEDLINE/PubMed (the US National Library of Medicine database) and Google Scholar were used to add missing data when necessary. Descriptive analyzes were made from all these obtained data.
Results
In total, 375 pediatric COVID-19 publications originating from Turkey were identified. Of these, 36 (9.6%) were published in 2020, 158 (42.2%) in 2021 and 181 (48.2%) in 2022 (Figure 1). Considering the monthly distribution of publications, the highest number of publications belongs to January 2022 (28, 7.4%).
The top ten most active authors and organizations publishing on pediatric COVID-19 in Turkey are listed in Table 1. The author with the most publications was Yasemin Ozsurekci from Hacettepe University [22 (5.8%) publications and 181 citations].
The organization with the highest number of publications was University of Health Sciences Turkey [80 (21.3%) publications and 277 citations].
The top ten most active Journals of pediatric COVID-19 Turkey publications are listed in Table 2. In total, 375 publications that we have identified have been published in 167 different journals. The journal with the highest number of publications (25 [6.6%]) and citations (73) was Turkish Archives of Pediatrics. The most active document types were research articles 295 (78.9%), editorial materials 15 (4%), letters 43 (11.5%) and review articles 22 (5.9%).
Most used keywords in pediatric COVID-19 publications originating from Turkey are shown in Figure 2. The most commonly used keywords were ‘’child, patient, pandemic, SARS-CoV and vaccine. The most active document types were research articles (295 (78.6%)), editorial materials (15 (4.0%)), letters (43 (11.5%)) and review articles (22 (5.9%)).
Discussion
The COVID-19 pandemic was an extraordinary situation for scientists as well as for the whole world. A situation similar to the confusion experienced by health systems all over the world has also raised questions among scientists, scientific journals, editors and authors. In fact, this confusion has spawned a great deal of literature. In this whole process, published articles, retracted articles and changing diagnosis, treatment and prevention strategies actually reveal the chaos even more clearly. At the moment, scientists seem to have the opportunity to look behind them and evaluate more clearly what is happening. In our article, we analyzed the COVID-19 publications originating from Turkey. Bibliometric analyzes reveal productivity, impact, and trends. These data not only indicate a scientific trend, but also affect the future scientific process and course. It will guide enthusiastic scientists who do not know or are wondering what topics they should research in a chaotic process like the pandemic. At the same time, using data obtained from bibliometric analyzes, it is possible to follow the relevant centers and authors and benefit from their experience.
With the emergence of COVID-19 in the Chinese province of Wuhan towards the end of 2009 and the WHO declared a pandemic in March 2020, the world has entered into a chaos. At the beginning of the pandemic, especially with the pediatric population being less affected, adequate and accurate recommendations for children did not emerge. It has evolved into a period in which the pediatric population is affected and serious clinical manifestations have emerged [9,10]. This situation also directly affected the distribution of pediatric COVID-19 publications by months/years [11,12]. In our analysis, it is seen that the publications have increased over the years.
In the bibliometric analysis published by Hu et al., it is stated that the USA is the country with the highest number of pediatric COVID-19 publications in the world [12]. Turkey is in fifth place in this study. In the present study, it is seen that the majority of pediatric COVID-19 publications in Turkey are affiliated with the University of Health Sciences Turkey. In this case, we consider the main factor to be the University of Health Sciences Turkey’s many affiliated education research centers and the high number of academics that have emerged as a result. In this list, it is seen that other well-established universities of Turkey such as Hacettepe University and Istanbul University come after the University of Health Sciences Turkey. Perhaps one of the most interesting data in the present study is that a young and new hospital such as City Hospital Ankara, which started its operations in February 2019, ranked third in the “Most active organization” list. Ankara We think that the reason for this situation is the strengthening of the academic staff of the city hospitals with the effect of the health policies implemented in Turkey.
In the bibliographic analysis of pediatric COVID-19 studies, it was stated that the majority of publications were from the USA [12,13]. This result can be attributed to the fact that the USA is the country most affected by the pandemic and has strong data management and academic systems. Another noteworthy country in this ranking is China. We think that the main reason why China is at the top of the list is its population size. Similarly, in our study, all university/education research hospitals/hospitals in the ‘’Top ten most active organisation’’ list are located in the 3 largest cities in Turkey by population.
There has been and continues to be a wide range of publications on COVID-19 in both adults and children. New articles are published almost every day as new data and experiences emerge. Evaluating the quality and content of publications as a result of bibliometric analyzes is of vital importance in terms of assisting future studies.
Conclusion
In the present study, pediatric COVID-19 publications with Turkey margins in the WoS database were analyzed and we believe that it is necessary to evaluate the impact of the pandemic on pediatric publications from a long-term and more comprehensive perspective.
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. Wang C, Horby PW, Hayden FG, Gao GF. A novel coronavirus outbreak of global health concern [published correction appears in Lancet. 2020 Jan 29;:]. Lancet. 2020;395(10223):470-3.
2. Hui DS, I Azhar E, Madani TA, Ntoumi F, Kock R, Dar O, et al. The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health – The latest 2019 novel coronavirus outbreak in Wuhan, China. Int J Infect Dis. 2020;91:264-6.
3. de Souza TH, Nadal JA, Nogueira RJN, Pereira RM, Brandão MB. Clinical manifestations of children with COVID-19: A systematic review. Pediatr Pulmonol. 2020;55(8):1892-99.
4. Borrelli M, Corcione A, Castellano F, Fiori Nastro F, Santamaria F. Coronavirus Disease 2019 in Children. Front Pediatr. 2021;9:668484.
5. Kabeerdoss J, Pilania RK, Karkhele R, Kumar TS, Danda D, Singh S. Severe COVID-19, multisystem inflammatory syndrome in children, and Kawasaki disease: immunological mechanisms, clinical manifestations and management. Rheumatol Int. 2021;41(1):19-32.
6. Sözeri B, Demir F, Kalın S, Hasbal Akkuş C, Salı E, Çakır D. SARS-CoV-2 infection in children with rheumatic disease: Experience of a tertiary referral center. Arch Rheumatol. 2021;36(3):381-8.
7. McGlacken-Byrne SM, Drew SEV, Turner K, Peters C, Amin R. The SARS-CoV-2 pandemic is associated with increased severity of presentation of childhood onset type 1 diabetes mellitus: A multi-centre study of the first COVID-19 wave. Diabet Med. 2021;38(9):e14640.
8. Kurup S, Burgess R, Tine F, Chahroudi A, Lee DL. SARS-CoV-2 Infection and Racial Disparities in Children: Protective Mechanisms and Severe Complications Related to MIS-C. J Racial Ethn Health Disparities. 2022;9(4):1536-42.
9. Gürlevik SL, Günbey C, Ozsurekci Y, Kesici S, Gocmen R, Temucin Ç, et al. Neurologic manifestations in children with COVID-19. Eur J Paediatr Neurol. 2022;39:118-119.
10. Akca UK, Kesici S, Ozsurekci Y, Aykan HH, Batu ED, Atalay E, et al. Kawasaki-like disease in children with COVID-19. Rheumatol Int. 2020;40(12):2105-15.
11. Maniu I, Maniu G, Totan M. Clinical and Laboratory Characteristics of Pediatric COVID-19 Population-A Bibliometric Analysis. J Clin Med. 2022;11(20):5987.
12. Hu S, Wang X, Ma Y, Cheng H. Global Research Trends in Pediatric COVID-19: A Bibliometric Analysis. Front Public Health. 2022;10:798005.
13. Monzani A, Tagliaferri F, Bellone S, Genoni G, Rabbone I. A Global Overview of COVID-19 Research in the Pediatric Field: Bibliometric Review. JMIR Pediatr Parent. 2021;4(3):e24791.
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Fatma Sargın. Turkey-based COVID-19 publications in pediatrics: A bibliographic analysis. Ann Clin Anal Med 2023;14(5):414-417
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Which of the recommended home exercises for low back pain is easier to learn and remember?
Serap Satis 1, Veysel Delen 1, Selcen Cicek 2
1 Department of Physical Medicine and Rehabilitation, Faculty of Medicine, Harran University, 2 Department of Physical Medicine and Rehabilitation, Sanliurfa Balıklıgöl State Hospital, Sanliurfa, Turkey
DOI: 10.4328/ACAM.21558 Received: 2022-12-21 Accepted: 2023-03-02 Published Online: 2023-03-11 Printed: 2023-05-01 Ann Clin Anal Med 2023;14(5):418-422
Corresponding Author: Serap Satis, Department of Physical Medicine and Rehabilitation, Faculty of Medicine, Harran University, 63300, Sanlıurfa, Turkey. E-mail: mdseraps@gmail.com P: +90 414 318 30 27 Corresponding Author ORCID ID: https://orcid.org/0000-0002-5496-197X
This study was approved by the Ethics Committee of Harran University (Date: 2020-06-01, No: 20.10.01)
Aim: In this study, we aimed to evaluate learning time and remembering of the exercises given as a home exercise program for low back pain patients.
Material and Methods: The study included patients aged 20-65 years who suffered from mechanical low back pain. All patients were informed about the study and informed consent was obtained from each of them. A socio-demographic form probing age, gender, and educational status was filled in by the patients. All the patients were taught five exercises, which were aimed at increasing trunk and lower extremity muscle length, strength, and endurance by the same physiotherapist and the exercises were repeated by the patients in the presence of the physiotherapist until they were performed fully and appropriately. In the meantime, the total number of repetitions and the duration of learning the exercises (seconds) were noted for each patient. Patients were instructed to perform these exercises for 15 days with 10 sets a day. At a 15-day follow-up session, patients were asked to perform the assigned exercises, and those who performed them correctly were recorded as “remembering”.
Results: Patients learned the hamstring stretch, lumbar stretch, and flexor stretch in a shorter period and learned the hamstring stretch with fewer repetitions compared to other exercises. Additionally, the lumbar stretch was the most remembered exercise.
Discussion: We suggest that instead of giving patients multiple complex exercises, patient-specific exercises that can be easily learned and performed without forgetting can be selected, and thus lumbar stretch is a suitable option for this purpose.
Keywords: Low Back Pain, Home Exercise Program, Time, Remember, Repetition
Introduction
Therapeutic exercise is defined as bodily movement prescribed to correct an impairment, improve musculoskeletal function, or maintain an optimal state of well-being. The importance of exercise in low back pain treatment has increased over recent years, and this importance was first emphasized in a study conducted in 1964 [1].
Low back pain, which peaks between the ages of 40-80, is a common health problem [2]. Common drugs prescribed for the pharmacological treatment of low back pain include nonsteroidal anti-inflammatory drugs, muscle relaxants, opioids, benzodiazepines, antidepressants, acetaminophen, systemic corticosteroids and pregabalin or gabapentin, Therapeutic exercise is a primary non-pharmacological treatment [3]. Moreover, it speeds up recovery and facilitates early return to work [4].
Therapeutic exercises are given as a home exercise program or as a component of physical therapy. Often, patients find it difficult to understand and remember the exercises [5, 6]. Expectedly, the exercises are not fully learned and remembered, and thus difficult to perform. There are many factors that affect learning and remembering. Although there have been many studies on exercise efficiency and compliance, to our knowledge, there has been no study investigating the duration of learning home exercise programs and the extent to which these programs were correctly remembered by patients who were assigned to perform home exercises.
The aim of this study was to analyze the duration of learning and the extent of remembering the exercises in patients who were assigned to perform home exercises and compare these parameters with patients’ educational status and age in order to help develop patient-based strategies in exercise training.
Material and Methods
The Ethics Committee of Harran University approved this study. Written informed consent was obtained from all participants. The study included patients aged 20-65 years who had been suffering from mechanical low back pain for at least 12 weeks. Patients with vision, hearing, comprehension problems, neurological and orthopedic deficits in the lower extremities were excluded from the study. All patients were informed about the study and informed consent was obtained from each of them. The patients filled in a socio-demographic form probing age, gender, and educational status. Patients were divided into three groups according to their educational status: (i) below high school level, (ii) high school level, and (iii) university level. All patients were taught five exercises, which were aimed at increasing trunk and lower extremity muscle length, strength, and endurance by the same physiotherapist, and the exercises were repeated by the patients in the presence of the physiotherapist until they were performed fully and appropriately. In the meantime, a total number of repetitions and the duration of learning the exercises (seconds) were noted for each patient. Patients were instructed to perform these exercises for 15 days with 10 sets a day. At a 15-day follow-up session, patients were asked to perform the assigned exercises, and those who performed them correctly were recorded as “remembering”. On the same day, the total number of repetitions made and the total duration of time, (seconds) spent learning the exercises and the extent of remembering these exercises were recorded for each patient.
Exercises
Hamstring Stretch reduces the load on the disc and paraspinal muscles by relaxing the hamstrings. When one knee is in flexion and the other leg is in extension, the subject attempts to touch the tip of the toe of the extended leg with the hand. When tension is experienced in the hamstrings, they are loosened and the same procedure is repeated.
Anterior Pelvic Tilt strengthens the back muscles. The subject lies on his/her back with the knees in flexion. The pelvic bone is lifted upwards by contracting the gluteus muscle. After waiting for five seconds, the subject returns to the initial state.
Posterior Pelvic Tilt strengthens the abdominal and gluteal muscles, resolves muscle spasms, and corrects lordosis. The subject lies on his/her back with the knees and hips in flexion. The abdominal muscles contract for five seconds and then relax to ground the low back. While the low back is pressed to the floor, the hips are slightly lifted off the ground and then relax.
Lumbar Stretch increases flexibility by resolving the spasm of the paravertebral muscles. When lying on the back and pulling the knees into the chest with the help of hands, the subject attempts to touch the knees with the forehead.
Flexor Stretch reduces lumbar lordosis. In the supine position, one knee is pulled towards the chest, while the other leg is press towards the ground
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
Among 69 patients, 39 (56.5%) were women and 30 (43.5%) were men. No significant difference was found among the three groups with regard to gender distribution (p=.770). The mean age was 46.71±11.42 (range, 20-65) years and no significant difference was found among group I, II, and III with regard to mean age (48.50±1.77, 45.00±3.03, and 40.45±1.66 years respectively) (p=.094).
Table 1 presents the duration of learning (seconds), the number of repetitions, and the extent of remembering for each exercise. The results indicated that the patients learned the hamstring stretch, lumbar stretch, and flexor stretch in a shorter period and learned the hamstring stretch with fewer repetitions compared to other exercises. Additionally, the lumbar stretch was the most remembered exercise.
At the 15-day follow-up session, 28.98% of the patients remembered all the exercises correctly. Table 2 provides the distribution of patients who correctly remembered all the exercises according to gender, age, and educational status. The mean age of patients that remembered all the exercises correctly was significantly lower than that of patients who did not (p=.000). It was also noted that the university graduates remembered all exercises significantly better than other patients (p=.000). However, no significant difference was found in terms of gender (p=.332).
Table 3 presents a comparison of patients’ duration of learning and their educational status. The comparison indicated that university graduates learned all five exercises in a significantly
shorter time compared to other patients (p=.004, p=.000, p=.000, and p=.004, respectively).
A significant difference was found among the three groups with regard to the number of repetitions performed for learning anterior pelvic tilt, posterior pelvic tilt, and flexion stretch (p=.000, p=.001, and p=.006, respectively). It was noted that patients with an educational level lower than high school education learned these exercises with more repetitions (Table 3).
On the 15-day follow-up session, all university graduates remembered the anterior pelvic tilt, posterior pelvic tilt, and lumbar stretch correctly. Additionally, all high school graduates remembered lumbar stretch correctly as opposed to 89.5% of the patients with an educational level lower than high school education. Moreover, the lumbar stretch was the most remembered exercise. It was also found that patients with an educational level lower than high school education remembered the anterior pelvic tilt and posterior pelvic tilt significantly less than other patients (p=.001 and p=.003, respectively) (Table 3).
Discussion
The present study, for the first time in the literature, analyzed the duration of learning and the extent of remembering the exercises in patients assigned to perform home exercises and found that the lumbar stretch and the flexor stretch were learned and remembered in a shorter time compared to other exercises. We also observed that university graduates showed better performance compared to other patients in terms of duration of learning, number of repetitions, and the extent of remembering. Selecting exercises that can be easily understood and performed by the patients is as important as selecting appropriate exercises for each patient.
The choice of exercise for low back pain depends on the preference of the patient and the therapist and also on the cost and safety of the exercises [7]. Home exercise programs typically consist of exercises that can be performed by patients in their social environment. Prior to implementation, the patients were mostly instructed by a physiotherapist about the number of repetitions and the total duration of the exercise. Sometimes they may be provided with exercise brochures or even audio or video recordings of the exercises [8].
Weakness in the back extensor and flexor muscles was reported in patients with low back pain [9]. Accordingly, patient-specific stretching and strengthening exercises constitute the most important part of the treatment. However, only properly performed exercises contribute to the effectiveness of the treatment. The effectiveness of exercise programs for low back pain has been shown in numerous studies [10, 11]. However, there is little or no data on which exercise is more effective for low back pain. Most of the studies available in the literature have compared stabilizing exercises with various types of exercises and found that all of these exercises reduce pain and that the exercises are not superior to each other [12-17].
Isolated lumbar stabilization exercises have been shown to have positive effects on pain [18]. Moreover, it was shown that isokinetic and standard exercise programs have no superiority over each other [19].
Most of the studies investigating home exercise programs have evaluated patient compliance rather than the effect of these programs. A previous study evaluated the adherence of the patients to home exercise programs and factors affecting adherence and revealed that 39% of the patients showed full adherence to home programs and also found a significant relationship between adherence and parameters such as age, environmental motivation, understanding of the exercises, physiotherapist’s explanation quality, control and assessment of home exercises by the physiotherapist, and patient’s trust in the physiotherapist [5]. Another study reported that the compliance rate was 9%, 73%, and 18% in patients aged 15-25, 26-44, and 45 years and older, respectively. The authors also noted that fatigue, forgetting or avoiding exercises, lack of time for the exercises, and the belief that exercises were not beneficial all negatively affected patient compliance [20].
Campbell et al. reported that their patients’ initial compliance with the home exercise program decreased over time [21]. In another study investigating compliance with home exercise programs, patients were given three exercises and brochures, and the results indicated that there was 71.6% compliance with the exercises regardless of gender [10]. In contrast, another study found that women showed less compliance with the exercise program compared to men [22]. Despite these conflicting results, we did not observe any difference between the two genders in terms of duration of learning and the extent of remembering.
Rastall et al. compared young and old patients with regard to the capacity for remembering and performing home exercises and suggested that although the elderly forgot the exercises more, the rate of forgetting was also high in young people and thus brochures should be given to all patients [6]. In our study, the mean age of the patients who did not remember the exercises was higher than that of patients who remembered them correctly, which could be due to the adverse effect of degenerative changes in the brain and neurons caused by an age-related decrease in cerebral blood flow on the cognitive functions such as learning, memory, and problem-solving. [23]. Based on these findings, we also suggest that patients aged over 50 years should be given longer education and should be provided with visual or auditory support.
Peek et al. reported that only 16.6% of the patients remembered the exercises correctly [24]. In our study, 28.98% of the patients remembered all five exercises correctly, whereby the most remembered exercise was a lumbar stretch (92.7%) and the least remembered exercise was anterior pelvic tilt (60.8%). Accordingly, we suggest that the lumbar stretch, which is the most important exercise in terms of relaxing the paravertebral muscles, provides significant relaxation, thus, patients should take utmost care to remember this exercise.
Our study was limited since the patients’ social environment prevented them from exercising, their psychological conditions were not evaluated, and the study included a small sample of patients.
Conclusion
In conclusion, the results indicated that educational status and age are important factors affecting the duration of learning and the extent of remembering home exercises, and that patients had difficulty particularly in learning and remembering the anterior pelvic tilt and posterior pelvic tilt. Additionally, the lumbar stretch was the most remembered exercise, mainly because patients experienced greater relaxation after this exercise.
We suggest that instead of giving patients multiple complex exercises, patient-specific exercises that can be easily learned and performed without forgetting can be selected, and thus lumbar stretch is a suitable option for this purpose. Additionally, when assigning multiple exercises to patients aged over 50 years, the exercises should be clearly explained by the physiotherapist within a minimum period of 30 seconds with at least 5 repetitions, and also audio or video support should be provided.
Acknowledgment
We would like to thank Physiotherapist Celal Erdem for her help.
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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4. Kamper SJ, Apeldoorn AT, Chiarotto A, Smeets RJ, Ostelo RW, Guzman J, et al. Multidisciplinary biopsychosocial rehabilitation for chronic low back pain: Cochrane systematic review and meta-analysis. BMJ. 2015;18:350-444.
5. Chan D, Can F. Patients’ adherence/compliance to physical therapy home exercises, Fizyoterapi Rehabilitasyon/ Physiotherapy Rehabilitation. 2010;21(3):132-9.
6. Rastall M, Brooks K, Klarneta K, Moylan N, McCloud W, Tracey S. An Investigation into Younger and Older Adults’ Memory for Physiotherapy Exercises. Physiotherapy. 1999;85:3.
7. Saragiotto BT, Maher CG, Yamato TP, Costa LO, Menezes Costa LC, et al. Motor control exercise for chronic non-specific low-back pain. Cochrane Database Syst Rev. 2016; 2016(1):CD012004.
8. Salik Sengul Y, Kaya N, Yalcinkaya G, Kirmizi M, Kalemci O. The effects of the addition of motor imagery to home exercises on pain, disability and psychosocial parameters in patients undergoing lumbar spinal surgery: A randomized controlled trial. Explore (NY). 2021;17(4):334-9.
9. Bayramoğlu M, Akman MN, Kilinç S, Cetin N, Yavuz N, Ozker R. Isokinetic measurement of trunk muscle strength in women with chronic low-back pain. Am J Phys Med Rehabil. 2001;80(9):650-5.
10. Kolt GS, McEvoy JF. Adherence to rehabilitation in patients with low back pain. Man Ther. 2003;8(2):110-6.
11. Durmus D, Unal M, Kuru O. How effective is a modified exercise program on its own or with back school in chronic low back pain? A randomized-controlled clinical trial. J Back Musculoskelet Rehabil. 2014;27(4):553-61.
12. Suh JH, Kim H, Jung GP, Ko JY, Ryu JS. The effect of lumbar stabilization and walking exercises on chronic low back pain: A randomized controlled trial. Medicine (Baltimore). 2019;98(26):e16173.
13. Oh YJ, Park SH, Lee MM. Comparison of Effects of Abdominal Draw-In Lumbar Stabilization Exercises with and without Respiratory Resistance on Women with Low Back Pain: A Randomized Controlled Trial. Med Sci Monit. 2020;26:e921295.
14. Sipaviciene S, Kliziene I. Effect of different exercise programs on non-specific chronic low back pain and disability in people who perform sedentary work. Clin Biomech (Bristol, Avon). 2020;73:17-27.
15. Shamsi MB, Rezaei M, Zamanlou M, Sadeghi M, Pourahmadi MR. Does core stability exercise improve lumbopelvic stability (through endurance tests) more than general exercise in chronic low back pain? A quasi-randomized controlled trial. Physiother Theory Pract. 2016;32(3):171-8.
16. Koumantakis GA, Watson PJ, Oldham JA. Trunk muscle stabilization training plus general exercise versus general exercise only: randomized controlled trial of patients with recurrent low back pain. Phys Ther. 2005;85(3):209-25.
17. Moon HJ, Choi KH, Kim DH, Kim HJ, Cho YK, Lee KH, et al. Effect of lumbar stabilization and dynamic lumbar strengthening exercises in patients with chronic low back pain. Ann Rehabil Med. 2013;37(1):110-7.
18. Hadała M, Gryckiewicz S. The effectiveness of lumbar extensor training: local stabilization or dynamic strengthening exercises. A review of literature. Ortop Traumatol Rehabil. 2014;16(6):561-72.
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Serap Satis, Veysel Delen, Selcen Cicek. Which of the recommended home exercises for low back pain is easier to learn and remember? Ann Clin Anal Med 2023;14(5):418-422
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Orthopedic surgical scoring in asymptomatic COVID-19 patients
Yunus Demirtaş 1, Özgür Kaya 2, Gökhan Çakmak 1
1 Department of Orthopedics and Traumatology, Faculty of Medicine, Yüksek İhtisas University, 2 Department of Orthopedics and Traumatology, Faculty of Medicine, Lokman Hekim University, Ankara, Turkey
DOI: 10.4328/ACAM.21568 Received: 2022-12-30 Accepted: 2023-02-07 Published Online: 2023-02-27 Printed: 2023-05-01 Ann Clin Anal Med 2023;14(5):423-427
Corresponding Author: Yunus Demirtas, Department of Orthopedics and Traumatology, Faculty of Medicine, Yüksek İhtisas University, Çankaya, Ankara, Turkey. E-mail: yunus832002@yahoo.com P: +90 505 891 72 39 Corresponding Author ORCID ID: https://orcid.org/0000-0002-4866-4127
This study was approved by the Ethics Committee of Lokman Hekim University, (Date: 2021-10-06, No: 2021116)
Aim: The purpose of this study is to create a scoring system to decide which patient will take maximum precautions while the covid 19 disease continues.Taking maximum precautions is not always possible in all surgical procedures. Therefore, surgical scoring in asymptomatic patients, selecting patients who need maximum precautions, and taking the necessary precautions for these patients will prevent unnecessary use of the equipment.
Material and Method: A total of 347 who were surgically treated for emergency or elective procedures between March 11 and November 11, 2020 were included in the study. Of these patients, 277 patients whose data could be accessed were included in the study. A scoring system has been created. Patients were divided into 2 groups: bearing low and high risk. Patients with a score above 10 were identified as having a high surgical risk, and those with a score below 10 were identified as having a low surgical risk.
Results: There were 132 patients in Group 1 and 145 patients in Group 2. It was observed that 29 of 277 patients became positive within the first month. Two of these patients were in Group 1 and 27 of them were in Group 2. It was observed that COVID-19 antibody or PCR tests gave more positive results in patients in Group 2 in the first month compared to two patients in Group 1. The highest positivity rate in Group 2 was observed in the arthroscopy group.
Discussion: Advanced precautions should be taken in patients with high surgical risk scores. In patients with low surgical risk scores, less strict precautions can be taken.
Keywords: COVID-19, Surgical Score, Surgical Risk
Introduction
Although our experiences with Sars-CoV2 (COVID-19) disease, which was declared a pandemic on 11 March 2020, are progressively increasing, problems with the diagnosis still continue. Surgery of asymptomatic patients, known as supercarriers, poses a risk for us, surgeons, and operating room staff as well as to other cases taken to the operating room. In addition, surgeries performed during the incubation period of the disease and negative tests and findings increase the risk of infection of healthcare staff. Under these circumstances, it is essential to protect the surgical team. However, it is not clear whether the same precautions should be taken for all patients undergoing surgery.
Although developments in the treatment of the new type of coronavirus continue, an effective treatment method has not yet been found. Vaccination-related developments are promising and although some vaccines have completed Phase 3, it is obvious that it will not be sufficient to allow us to terminate the measures. Although vaccination studies continue, there is no doubt that it will take some time for vaccination programs to be put into use all over the world due to factors such as adequate health equipment and time. Information about the recently identified mutant virus such as omicron has increased and there is a common opinion that its infectiousness is high.
Personal protective equipment has been defined for all suspicious surgical procedures, which are determined by the World Health Organization and the Ministry of Health in our country. However, it is not possible to reach a sufficient amount of equipment everywhere, and unfortunately, it is not possible to use all this equipment in every patient regularly. To this end, grouping of patients by creating a surgical scoring and performing surgeries by taking higher safety measures in patients with a high surgical score will ensure that all surgeries are performed more safely.
Material and Methods
A total of 347 patients who were surgically treated for emergency or elective procedures between March 11 and November 11, 2020 were included in the study. Patient data were accessed using the hospital automation system. A total of 277 patients whose follow-up data were available were included in the study. COVID-19-positive patients who were taken to emergency surgery were not included in the study. Data such as age and gender of these patients, the reason for the surgery, comorbid diseases, duration of hospitalization, date of the surgery, blood parameters, postoperative COVID-19 antibody Ig M or Ig G test or Pcr test positivity obtained from the hospital automation system when they visit hospital for checkup in the first month postoperatively. In addition, the surgery notes of the patient were examined, and it was recorded whether there were any intraoperative complications, the amount of intraoperative bleeding, the type of anesthesia, and whether they were treated in a positive or negative pressure room. Their complete blood count, Crp, LDH, D-Dimer results were recorded as blood parameters.
The patients were divided into 2 groups and the surgery time, surgical procedure, type of anesthesia, intraoperative complication, expected bleeding amount, operating room feature, neutrophilia, lymphopenia, thrombocytopenia, Crp, Ldh, D-Dimer levels were evaluated by evaluating 1 point. Surgical score was established by giving 2 points to the patients in the high surgical group (Table 1). According to this table, patients who scored less than 10 points in total were named as low surgical risk, and patients who scored above 10 points as high surgical risk. Rapid antibody test (for S and N antigens) was used for preoperative diagnosis of Covid -19 disease between March and June 2020 in our hospital, and a viral PCR test was used as of June.
The results were evaluated with the SPSS 22 program. Comparisons between groups were carried out by Pearson’s chi-square test.
Approval for our study was obtained from the Ministry of Health with the registration number 2020-12-04T14_53_09.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
One hundred and sixty-one patients were male and 116 of them were female. The mean age was 42.8 years. In Group 1, there were a total of 132 patients, 87 men and 45 women. In Group 2, there were 145 patients, 74 men and 71 women. The reasons for surgery and their positivity in terms of COVID-19 in Groups 1 and 2 are shown in Table 2. COVID-19 PCR or antibody positivity was detected in 29 of 277 patients within the first 1 month postoperatively. It was seen that 27 of these patients were in Group 2 and only 2 of these patients were in Group 1. Eleven were men and 16 were women among the patients who tested positive in Group 2. When the distribution of 29 patients by month was examined, it was observed that positive results were more common in June, August and September. When 2 patients in Group 1 were examined, it was found that 1 patient tested positive in August and 1 patient resulted positive in October. When the reasons for the surgery were examined in these patients, it was found out that 1 patient was operated for the end fracture of the proximal humerus and 1 patient was operated for the humerus shaft fracture.
When the positivity rates of both groups for COVID-19 in the first month were compared, it was observed that the positivity rate was higher in Group 2 and there was a significant difference between the groups (p<0.05).
When the reasons for the surgery were examined in Group 2, it was seen that COVID-19 positivity was detected mostly after arthroscopic procedures (25.3%) (Table 3). This result was not statistically significant (p>0.05). When arthroscopic procedures were examined, it is seen that positivity was mostly detected after shoulder arthroscopy (29%). This result was not statistically significant either (p>0.05).
Discussion
Six types of coronaviruses (229E, OC43, NL63, HKU1, SARS-CoV, MERS-CoV) are known to be capable of causing disease in humans.[1] A new type of virus that emerged in Wuhan, China, in December 2019 was identified. Then, it was referred to as Sars-Cov-2 by the International Virus Taxonomy Committee. The disease caused by this virus was specified as COVID-19 disease by World Health Organization [2, 3].
As is known, this virus was found to be first transmitted from wild animals to humans in Wuhan, China, and then the virus showed its effects worldwide through human-to-human transmission [4, 5]. The disease is primarily transmitted through droplets. It is also known to be transmitted directly through the mucosa. In experimental studies, its infectivity was demonstrated to last for 3 hours in aerosols formed. Additionally, transmission depends on the time of contact with the virus carrier, the manner of contact, the application of protective measures, the virus load in the infected secretions and the incubation period. Moreover, there are studies evidencing that the virus can be easily transmitted in closed environments. Another important point to keep in mind in the transmission is environmental contamination. A study in Singapore demonstrated that coronavirus RNA was identified in samples collected from surfaces in a room where a COVID-19 patient was staying [6-10]. Furthermore, there is a common opinion indicating that the infectious rate of the new mutant virus is high.
Even though there are various procedures in the literature regarding what to pay attention to when various interventional procedures are performed for almost all branches, it is obvious that routine application is not possible for every patient. For this purpose, we think that it would be appropriate to perform surgical scoring on patients undergoing surgery and determine a risk scale after scoring and increase the measures accordingly. While making this scoring, we selected parameters in which the probability of transmission will increase by contacting the patient. The first one of these parameters is the surgical time. As it is known, the most important way of transmission of COVID-19 disease is by droplets. [11] The amount of time spent in close proximity to the patient increases with increasing surgery time, which also increases the risk of transmission. Another parameter is the number of people involved in the surgery. In addition, we think that surgical procedures increase the probability of transmission of the disease. For example, while the risk of contamination is low in short surgeries where there is less bleeding, in surgical procedures where there is more use of cautery and the amount of bleeding might be greater, and surgical procedures with drills, reamers, cutters where the amount of aerosol increases as well as arthroscopic surgeries and long-term surgeries will cause a great increase in terms of transmission risk due to the increased amount of droplet contact and aerosol [12, 13]. Again, in patients undergoing general anesthesia, the risk of transmission increases due to the increased amount of aerosols. According to this, preoperative patients who score less than 10 points carry a low risk of transmission, whereas patients who score more than 10 points carry a high risk of transmission. Furthermore, it is known that droplets stay in the air for 3 hours. If the aforementioned issues about COVID-19 disease antibody screening are taken into account, we think that the test must be done despite false negative results. Preoperative complete blood count, coagulation time, biochemical parameters should also be evaluated. Increased number of leukocytes and neutrophils, decreased levels of lymphocytes and platelets, increased APTT and PT, increased levels of IL 6, procalcitonin, ferritin, D-Dimer and decreased levels of albumin and fibrinogen are among the laboratory findings of COVID-19 disease. Hyponatremia, hypocalcemia, hypokalemia, increased sedimentation, Crp, BUN, creatinine, AST, ALT are biochemical parameters observed for this disease [14, 15]. Even if these blood parameters are not specific to COVID-19, detection of such changes should be a warning for us, surgeons, and should be a warning for the disease. The fact that intraoperative complications increase the duration of the surgery and increase the possibility of bleeding, the increase in the use of physical force and tachypnea of those participating in the surgery are other reasons that increase the risk in terms of contamination. It is recommended in the literature to perform intubation in a negative pressure room and surgical procedure in a positive pressure room especially in orthopedic cases treated under general anesthesia [15, 16]. This practice cannot be carried out in most operating rooms.
In our study, we observed that the cases positive for COVID-19 were more common in surgeries performed in April, when the COVID-19 disease first peaked, and in July and September, when it increased. It is significant that patients who tested positive during this period were in Group 2. When arthroscopy, arthroplasty and oncological surgeries and spine surgery in Group 2 were compared, the highest positivity rate was observed in arthroscopy at 25.3%. This may be due to the insufficient number of patients within the groups. Nevertheless, due to the high positivity rate in the arthroscopy group, we recommend that high-level precautions are taken while performing these surgeries. When the subgroups of the arthroscopy group were examined, it was seen that there was a positivity rate of 29% in the shoulder arthroscopy group. Due to the low number of patients in the hip and ankle arthroscopy groups, these groups were not included in the comparison when comparing the groups. When the knee arthroscopy group was compared with the shoulder arthroscopy group, it was seen that shoulder arthroscopy is more risky, even though the difference is not statistically significant.
In our study, patients who were positive in the first month may have been positive for other reasons. This situation may be due to the patients’ failure to comply with their own infection control measures, as well as to the people with whom they had close contact during treatment and the patients’ socioeconomic levels. However, the high rate of positivity in the patients in group 2 and its statistical significance are likely to infect the surgeon and other healthcare personnel during or after the surgery of the patients in this group. Another limitation of our study is the verification of the scoring system we determined in repeat cases. For this, advanced studies are needed.
In conclusion, the use of this risk scale and similar ones until we have satisfactory knowledge of COVID-19 and until the pandemic is brought under control, will help us, surgeons, to increase precautions against the risk of infection and hence prevent the use of unnecessary equipment. However, the risks will continue until adequate immunization is achieved in terms of the whole population. It is known that the immunity rate is around 95% at best. Due to the high postoperative positivity rate of Group 2 patients as observed in our study, we recommend taking maximum precautions (n95 mask, face shield etc..) for contamination while performing surgeries in patients with a high surgical score. We believe that routine precautions will be sufficient for Group 1 patients who have a low surgical score.
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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Yunus Demirtaş, Özgür Kaya, Gökhan Çakmak. Orthopedic surgical scoring in asymptomatic COVID-19 patients. Ann Clin Anal Med 2023;14(5):423-427
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Evaluation of serum C-terminal telopeptide (CTX) value for the risk of medication related osteonecrosis of the jaws
Fatma Dogruel 1, Canay Yilmaz Asan 1, Emine Fulya Akkoyun 2, Taha Pergel 2, Erdem Kilic 2, Fahri Bayram 3
1 Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Erciyes University, Kayseri, 2 Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Bezmialem Vakıf University, Istanbul, 3 Department of Endocrinology, Faculty of Medicine, Erciyes University, Kayseri, Turkey
DOI: 10.4328/ACAM.21574 Received: 2023-01-03 Accepted: 2023-02-17 Published Online: 2023-03-11 Printed: 2023-05-01 Ann Clin Anal Med 2023;14(5):428-432
Corresponding Author: Canay Yilmaz Asan, Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Erciyes University, Kayseri, Turkey. E-mail: dtcanayasan@gmail.com P: +90 533 167 32 38 F: +90 352 438 06 57 Corresponding Author ORCID ID: https://orcid.org/0000-0001-9868-6415
This study was approved by the ethics committee of Erciyes University Scientific Research Projects (Date: 2015, No: TSA-2015-5965)
Aim: The aim of this study was to evaluate pre- and post-treatment serum CTX levels of patients treated with bisphosphonate (BP) and the correlation of levels with MRONJ risk.
Material and Methods: Patients treated with BP by the Endocrinology and Oncology Departments were included in this study. Blood samples were taken before and 12 months after BP treatment, and serum CTX values were determined with clinical examinations.
Results: A total of 72 patients were included in the study. Of these patients, 32 had oncological and 40 had endocrinological disorders. The mean CTX value of all the patients was 453.7 (245.7-734.3) pg/ml, in oncology patients, it was 705.9 (398.6-945.6) pg/ml and in endocrine patients, it was 360.4 (209.2-598.2) pg/ml (p <0.001). The mean post-treatment CTX value of the remaining patients was 164.1 (106.9-301.8) pg/ml, and the difference was statistically significant before and after BP treatment (p <0.001). Among the patients included in the study, MRONJ was only observed in one oncology patient 18 months after the initial BP treatment.
Discussion: MRONJ can be prevented by performing all dental treatments before BP treatment and eliminating local risk factors. CTX values should not only be evaluated after BP treatment, but also it may be useful to check before BP treatment to determine the course of the treatment.
Keywords: Bisphosphonate, Osteonecrosis, Jaw, MRONJ, BRONJ, CTX
Introduction
Bisphosphonates (BP) are antiresorptive agents that are frequently used in metabolic bone diseases, bone metastases of solid tumors, and in the control of skeletal complications of multiple myeloma [1]. BPs are used orally or intravenously and are divided into two main groups with and without amino groups [2]. Nitrogen-containing BPs (pamidronate, alendronate, risedronate, ibandronate, zoledronate) have a higher potential for side effects than BPs without nitrogen (etidronate) [3]. Although both groups show their effects through different enzymes in the intracellular cycle, their activities on bone metabolism are mainly through the inhibition of osteoclast functions [4].
Medication related osteonecrosis of the jaws (MRONJ) is a side effect of BP treatment and characterized by exposed bone localized in the maxilla or mandible for more than 8 weeks in a patient actively or previously using antiresorptive without any history of radiation [5]. MRONJ was first reported in 2003. Since then, it has become a common complication, seen in many published studies [6,7]. Not only BP treatment is responsible for MRONJ, but also denosumab and other antiresorptive agents are found to be associated with MRONJ. Therefore, the term antiresorptive agent-related osteonecrosis of the jaws (ARONJ) also have been used in the literature [8].
Most of the patients using BPs are exposed to intense hospital visits and these patients mostly consist of individuals with low daily vital activity levels. For this reason, methods, which could reduce hospital visits, and be applied easily in all centers, were investigated. Studies in recent years have focused on bone formation and destruction biomarkers in the blood. In addition, the number of genetic research studies has increased. Bone destruction markers may be useful in determining the bone resorption rate in these patients. Cross-linked carboxy terminal telopeptide (CTX) of type 1 collagen is one of the most commonly used markers. Marx et al. firstly, described the CTX as a marker for MRONJ risk in 2008, and a value of less than 100 pg/ml was found to be related to a high risk of MRONJ [9].
A literature survey was performed and, it was concluded that CTX levels of patients under BP treatment were measured before dentoalveolar surgery for the determination of the risk of MRONJ or after the development of MRONJ. However, preoperative CTX levels were unknown in these MRONJ patients. For this reason, the study aimed to evaluate the significance of pre- and post-treatment CTX values in terms of MRONJ risk in patients, who will be started on BP therapy, and to use it as a prognostic marker for early diagnosis.
Material and Methods
This study was carried out with the approval of the Local Ethics Committee of Erciyes University and followed the Declaration of Helsinki on Medical Protocol and Ethics. Erciyes University Scientific Research Projects Unit supported the study (TSA-2015-5965), and carried it out at the Dentistry Faculty, Department of Oral and Maxillofacial Surgery, in cooperation with the Hematology and Endocrinology Departments at the Faculty of Medicine. Patients, who started BP therapy for metabolic bone disorders (endocrinology patients) and to prevent bone metastasis (oncology patients), were included and detailed consent was given by all volunteers. Patients, who did not want to participate voluntarily in the study, refused drug treatment and stated they would not attend the control visits were excluded from the study. A power analysis indicated the adequacy of 72 patients in the study.
Preoperative Procedures
In the first step of the study, to determine the preoperative CTX value of the included patients, approximately 10 ml of blood samples were drawn into the biochemistry tube and the serum was separated by centrifugation at 4000 rpm for 15 minutes in the morning while fasting and the separated serum was stored in a -800. In addition, the clinical and radiological dental examinations of the participants were performed by the same maxillofacial surgeon, and all dental treatments were completed before BP therapy. Patients were referred to the relevant departments to start BP treatment and were recalled for follow-up visits 12 months later.
Postoperative Procedures
Detailed clinical and radiological examinations of the maxillofacial region were performed for possible osteonecrosis and MRONJ risk in the patients six months after BP treatment. Dental treatments were completed in consultation with the relevant departments, if necessary.
Blood samples were taken to determine the postoperative serum CTX levels of the patients 12 months after initial BPs treatment. All patients were informed about MRONJ and were recalled every 6 months for a determination of the earliest possible symptoms of MRONJ and routine dental examination.
ELISA Assay
Preoperative and postoperative blood samples were analyzed with the Enzyme-Linked Immunosorbent Assay (ELISA) with the use of specific kits (Elecsys β-Crosslaps®, Roche Diagnostics, Manheim, Germany) for the determination of preoperative and postoperative serum CTX levels. Enzyme-labeled antibody was inserted into the antibody-coated sample and standard wells. Substrate solution was added to each well and incubated. After incubation, color change occurred in the presence of CTX. The concentration of CTX in the blood samples was determined by comparing the O.D. to the standard curve.
Statistical analysis
Data normality was assessed with the Shapiro-Wilk test and histogram, q-q graphs. The homogeneity of the variance was examined using the Levene test. Independent two samples, the Mann-Whitney U, dependent two samples, and Wilcoxon tests were used for the comparisons. Data were indicated as mean ± standard deviation, median (1st-3rd quartiles), or frequencies (percentages). TURCOSA (Turcosa Analytics Ltd. Co., Turkey, www.turcosa.com.tr) was used for the analysis, and a p-value of less than 5% was considered statistically significant.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
The study included 72 patients. 23.6 % of all patients were men (n = 17) and 76.4% (n = 55) were women. Forty patients in Group 1 (55.5%) were referred by the Endocrinology Department, and 32 patients (44.5%) in Group 2 were referred by the Oncology Department. Osteoporosis is the main reason for BP treatment in endocrine patients and BP treatment was performed in Group 2 patients to prevent bone metastasis of solid tumors. According to the group of the patients, 90% (n =36) of patients in Group 1 consisted of women, and 47% (n = 15) of the patients in Group 2 were women, and the difference was significant (p<0,001). The mean age of all patients was 61.3 ± 9.8 years (min=34, max= 84). The mean age in Group 1 was 61.4±9.6 and 61.1±10.4 in Group 2 (p=0.83).
When the pre-treatment CTX values of the patients were measured, the mean CTX value of all patients was 453.7 (245.7-734.3) pg /ml. According to the groups, pre-treatment CTX value was 360.4 (209.2-598.2) pg /ml in Group 1 and 705.9 (398.6-945.6) pg /ml in Group 2, with significant difference (p <0.001).
In the second step of the study, 38 patients were excluded from the study. In the endocrinology group, 19 patients were excluded due to discontinuation of the drug treatment (n=9), not coming to the follow-ups (n=5), and withdrawal from the study (n=5). In the oncology group, 19 were excluded because of a short survey of the diseases leading to death in stage 4 cancers. Post-treatment CTX values of the remaining 34 patients were measured after 12 months of initial BP treatment. Twenty-one (62%) patients were in the endocrine group and 13 (38%) were oncology patients. The post-treatment serum CTX value of all patients was 164.1 (106.9-301.8) pg /ml. According to the groups, the post-treatment mean CTX was 231±131.9 pg/ml in Group 1 and 140.1 (100-187.6) pg /ml in Group 2, with no difference (p=0.19).
The mean pre-treatment CTX value of the 34 patients, whose second blood samples were obtained, was 413.3 (234.2-641.6) pg/ ml, and the postoperative CTX value was 164.1 (106.9-301.8) pg/ml, and the difference was significant (p <0.001) (Table 1).
The systemic conditions of the remaining 34 patients were also evaluated. In these patients, 5 patients have used 70 mg alendronate once a week; 9 patients have used 35 mg risedronate once a week, and 7 patients have used 150 mg ibandronate once a month orally. Five patients used 6 mg ibandronate once a month and 8 patients used 4 mg zoledronate once a month intravenously. The mean treatment time was 12 months in Group 1 (min:2- max: 36). All patients in Group 2 had been treated with BPs for 12 months except for 2 patients whose treatment times were 24 months (Table 2).
BP treatment was applied for breast (n=5), colon (n=2), prostate(n=2), lung (n=2), gastric (n=1) and renal cancers (n=1) in Group 2. A total of 18 patients had other systemic conditions such as diabetes mellitus (n=7), hypertension (n=9), thyroid diseases (n=3), and cardiac arrhythmia (n=2). Only one osteoporotic patient had been using steroid treatment (40 mg Fluocortolone once a day for 2 years) in addition to IV BP therapy in Group 1.
MRONJ was observed in only a male patient, who had intravenous BPs treatment (6 mg ibandronate for 12 months) because of a gastrointestinal stromal tumor and colon cancer 18 months after the initial BP treatment. In addition, the patient used 50 mg of sunitinib daily as an antineoplastic agent. Considering the CTX values of the patient, the preoperative CTX value was 428 pg/ml and the postoperative CTX value was 109 pg/ml. Although no dental treatment, such as tooth extraction or periodontal surgery, was performed, MRONJ development was thought to be caused by irritation of the dentures during sunitinib therapy. In the clinical and radiological examination, stage 2 MRONJ was diagnosed according to the AAOMS (American Association of Oral and Maxillofacial Surgeons) criteria and the treatment of MRONJ was performed according to the relevant guideline [5] by the same surgeon (Figures 1, 2). A consultation was performed with the oncology department for a drug holiday and no additional BP treatment was required for the patient who had previously completed BP treatment and sunitinib therapy was continued. After the antimicrobial therapy, the necrotic bone was surgically debrided and complete wound healing was observed 3 months later (Figure 3). The patient was checked for 12 months and no additional MRONJ occurred during sunitinib usage.
Discussion
MRONJ is an uncontrollable consequence in osteoporosis and metastatic cancer patients who are treated with antiresorptive medicines, such as BPs, denosumab, a human IgG2 monoclonal antibody against the receptor activator of nuclear factor-kappa B ligand (RANKL). In cancer patients receiving BP, antiangiogenic drugs, denosumab, and molecularly targeted medicines such as tyrosine kinase inhibitors are also linked to MRONJ or enhance the risk of MRONJ [10]. The incidence of MRONJ is greater in oncological patients because of higher BPs doses than in those with osteoporosis [11]. MRONJ is a difficult and complex clinical condition to treat. Although appropriate treatment protocols are applied according to the clinical staging system, surgical interventions fail due to impairment in wound healing. Therefore, the prevention of MRONJ and early diagnosis are very important in the clinical aspect.
CTX, which is a bone-specific marker, is a breakdown product of type 1 collagen, and serum CTX levels increase in patients with osteoporosis and metastatic bone tumors while it tends to decrease during antiresorptive therapy [12]. Marx et al. have suggested the use of CTX estimation as an indicator of the risk of MRONJ. A value of less than 100 pg/ml was represented as a high risk, 100 to 150 pg /ml, a moderate, and greater than 150 pg/ml, minimal or no risk [9]. However, in different studies, serum CTX values are reported as not a significant predictor of MRONJ risk [13-15].
Determination of serum CTX level is useful in evaluating the effectiveness of osteoporosis treatment and skeletal complications. Studies have shown that high concentrations of serum CTX reduce the survival rate of cancer patients [16]. However, it is also argued that CTX will be higher in cancer patients, due to high collagen destruction and is not a significant determinant [16]. In the present study, the serum CTX concentration in oncology patients was higher than in osteoporotic patients before BP treatment, and the CTX values decreased rapidly in a short time. Therefore, it is recommended to check CTX values in oncology patients at short intervals.
Comorbid conditions in oncology patients are related to a greater risk of MRONJ such as diabetes [5]. Although 7 patients had diabetes mellitus as a comorbid condition in the present study, MRONJ did not develop in any of them. Also, there was one patient in Group 2 who received steroids additionally to IV BP treatment, MRONJ did not occur in this patient.
Furthermore, local factors also have a great impact on MRONJ development as well as systemic conditions. Dentoalveolar surgical procedures, such as tooth extraction, periapical and periodontal surgical procedures, dental implant placement, regional anatomical differences, and accompanying oral problems can be classified as local risk factors [17]. The risk of MRONJ in patients using oral BPs after dental extraction is 0.5% and ranges from 1.6 to 14.8% in IV users [5]. Therefore, such interventions should be avoided in patients using BPs and all dental treatments should be completed before BP treatment.
In this study, although, all dental procedures were completed before BP treatment in all patients, MRONJ developed in a patient because of denture irritation. The non-healing mucosal defect caused by dentures is known as a way for oral flora to access the bone. The patient had been using sunitinib daily as an antineoplastic agent after BP treatment and MRONJ occurrence was thought to be associated with sunitinib usage. However, serum CTX values of 15 patients after BP treatment were lower than 150 pg /ml and MRONJ did not develop in any other patients during the follow-up visits for 2 years. Therefore, CTX is not an exact definitive marker, and it may be more favorable to evaluate changes in the pre- and post-treatment CTX levels, rather than only evaluating CTX levels during active BP treatment for MRONJ risk assessment.
There are some limitations of this study. Although the study started with 72 patients, most of the patients left the study for various reasons and the study was completed with 34 volunteers. In addition, although oncology patients were treated with IV BP, all the endocrine patients included in the study were started on oral BP treatment. It was reported that the MRONJ occurrence rate in osteoporotic patients receiving long-term oral BP was reported at 0.1%, which increased to 0.21% when used for more than 4 years [5]. Considering that the possibility of MRONJ occurrence in patients using oral BP increased after 4 years, it was concluded that the 12-month period determined for this study was insufficient to determine MRONJ risk in endocrine patients. For this reason, clinical studies with more patients, who have the same type of BP treatment, are needed to obtain better results.
In conclusion, CTX values are not only evaluated after BP treatment, but also may be checked before BP treatment to determine the course of the treatment. MRONJ can be prevented by performing all dental treatments before BP treatment and eliminating local risk factors. Thus, clinicians should consult with oral surgeons before BP treatment even if the patient has no dental complaints.
Acknowledgment
This study was reported as an oral presentation in 13th International Congress of ACBID with EACMFS Endorsement, in 2019.
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: Erciyes University Scientific Research Projects Unit supported this study (TSA-2015 5965).
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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Fatma Dogruel, Canay Yilmaz Asan, Emine Fulya Akkoyun, Taha Pergel, Erdem Kilic, Fahri Bayram. Evaluation of serum C-terminal telopeptide (CTX) value for the risk of medication related osteonecrosis of the jaws. Ann Clin Anal Med 2023;14(5):428-432
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Effects of lidocaine, gabapentin, and dexmedetomidine on hemodynamic response during laryngoscopy and intubation
Arif Coskun Uzun 1, Lutfiye Pirbudak 2, Elzem Sen 2, Ayse Mizrak Arslan 2
1 Department of Anesthesiology and Reanimation, Düzce Atatürk State Hospital, Düzce, 2 Department of Anesthesiology and Reanimation, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey
DOI: 10.4328/ACAM.21586 Received: 2023-01-11 Accepted: 2023-02-11 Published Online: 2023-03-08 Printed: 2023-05-01 Ann Clin Anal Med 2023;14(5):433-437
Corresponding Author: Elzem Sen, Department of Anesthesiology and Reanimation, Faculty of Medicine, Gaziantep University, 27310, Gaziantep, Turkey. E-mail: drelzemsen@gmail.com P: +90 532 784 21 51 F: +90 342 360 39 98 Corresponding Author ORCID ID: https://orcid.org/0000-0003-3001-7324
This study was approved by the Ethics Committee of Gaziantep University (Date: 2008-06-30, No: 06-2008/133)
Aim: In this study, we aimed to compare the preventive effects of lidocaine, gabapentin and dexmedetomidine on hemodynamic response secondary to laryngoscopy and intubation.
Material and Methods: One hundred twenty ASA I-II patients, aged between 18-50 years who underwent elective tympanomastoidectomy under general anesthesia were enrolled in the study. Patients were randomly divided into 4 groups, each containing 30 patients. Groups 1, 3, and 4 were given placebo tablets orally 1 hour before the operation, Group 2 was given 1600 mg of gabapentin. Ten minutes before the operation, 1.5 mg/kg of 2 % lidocaine was applied to Group 1, 10 ml iv physiological serum was applied to Group 2, 1 mg/kg dexmedetomidine was applied to Group 3 and 10 ml iv physiological serum was applied to Group 4.
Results: Heart rates were significantly lower in Group 3 during induction, 3, 5. minutes after induction and in Group 2, 3, 5. minutes after induction when compared to other groups (p<0.05). OAP values in Groups 1 and 4 at 3 minutes after induction were significantly higher than basal values at 3 minutes (p<0.05).
Discussion: Dexmedetomidine and gabapentin applied before induction were found to be successful in the suppression of hemodynamic response secondary to intubation and in providing a stabilized hemodynamic status.
Keywords: Dexmedetomidine, Gabapentin, Hemodynamic Response, Intubation, Lidocaine
Introduction
Laryngoscopy and tracheal intubation performed during general anesthesia have been known to produce adverse hemodynamic stress responses, such as tachycardia, systemic hypertension, and arrhythmia [1]. Adverse effects are more pronounced in patients with conditions such as coronary artery disease, myocardial infarction, or intracranial aneurysm. Certain medications such as beta-blockers, lignocaine, and opioids are used to mitigate the negative effects of laryngoscopy and intubation [2].
Gabapentinoids are second-generation anticonvulsants that are effective in the treatment of chronic neuropathic pain. Gabapentin binds to the α2δ subunit of voltage-gated Ca2+ channels that maintain increased release of pain transmission at nerve connections between primary afferent fibers and secondary common sensory nerves in chronic pain states. At the same time, it has been argued that its perioperative use effectively reduces the response to postoperative analgesia, preoperative anxiolytics, laryngoscopy, and intubation, while preventing postoperative chronic pain, postoperative nausea, vomiting, and delirium [3,4].
Lidocaine is a local anesthetic and is thought to effectively suppress the hemodynamic response to endotracheal intubation [5]. Dexmedetomidine is an imidazole derivative that binds with high selectivity to α2 receptors. These receptors are located in various structures such as blood vessels that regulate vasodilation, sympathetic terminals that inhibit the release of norepinephrine, the central nervous system that reduces both sedation and activity of the vagus, and the spinal cord that regulates analgesia [6].
This study was designed to compare the efficacy of lidocaine, gabapentin, and dexmedetomidine in suppressing the stress response induced by laryngoscopy and endotracheal intubation.
Material and Methods
The study was conducted after obtaining the written informed consent from the patients and the approval of the local ethics committee (06-2008/13). A total of 120 patients between the ages of 18 and 50 in the American Society of Anesthesiologists (ASA) I–II risk group who were planned to undergo elective tympanomastoidectomy were included in the study. This study was conducted in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki revised in the year 2000.
The following patients were excluded from the study: those allergic to anesthetics or any other drugs, those with an alcohol or drug addiction, psychiatric and neurological disorders, asthma, hematologic disorders, hepatic and renal failure, cardiac disease, uncontrolled hypertension, hypovolemia or dehydration, or those found to be obese (body mass index over 30), pregnant or in ASA II, which were considered to cause difficulty in intubation or providing airway (a Cormack–Lehane and Mallampati score of III or IV).
One day before surgery, the patients were informed in detail and in an understandable way about the procedure to be performed and their written consent was obtained. The ASA and Mallampati classifications were determined through physical examination of the patients. No premedication was administered to them. The patients were randomly divided into four groups each with 30 subjects. Group 1 (lidocaine, n=30) cases: supplemented to 10 ml with an oral placebo tablet (sugar tablet) one hour before surgery and 1.5 mg/kg IV lidocaine (Aritmal®, Biosel, Istanbul) SF 10 minutes before surgery. Group 2 (gabapentin, n=30) cases: 1600 mg gabapentin orally (Neurontin®, Pfizer, Istanbul) one hour before surgery and 10 ml IV saline (SF) 10 minutes before surgery. In Group 3 (dexmedetomidine, n=30) cases: supplemented to 10 ml one hour before surgery with an oral placebo tablet and with 1 μg/kg IV dexmedetomidine (Precedex®, Abbott, USA) SF 10 minutes before surgery. Group 4 (control, n=30) cases: administered an oral placebo tablet one hour before surgery and 10 ml IV saline 10 minutes before surgery. The gabapentin and oral placebo tablets used in the study were administered by a nurse who had no affiliation with the study. Patients were routinely monitored with electrocardiogram (ECG), peripheral oxygen saturation (SpO2), and mean arterial pressure (MAP). After preoxygenation with a mask for 5 minutes with 6 l/min 100% O2, intravenous induction was performed with 1 µg/kg fentanyl (Fentanyl®, Abbott, USA), 2 mg/kg propofol (Propofol® 1%, Fresenius Kabi, Germany) or 0.1 mg/kg vecuronium bromide (Norcuron®, Organon, Netherlands). At 3 minutes after loss of verbal response and ciliary reflex, intubation was performed. Anesthesia was maintained with a gas flow of 3 l/min from 50% oxygen, 50% air, and one MAC sevoflurane (Sevorane, Abbott, UK) inhalation. To maintain muscle relaxation, an additional 0.02 mg/kg of vecuronium was administered as required. Cormack–Lehane classification was recorded for each patient.
HR, SpO2, and MAP values were recorded preoperatively, during induction, at 1, 3, 5, 10 and 15 minutes after induction, and every 30 minutes thereafter. After discontinuation of sevoflurane five minutes before the end of skin suture removal, and spontaneous breathing or muscle movement in the patient, neuromuscular blockade was antagonized with 0.02 mg/kg atropine (Atropine®, Biosel, Istanbul) and 0.06 mg/kg neostigmine (Neostigmine®, Adeka, Samsun). Patients were extubated when they had adequate spontaneous breathing. Anesthesia duration was determined as the time from IV induction drug administration to inhalant occlusion, and surgical duration was determined as the time from skin incision to the removal of the last skin suture. The duration of extubation was also measured and recorded. The duration of the Aldrete score of 8 was recorded.
Any side effects experienced by the patients were recorded. If hypotension (more than 30% decrease from the initial MBP value) or bradycardia (HR < 45 beats/min.) developed, the inhalant concentration was to be reduced by 50% and 250 ml of saline was to be rapidly administered. If these findings persisted, hypotension would be treated with 5–10 mg IV ephedrine (Efedrin®, Biosel, Istanbul) and by administering 0.5 mg IV atropine if bradycardia occurred. If HR and MAP exceeded 30% of the control value, the inhalant concentration would be increased by 50%. Any side effects (hypotension, nausea, vomiting, tremor, headache) within the first 10 minutes after surgery were recorded.
The SPSS (Statistical Package for Social Sciences) package program for Windows 13.0 was used for statistical analysis of the findings obtained in the study. The chi-square test was used to compare categorical measurements. A one-way ANOVA test was used for statistical analysis. Any significantly altered parameters were then compared with Tukey’s test as a post-hoc test. In the evaluation of hemodynamic parameters, group comparison was performed using a one-way ANOVA test. The results were within the 95% confidence interval and p < 0.05 was considered statistically significant. Data were expressed as mean ± standard deviation.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
The demographic characteristics of the cases included in the study, their Cormack–Lehane (C-L) classification, and their Mallampati classification, duration of anesthesia, and surgical duration are shown in Table 1.
There was no statistically significant difference between the groups in terms of loss of response to verbal stimuli and duration of loss of eyelash reflex (Table 2).
When comparing the groups in terms of HR, HR values were found to be significantly lower at induction, immediately after intubation (3rd minute after induction), and at the 5th minute after induction in Group 3 compared to the other three groups. HR values immediately after intubation (3rd minute) and at the 5th minute after induction were significantly lower in Group 2 compared to Group 1 and Group 4. When the groups were compared in terms of mean arterial pressure (MAP), MAP values immediately after intubation (3rd minute after induction), and at the 5th, 10th, and 15th minutes after induction were significantly lower in Group 3 compared to the other three groups (Figure 1).
When spontaneous breathing time, extubation time, eye-opening time, and Aldrete score of 8 were evaluated between groups, it was found that the recovery data for Group 4 was significantly longer than for all other groups (Table 2).
Discussion
The main problems resulting from the hemodynamic response to laryngoscopy and tracheal intubation are tachycardia and hypertension. The hemodynamic response to laryngoscopy and tracheal intubation is suppressed by various medications, such as narcotic analgesics, deep inhalation anesthetics, local anesthetics, adrenoreceptor blockers, and vasodilators.
When the groups were compared in this study, HR values during induction, at the 3rd and 5th minutes after induction, MAP at the 3rd, 5th, 10th, and 15th minutes after induction, in the dexmedetomidine group were significantly lower than those of the other three groups. It was also found that HR values were significantly lower in the gabapentin group at 3 and 5 minutes after induction compared with the lidocaine and placebo groups. Dexmedetomidine generated better outcomes than the other three groups in terms of hemodynamic response to intubation. Gabapentin neither suppressed nor induced a pressure response. The hemodynamic data of the lidocaine group did not differ from that of the placebo group.
Cardiovascular problems resulting from sympathetic and sympathoadrenal reflexes are common complications of intubation [7]. Mendonça et al. compared the effects of esmolol and lidocaine in preventing a hemodynamic response due to endotracheal intubation. In their study, 69 ASA I–II patients aged between 18 and 70 years were randomly divided into two groups. Esmolol was found to be safer and more effective in reducing the incidence of tachycardia and controlling heart rate after tracheal intubation compared with lidocaine [8]. In this present study, it was found that lidocaine does not adequately suppress the hemodynamic response to laryngoscopy and intubation, similar to the findings of the cited study. In addition, Zou et al. [9] reported that 1 6and 1.5 mg/kg intravenous lidocaine as an adjunct to sufentanil for induction of general anesthesia slightly lowered blood pressure after endotracheal intubation, without side effects. However, it was emphasized that it was unable to suppress the increase in heart rate caused by endotracheal intubation.
Mahiswar et al. [10] compared two groups administered 0.5 μg/kg dexmedetomidine (Group D) and 2 μg/kg fentanyl (Group F) before induction to reduce hemodynamic response to tracheal intubation. Conducted with 100 patients, this study concluded that dexmedetomidine 0.5 μg/kg administered as a bolus is as effective as fentanyl in attenuating the hemodynamic response to tracheal intubation. Reddy et al. [11] showed that the use of a single dose of dexmedetomidine before induction of general anesthesia is an effective method of reducing hemodynamic response to tracheal intubation.
In their study, Gulabani et al. concluded that administration of 1 μg/kg dexmedetomidine 10 minutes before induction of anesthesia effectively reduced hemodynamic response to laryngoscopy and intubation. In addition, 1.5 mg/kg lignocaine administered three minutes before laryngoscopy and intubation was more effective than 0.5 µg/kg dexmedetomidine in reducing the increase in systolic and diastolic blood pressure three minutes and five minutes after endotracheal intubation [12]. In this present study, the hemodynamic data of the lidocaine group did not differ from that of the placebo group, but it was found that 1 μg/kg IV dexmedetomidine 10 minutes before surgery was an effective agent that can be used to prevent hemodynamic response to intubation.
Gupta et al. [13] compared dexmedetomidine and clonidine as adjuvants to low dose opioids in attenuation of hemodynamic response to intubation. They found that the rise in HR and MAP at laryngoscopy and intubation was less in clonidine group as compared to fentanyl group, and dexmedetomidine was able to attenuate this rise completely.
Parida et al. [14] found that oral gabapentin (800 mg) administered alone as premedication two hours before laryngoscopy and intubation did not cause a significant decrease in hemodynamic responses compared with intravenous fentanyl administered five minutes before induction of anesthesia. They also found that the administration of both drugs had no additional benefit over administration of IV fentanyl alone. For this reason, they indicated that it may not be possible to obtain a satisfactory outcome in response to tracheal intubation with the anesthetic regimen they followed using an oral dose of gabapentin. In their study on 100 patients with controlled hypertension, Bala et al. found that a single or double dose of 800 mg gabapentin was equally effective as premedication for laryngoscopy and tracheal intubation [15]. In this present study, gabapentin was found to suppress the tachycardic response to intubation well. In addition, it was found that it provides stable hemodynamics by not causing an increase in blood pressure in response to intubation.
Ninety minutes before surgery, Kapse et al. gave 5 μg/kg clonidine orally to 30 patients and 800 mg gabapentin orally to another 30 patients. They found that both drugs effectively reduced the hemodynamic response to direct laryngoscopy. They reported that they lowered blood pressure equally, while gabapentin induced greater postoperative sedation. In this present study, gabapentin was found to be effective at suppressing the tachycardic response [16]. Similarly, Sharma et al. reported that 900 mg gabapentin administered orally two hours before induction of anesthesia is an effective premedication agent that can be used to reduce the hemodynamic response to laryngoscopy and intubation [17]. In their study on 90 patients, Vijayan et al. [18] showed that 1 μg/kg dexmedetomidine administered 10 minutes before induction is a valuable assistant to the balanced anesthesia technique to maintain hemodynamic stability. Singhal et al. [19] reported that 200 μg/kg clonidine administered orally 90 minutes before anesthesia was more effective in reducing the hemodynamic response to laryngoscopy and intubation compared with orally administered gabapentin (900 mg). In their meta-analysis, Doleman et al. [20] demonstrated the beneficial effects of gabapentin in reducing the hemodynamic response to intubation. In this present study, gabapentin was more effective than lidocaine and placebo in suppressing the hemodynamic response to laryngoscopy and intubation.
It has been reported that administration of 0.6 μg/kg dexmedetomidine before induction of anesthesia can reduce the stress response during intubation and stabilize hemodynamics. In addition, it has been shown that the onset of spontaneous breathing and extubation time are prolonged in dexmedetomidine-treated groups compared with non-administered groups [21].
In this present study, dexmedetomidine was effective in suppressing the hemodynamic response, similar to the results reported by Ye et al. [22]. This present study also found that dexmedetomidine was superior to both the control group and the lidocaine and gabapentin groups in suppressing the hemodynamic response. In addition, recovery time and time to leave the operating room were found to be shorter in the groups given lidocaine, gabapentin, and dexmedetomidine compared to the placebo group.
Conclusion
In conclusion, gabapentin and dexmedetomidine was more effective than lidocaine and placebo in suppressing the hemodynamic response to laryngoscopy and intubation. Hemodynamic parameters were more stable in patients treated with gabapentin and dexmedetomidine compared to those treated with lidocaine and placebo. Administration of dexmedetomidine before induction in patients undergoing tympanomastoidectomy provided acceptable surgical conditions by reducing the heart rate and blood pressure to acceptable levels throughout surgery. Dexmedetomidine and gabapentin have therefore been found to be effective agents in preventing hemodynamic response to intubation.
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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Arif Coskun Uzun, Lutfiye Pirbudak, Elzem Sen, Ayse Mizrak Arslan. Effects of lidocaine, gabapentin, and dexmedetomidine on hemodynamic response during laryngoscopy and intubation. Ann Clin Anal Med 2023;14(5):433-437
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Approaches of pediatricians about vaccines: Meningococcal, rotavirus and human papillomavirus vaccines
Özlem Üzüm 1, Gülberat İnce 1, Eda Karadağ Öncel 2
1 Department of Pediatrics, University of Health Sciences, Tepecik Education and Research Hospital, 2 Department of Pediatric Infectious Diseases, University of Health Sciences, Tepecik Education and Research Hospital, Izmir, Turkey
DOI: 10.4328/ACAM.21591 Received: 2023-01-16 Accepted: 2023-02-17 Published Online: 2023-02-24 Printed: 2023-05-01 Ann Clin Anal Med 2023;14(5):438-442
Corresponding Author: Özlem Üzüm, Department of Pediatrics, University of Health Sciences, Tepecik Education and Research Hospital, Izmir, Turkey. E-mail: baspinarozlemm@hotmail.com P: +90 507 785 96 37 Corresponding Author ORCID ID: https://orcid.org/0000-0003-3297-7476
This study was approved by the Ethics Committee of Tepecik Education and Research Hospital (Date: 2022-07-18, No: 2022/07-11)
Aim: Vaccination rates change among countries. Except for vaccinations from the Ministry of Health, special vaccination programs such as meningococcal, rotavirus, and human papillomavirus are also effective for the diseases. In this study, it was aimed to evaluate the knowledge of pediatricians working in the pediatric clinic about meningococcal, rotavirus, and HPV vaccines.
Material and Methods: In this cross-sectional survey study, age, gender, and work duration were recorded in the questionnaire. Recommendations for meningococcal, rotavirus, and HPV vaccines, the vaccination preferences of the physicians, and the information about the times and side effects of vaccinations were recorded. Relationships between physicians’ knowledge, approaches to these vaccines and gender, and work durations were evaluated.
Results: General pediatric residents were 66.3% (n=59) of the physicians, and 43.7% (n=30) were general pediatricians. Twenty-four (27%) of the residents had less than two years, and 35 (39.3%) had more than two years of work. Nearly all physicians recommended meningococcal, rotavirus, and HPV vaccines. Between residents and specialists, no difference was observed. However, it was seen that more accurate vaccination information was chosen in 2-4 years workers of residents and 1-10 years workers of specialists.
Discussion: Physicians should have sufficient and updated information about vaccines to prevent diseases. The survey studies like this study provide an opportunity for physicians to update their knowledge, and to be sensitive to these diseases, which are not included in the routine vaccination program.
Keywords: Human Papillomavirus Vaccines, Meningococcal, Pediatrician, Rotavirus, Vaccine
Introduction
Vaccines are the best and most effective public health intervention in all health protection approaches due to protecting against morbidity and mortality from many diseases [1]. Vaccination rates change across countries, but they tend to decrease due to vaccine hesitancy and rejection all over the world [1,2]. With the Immunization Program in our country, significant progress has been made in combating infectious diseases, but the study made by Kara et al., found that the rates of fully vaccinated 18-24 months-old children during the pandemic have decreased by nearly 0.4–6,9% [3].
The recommendation of Meningococcal vaccinations by pediatricians ranks first due to the high morbidity and mortality rates it causes [4,5]. Of the meningococcal vaccines, MenACWY-DT (Menectra®) has been licensed for use in our country since 2012, MenACWY-CRM (Menveo®) since 2016, MenACWY-TT (Nimenrix®) since 2016 and MenB-4C (Bexsero®) since 2018 [5,6].
The most common cause of diarrhea in this age group is rotavirus among viral causes, and its frequency varies between 32.4% and 67.4% in studies [7,8]. There are 2 licensed oral rotavirus vaccines in our country; five-valent RotaTeq® (RV5) and monovalent Rotarix® (RV1) vaccines [7].
Human papillomavirus (HPV) is the most common sexually transmitted viral agent that causes cervical, anogenital, and oropharyngeal cancers [4,9,10]. The quadrivalent vaccine (Gardasil), covering HPV types 6, 11, 16, and 18, was approved for girls aged 9-26 in 2006 and for boys in the same age group in 2009 [4]. In studies of our country, vaccination rates change between 1.4-29% [11,12].
Data showed that pneumococcal vaccines alone are not sufficient to protect against meningitis, and meningococcal infections cause meningitis after the increase in international visits in our country, as in the whole world, and the continuity of vaccination should be ensured in the study of our country; Neisseria meningitides was detected in 56.5%, Streptococcus pneumoniae in 22.5%, and Haemophilus influenzae type b in 20.5% of the meningitis cases [13,14]. The effectiveness of the rotavirus vaccine in the dehydration period and the absence of side effects like invagination have also been shown. The efficacy and safety of the HPV vaccine have been proven many times. For this reason, the knowledge and approaches of pediatricians should be at such a level as to convince the family of the need for these vaccines.
In this study, we aimed to evaluate the knowledge and preferences of pediatricians working in the pediatric clinic of our tertiary hospital about meningococcal, rotavirus, and HPV vaccines and to draw the attention of our physicians to this issue.
Material and Methods
In this cross-sectional survey study, a questionnaire prepared by the authors was applied to pediatric residents, pediatric specialists, and pediatric subspecialists working in our hospital between July and September 2022. The study started with the permission of the local ethics committee (18/07/2022, decision no: 2022/07-11). Verbal and written consent was obtained from volunteer physicians before starting the survey. Physicians whose consent could not be obtained face-to-face due to permissions, physicians who did not consent to participate, or questionnaires with missing data were not included in the study.
Age, gender, and work duration were recorded in the questionnaire. Pediatric specialists and pediatric subspecialists were accepted as specialists. Recommendations for Meningococcal, rotavirus, and HPV vaccines, the reasons why the physicians did not recommend it, vaccination preferences of the physicians who recommended it, and information about the times and side effects of vaccinations were recorded. Two months for the first dose of meningococcal vaccine, 6 weeks to 14 weeks-6 days for the first dose of rotavirus vaccine, 8 months for the last dose of rotavirus vaccine, and the age of 9 years for the first dose of HPV vaccine were accepted as correct answers. The duration of practice was grouped as less than two years and more than two years for residents, and less than ten years and more than ten years for specialists. The relationships between physicians’ knowledge and approaches regarding meningococcal, rotavirus, and HPV vaccines with gender, and work durations were evaluated.
Statistical analysis
Statistical analysis was performed in SPSS Software 22.0 (Statistical Package for Social Sciences, Chicago, IL, USA). In the analysis of data on categorical (qualitative) variables, number and percentage values were used. The Chi-square test was used to compare group ratios. Student-t test was used to compare group means. The finding of p<0.05 as a result of statistical analysis was accepted as significant.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
At the time of the study, there were 82 pediatric specialists and subspecialists, and 65 pediatric residents in the pediatrics clinic of our hospital. A total of 89 physicians participated in the survey. The mean age was 30.7±5.0 years and 83.1% of the cases were female. General pediatric residents were 66.3% (n=59) of the physicians, 43.7% (n=30) were general pediatricians, and the duration of work was 6.5±5.4 (1-22) years. Twenty-four (27%) of the residents had less than two years, and 35 (39.3%) had more than two years of work. Eight of the specialists (9%) had been practicing for less than ten years and 22 (24.7%) had been practicing for more than ten years.
In this study all physicians recommended meningococcal vaccine, 91% of the physicians recommended the Rotavirus vaccine, and 96.6% of the physicians recommended the HPV vaccine (Table 1). While 92.1% (82) of the physicians suggested all serotypes of meningococcus, 4.5% (4) of them suggested ACWY serotype and 1.1% (1) B serotype, while two physicians stated that they were undecided. 87.6% (78) of the physicians stated that they recommend the HPV vaccine to both genders. The knowledge and approaches of physicians regarding these three vaccines are summarized in Tables 1, 2, 3.
There were no differences between residents and specialists in recommending rotavirus and HPV vaccines, correctly knowing the dose times of vaccines, and adding these vaccines to the routine. When residents and specialists were evaluated according to their duration of work, it was seen that more accurate vaccination information was chosen in 2-4 years workers of residents and 1-10 years workers of specialists (Table 3).
Discussion
In this study, nearly all physicians recommended meningococcal, rotavirus, and HPV vaccines. There were no differences between residents and specialists in recommending rotavirus and HPV vaccines, correctly knowing the dose times of vaccines, and adding these vaccines to the routine. However, it was seen that more accurate vaccination information was chosen among residents working 2-4- years and among specialists working 1-10- years.
The majority of the physicians participating in our study were women. In the pediatric clinic, 37 (25.2%) male and 110 (74.8%) female pediatricians provide health services. Therefore, the participation rate of females was thought to be similar to the rate of total physicians.
In our study, all of the physicians recommended the meningococcal vaccine and almost all wanted it to be added to the routine vaccination program. Nearly 80% of physicians recommended rotavirus and HPV vaccines and wanted them to be added to the routine. In different studies conducted in our country and the world, it has been observed that all physicians recommend the meningococcal vaccine, especially 40.7% of physicians recommend it to all patients regardless of risk, while 80% of physicians recommend rotavirus and HPV [15-17]. After the routine vaccination program for Haemophilus influenzae type b and Streptococcus pneumonia, N. meningitis ranked first etiology in meningitis [5,17]. The clinical course of N. meningitis cases is severe, the morbidity and mortality are high in these cases, especially in children younger than one year of age [18,19]. This situation was thought to cause physicians to be more sensitive and knowledgeable about meningococcus. However, in the study, it was observed that one-fourth of the physicians did not know the first dose time of the vaccine. There are four licensed vaccines for meningococcus in our country. Due to the different times, and number of doses among vaccinations, it was thought that there were different answers.
In the study, 92% of the physicians recommended both strains of the meningococcal vaccine. As in the whole world, meningococcal serotypes vary from year to year and country to country. While A, C, and Y strains were ranked first in the first studies, W and B strains were ranked first in the current studies [20,21]. Our hospital is a comprehensive tertiary hospital located in this region and is a center where severe cases are referred, patients with this condition are treated frequently, and examination and treatment, are considered in every suspected case. It was thought that the data on the meningococcal vaccine was sufficient for our physicians to have sufficient knowledge, but updating the information about licensed vaccines would be beneficial in terms of attracting the attention of physicians, completing their deficiencies, and raising their awareness.There was no difference between residents and specialists in this study. Different results have been reported in many studies about the recommendation of physicians for non-routine vaccines. In many studies, physicians with long working duration were found to recommend non-routine vaccines more frequently due to more experience [22,14]. However, there are studies in which there has been no difference in the duration of working [5,14]. Due to the close follow-up of a healthy child and the frequent training on the importance of vaccines in these pediatric clinics, the information of the residents and specialists was found to be similar. However, it was observed that residents in the last two years had more true information than the first two years. The duration of the first two years of residents is short for the experience. The residents of the first two years generally work in the pediatric service and intensive
care units, these physicians have little experience in vaccinations due to their low outpatient experience. In addition, physicians who were in the first 10 years of their specialization in our study had more correct information. Due to the freshness of their educational information, it is seen that physicians who have just started their specialization are more sensitive to these issues. For this reason, the sensitivity about the learning information about vaccines should be imparted for the vaccination of inpatients too, and these physicians with high recommendations rate for vaccinations should be expected to have sufficient data about vaccines.
Vaccine hesitancy has increased in our country as well as all over the world. In addition, the high cost of vaccines that are not in routine vaccination programs according to the countries also causes a decrease in the application of these vaccines. These are reasons for reducing vaccination for families. The most common reason for not recommending vaccines by physicians was generally lack of knowledge [4]. Additionally, the cost of non-routine vaccines cause pediatricians and family members to prefer vaccines such as meningococcus vaccines with a high risk of being fatal when infected, rather than rotavirus and HPV vaccines [4,24,25]. HPV is a sexually transmitted disease and recommending a vaccine against this disease is perceived by some pediatricians and parents that children under eighteen can be sexually active and be allowed this [21,22]. For this reason, this vaccine is generally recommended at nearly 30%, less than other non-routine vaccines [23-25]. It is even seen that due to the duration of sexual intercourse, some physicians prefer to recommend vaccination after the age of 12 [17,25].
Conclusion
Vaccination is the most effective, least costly, and safest approach to protect the health of society. Due to this, physicians should have sufficient and updated information about vaccines to prevent diseases. Also, they should have safe communication with parents, which is seen as the most effective method in reducing vaccine refusal or hesitancy. Survey studies like this study provide an opportunity for physicians to update their knowledge, and to be sensitive to these diseases, which are not included in the routine vaccination program.
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. Bozkurt HB. An Overview of Vaccine Rejection and Review of Literature. Kafkas J Med Sci. 2018; 8(1): 71–6.
3. Kara A, İlbay S, Topaç O, Arabulan EA, Tezer H, Tavukçu N, et al. Alteration in vaccination rates and an evaluation of physicians’ perceptions of the possible impact of the SARS-CoV-2 pandemic on childhood vaccinations in Ankara, Turkey. Hum Vaccin Immunother. 2021; 17(10): 3457–62.
4. Adıgüzel A, Akgül S, Düzçeker Y, Derman O, Kanbur N. Knowledge and attitudes of pediatricians to the human papillomaviruses vaccines. Çocuk Sağlığı ve Hastalıkları Dergisi/ Journal of Child Health and Diseases. 2018; 61: 53-8.
5. Kapar A, Yilmaz S, Ergen Dibeklioğlu S, Akay A, Turan T. The evaluation of approaching to meningococcal vaccines and knowledge levels of residents and pediatricians. Troia Med J. 2021; 2(3): 90-6.
6. Assaf-Casals A, Dbaibo G. Meningococcal quadrivalent tetanus toxoid conjugate vaccine (MenACW-TT, NimenrixTM): A review of its immunogenicity, safety, co-administration, and antibody persistence. Hum Vaccin Immunother. 2016; 12(7): 1825-37.
7. Kocabaş E, Timurtaş Dayar G. Rotavirus Vaccines. J Pediatr Inf. 2015; 9: 166-74.
8. Liu L, Johnson HL, Cousens S, Perin J, Scott S, Lawn JE, et al. Global, regional, and national causes of child mortality: an updated systematic analysis for 2010 with time trends since 2000. Lancet. 2012; 379 (9832): 2151-61.
9. Satterwhite CL, Torrone E, Meites E, Dunne EF, Mahajan R, Bañez Ocfemia C, et al. Sexually transmitted infections among US women and men: prevalence and incidence estimates, 2008. Sex Transm Dis. 2013; 40(3): 187-93.
10. Ozyer S, Uzunlar O, Ozler S, Kaymak O, Baser E, Gungor T, et al. Awareness of Turkish female adolescents and young women about HPV and their attitudes towards HPV vaccination. Asian Pac J Cancer Prev. 2013; 14(8): 4877-81.
11. Yilmazel G, Duman NB. Knowledge, attitudes and beliefs about cervical cancer and human papilloma virus vaccination with related factors in Turkish university students. Asian Pac J Cancer Prev. 2014; 15(8): 3699-704.
12. Güvenç G, Akyüz A, Seven M. Determination of the knowledge and attitudes of nursing students about human papilloma virus infection and its vaccines. Gülhane Med J. 2012; 54(2):104-10.
13. Ceyhan M, Yildirim I, Balmer P, Borrow R, Dikici B, Turgut M, et al. Prospective Study of Etiology of Childhood Acute Bacterial Meningitis. Emerg Infect Dis. 2008; 14(7): 1089-96.
14. Özkaya Parlakay A, Yiğit M, Gülhan B, Bedir Demirdağ T, Kanik Yüksek S. Evaluation of Opinions of Pediatrists in A Tertiary Healthcare Hospiatal About Meningococcal, Rotavirus, Human Papilloma Virus Vaccines and İncidence of Encountering Vaccine Refusal and Reasons of Vaccine Refusal. Turkish J Pediatr Dis. 2020; 14:264-7.
15. Yıldırım M, Düzovalı Ö, Kanık A, Kırık Ö. Knowledge and Attitudes of The Pediatricians in Turkey Regarding Human Papillomavirus (HPV) Vaccine. J Pediatr Inf. 2009; 3:62-8.
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19. Dinleyici EC, Ceyhan M. The dynamic and changing epidemiology of meningococcal disease at the country-based level: The experience in Turkey. Expert Rev Vaccines. 2012; 11(5): 515-8.
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Download attachments: 10.4328.ACAM.21591
Özlem Üzüm, Gülberat İnce, Eda Karadağ Öncel. Approaches of pediatricians about vaccines: Meningococcal, rotavirus and human papillomavirus vaccines. Ann Clin Anal Med 2023;14(5):438-442
Citations in Google Scholar: Google Scholar
Investigation of DKK-1 (DICKKOPF-1) and DKK-3 (DICKKOPF-3) levels before and after cardiopulmonary bypass
Ali Kaçan 1, Mehmet Salih Aydın 2, Reşat Dikme 3, Mahmut Padak 4
1 Department of Perfusion Techniques, 2 Department of Cardiovascular Surgery, Faculty of Medicine, 3 Department of Dialysis Program, 4 Department of Perfusion Techniques, Harran University, Şanlıurfa, Turkey
DOI: 10.4328/ACAM.21603 Received: 2023-01-19 Accepted: 2023-02-21 Published Online: 2023-02-25 Printed: 2023-05-01 Ann Clin Anal Med 2023;14(5):443-447
Corresponding Author: Reşat Dikme, Department of Dialysis Program, Harran University, 63300, Haliliye, Şanlıurfa, Turkey. E-mail: rdikme@harran.edu.tr P: +90 535 458 78 44 F: +90 414 318 32 09 Corresponding Author ORCID ID: https://orcid.org/0000-0001-9157-7830
This study was approved by the Clinical Research Ethics Committee of Harran University Faculty of Medicine (Date: 2019-12-30, No: 21)
Aim: According to recent studies related to coronary artery diseases, Dkk-1(Dickkopf-1) and Dkk-3(Dickkopf-3) levels in the blood have been found to be associated with the onset and progression of atherosclerosis. This study was carried out to investigate Dkk-1 and Dkk-3 levels in patients who underwent surgery with the cardiopulmonary bypass method.
Material and Methods: Thirty patients who were operated on by the cardiopulmonary bypass method were included in this study. Venous blood samples were taken from the patients before and after cardiopulmonary bypass, and Dkk-1 and Dkk-3 proteins were measured using the ELISA method.
Results: As a result of the study, a statistically significant difference was observed between Dkk-1 values measured before and after cardiopulmonary bypass (p<0.01). Likewise, there was a statistically significant difference between Dkk-3 values measured before and after cardiopulmonary bypass (p<0.05).
Discussion: The decrease in Dkk-1 and Dkk-3 levels before cardiopulmonary bypass after surgery shows that these values are important in terms of protection against atherosclerosis. With these parameters, which have been observed to have protective effects against the formation of atherosclerosis and against atherosclerosis, possible heart damage can be prevented with therapeutic strategies that reduce myocardial damage.
Keywords: Atherosclerosis, Dkk-1(Dickkopf-1), Dkk-3(Dickkopf-3), Cardiopulmonary Bypass
Introduction
Coronary artery disease (CAD) is the third leading cause of death worldwide and is associated with 17.8 million deaths per year [1].
Atherosclerosis is a progressive inflammatory disease of the arterial wall that can remain clinically asymptomatic for years before triggering acute attacks such as myocardial infarction or stroke, which are among the first symptoms of CAD [2].
The condition has been reported to be generally associated with cholesterol deposition, macrophage infiltration, smooth muscle cell proliferation, connective tissue deposition, and the presence of a thrombus. In the early stages of atherosclerosis formation, thin fatty streaks form on the arterial wall due to endothelial cell damage. The accumulation of materials such as lipids and the proliferation of smooth muscle cells leads to the formation of advanced lesions known as atherosclerotic plaques containing fibrous layers of varying thickness. In humans, atherosclerotic plaques consisting of thin fibrous structures are irregular and in some cases break up, causing acute coronary syndromes [3].
The number of patients with ischemic heart disease (IHD) associated with CAD is also increasing, and IHD continues to be a significant health burden worldwide [4]. IHD manifests clinically as myocardial infarction and ischemic cardiomyopathy. IHD is the number one cause of death, disability, and human suffering globally. Age-adjusted rates show a promising decrease. However, health systems have to manage an increasing number of cases due to population aging [5].
There is a great need for studies aimed at finding effective ways for the prevention and treatment of CAD and to discover targeted molecules. In recent years, in studies on CAD, interest in primary prevention research has increased; studies on this subject are of great importance in reducing the incidence of CAD. Although many important advances have been made in the treatment of CAD, it is necessary to take steps to address the causes of the success of targeted therapies because it is important to determine the causes before applying a beneficial treatment [6]. Recently, new biomarkers have been investigated in addition to cardiac damage biomarkers, including Dkk-1 and Dkk-3.
Dkk-1, a founding member of the Dickkopf family, is a secreted glycoprotein most extensively characterized as an inhibitor of the canonical β-catenin-dependent Wnt pathway [7]. Wnt proteins regulate a variety of physiological processes including cell proliferation, differentiation, migration and apoptosis [8].
It acts by blocking 5 or 6 binding of Wnt ligands coreceptors to LRP (low-density lipoprotein receptor-related protein). This mode of action is not fully understood. However, this mechanism of action is indirect and involves the Wnt signal balance of Dkk-1 shifting from β-catenin-dependent pathways to β-catenin-independent pathways. Finally, in addition to binding to LRP5/6, Dkk-1 is a high-affinity ligand for the Krm (Kremen) 1 and 2 transmembrane proteins. The interaction between LRP6, Dkk-1 and Krm triggers LRP receptor internalization and degradation, thus providing an additional mechanism for Wnt signaling inhibition [9].
Dickkopf-3 (Dkk-3), on the other hand, appears to be a different member of the Dickkopf family. In contrast to the more closely related Dkk-1, 2 and 4, Dkk-3 is reported to be associated with Dickkopf-like protein 1, a potentially distant Dkk family member [10].
Human DKK-1, 2 and 4 are located on the same paralog chromosome set. However, DKK-3 is not part of this group. Also, unlike other members of the Dkk protein family, Dkk-3 does not affect the canonical Wnt/β-catenin pathway and does not bind to Krms, but rather regulates TGF-β signaling [11]. Moreover, in a pathological study in mice, DKK-3 was identified as a hormone that can induce endothelial cell migration, promote re-endothelialization, and prevent lesion formation in arterial vessels [12].
Like Dkk-1, Dkk-3 has been mainly investigated in oncology. It shows a suppressive effect in various types of cancer in humans and has been suggested to act therapeutically [10].
Material and Methods
Ethics committee approval
This study was approved by the Harran University Faculty of Medicine Clinical Research Ethics Committee, with the decision dated 30.12.2019, session numbered 08 and numbered 21.
Patients included in the study
This study was conducted in accordance with the Helsinki Declaration, which was revised in 1989. Thirty patients who were operated on by the cardiopulmonary bypass method were included in this study. Venous blood samples were obtained from the patients included in the study.
Obtaining Blood Plasma
In patients who underwent cardiac surgery with the CPB method, blood was drawn before and after CPB and put into sterile tubes with anticoagulant (heparin). The tube from which blood was drawn was immediately transferred to an ice-filled container and transported to the laboratory. The sterile tube was then centrifuged at 5000 rpm for 5 minutes. After the centrifugation step, the plasma, which is the supernatant part, was taken into an RNase-free tube (Eppendorf tube) and stored at -80 to be studied.
Analysis of Dkk-1(Dickkopf-1) and Dkk-3(dickkopf-3)
Enzyme-linked immunosorbent assay (ELISA) kit protocol was applied. The samples to be studied (Serum) were brought to room temperature at least 2 hours before. Samples in the 96-well plate were washed before adding, and standard/sample (100 μl) was added and incubated at 37°C for 90 minutes. The samples were removed and biotinylated detection antibody (100 μl) was added and incubated for 60 minutes. After washing, 100 μl of SABC working solution (HRP) was added to all wells. After 30 minutes of incubation, 90 μl of TMB substrate was added and when a visible color change was observed, stop solution (50 μl) was added and yellow color formation was observed. Optical density (OD) value at 450 nm (OD450 nm) was determined and the data were evaluated.
Measurement of Antioxidant and OS Parameters in Plasma
Total Antioxidant Status (TAS) Measurement
Measurement of (TAS in PS and plasma was performed using Rel Assay Diagnostics total oxidant capacity measurement kit (Rel Assay Diagnostics, Lot. No: HN20106A, Turkey). Plasma TAS levels were determined using a new automated measurement method developed by Erel [13].
Total Oxidant Status (TOS) Measurement
Rel Assay Diagnostics total oxidant capacity measurement kit (Rel Assay Diagnostics, Lot. No: OK20115O, Turkey) was used for the measurement of TOS in PS and plasma. Plasma TOS levels were determined using a new automated measurement method developed by Erel [14].
Oxidative Stress Index (OSI) Measurement
OSI was calculated by dividing it as Total Oxidant Level (TOS)/Total Antioxidant and expressed as Arbitrary Unit (AU).
Statistical analysis
The conformity of the data to the normal distribution was tested with the Kolmogorov-Smirnov and Shapiro-Wilk tests. Independent Samples t-test was used for those with the normal distribution of numerical variables, the Mann-Whitney U test was used for comparisons of two independent groups for those who did not, and One-way analysis of variance (ANOVA) and LSD multiple comparison tests were used for normally distributed features in comparisons of non-normally distributed features in more than two independent groups. For features, the Kruskal-Wallis test and all pairwise multiple comparison tests were used. As descriptive statistics, mean±standard deviation for numerical variables, number and percentage values for categorical variables are given. SPSS Windows version 24.0 package program was used for statistical analysis and p<0.05 was considered statistically significant.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
Demographic Data of the Working Group
Of the patients included in the study, 14 were female and 16 were male, with a mean age of 58 (years), height of 165.25 (cm), weight of 72.55 (kg) and body surface area (BSA) of 1.793 (m2) aspect calculated. The demographic characteristics of 30 patients included in the study are shown in Table 1.
ELISA Results in Plasma
The results of the optical density reading at 450 nm using commercial kits for the level determination of Dkk-1 and Dkk-3 in plasma by ELISA method and the results of OS Parameters are shown in Table 2.
Biochemical analysis results of blood samples taken from patients before and after CPB at the values indicated in Table 2, TOS, OSI and DKK-1 values were found to be statistically significant (*p<0.05, p<0.001). When the total antioxidant capacity (TAS) of the patients before and after CPB was compared, a significant increase was observed.
According to the correlation result in Table 3, there was a moderately significant negative correlation between TAS value and OSI value. There is a highly significant positive correlation between the TOS value and the OSI value.
Discussion
Considering the conditions that cause ischemic heart disease, factors such as unstable angina, myocardial infarction and acute coronary syndrome causing sudden death, fragmentation of irregular thrombotic plaques and coronary atherosclerosis can be mentioned [15].
It has been found over the years that the composition and fragility of the plaque, rather than the size of the plaque or the severity of the stenosis, are important determinants in the development of acute coronary syndrome. Because soft irregular plaques are more prone to disintegration than collagen-rich hard plaques, they become thrombogenic after degradation [16].
One of the most important factors that should be evaluated for the development of atherosclerosis that may develop in the coronary vessels, as well as the development of CAD, is the follow-up of irreversible cell and tissue damage. As a result of not following this situation and not taking the necessary precautions, the processes starting from the cell can manifest itself deeply with organ damage and sudden death. Before reaching this stage, the cell or tissue synthesizes biomarkers that provide information about its state. For example, with the formation of atherosclerosis, proteins such as DKK-1 and DKK-3 can actively provide some information about the current situation. Therefore, it may be necessary to monitor these parameters at certain intervals before the development of atherosclerosis and to take measures accordingly. In our study, pre- and postoperative Dkk-1(Dickkopf-1) and Dkk-3 (Dickkopf-3) levels of the patients were examined and the effect of the surgery on Dkk-1(Dickkopf-1) and Dkk-3 (Dickkopf-3) levels was investigated.
It is not known exactly how Dkk-1 protein affects the cardiovascular system. In a study by Ueland et al., they described the occurrence of increased Dkk-1 concentrations in patients with atherosclerotic disorders and in patients with symptomatic aortic stenosis [17].
Another study evaluated Dkk-1 levels in serum samples obtained at different times in a subgroup of approximately 5000 patients with acute coronary syndrome, based on the hypothesis that Dkk-1 may be associated with cardiovascular diseases. In the PLATO study, they reported that dual antiplatelet therapy (Platelet Inhibition and Patient Outcomes) was associated with a combination of cardiovascular death, myocardial infarction, or stroke, independent of the normal level of Dkk-1, in these patients [18]. In our study, the mean Dkk-1 value of the patients before CPB was 76.04 ng/ml, and the mean Dkk-1 value after CPB was 56.13 ng/ml. As a result of the study, it was observed that there was a statistically significant difference between the Dkk-1 values measured before and after CPB. This situation shows that the Dkk-1 value is important for the formation of atherosclerosis in parallel with other studies and that Dkk-1 level decreases after CPB.
Studies indicate that Dkk-1 is directly involved in proatherogenic states, suggesting that Dkk-1 activity may affect the pathophysiology of the arterial wall by modulating Wnt signaling. Guo et al. reported in their mouse studies that suppression of Wnt/β-catenin signaling by platelet-derived Dkk-1 causes acute lung injury and strengthens the infiltration of neutrophils into the pulmonary parenchyma [19].
A study using tandem stenosis model 13 vessel graft and rabbit models of atherosclerotic plaques was conducted to determine the therapeutic potential of DKK-3 in altering plaque composition. As a result of this study, they stated that DKK-3 has vascular effects associated with cardiovascular pathologies in addition to its strong tumor-suppressive effect [20].
The role of Dkk-3 in atherosclerosis has recently been discovered. In a prospective study, in contrast to Dkk-1, plasma Dkk-3 levels were inversely and independently associated with common carotid artery intima-media thickness and 5-year progression of carotid atherosclerosis, suggesting that this may protect against both early and advanced stages of atherogenesis stated [21].
In our study, the mean Dkk-3 (Dickkopf-3) value of the patients before CPB was 21.47 ng/ml, and the mean Dkk-3 (Dickkopf-3) value after CPB was 17.90 ng/ml. As a result of the study, it was observed that there was a statistically significant difference between Dkk-3 (Dickkopf-3) values measured before and after CPB. This shows that Dkk-3(Dickkopf-3) value is important in terms of protection against atherosclerosis, and Dkk-3(Dickkopf-3) level decreases after cardiopulmonary bypass.
When examined in terms of oxidative stress in our study, the mean preoperative OSI value was 1.35 ng/ml, the mean postoperative OSI value was 1.17 ng/ml. As a result of the study, it was observed that there was a statistically significant difference between the OSI values measured before and after the surgery. This shows us that the low mean postoperative OSI value is an important criterion for myocardial tissue damage and myocardial ischemia, and the OSI level decreases after cardiopulmonary bypass.
Conclusion
In the study, the protective effects of Dkk-1(Dickkopf-1) and Dkk-3(Dickkopf-3) against the formation of atherosclerosis and atherosclerosis were observed, and results were obtained in parallel with previous studies. Significant differences were observed in the levels of Dkk-1(Dickkopf-1) and Dkk-3(Dickkopf-3) proteins of the patients whose blood samples were taken before and after CPB. We can say that Dkk-1(Dickkopf-1) and Dkk-3(Dickkopf-3) proteins are important in cardiovascular diseases. In our study, mean Dkk-1(Dickkopf-1) values of the patients after CPB were 56.13 ng/ml, and these values were below the preoperative values. In this case, it was understood that the low Dkk-1(Dickkopf-1) value has a reducing effect on the formation of atherosclerosis. In our study, mean Dkk-3(Dickkopf-3) values of the patients after CPB were 17.90 ng/ml, and these values were below the preoperative values. This shows us that high Dkk-3(Dickkopf-3) values are important in preventing atherosclerosis.
It is anticipated that the results of this research, which examines the formation of atherosclerosis and the reducing effects of Dkk-1(Dickkopf-1) and Dkk-3(Dickkopf-3) proteins, will be a guide for scientists. In order for the research to be more inclusive, it is necessary to conduct research in larger sample groups.
Acknowledgment
Thanks to all the authors who contributed to the realization of this work.
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.21603
Ali Kaçan, Mehmet Salih Aydın, Reşat Dikme, Mahmut Padak. Investigation of DKK-1 (DICKKOPF-1) and DKK-3 (DICKKOPF-3) levels before and after cardiopulmonary bypass. Ann Clin Anal Med 2023;14(5):443-447
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The correlation between computed tomography reports and histopathological results in acute appendicitis
Fatih Yıldırım, Burak Uçaner, Oğuz Hançerlioğulları
Department of General Surgery, University of Health Sciences, Gülhane Training and Research Hospital, Ankara, Turkey
DOI: 10.4328/ACAM.21608 Received: 2023-01-21 Accepted: 2023-02-25 Published Online: 2023-03-11 Printed: 2023-05-01 Ann Clin Anal Med 2023;14(5):448-453
Corresponding Author: Burak Uçaner, Department of General Surgery, University of Health Sciences, Gülhane Training and Research Hospital, 06010, Etlik, Ankara, Turkey. E-mail: burakucaner@hotmail.com P: +90 312 304 51 50 F: +90 312 304 27 00 Corresponding Author ORCID ID: https://orcid.org/0000-0002-5420-3810
This study was approved by the Ethics Committee of University of Health Sciences Gülhane Training and Research Hospital (Date: 2021-12-15, No: 2021/104)
Aim: Preoperative correct diagnosis is very important in reducing negative appendectomy rates. In patients with suspected acute appendicitis (AA), computed tomography (CT) is frequently preferred along with other diagnostic methods to reduce diagnostic uncertainty. The aim of this study is to evaluate the diagnostic performance of CT findings in the histological findings of AA.
Material and Methods: In this study, 319 patients who underwent abdominopelvic CT imaging between January 1, 2017 and May 1, 2022 and who were operated due to AA suspicion were evaluated retrospectively. CT imaging findings, such as appendix diameter, presence of appendicolith, appendix wall thickening, heterogeneity in periappendicular fatty tissue, presence of fluid accumulation/abscess and lymphadenopathy in the right lower quadrant were evaluated. Only patients who were operated due to the suspicion of AA in CT findings were included in the study.
Results: The mean age of the patients was 36.1±14.7 years. In the study, the male/female ratio was 1.7/1. In CT imaging, appendix diameter (AUC=0.997), heterogeneity in fatty tissue (AUC= 0.704), appendicolith (AUC= 0.702) and appendix wall thickening (AUC=0.671) were found to be determinants in gangrenous appendicitis compared to normal histology.
Discussion: Appendiceal diameter (over 9 mm) was found to be a determinant in gangrenous appendicitis with 100% sensitivity and 92.9% specificity. Appendicolith (AUC=0.619) and appendix wall thickening (AUC=0.593) had high sensitivity in appendix neoplasms, but their specificity was quite low (23.7% and 18.5%, respectively). Histologically, preoperative CT findings may be useful indicators in the diagnosis of gangrenous appendicitis.
Keywords: Acute Appendicitis, Computed Tomography Imaging, Histopathological Correlation, Gangrenous Appendicitis
Introduction
Acute appendicitis (AA), which is the most common surgical emergency worldwide, is an important cause of morbidity and mortality, especially in developing countries. AA symptoms and findings are not always specific and may mimic other surgical pathologies, making accurate diagnosis difficult. AA management has become more up-to-date and more precise with imaging, scoring methods and wide treatment options [1].
Various physical examination methods can be used in the diagnosis of AA, but due to their insufficient diagnostic performance for AA, imaging methods are frequently used in diagnosis [1, 2]. Today, computed tomography (CT) imaging is the most preferred imaging method in cases with suspected AA in adolescents and adult patients. A significant decrease in negative appendectomy rates was achieved with CT imaging, and the high sensitivity of CT imaging in differential diagnoses, such as appendix neoplasms, is an important advantage [3, 4].
In CT imaging other than the appendix diameter, findings such as periappendicular inflammatory changes, abscess, free fluid, inflammation in adjacent structures, the presence of appendicolith and appendix wall thickening are used in the diagnosis of AA. Although it has a high sensitivity in the diagnosis of appendicitis, the correlation of CT findings with histopathological findings of the removed appendix tissue is not known completely [5, 6].
Material and Methods
This study was approved by University of Health Sciences Gülhane Training and Research Hospital Ethics Committee on December 15, 2021 with decision number 2021/104. The study was carried out in accordance with the World Medical Association Helsinki Declaration and Good Clinical Practice.
Patients who were admitted to our clinic between January 1, 2017 and May 1, 2022 due to abdominal pain and evaluated by our clinic and operated by confirming the diagnosis of AA with CT imaging were planned to be included in this study. Among the specified descriptions, 412 patients over the age of 18 were operated with the suspicion of AA. CT scans of 73 of these patients could not be reached. CT results of 20 patients were not explanatory. Therefore, this study was conducted with 319 patients.
Demographic information, comorbidities, body mass index (BMI), preoperative WBC, neutrophil, lymphocyte and platelet counts, CRP levels, and symptom duration of 319 patients included in the retrospectively designed study were recorded from the hospital patient records. The surgical method used in patients operated with the suspicion of AA, whether additional surgery was required, the duration of surgery, the presence of surgical complications, the presence of reoperation during follow-up, and the time between hospital admission and surgery were recorded. CT reports were examined one by one and the presence of six main findings was examined: appendix diameter, presence of appendicolith, appendix wall thickening, heterogeneity in fatty tissue around the appendix, periappendicular free fluid and abscess, lymphadenopathy in the right lower quadrant.
The normal histopathological examination was evaluated as a negative appendectomy. The distribution of CT findings according to the histopathological evaluation results of the removed appendix was examined. The sensitivity and specificity of CT findings in gangrenous and normal histology were analyzed. The determinants of CT findings in histopathological results were evaluated.
Statistical analysis
Statistical analyses were performed using the SPSS version 21.0 (Chicago, USA) software. After examining the distribution of the variables, “t-test” and the Mann Whitney-U test were used in the group comparison. Categorical data were analyzed with Pearson’s Chi-square and Fisher’s Exact test. The predictiveness of CT findings in histopathological findings was evaluated by the “Receiver Operating Characteristic (ROC)” analysis. The results of the ROC analysis were expressed in the area under the curve (AUC) and 95% confidence interval. By evaluating the diagnostic performance of CT methods, sensitivity, specificity, positive predictive value (PPD) and negative predictive values were determined for their predictiveness in histopathological findings. In the statistical analyses in the study, values below p<0.05 were considered statistically significant.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
The mean age of 319 patients included in the study was 36.1±14.7 years (18-84 years). In the study, the male/female ratio was 1.7/1. One hundred seventy patients (53.3%) underwent open appendectomy and 149 patients (46.7%) underwent laparoscopic appendectomy. Thirteen (4.1%) patients had at least one complication requiring surgical or interventional procedures (Clavien-Dindo Classification System Grade>3). In this study, 3 patients (0.9%) were re-operated due to complications.
CT imaging findings were appendix wall thickening (82.1%), increased heterogeneity in fatty tissue around the appendix (78.4%), appendicolith (22.9%), lymphadenopathy in the right lower quadrant (21.6%) and periappendicular free fluid/abscess (19.4%), respectively. On CT imaging, the median appendix diameter was 10.2 mm (between 5.5-22 mm). In the histopathological examination of patients operated with the preliminary diagnosis of AA, the most common pathologies were acute focal appendicitis (50.2%), acute suppurative appendicitis (36.1%), and acute gangrenous/perforated appendicitis (5.3%), respectively. However, histopathological examination of 15 patients (4.7%) was normal. Therefore, the negative appendectomy rate of this study was found to be 4.7%. Histopathological examination revealed tumoral lesions in 3.4% of the patients, were detected: 6 patients had sessile serrated adenoma, 3 patients had mucinous neoplasia, 1 patient had adenocarcinoma and 1 patient had a hyperplastic polyp. In addition, a parasite (Enterobius vermicularis) was the cause of appendicitis in one patient.
Patients with and without acute gangrenous appendicitis were compared in terms of demographic and clinical features. Patients with acute gangrenous appendicitis had higher age (p<0.001), lower lymphocyte count (p=0.004), higher CRP (p<0.001) and ASA score (p=0.023), longer symptom duration (p<0.001) and longer hospital stay (p<0.001). Additional surgery (p<0.001) and complication rate (p=0.001) were higher in patients with acute gangrenous appendicitis (Table 1).
CT findings were compared between patients with and without acute gangrenous/perforated appendicitis as a result of histopathological examination. In patients with acute gangrenous appendicitis, appendix diameter (p<0.001) was larger, the presence of appendicolith (p=0.032) and periappendicular free fluid (p<0.001) were more frequent. No significant difference was observed in other CT findings. The appendiceal diameter was smaller (p<0.001), appendix wall thickening (p=0.034) and heterogeneity in periappendicular fatty tissue (p=0.024) were lower in patients with normal histopathology. No significant difference was observed in other CT findings (Table 2).
The role of CT findings in differentiating patients with acute gangrenous appendicitis from patients with normal histopathology was evaluated with ROC analysis. In the ROC analysis, appendix diameter (AUC=0.997, p<0.001), heterogeneity in periappendicular fatty tissue (AUC=0.704, p = 0.005), presence of appendicolith (AUC = 0.702, p = 0.004) and appendix wall thickening (AUC = 0.671, p=0.017) were found to be determinant in acute gangrenous appendicitis in patients with acute gangrenous appendicitis, respectively. The diameter of appendix more than 9 mm was the determining factor in acute gangrenous appendicitis with 100% sensitivity and 92.9% specificity in acute gangrenous appendicitis, 94.1% sensitivity and 46.7% specificity in heterogeneity in periappendicular fatty tissue, 47.1% sensitivity and 93.3% specificity in the presence of appendicolith, 94.1% sensitivity and 40% specificity in appendix wall thickening. Appendiceal diameter (AUC=0.877, p<0.001) and the presence of appendicolith (AUC=0.585, p=0.017) were found to be determinants in negative appendectomy patients with normal histopathology, respectively The appendix diameter less than 9 mm was determinant for negative appendectomy with 92.9% sensitivity, and 71.2% specificity, and the absence of appendicolith was determinant with 93.3% sensitivity and 23.7% specificity. In patients with histopathology of neoplasia, the presence of appendicolith, appendix diameter (AUC=0.619, p<0.001) and wall thickening (AUC=0.593, p<0.001) were found to be determinants, respectively. The sensitivity of the presence of appendicolith for neoplasia was 100%, the specificity was 23.7%, the sensitivity of wall thickening was 100%, and the specificity was 18.5% (Table 3).
Discussion
AA is an important surgical emergency pathology that should be considered in the differential diagnosis of all acute abdominal patients, so it is important that AA can be differentiated from other pathologies. In addition to physical examination findings, laboratory findings and scoring systems based on these findings have been used in the diagnosis of AA for a long time. However, imaging methods are frequently used when there is doubt about the diagnosis [7]. Although the diagnostic importance of CT imaging for AA has been demonstrated in many studies [8,11], the relationship of CT imaging findings with the histopathological features of patients operated for AA has been examined in a very limited number of studies [12-14].
In this study, the efficacy of CT imaging findings was evaluated in patients with acute gangrenous appendicitis due to its clinical significance. According to the CT findings, the diameter of the appendix (over 9 mm) had a very high diagnostic performance for perforation. However, among the CT findings, it was seen that increased heterogeneity in periappendicular fatty tissue and appendix wall thickening could be used in the diagnosis of perforation, but the diagnostic performance of the findings except for the appendix diameter was low for acute gangrenous appendicitis. The predictiveness of CT findings in acute perforated appendicitis has been evaluated in many studies, but in these studies, perforation has often been defined surgically [15, 16].
In the study by Ali et al., contrast defects in the appendix wall, extraluminal air, appendicolith and abscess image were used for perforation diagnosis among CT findings in 236 patients [13]. The sensitivity of CT for perforated appendicitis was 71.4% and the specificity was 90.7%. However, contrary to our findings, the diagnostic performance of CT findings was not evaluated separately in this study and routine imaging protocol was not used in CT imaging. Failure to use the routine CT protocol may make it difficult to evaluate patients with suspected AA, especially in the emergency service environment. Hansen et al. evaluated the association of CT imaging findings with histological AA severity in 105 patients, and the histological severity was ranked from mild to severe, including acute mucosal appendicitis, acute suppurative appendicitis, and gangrenous appendicitis [14]. Among the CT findings, it was stated that the diameter of the appendix, heterogeneity in periappendicular fatty tissue, and the intensity of CT imaging formed using fluid, appendicolith and free air correlated with the severity of histological appendicitis. However, as in this study, the relationship of CT imaging findings with individual histological diagnoses was not evaluated. In a recent study by Naya et al., CT findings that may be determinant in gangrenous histology were evaluated in 146 patients operated with the suspicion of AA [17]. In the study, it was reported that the appendix diameter was larger in the gangrenous group, and the presence of appendicolith and heterogeneity in periappendicular fatty tissue were higher. In the study, the diagnostic performance of CT findings in gangrenous appendicitis was not evaluated separately, instead, CT findings were evaluated by combining them with total bilirubin level, but contrary to our findings, sufficient specificity could not be reached for gangrenous appendicitis.
Contrary to our findings, there were also studies reporting that CT findings could not be used in the diagnosis of perforated AA. In the study of Gaskill et al., 89 patients who were operated due to suspected AA with CT imaging were examined and it was stated that none of the CT findings such as appendicolith, cecal wall thickening and fluid accumulation were determinant in pathologically demonstrated perforation [18]. However, it is noteworthy that only 89 patients were evaluated in this study and the perforation rate was approximately 50%.
Several studies have evaluated the sensitivity of CT findings in perforated appendicitis. In these studies, 34-62% sensitivity and 81-99% specificity were reported for CT imaging [15, 16, 19]. In these studies, which frequently reported high perforation rates and were performed with a limited number of patients, perforation was evaluated surgically, and the perforation diagnosis evaluated by radiologists in the light of CT findings was generally taken into consideration in the perforation decision. In this study, the histopathological method, which is the gold standard in the diagnosis of perforation, was preferred and the predictiveness of CT findings in histology compatible with perforation was evaluated separately. In addition, the number of patients included in this study is greater than in the previous studies [15, 16, 19]. Therefore, it can be said that this study yielded more objective findings.
In this study, it was observed that appendix diameter (less than 9 mm) and absence of appendicolith could be used among CT findings in patients with negative appendectomy. Particularly, the appendix diameter being 9 mm below the diameter of the appendix had high sensitivity (92.9%) and specificity (71.2%) for negative appendectomy. Similar results have been reported before. In this study, it was observed that the value showing the best sensitivity and specificity in differentiating the appendix diameter from normal histology was above 9 mm. It has been stated in some studies that 6-7 mm threshold values can be used in the diagnosis of AA [20]. The high appendix diameter value reported in this study was an important reason for the fact that all the patients included in this study were patients who were operated due to suspected AA. In studies in which appendix diameter was reported to be lower, the inclusion of patients who were not operated may have resulted in smaller appendix diameter values.
In this study, the predictiveness of CT findings in patients with neoplasia was not sufficient. It was observed that appendicolith and wall thickening could be used in the diagnosis of neoplasia, but the specificities were quite low (18.5-23.7%). Previous studies have also reported that CT findings were not specific to appendix neoplasms [21, 22].
Study Limitations
This study has some limitations. In this study, patients who were operated with suspected AA as a result of clinical evaluation and CT imaging were evaluated. Therefore, the diagnostic performance of CT imaging in the diagnosis of AA could not be evaluated. In addition, common findings used in the diagnosis of AA among CT imaging findings were evaluated. However, apart from these findings, there are also CT findings such as the general opinion of the radiologist and suspected mass consistent with appendix malignancies. In addition, the diagnostic performance of CT findings in gangrenous appendicitis was obtained by comparing patients with normal histology. However, comparing gangrenous histology with other AA-compatible histologies will reduce the diagnostic performance of CT findings for perforation.
Conclusion
According to the data of this study, the increase in the diameter of the appendix, the presence of appendicolith and the presence of periappendicular free fluid among the preoperative CT findings were found to be determinants in histologically demonstrated perforated appendicitis. Especially the appendix diameter greater than 9 mm has high sensitivity and specificity for perforated appendicitis. In this study, appendix neoplasia was observed in 3.4% of the patients who were operated with the suspicion of AA as a result of CT imaging. The sensitivity and specificity of CT findings in appendix neoplasms are not at the desired level. As the number of homogeneous studies conducted with larger patient series will increase in the future, a question on this subject will also be answered.
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.21608
Fatih Yıldırım, Burak Uçaner, Oğuz Hançerlioğulları. The correlation between computed tomography reports and histopathological results in acute appendicitis. Ann Clin Anal Med 2023;14(5):448-453
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Relationships between depression, anxiety, sleep and coping skills among medical students: A cross-sectional study
Mesut Yildiz
Department of Psychiatry, Faculty of Medicine, Marmara University, Istanbul, Turkey
DOI: 10.4328/ACAM.21614 Received: 2023-01-23 Accepted: 2023-02-25 Published Online: 2023-03-06 Printed: 2023-05-01 Ann Clin Anal Med 2023;14(5):454-458
Corresponding Author: Mesut Yildiz, Department of Psychiatry, Faculty of Medicine, Marmara University, Istanbul, Turkey. E-mail: mesutdr@gmail.com P: +90 216 625 45 45 Corresponding Author ORCID ID: https://orcid.org/0000-0002-6965-370X
This study was approved by the Clinical Research Ethics Committee of Marmara University Faculty of Medicine (Date: 2019-05-03, No: 09.2019.508)
Aim: Depression, anxiety and sleep problems may be elevated among medical students. No study up to now evaluated the relationships of those problems with coping skills among Turkish medical students. In this study, we aimed to evaluate the relationship between depression, anxiety, sleep and coping skills among medical students.
Material and Methods: This cross-sectional survey included 341 medical students and evaluated depression (Patient Health Questionnaire-9, PHQ-9), anxiety (Generalized Anxiety Disorder Scale, GAD-7), sleep problems (Pittsburgh Sleep Quality Index, PSQI) and coping skills (Coping Orientation to Problems Experienced, COPE) with self-reports. Preclinical and clinical students as well as female and male students were compared. Predictors of impaired sleep were evaluated with ordinal logistic regression. P-value was set at 0.05.
Results: Depression and sleep impairment were significantly more frequent among preclinical students while anxiety was significantly elevated among female students. Clinical students employed emotion-focused coping significantly more frequently. Dysfunctional coping correlated with self-reported depression, anxiety and sleep problems. The sole significant predictor of sleep impairment in the regression was the depressive symptom score.
Discussion: Preclinical students may benefit from interventions supporting active coping as well as social interactions. Clinical students may benefit from interventions targeting nicotine and alcohol use.
Keywords: Depression, Anxiety, Medical Students, Coping, Sleep
Introduction
Medical school may be especially taxing for emerging adults attending university due to its duration and intensity of education, the stress of frequent examinations [1]. Previous studies have shown that depression, anxiety, and sleep problems may be elevated among medical students while their social support and coping may be reduced [2-4]. The ongoing COVID-19 pandemic may have compounded those problems [5].
Rates of depression among medical students may vary between 30.0-40.0 %, and students from Middle Eastern countries and female students may have higher rates [2-4]. Previous cross-sectional studies on Turkish medical students found that rates of depression varied between 13.2- 41.0%. Depression in those studies was associated with female gender, preclinical education, lower income, older age, a history of violence victimization, nicotine abuse, sleep disruption and residence in dormitories [2, 3].
Anxiety rates may also be elevated among medical students with rates varying between 7.7- 65.0 % globally [2]. The rates of anxiety varied between 4.0- 45.0 % in Turkish samples [4]. Factors associated with anxiety were female gender, residency examinations and uncertainty about the future [1]. Anxiety in medical students may also impair empathy and academic motivation [6].
Sleep quality may also be impaired among medical students [5]. In a recent meta-analysis of 29 studies conducted on 14.170 students, 39.8 % of students may complain of impaired sleep (95% Confidence Interval = 39.0-40.6%, 5). Sleep impairment may primarily consist of insufficient sleep duration and excessive daytime sleepiness, with deleterious effects on academic achievement [5]. Impairment in sleep quality among Turkish medical students varied between 42.0-70.0% [7]. Sleep problems among medical students may be related with female gender, nicotine/psychopharmacological treatment use, shiftwork, lower income, and elevated academic stress [5,7].
In contrast to depression, anxiety, and sleep problems, coping skills among medical students have received relatively limited attention [8]. Coping is defined as a voluntary effort to regulate emotions, thoughts and behaviors while experiencing stress and may be classified as problem- or emotion-focused [9, 10]. Coping behaviors may also be divided into adaptive (i.e., “active”) and maladaptive (i.e., “passive” or “avoidant”). Ineffective/avoidant coping strategies may be related to anxiety, depression, and sleep problems among medical students [11].
Although depression, anxiety, sleep problems and coping skills have been previously studied among Turkish medical students, none of the studies evaluated the relationships between those four constructs simultaneously [1,3,7]. Therefore, this study aimed to evaluate the prevalence of clinically significant depressive/anxiety symptoms and sleep problems, and to evaluate coping skills among Turkish medical students according to education tiers (i.e., preclinical vs. clinical). We also aimed to evaluate the relationships between depression, anxiety, sleep impairment and coping skills.
Material and Methods
Study center, sampling and ethics
This study was conducted as a cross-sectional survey of 1200 medical students receiving education at the Marmara University Faculty of Medicine within the academic year 2021-2022. The dependent variable with the highest expected frequency according to the literature was sleep impairment (i.e., 41.1 %). Therefore, 426 participants from a 1200 population would be required with a 95% confidence interval and a design effect of 1.5. Stratified sampling according to educational tiers was used in selecting participants. IRB approval was acquired prior to the commencement of study and all the study procedures were in accordance with the Declaration of Helsinki. The study was approved by the Clinical Research Ethics Committee (09.2019.508).
Measures:
1. Generalized Anxiety Disorder Scale (GAD- 7): GAD-7 is a seven-item, four-point, Likert-type self-report evaluating anxiety with 5, 10 and 15 denoting mild, moderate and severe levels of anxiety [12, 13].
2. Patient Health Questionnaire (PHQ-9): PHQ-9 is a nine-item, four-point Likert-type self- report including DSM-IV criteria for major depression (5-9: mild depression, 10: -14: moderate, 15-19: moderate/severe, 20-27: severe depression) [14,15].
3. Pittsburgh Sleep Quality Index (PSQI): This self-report instrument evaluates sleep quality, latency, duration, habits, problems, use of hypnotics and daily functioning for the past month. Each domain is graded from 0 to 3 with higher scores denoting greater impairment. Total PSQI score varies between 0- 21 with 0-5 denoting healthy sleep. Scores between 6-10 denote impaired sleep while ≥ 10 correlates with chronic impaired sleep [16,17].
4. Coping Orientation to Problems Experienced (COPE): The COPE is a 60-item, 4-point self-report scale consisting of 15 subscales. The COPE consists of three main groupings -focused coping, emotion-focused coping and dysfunctional coping [18,19].
Statistical analysis
The data were entered into a database and analyzed with SPSS Version 23.0 (IBM Inc., Armonk, NY) and Jamovi Version 2.0 (The Jamovi project. 2021; https://www.jamovi.org). Nominal data were summarized with counts and frequencies, while quantitative data were summarized with means and standard deviations. Distributions of nominal data across groups were compared with a chi-square test with Fisher’s exact test, Yates’ correction, and linear-by-linear association as required. Assumptions of normality were evaluated with the Kolmogorov-Smirnov test and due to non-normality, quantitative variables across groups were compared with the Mann-Whitney U test. Bivariate correlations across quantitative variables were conducted with Spearman’s rank order correlation analysis. Ordinal logistic regression with enter method was used to evaluate sleep impairment according to PSQI and predictors were entered in blocks. Model fit was evaluated with chi square tests, deviance, Akaike Information Criteria (AIC) and Bayesian Information Criteria (BIC). Models were compared with chi-square tests. Omnibus likelihood ratio tests were conducted for predictors.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
Although 426 participants were planned, 85 students could not be enrolled due to non-attendance, resulting in 341 participants (i.e., 80.1 % of the planned sample, 50.4 % females) with a mean age of 22.1 (S.D.= 2.2, Range= 18.0- 28.0) years. There was no significant difference in terms of gender (χ2= 0.3, p=0.871).
Preclinical students were significantly more likely to live with their families as well as in dormitories compared to clinical tier medical students. Clinical tier students were significantly more likely to use nicotine and alcohol. Other than those the groups did not differ significantly.
Mean GAD- 7, PHQ-9 and PSQI scores of preclinical and clinical tier students were 6.4 (SD= 4.3) vs. 7.0 (SD= 4.2), 9.9 (SD= 5.0) vs. 7.9 (SD= 4.8) and 9.0 (SD= 2.5) vs. 8.8 (SD= 3.1), respectively. None of the tests displayed normality (p< 0.001, Kolmogorov- Smirnov test). According to bivariate comparisons, preclinical students had significantly elevated PHQ-9 scores (Z= 3.9, p < 0.001, Mann-Whitney U test), while GAD-7 and PSQI scores did not differ significantly between groups. The sociodemographic features of the participants and symptom severities according to educational tiers are illustrated in Table 1.
In bivariate comparisons, preclinical students were significantly more likely to be classified with moderate, moderate- severe and severe depression, as well as report greater impairment due to symptoms in PHQ-9. Impaired and chronically impaired sleep were also significantly more common among preclinical students. However, the groups did not differ in terms of anxiety severity. Impairing depressive symptoms were not affected significantly by gender (χ2=0.3, p=0.558), living with family (χ2=1.6, p=0.200), nicotine, alcohol and substance use (χ2= 0.2, p=0.694; χ2=0.6, p= 0.452 and χ2= 1.7, p= 0.190; respectively). However, they were significantly related with impaired sleep (χ2=29.8, p<0.001; Eta=0.31, all linear-by-linear association). Moderate- severe anxiety was significantly more frequent among females (χ2=6.0, p=0.015, Eta=0.14). It was also significantly associated with sleep impairment (χ2=17.9, p<0.001, Eta= 0.24). Sleep impairment was significantly more frequent among students not living with their families (χ2=11.6, p=0.003, Eta=0.10). In bivariate comparisons, clinical tier students were significantly more likely to use emotion-focused coping compared to preclinical tier students. Male students were significantly more likely to use problems-focused coping (Z= 2.6, p=0.011, Effect size= 0.14), while female students were more likely to use emotion-focused (Z= 2.4, p=0.018, Effect size= 0.13) and dysfunctional (Z= 3.7, p< 0.001, Effect size= 0.20) coping.
Relationships between anxiety, depression, sleep impairment and coping skill domains in the whole sample were evaluated with Spearman’s rank order correlation (Table 2).
In the whole sample, problem-focused coping displayed negligible, negative but significant correlations with depressive and anxious symptoms. Dysfunctional coping displayed low, positive, significant correlations with depressive and anxious symptoms, while its correlation with sleep problems was negligible and positive. Emotion-focused coping did not correlate with any of the symptoms. In the preclinical group, problem-focused coping did not correlate with any of the symptoms, while emotion-focused coping displayed negligible positive correlation with sleep problems (rho= 0.15, p=0.044). Dysfunctional coping displayed low, positive and significant correlations with all symptom domains (Rho= 0.35, 0.33 and 0.32; respectively for GAD-7, PHQ-9 and PSQI; all p< 0.001) among preclinical students. Among clinical tiers students, problem-focused coping displayed a negligible, negative correlations with PHQ-9 (rho= -0.19, p=0.020) and PSQI (rho= -0.25, p= 0.002). Emotion-focused coping displayed a negligible, negative correlation with PSQI (rho= -0.26, p=0.001). Dysfunctional coping displayed low, positive and significant correlations with GAD-7 (rho= 0.41, p< 0.001) and PHQ-9 (rho= 0.37, p< 0.001).
Ordinal logistic regression with enter method was used to evaluate sleep impairment according to PSQI. Predictors were gender, living with family, educational tier, GAD-7, PHQ-9, alcohol use, nicotine use, problem focus, emotion focus and dysfunctional coping scores. Gender was entered first, followed by educational tier then living with family, alcohol and substance use were entered in the fourth step, GAD-7 and PHQ-9 in fifth and COPE domains in the last step.
At the last step, the overall model was significant and could explain 18.1 % of the variance in sleep impairment. Among omnibus likelihood ratio tests for predictors at this step, only PHQ-9 was significant (χ2= 38.7, p< 0.001), while gender (χ2= 2.7, p=0.099), problem focus (χ2=3.6, p=0.056) and emotion focus (χ2=3.0, p=0.085) remained at trend levels (Table 3).
Discussion
Previous studies have reported that 30.0- 40.0% of medical students may have clinically significant depressive symptoms [1-3]. Previous studies on Turkish medical students have shown depression rates of 13.2- 41.0% [1]. Almost half of the participants (n= 144, 42.2 %) reported mild depressive symptoms in the present study. Rates of severe, high and moderate impairment due to depressive symptoms were 0.9% (n= 3), 8.5 % (n= 29) and 32.3 % (n= 110), respectively. Therefore, the rate of depression in our sample is similar to those previously reported. Also, depressive symptoms in our sample were significantly associated with impaired sleep. The elevated rates of depression and impairment among preclinical students may reflect problems in adaptation to coursework and to physician identity. Alternatively, increased responsibilities for housing, transportation, socialization and education along with a focus on identity exploration, may lead to increased rates of depression. The lack of effects of gender and residence may be due to sampling bias, while that of nicotine/alcohol use may reflect limited numbers of students using those substances [1].
Anxiety may also be elevated among medical students and studies have reported rates of significant anxiety symptoms ranging from 7.7 to 65.0 % [2]. In our whole sample, rates of severe, moderate and mild anxiety were 18.2 % (n= 62), 36.4 % (n= 124) and 45.5 % (n= 155), respectively, and those rates are in accordance with the literature. Anxiety among medical students may be associated with female gender, impending residency examinations, uncertainty about the future, preclinical education, and lower academic achievement [1,2]. We found that female gender and disrupted sleep were significantly associated with anxiety although educational tier was not. This difference may be due to the features of our sample.
Medical students may also experience impaired sleep quality with almost two-fifths reporting impaired sleep-in meta-analyses [5]. The main problems may be reduced sleep duration and daytime sleepiness affecting academic achievement [5]. In our whole sample, the rates of chronic impaired and impaired sleep were 25.8 % (n= 84) and 65.0 % (n= 212), respectively, and those rates are in accordance with the literature. In our sample, independent living status (i.e., dormitories or housemates) and anxiety were significantly related with impaired sleep in bivariate analyses. However, multivariate analyses revealed that depressive symptoms were the most significant predictor of impaired sleep.
Available studies suggest that ineffective and avoidant coping strategies may be related to anxiety, depression, and sleep problems in medical students [11]. Supporting this position, dysfunctional coping strategies displayed low, positive correlations with anxiety, depression and sleep impairment in preclinical students and with anxiety/depression among clinical students. In bivariate comparisons, clinical students were significantly more likely to use emotion focused coping and preclinical students were significantly less likely to employ positive reinterpretation, instrumental and emotional social supports and substance use compared to clinical students. These results may suggest less use of active coping strategies among preclinical students in our sample, while substance use for coping may increase among clinical students. Similarly, it was found that preclinical students used denial and behavioral disengagement significantly more frequently compared to clinical students [8]. Transition from preclinical to clinical tiers may affect the perception of medical students and may correlate with a change in predominant coping styles [20,21]. Those female students in our sample used emotion-focused and dysfunctional coping significantly more frequently. Some of the available studies report that gender of medical students did not affect predominantly used coping skills [22]. However, some studies suggest that male medical students may use active coping skills or even maladaptive ones more frequently [23]. This discrepancy may be due to cultural differences between our sample and those previously evaluated.
Our results should be evaluated within their limitations. Firstly, we could reach only 80.1 % of the planned sample, and this may have affected our results. Secondly, our results may only be valid for our medical faculty. Thirdly, since we evaluated depression, anxiety and sleep quality with self-reports, they may be subject to recall and response bias. Fourth, study data were collected prior to the COVID-19 pandemic and the pandemic may have affected the results [24]. Fifth, inclusion of clinical interviews with the students may have enabled us to discern clinically significant levels of depression, anxiety and sleep impairment more objectively.
Conclusion
Regardless of those limitations, our results suggest that Turkish medical students may display elevated rates of depression, anxiety and sleep impairment especially in the preclinical years. Also, depressive symptoms significantly predict sleep impairment in this sample, and dysfunctional coping may correlated with depression, anxiety and sleep impairment. Preclinical students may benefit from mental and behavioral interventions including counselling, while clinical students may benefit from interventions targeting nicotine and alcohol use.
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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3. Akdemir M, Aktekin MR, Yiğiter ŞY, Sönmez Y, Doğanavşargil BÖ, Mamakli S, et al. Depression and psychological distress in medical students, a prospective study. Noro Psikiyatr Ars. 2022; 59 (2):116-22.
4. Seoane HA, Moschetto L, Orliacq F, Orliacq J, Serrano E, Cazenave MI, et al. Sleep disruption in medicine students and its relationship with impaired academic performance: A systematic review and meta-analysis. Sleep Med Rev. 2020; 53:101333.
5. Santabárbara J, Olaya B, Bueno-Notivol J, Pérez-Moreno M, Gracia-García P, Ozamiz-Etxebarria N, et al. Prevalence of depression among medical students during the COVID-19 pandemic. A systematic review and meta-analysis. Rev Med Chil. 2021; 149 (11):1579-88.
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7. Ergin N, Kılıç BB, Ergin A, Varlı S. Sleep quality and related factors including restless leg syndrome in medical students and residents in a Turkish university. Sleep Breath 2022; 26 (3):1299-307.
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Mesut Yildiz. Relationships between depression, anxiety, sleep and coping skills among medical students: A cross-sectional study. Ann Clin Anal Med 2023;14(5):454-558
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Evaluation of clinical and radiographic features of impacted premolar teeth in the central black sea region
Sefa Çolak 1, Aras Erdil 2, Ahmet Altan 3
1 Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Tokat Gaziosmanpaşa University, Tokat, 2 Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Uşak University, Uşak, 3 Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Necmettin Erbakan University, Konya, Turkey
DOI: 10.4328/ACAM.21620 Received: 2023-01-27 Accepted: 2023-03-02 Published Online: 2023-03-11 Printed: 2023-05-01 Ann Clin Anal Med 2023;14(5):459-463
Corresponding Author: Sefa Çolak, Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Tokat Gaziosmanpaşa University, 60100, Merkez, Tokat, Turkey. E-mail: dr.sefacolak@gmail.com P: +90 356 212 42 22 / +90 541 784 7563 F: +90 356 212 42 25 Corresponding Author ORCID ID: https://orcid.org/0000-0002-0807-9089
This study was approved by the Clinical Research Ethics Committee of Tokat Gaziosmanpaşa University, Faculty of Medicine (Date: 2022-08-15, No: 22-KAEK-147)
Aim: The aim of this study was to evaluate the clinical and radiographic features, associated pathologies and treatment planning of impacted premolar teeth among a specific population.
Material and Methods: Patients who applied to an oral and maxillofacial surgery clinic with the complaint of impacted premolars between 2017 and 2022 were included in this retrospective study. Demographic data, panoramic radiographs, treatments and associated pathologies of 83 patients included in the study were recorded. Impacted premolars were classified according to depth and angulation.
Results: A total of 63 teeth were observed in 51 female patients and a total of 45 teeth were observed in 32 male patients. Of 108 impacted premolars, 32 teeth were detected in the maxilla and 76 in the mandible. The impaction depth classification revealed that 44 of 108 teeth were in Class 1, 58 of them were in Class 2, and 6 of them were in Class 3. Angulation classification revealed that 43 teeth were vertically located, 41 were mesioangular, 13 teeth were horizontally located, nine teeth were distoangular, one was buccolingual, and one was located ectopically regarding the associated pathologies, of the 108 impacted premolars, dentigerous cysts were observed with 13 teeth, odontomas with four teeth, persistent primary teeth with four teeth, and root resorption in the adjacent teeth with two teeth.
Discussion: Mandibular and maxillary second premolars tend to be impacted at a higher rate than first premolars. Orthodontic treatment procedures can be applied in cases where the amount of impaction is less and severe angulation is not observed.
Keywords: Dentigerous Cyst, Impacted Teeth, Premolars, Surgical Removal
Introduction
Impacted teeth are those that remain entirely or partially impacted in jaw bones or mucous membranes for two years or more from the eruption [1,2].
Various local factors such as facial growth deficiencies, eruption problems due to adjacent teeth, insufficient maxillomandibular growth, trauma, early physical maturation, persistent primary teeth, early loss of primary teeth, excessive mineralization in jaw bones, chronic inflammation in adjacent mucosal tissues, genetic factors, and diseases like rickets, anemia, congenital syphilis, tuberculosis, endocrine disorders, and various syndromes may cause impaction [3,4]. Failure to determine treatment plans at appropriate time intervals may result in the impaction of canines, premolars, or second molars, which erupt later than others.
An impacted tooth can cause pulpal diseases, periapical and periodontal pathologies, temporomandibular joint problems, facial infections, cystic lesions, and odontogenic tumors [5]. Diagnosis and treatment can be challenging for clinicians. Also, managing of impacted teeth are aesthetically and functionally essential for patients [5].
Conventional radiographs are routinely performed methods for determining the localization of impacted teeth. Panoramic, occlusal, anteroposterior, and lateral cephalometric radiographs are conventional radiographs that provide localization of impacted teeth in two dimensions [4]. Panoramic radiographs are widely preferred in routine clinical use because of their economical and practical features, which can give an idea about dental arches and surrounding anatomical structures. Also, computed tomography (CT) or cone-beam computed tomography (CBCT) have become widely adopted techniques in recent years to accurately determine the localization of the impacted tooth in all three dimensions [6,7].
Mandibular third molars have the highest impaction rates, followed by maxillary third molars, maxillary canines, mandibular canines, premolars, and central incisors [8–10]. Various impaction patterns can be observed regarding the vertical axis of adjacent teeth, such as vertical, mesioangular, horizontal, buccolingual, distoangular, inverted, and ectopic. Also, impaction level relative to the occlusal plane can be at different depths from the level of the cementoenamel junction (CEJ) of adjacent teeth, to be positioned inferior to the apical third of adjacent roots [10].
The impacted premolar teeth, although rarer, can cause local problems such as aesthetic problems, mastication disorders, oral hygiene problems, pathologies arising from follicular tissues, and root resorption or caries on adjacent teeth. In the literature, studies on impacted premolar teeth, except for the study of Şimşek-Kaya et al. [11], are generally observed as case reports [12–14]. This study aims to determine the prevalence, impaction patterns, related pathologies, and management strategies of impacted premolar teeth among a particular population.
Material and Methods
Ethical approval for the current study was obtained from Tokat Gaziosmanpaşa University Clinical Research Ethics Committee (Project no: 22-KAEK-147) and was carried out in accordance with the Helsinki Declaration of Ethical Principles for Medical Research Involving Human Subjects. Due to a retrospectively conducted database search, 94 patients who applied or were referred to Tokat Gaziosmanpaşa University, Department of Oral and Maxillofacial Surgery with the complaint of impacted premolars between January 2017 and August 2022 were included. Patients older than 12 years of age and with impacted teeth two years or more past the time they should have erupted were included in the study. Patients with genetic diseases (2 patients), insufficient demographic data (4 patients), radiographic distortions (1 patient), and patients under 12 years of age (4 patients) were excluded. Consequently, a total of 83 patients were included.
All panoramic radiographs were obtained with Morita Veraviewepocs 2D (Kyoto, Japan) at 70 kVp and 10 mA for 9 seconds. Panoramic radiographs were evaluated independently and blindly at different times by two oral and maxillofacial surgeons (SÇ and AE). The number of impacted maxillary and mandibular premolar teeth, their localization, angulation, and the presence of associated pathologies were recorded and categorized by the researchers. In addition, demographic data and management methods were recorded. Impacted premolars were categorized according to their depth and angulation using a classification system similar to the Pell & Gregory and Winter third molar classification [10].
Regarding the depth of impaction, the premolars were grouped under three classes;
Class 1: The most superior occlusal point of the impacted tooth is between the occlusal surface of the adjacent premolar or molar tooth and the CEJ.
Class 2: The most superior occlusal point of the impacted tooth is between the CEJ of the adjacent premolar or molar tooth and the apex.
Class 3: The most superior occlusal point of the impacted tooth is located below the apex of the adjacent premolar or molar tooth.
Regarding the angulation, the impacted premolars were classified relative to the long axes of the adjacent teeth as Vertical (between 0° and 10°), Mesioangular (between 10° and 70°), Distoangular (between 10° and 70°), Horizontal (71°<), Inverted or Buccolingual, and Ectopic.
Statistical analysis
SPSS 19 (IBM SPSS Statistics 19, SPSS inc., an IBM Co., Somers, NY) program was used to analyze the obtained data statistically. The Shapiro-Wilk test was utilized to verify the normality of the data. Descriptive analyses were reported as mean ± standard deviation. Pearson’s chi-square test was performed to determine the association between categorical variables (such as gender, angulation, associated pathologies, e.g.) and the outcome variables. The relationship between age, number of impacted teeth, and applied treatment methods were analyzed using the Mann-Whitney U test or Kruskal-Wallis test followed by the post-hoc Dunn’s test. The p-values below .05 were interpreted as significant.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
The study population consisted of 83 patients (32 M [38.55%], 51 F [41.45%]). The mean age of males was 24.21 ± 11.73 years (min:12, max:72), the mean age of females was 26.37 ± 13.77 (min:13, max:73), and the mean age of the study population was 25,54 ± 12.98 years (min:12, max:73). The distribution of impacted premolars due to gender was examined, and 63 teeth (58.33%) were observed in 51 females, and 45 teeth (41.66%) were observed in 32 male patients. It was observed that the data were not normally distributed. According to the results of the Mann-Whitney U test, no significant relationship was found between gender and the number of impacted teeth (p: 0.24). Of 108 impacted premolars, 32 teeth were detected in the maxilla and 76 in the mandible. Of the 83 patients, 63 had one impacted premolar, 16 had two impacted premolars, three had three impacted premolars, and one had four impacted premolars. The impaction depth classification revealed that 44 of 108 teeth were in Class 1 (40.74%), 58 of them were in Class 2 (53.70%), and 6 of them were in Class 3 (5.55%). In the examination made according to the depth of the impacted teeth, it was seen that the data were normally distributed as a result of the Shapiro-Wilk test. According to the results of the chi-square test, there was no significant difference between class 1, class 2 and class 3 impacted teeth (p=0.620).
Regarding the frequency of impaction, it was observed that the lower left second premolars were the highest (38 teeth), followed by lower right second premolars (30 teeth), upper right second premolars (14 teeth), upper left second premolars (13 teeth), and lower left first premolars (5 teeth). The least impacted teeth were upper right first premolars (3 teeth), lower right first premolars (3 teeth), and upper left first premolars (2 teeth) (Table 1). The angulation classification revealed that 43 teeth were vertically located, 41 were mesioangular, 13 teeth were horizontally located, nine teeth were distoangular, one was buccolingual, and one was ectopically located (Table 2) (Figure 1). When the angulations of the impacted premolar teeth were examined, no significant difference was found with the chi-square test (p=0.171). Regarding the associated pathologies, of the 108 impacted premolars, dentigerous cysts were observed with 13 teeth, odontomas with four teeth, persistent primary teeth with four teeth, and root resorption in the adjacent teeth with two teeth (Table 1) (Figure 1).
Among the treatment methods applied to 83 patients, 95 impacted teeth were surgically removed, ten impacted teeth were surgically exposed with orthodontic intervention, and three impacted teeth were followed-up clinically and radiologically. Indications in patients who underwent surgical removal were observed as space-saving in orthodontic treatment, prosthetic applications, presence of associated pathologies, and at the request of patients (Table 3). When the age of the patients and the depth of the impacted teeth and the treatments applied were compared, it was observed that the data were not normally distributed with the Shapiro-Wilk test and the Kruskal-Wallis test was applied. There was no significant difference between age and depth (p=0.136). A significant difference was observed between age and treatment option (p<0.0001). In the comparison between the groups, it was determined that the patients who underwent extraction according to the Dunn Post-hoc test were significantly older than the patients who underwent orthodontic procedures (p<0.0001). All invasive treatment applications were performed under local anesthesia with intraoral approaches.
Discussion
Impacted teeth usually follow an asymptomatic clinical course. Therefore, fewer patients seek treatment than the current population. In most cases, impacted teeth are noticed during routine clinical or radiological examinations. Consequently, it is essential to inform patients about this phenomenon, frequently observed in daily clinical practice, and to emphasize early diagnosis-treatment planning [9].
The distribution of impacted premolars in the current study revealed that the most impacted teeth out of 108 impacted premolars are mandibular second premolars (68 teeth), maxillary second premolars (27 teeth), and mandibular first premolars (8 teeth), and maxillary first premolars (5 teeth). The results are consistent with the study of Şimşek-Kaya et al.[11]. This result suggests that the incidence of impaction between premolar teeth is highest in mandibular second premolars. Maxillary second premolars follow mandibular second premolars. Later eruption of mandibular and maxillary second premolars than the first premolars may be effective at the higher incidence of impaction [15,16]. When the depth classifications and angulations of the impacted premolar teeth were evaluated, 44 teeth (28 females, 16 males) were at the level of class 1, 58 teeth were at the level of class 2 (31 females, 27 males), and six teeth were at the level class 3 (four females, two males). Also, regarding the results of the current study, the most impacted premolars were observed in the vertical position, as reported by Şimşek-Kaya et al [11].
The most common complications associated with untreated impacted teeth in the current literature are retention of primary teeth, migration of adjacent teeth, pathologies of odontogenic origin, root resorption in adjacent teeth, alveolar bone loss, ankylosis, orthodontic disorders, pain, infected cysts, and odontogenic tumors [2,9]. Likewise, of the 108 impacted teeth included in the study, 23 (21.29%) were associated with dentigerous cysts, odontomas, root resorption in the adjacent teeth, and persistent primary teeth, as indicated in previous studies [11].
Treatment applications for impacted premolar teeth were grouped under three options: surgical extraction, orthodontic traction, and follow-up. The outcomes revealed that 95 impacted premolars, four primary and two permanent teeth with root resorption were surgically extracted. Surgical exposure with orthodontic traction was performed in 10 patients, clinical and radiological follow-ups were performed in 3 patients. Although spontaneous eruption of the impacted tooth is observed in appropriate cases after the surgical exposure of impacted teeth, orthodontic traction provides more precise results, especially in deep impactions with angulation. Various studies on the eruption tendency of impacted third molars have supported the conclusion that the planned extractions of premolars positively affect the proper eruption of third molars[17,18]. However, in another study, it was mentioned that the alterations in the angulation of the impacted third molars progressed independently of the extractions of premolars and that even premolar extractions for this purpose caused further occlusion problems [19]. In the current study, premolar extractions were performed only with indications for the treatment of impacted premolar teeth.
In the current study, dentigerous cysts accompanied 13 of 95 impacted premolars that underwent surgical extraction. In the treatment of dentigerous cysts, the excision of the follicular origin lesion and the extraction of the related impacted tooth is performed to prevent the recurrence of the cystic lesions. In some impacted teeth that are aesthetically and functionally essential, excision of the cystic lesion and orthodontic traction of the impacted tooth can also be considered. Apart from this, a similar treatment approach was adopted in four odontomas associated with impacted premolars. Also, surgical extractions of two impacted premolars, which caused root resorption in the adjacent teeth, were performed with the affected permanent teeth.
Factors such as the need for extraoral approaches, a large amount of alveolar bone loss, and the risk of damage to adjacent teeth or anatomical structures (inferior alveolar nerve, mental nerve, nasal floor, and maxillary sinus, e.g.) in the extraction of impacted premolars affect the surgical difficulty and the clinical decision to be made. In particular, the extraoral approach risks functional problems such as facial nerve damage and cosmetic problems such as scar tissue on the skin [20]. As a result, regular follow-up of impacted teeth, predominantly asymptomatic and not associated with any pathology, can provide more positive results with clinical profit-loss assessment. In this context, it was decided to observe three impacted premolars with regular clinical and radiological follow-ups in the current study.
Conclusion
To conclude, mandibular and maxillary second premolars tend to be impacted at a higher rate than first premolars. The outcomes of the current study indicated that clinical and radiological follow-up is an acceptable alternative in the absence of pathologies of odontogenic origin, mainly in premolar teeth with deep impaction or in close relation with vital structures. In the presence of associated pathologies, radical treatments such as surgical extraction can be prioritized. Orthodontic treatment procedures can be applied especially in cases such as with a depth of class 1, where the amount of impaction is nominal and severe angulation is not observed.
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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5. Hou R, Kong L, Ao J, Liu G, Zhou H, Qin R, et al. Investigation of impacted permanent teeth except the third molar in Chinese patients through an X-ray study. J Oral Maxillofac Surg. 2010;68(4):762-7.
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11. Şimşek-Kaya G, Melih-Ömezli M, Yapici G, Dayi E, Ertaş U. Prevalence of impacted premolars in a Turkish population and considerations for surgical treatment. Med Oral Patol Oral Cirugia Bucal. 2011;16(6):781-6.
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Sefa Çolak, Aras Erdil, Ahmet Altan. Evaluation of clinical and radiographic features of impacted premolar teeth in the central black sea region. Ann Clin Anal Med 2023;14(5):459-463
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Efficacy of topical tranexamic acid in bilateral cementless total knee arthroplasty
Ahmet Atilla Abdioğlu 1, Yılmaz Güvercin 2
1 Department of Orthopaed & Traumatol, Fatih State Hospital, 2 Department of Orthopaed & Traumatol, Trabzon Kanuni Training and Research Hospital, Trabzon, Turkey
DOI: 10.4328/ACAM.21624 Received: 2023-01-29 Accepted: 2023-03-12 Published Online: 2023-03-27 Printed: 2023-05-01 Ann Clin Anal Med 2023;14(5):464-468
Corresponding Author: Ahmet Atilla Abdioğlu, Department of Orthopaed & Traumatol, Fatih State Hospital, 61100, Trabzon, Turkey. E-mail: ahmetatilla@hotmail.com P: +90 505 925 31 87 Corresponding Author ORCID ID: https://orcid.org/0000-0002-0206-8135
This study was approved by the Ethics Committee of Trabzon Kanuni Training and Research Hospital (Date: 2022-04-30, No: 11451)
Aim: Tranexamic acid (TXA) can be used to reduce local and systemic blood transfusion in the total knee prosthesis. In this study, the amount of bleeding in simultaneous cementless bilateral total knee prosthesis (SCBTKP) surgery has been analyzed in groups of patients who used/did not use intra-articular TXA, while considering the patients’ age, gender and additional diseases.
Material and Methods: This retrospective study was carried out by analyzing the data obtained from 227 patients who had SCBTKP operation. TXA was used in 158 patients, whereas TXA was not used in the other 69 patients. Evaluation was carried out considering various factors such as duration of operation, levels of hemoglobin and hematocrit, blood transfusion ratio, levels and types of anesthesia, age, additional diseases, antiaggregant usage history.
Results: The amount of total blood loss was significantly higher in the group, which did not use TXA and in relation to this fact, the amount of blood given to patients was significantly higher in the group, which used TXA. The length of hospital stay was significantly shorter for patients who used TXA. There were no differences in the rates of cases of venous thromboembolism in post-operative patients. For both groups, there were no differences in complications
Discussion: One of the important complications of the total knee prosthesis is blood loss. TXA is one of the methods used to reduce surgical bleeding or reduce traumatic bleeding. This study reveals that for patients who used TXA, blood loss and Hemovac drainage volumes were significantly low.
Keywords: Tranexamic Acid, Simultaneous Bilateral Cementless Total Knee Prosthesis, Bleeding, Venous Thromboembolism
Introduction
Osteoarthritis is one of the factors leading to a decrease in the quality of life of old patients. Pain causes structural changes in the joints. As a result, joint movements are limited. In the US, the percentage of patients over 60 years old with symptomatic knee arthritis is reported as 12%. If conservative treatment is insufficient, surgical treatment is performed. One of the surgical treatment options is total knee arthroplasty [1]. Future projections predict that up to 2050, 1.5 million operations will be performed annually. This will further increase the cost [2]. Part of this cost is blood transfusion cost.
The total knee prosthesis is an orthopedic surgical procedure used worldwide. It is most commonly used with cement but it can also be performed cementless, with successful results in recent years [3]. Lately, simultaneous bilateral knee prosthesis can be performed in accordance with the patient and the surgeon’s choice [4]. While there are disadvantages of simultaneous bilateral knee prosthesis such as pulmonary embolism, increased need for blood transfusion, deep vein thrombosis, cardiac side effects, wound complications, which are still being discussed [5]. It has some advantages like short recovery time and low cost [6] .
Approximately 50% of the patients need blood after total knee prosthesis operation and this need can be as much as 2-3 units per one-sided arthroplasty [7]. It has been reported that the amount of blood needed is higher in one-staged bilateral knee prosthesis [8]. Various drugs and mechanical precautions are used to reduce blood loss including non-pharmacological precautions such as various types of anesthesia, the use of tourniquet, drains, and some types of prosthesis [9,10]. Also, pharmacological agents, such as epinephrine, norepinephrine, tranexamic acid, epsilon aminocaproic acid can be used. Among these agents, tranexamic acid is commonly used [11].
TXA is a synthetic lysine analog [12]. TXA prevents the plasminogen from becoming plasmin, and this prevents the fragmentation of factor V, factor VIII, fibrin clot and fibrinogens [10]. There are oral, intravenous, intraarticular and periarticular applications of TXA [12]. In recent years, studies about TXA applications have reported a reduction in blood loss [13]. As far as we know, there are no studies in the literature investigating blood loss after SCBTKP operation and the efficiency of TXA.Our main goal in this study is to investigate the effect of post- SCBTKP intraarticular TXA usage on bleeding. The secondary goal is to evaluate the side effects of TXA regarding additional diseases of patients and the type of anesthesia.
Material and Methods
This study has been carried out with patients with an advanced degree of bilateral knee osteoarthritis who had SCBTKP operation between 2013 – 2021. The ages of patients were between 45 and 84 years. In total, 227 patients were included in the study. Patients with one-sided total knee prosthesis, infection-induced arthritis, advanced bleeding and thrombotic disorder, revision patients, and patients with chronic anemia were excluded. Patients who used anticoagulants stopped taking them 1 week before the study. In case of necessity, low molecular weight heparin was given. The study was approved by the Trabzon Kanuni Training and Research Hospital Ethics Committee.
In this study, which included 227 patients, patients were divided into 2 groups: Group A: SCBTKP surgery with local TXA application; Group B: SCBTKP surgery without local TXA. Two nurses recorded postoperative bleeding volumes on the files through visual inspection of drains. Anesthetic data, additional diseases of patients and bleeding records were also recorded in the files.
Surgical Method: All the surgeries were carried out by the same experienced surgical team using various anesthesia methods. The body part, on which the operation was to begin was chosen by the surgeon, and the preference for the part varied in accordance with the conditions of the case. After the necessary preparations, tourniquet pressure was increased up to 250 mm/hg, provided that the overall condition and blood pressure of the patient were appropriate. The knee joint was opened using the medial parapatellar approach. Cementless total knee prosthesis was used in all the cases. After the prosthesis application, 2mg of Traxamine capsules were applied intra-articularly. Additional cauterization was not performed. After the operation, at the end of the first day, drainage was removed and physical exercises started. On the second day, flexion and extension exercises, started and patients who could tolerate them were engaged in walking exercises.
Collection of results: Total blood loss: Hb and htc were recorded pre-operatively. They were recorded after 2 hours and 1 day after the surgery. The days of the record varied in accordance with the need for blood transfusion by the patient. Special attention was paid to keep the hemoglobin levels of the patients at 10 g/dl at the time of their discharge, which was between 5-7 days.
Patient information: Age, gender, body mass index, duration of operation, other diseases, history of antiaggregant use before the surgery,
Blood transfusion ratio: Blood transfusion to the patients was planned when the patients had symptomatic anemia (mild headache, fatigue, shortness of breath, palpitation) or when the Hb level was detected below 10.
Complications: In this group of evaluation, problems that occurred after the surgery were analyzed, such as deep vein thrombosis, myocardial infarction and wound problems.
Statistical analysis
Descriptive statistics were used to summarize patient characteristics. The change in baseline hemoglobin and hematocrit values over time and the difference between groups were analyzed by repeated measure two-way ANOVA test. The Chi-square test for categorical variables and Independent Samples T-test were processed to compare groups. A p-value of less than 0.05 was considered to be statistically significant between the variables. Statistics were performed with IBM SPSS Statistics for Windows, version 26 (IBM Corp., Armonk, N.Y., USA).
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
This study was conducted with 227 patients who had SCBTKP surgery between 2014 – 2020. The ages of the patients varied between 45 and 84. The average age was 65.5 + 8 years; 207 of the patients (90.3%) were females. The average BMI of the patients was 33.7 ± 4.9 and the dominant blood groups were A Rh+ (42.3%) and 0 Rh+ (30.4); 112 patients (49.3%) had hypertension, 37 (16.3%) had diabetes, 16 (7%) had hyperthyroid and 6 (2.6%) had coronary artery disease.
The local transamine was used for 158 (68.6%) patients, however, it was not used for 69 (31.4%) patients. The ages of the patients varied between 45-84, and the average age was 65.5 ± 8; 207 (90.3%) patients were women. Hb, htc, age, ASA, BMI, gender, additional diseases, type of anesthesia used in the surgery, operation duration, hospital stays, erythrocyte replacements are given in Table 1.
Total blood loss: Total blood loss was higher in the group, which did not use TXA. It was ensured that post operation hemoglobin levels of the patients did not drop below 10 gr/dL because of blood loss and symptomatic anemia. In time-related change of these levels, no statistical difference was observed between the groups, which used TXA and the group, which did not.
Erythrocyte replacement: Throughout the follow-up time, erythrocyte replacement was applied to 115 patients among the TXA applied group (72.8%); 98 of these patients (62%) had 1-2 units of erythrocyte suspension (ES) replanted, and 17 of them (10,8%) had 3 units of ES replanted. All patients of the group, in which TXA was not applied, had ES replacement and, this ES replacement was at least 3 units or more for 59 (85.5%) patients. This value referred to a statistically significant finding. With the ES replacement given to the patients in the follow-up time, patients’ hemoglobin levels were stable at approximately 10 when they left the hospital.
Previous diseases: Previous diseases and chronic diseases of the patients were considered before the surgery.
As is shown in the table above, the effects of past diseases on the patients were evaluated and their effects on blood transfusion were also evaluated regarding TXA usage and need. The results revealed that the relevance level between the patients’ use of anticoagulants, their hypertension and diabetes history, being obese and gender were not significant. It was found out that the relevance level regarding the ages of patients was significant.
Age: Erythrocyte suspension was not applied to 28.4% of the patients younger than 65, while for patients older than 65, this rate was 12.1 %. A minimum of 3 erythrocyte suspensions were applied to 22.1% of the patients younger than 65, while a minimum of 3 erythrocyte suspensions were replaced for 41.7% of the patients older than 65 (p<0.001).
Complications: Among all patients, 2 patients had infection, and revisions were made for 4 patients. There was no statistically significant difference between the ones who used transamine and who did not use (p=0.516, p=0.317, respectively).
Venous thromboembolism: 2 venous thromboembolism cases were observed during the follow-up of both groups. There was no statistically significant difference (p=0,516).
Discussion
One of the important complications of total knee prosthesis is blood loss [14]. Various methods are used to reduce blood loss. In this study, the effect of local TXA usage in patients, undergoing SCBTKP surgery on blood loss has been investigated. Secondly, the effect of the drugs used by the patients and the reasons of additional diseases of the patients on blood loss have been investigated. The results of the study revealed that, independent of the extra factors, blood need was reduced in patients who used TXA locally, and very few complications occurred.
TXA inhibits the conversion of plasminogen to plasmin. In this way, it is used to reduce surgical bleeding or to reduce traumatic bleeding [15]. Chambers et al. investigated the use of local TXA in cemented and hybrid prostheses in their study with 139 unilateral knee prostheses. The authors reported that tropical TXA was as effective as cement fixation in hybrid fixation. This study is important in terms of reporting that TXA reduces bleeding, although there is no cement at the bone-implant interface that does not prevent blood loss [16]. In their study, Santias M et al looked at the reduction of bleeding by TXA without the use of a tourniquet. In a study conducted with 268 patients, 2 g of topical TXA was given in 50 ml of saline after the surgery and the amount of bleeding was found to be 1094 ml in patients who did not use TXA, while the average amount of bleeding was found to be 620 ml in patients using TXA, and no blood transfusion was performed in any patient using TXA [17]. In this study, a significant reduction in blood loss in bilateral knee prosthesis without cement was compatible with the hypothesis of the study. It was determined that the need for 2gr of local TXA blood per knee was significantly reduced. Thus, 17% of the patients who received TXA had 3 or more erythrocyte replacements, while 85.5% of the patients who did not receive local TXA had at least 3 erythrocyte replacements.
TXA can be used orally, intraventricularly or topically. Intravenous administration of TXA can significantly reduce blood loss [18]. While dose-dependent oral TXA usage is reported to be linked with venous thromboembolism [19], in comprehensive meta-analyses, it is reported that it was not the cause of thromboembolic problems. Similarly, oral and iv TXA usage reduces the blood loss and there are hardly any complications due to reduced TXA usage, however, it is reported to increase DVT ratio [20,21]. Digas et al. reported that in-joint use of TXA reduces blood loss more than other methods, but they did not mention venous thromboembolic problems in their study [22]. In addition, 2 mg TXA usage in each knee has significantly reduced the amount of bleeding and the fact that there were limited complications gives us an idea about the effective dose, usage timing and method. There are many studies about TXA usage and method, however, timing or dose of usage has not been standardized in these studies [23]. Thus, it would be more meaningful to conduct this study in a wide series of bilateral cementless simultaneous cases, as no studies on this issue have been found in the literature.
As known, prosthesis surgeries are usually performed on old patients with risk factors. Studies report that age, gender, multi-comorbidity can increase the amount of bleeding [24]. In this study, medical histories of patients were recorded in detail and included in the study. This study reveals that the additional comorbidities of patients did not affect the amount of bleeding, and the amount of blood needed is higher in old patients.
Various types of complications can occur after knee prosthesis surgeries, such as bleeding, wound problems, thromboembolic problems, neurovascular injuries, ligament injuries, swelling, deep periprostatic infection and fractures [25]. Among these complications, venous thromboembolism is reported by some authors to be affected by transamine usage [21]. In the literature, other possible complications are not linked to TXA usage. In this study, venous thromboembolism was observed in 2 patients, and this rate of incidence is smaller than the rate reported in the literature. In addition, while not being statistically important, 2 patients had infection and 4 patients had their one-sided prosthesis revised due to loosening. Patients who took part in this study did not have any thromboembolic problems up to their last controls.
This study reveals that for patients who used TXA, blood loss and Hemovac drainage volumes were significantly low, hospital stays were shortened and complication ratios were relatively low. As a result, 2 g topical TXA application for each knee in patients undergoing SCBTKP surgery significantly reduced blood loss, did not increase additional risks and its use was beneficial during the operation.
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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12. Fan D, Ma J, Liu X, Zhang L. Peri-articular administration of tranexamic acid is an alternative route in total knee arthroplasty: a systematic review and meta-analysis. J Orthop Surg Res. 2022;7;17(1):211.
13. Hishimura R, Onodera T, Ohkoshi Y, Okada K, Matsuoka M, Matsubara S, et al. The effect of local injection of tranexamic acid into peri-articular tissue versus drain clamping in total knee arthroplasty: a randomized controlled trial. BMC Musculoskelet Disord. 2022;2;23(1):111.
14. Joufflineau S, Thienpont E. Lower total blood loss in total knee arthroplasty with a low pressure tourniquet than without. Acta Orthop Belg. 2021;87(3):461-8.
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Ahmet Atilla Abdioğlu, Yılmaz Güvercin. Efficacy of topical tranexamic acid in bilateral cementless total knee arthroplasty. Ann Clin Anal Med 2023;14(5):464-468
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Eosinophil counts in children with newly diagnosed celiac disease: Is there any association between celiac disease and eosinophil counts?
Yasin Sahin 1, Emine Tekingunduz 2, Ozlem Gubur 2, Evrim Gumuc Berkel 2
1 Department of Pediatric Gastroenterology, 2 Department of Pathology, Mersin City Training and Research Hospital, Mersin, Turkey
DOI: 10.4328/ACAM.21625 Received: 2023-01-29 Accepted: 2023-03-12 Published Online: 2023-03-21 Printed: 2023-05-01 Ann Clin Anal Med 2023;14(5):469-472
Corresponding Author: Yasin Sahin, Department of Pediatric Gastroenterology, Mersin City Training and Research Hospital, 33240, Mersin, Turkey. E-mail: ysahin977@gmail.com P: +90 532 602 10 63 Corresponding Author ORCID ID: https://orcid.org/0000-0002-7394-4884
This study was approved by the Clinical Research Ethics Committee of Mersin University (Date: 2019-06-27, No: 263)
Aim: In this study, we aimed to evaluate whether there is a relationship between celiac disease (CD) and eosinophils.
Material and Methods: Patients diagnosed with CD under the age of 18 were included in the study. Children who underwent gastroduodenoscopy for any reason and had no abnormalities detected in their biopsies were included in the control group.
Results: Of the 72 patients with CD, 41 were girls, and their mean age was 8.50±4.24 years. Patients with CD had increased eosinophil counts in biopsies taken from the duodenal bulb and the second part of the duodenum. There was no statistically significant difference between the patients and control groups (p>0.05). Using the Marsh criteria, three groups of CD patients were created. There were 36 patients (50.00%) in Marsh 3a, 24 (33.33%) in Marsh 3b, and 12 (16.66%) in Marsh 3c. When the peripheral eosinophil counts and eosinophil counts in biopsies of all three groups were compared, no statistically significant difference was discovered (p>0.05).
Discussion: We found a higher number of eosinophils in the peripheral blood, the second part of the duodenum biopsy, and the duodenal bulb biopsy of patients with CD in the current study. But we did not detect a statistically significant difference between the patient and control groups. This may be due to the cross-sectional nature of the study and the limited sample size. Our hypothesis that eosinophils may be involved in the pathophysiology of CD needs to be confirmed by larger case series studies.
Keywords: Celiac Disease, Children, Eosinophil, Gastroduodenoscopy, Intestinal Biopsy
Introduction
Gluten consumption in genetically predisposed people causes the systemic autoimmune disease known as celiac disease (CD), which is marked by a variety of clinical symptoms and malabsorption [1]. The pathophysiology of CD is influenced by gluten consumption, genetic susceptibility, and gluten-induced proinflammatory innate and inappropriate adaptive immune responses. Additionally, it is assumed that some immune system elements (neutrophils, eosinophils, or mast cells) play a role in the pathophysiology of the disease [1,2].
Eosinophil cells, immune system effectors, are found in the peripheral blood and in different tissues of several organs [3]. In healthy individuals, eosinophils are found at high rates in the lamina propria of the gastrointestinal (GI) system mucosa under physiological conditions, except for the esophagus [4]. Numerous medical diseases affecting the GI tract are associated with significant increases in cell numbers and activity [5]. Eosinophils in the GI mucosa that are involved in the immune system have been shown to play a major role in primary eosinophil-associated GI disorders, celiac disease, inflammatory bowel disease, and in host defense against parasite infection and dietary allergens, and their numbers increase when intestinal inflammation is present [6-8]. Eosinophils interact with other immune cells and store biologically active mediators in their granules [9]. They may disrupt the function of the intestinal barrier by increasing the permeability of direct mucosal cell damage as a result of interaction with other cells and increase permeability in the small intestine and colon [10]. It is well known that eosinophils are gastrointestinal immune system resident cells that are essential to the host’s defense, especially when helminths and bacterial infections are present [11,12].
The finding of eosinophils in the GI tract in recent decades has raised questions about their function in GI health and disease [13]. Recent information on the pathophysiology of eosinophils clearly shows that the eosinophil is a multifunctional leukocyte, capable of interacting with other immune cells at the border between innate and adaptive immunity [8,14].
Mild duodenal eosinophilic infiltration has been described in patients with CD and severe mucosal atrophy, and it is believed that these cells could be involved in mucosal inflammation [8,15]. Few studies have examined eosinophil levels and the relationship between CD and eosinophils in young CD patients [15-17]. The aim of this study was to evaluate whether there is a relationship between CD and eosinophils.
Material and Methods
This study was performed in the Clinic of Pediatric Gastroenterology between February 2017 and June 2019. The study was executed following the Declaration of Helsinki and approved by The Local Ethics Committee (Mersin University Clinical Research Ethics Committee, Mersin, Turkey, 27 June 2019/263).
The study patient population included patients diagnosed with CD under the age of 18 and diagnosed with CD by intestinal biopsy, as stated in the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) 2012 guideline [18]. Written informed consent was obtained from the patients and their parents before the upper gastrointestinal endoscopy was performed. Children who underwent gastroduodenoscopy for any reason and had no abnormalities detected in their biopsies were included in the control group. Those with concurrent type 1 diabetes mellitus, autoimmune disease, eosinophilic gastrointestinal disease, allergy, parasitic infection, or systemic disease were excluded from the study.
Histological evaluation of the samples
All duodenal biopsies for CD were histopathologically evaluated according to the modified Marsh classification [19].
The samples used for eosinophil count were assessed histologically using a light microscope Nikon Eclipse Ci-L microscope (Nikon, Tokyo, Japan). Regarding the technical aspects, there is a possibility of patchy uptake of eosinophils in healthy and diseased tissues in anatomical subregions. Therefore, the eosinophils in the duodenal lamina propria were counted from 10 randomly chosen non-overlapping high-power fields (HPFs) at a magnification of 400. Subsequently, an average value was established for each case, and eosinophil counts were expressed in mm2 [20].
Statistical analysis
Statistical analysis was performed using the Statistical Package for Social Sciences program version 22.0 (IBM Corporation, Chicago, IL, United States). For the frequencies, percentages, and mean standard deviations (SDs), descriptive statistics were used. The Kolmogorov-Smirnov test was employed to determine whether the data distribution followed a normal pattern. The independent samples t-test was used for nominal data. Using the Mann-Whitney U test, ranges of numerical variables were compared, while the categorical variables were compared using the chi-square test. The Kruskal-Wallis one-way analysis of variance (ANOVA) test was used to compare the three separate groups. A p-value ≤ 0.05 was considered statistically significant.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
Of the 72 patients with CD, 41 were female, with a mean age of 8.50±4.24 years. In the control group, 16 of 26 children were female, with a mean age of 7.77±4.51 years. Age and gender comparisons between the patient and control groups revealed no statistically significant difference (p>0.05). The tests revealed a 200 eosinophil (IQR 248.0) count/mm3 in the peripheral blood of CD patients. Although peripheral blood eosinophil counts were greater in patients with CD than in the control groups, there was no statistically significant difference between the patients and control groups (p>0.05). In the control groups, 20 children had a duodenal bulb biopsy. Eosinophil counts were higher in the biopsies from the duodenal bulb, and a second section of the duodenum in patients with CD. Still, there was no statistically significant difference between the patients and control groups (p>0.05) (Table 1).
In 55% of the cases, we found an eosinophil count more than 20/HPF in the biopsies from the second part of the duodenum. Using the Marsh criteria, three groups of CD patients were created. There were 36 patients (50.00%) in Marsh 3a, 24 (33.33%) in Marsh 3b, and 12 (16.66%) in Marsh 3c. There was no statistically significant difference in terms of age and gender between the three groups (p>0.05). When the peripheral eosinophil counts and eosinophil counts in biopsies of all three groups were compared, no statistically significant difference was discovered (p>0.05) (Table 2).
Discussion
In the current study, we detected a higher number of eosinophils in both biopsies from the second part of the duodenum, and duodenal bulb in our patients with CD, but no statistically significant difference was found between the patient and control groups. Peripheral blood eosinophil counts were detected also high in the patient group, but no statistical difference was found between them. Patients with CD were divided into three groups according to the Marsh classification (19). When compared in terms of eosinophil counts in the biopsies of duodenal bulb, and second part of the duodenum, there was no statistically significant difference between these three groups.
Eosinophils were detected at a high rate in gastrointestinal biopsies of patients with inflammatory bowel disease, patients with rheumatoid arthritis, patients with functional dyspepsia, and patients with irritable bowel disease [5,21-23]. It has been suggested that duodenal eosinophils play a role in the pathogenesis of these diseases [5,21-23]. However, their relationship with these diseases remains unclear [5,21-24].
It has been shown that eosinophil numbers are higher in patients with CD [6]. Consistent with these studies, we also found high eosinophil counts in our patients with CD, but no statistical difference was found compared to the control group.
In a case series of 150 patients newly diagnosed with CD, eosinophil counts of 3-50/HPF were shown in biopsy specimens. The fact that advanced histological staging of the illness has been linked to mucosal eosinophilia raises the possibility that eosinophils are responsible for the damage to the mucosa [15]. In the present study, a higher number of eosinophils were detected in biopsies in celiac patients compared to the control group. However, there was no statistically significant difference between them. We did not detect any relationship between the histological stages of the disease and the number of eosinophils. We found an eosinophil count of more than 20/HPF in 55% of cases, compared to Brown et al. ‘s report [15] that this occurred in 25% of cases. This finding may be because our study was cross-sectional and the sample size was small. Consistent with this study, eosinophil counts in biopsy samples of our patients with CD ranged from 0 to 53 /HPF.
It has been shown that eosinophil counts are higher in patients with CD than in healthy children [16,17]. In line with previous investigations, we discovered that patients with CD had higher eosinophil counts than the control group.
In an adult study by Potter et al. [6], a high levels of eosinophils were detected in the duodenum. However, it has been shown that a high rate of eosinophils is not correlated with villous atrophy or clinical symptoms. In parallel with this recent study, we also found high eosinophil counts in patients with CD, that were not correlated with villous atrophy.
Another study found significantly higher eosinophil counts in adult patients with CD whose symptoms persisted despite being on a gluten-free diet [25]. Since the ESPGHAN guideline does not recommend control endoscopy in children with CD, we did not perform this procedure in the follow-up of the patients. Therefore, we could not investigate whether there was any change in eosinophil counts after their gluten-free diet.
To our knowledge, there are few studies on the distribution of eosinophils in the lamina propria of children with CD. In parallel with our study, high counts of eosinophils were detected in some studies [6,16,17]. However, the relationship between this finding and the pathophysiology of CD still remains unclear.
Limitations of the study
First, this study is retrospective. Second, the sample of the control group was limited in size because it was not possible to perform an endoscopy on healthy controls. Third, there are no control biopsies to investigate whether and how eosinophil counts change in celiac patients after responding to a gluten-free diet. The reason for this is that control biopsies are not recommended for patients with CD according to the ESPGHAN guideline, so control biopsies were not obtained after treatment.
Conclusion
We found a higher number of eosinophils in the peripheral blood, second part of the duodenum biopsy, and the duodenal bulb biopsy of patients with CD in the current study. But we did not detect a statistically significant difference between the two groups. This may be due to the cross-sectional nature of the study and the limited sample size. Our hypothesis that eosinophils may be involved in the pathophysiology of CD has to be confirmed by larger case series studies.
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. Potter Michael D, Hunt James S, Walker Marjorie M, Jones M, Liu C, Weltman M, et al. Duodenal eosinophils as predictors of symptoms in coeliac disease: a comparison of coeliac disease and non-coeliac dyspeptic patients with controls. Scand J Gastroenterol. 2020; 55 (7): 780-4.
7. Mehta P, Furuta GT. Eosinophils in Gastrointestinal disorders- eosinophilic gastrointestinal diseases, celiac disease, inflammatory bowel diseases and parasitic infections. Immunol Allergy Clin North Am. 2015; 35 (3): 413-37.
8. Licari A, Votto M, D’Auria E, Castagnoli R, Caimmi SME, Marseglia GL. Eosinophilic Gastrointestinal Diseases in Children: A Practical Review. Curr Pediatr Rev. 2020; 16 (2): 106-14.
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Yasin Sahin, Emine Tekingunduz, Ozlem Gubur, Evrim Gumuc Berkel. Eosinophil counts in children with newly diagnosed celiac disease: Is there any association between celiac disease and eosinophil counts? Ann Clin Anal Med 2023;14(5):469-472
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Are pan-immune-inflammation value, systemic inflammatory response index and other hematologic inflammatory indexes clinically useful to predict first-trimester pregnancy loss?
Serife Ozlem Genc 1, Huseyin Erdal 2
1 Deparment of Obstetrics and Gynecology, 2 Department of Medical Genetics, Faculty of Medicine, Aksaray University, Aksaray, Turkey
DOI: 10.4328/ACAM.21626 Received: 2023-01-30 Accepted: 2023-03-12 Published Online: 2023-03-21 Printed: 2023-05-01 Ann Clin Anal Med 2023;14(5):473-477
Corresponding Author: Serıfe Ozlem Genc, Deparment of Obstetrics and Gynecology, Faculty of Medicine, Aksaray University, Aksaray, Turkey. E-mail: drserifeozlemgenc@hotmail.com P: +90 543 456 56 24 Corresponding Author ORCID ID: https://orcid.org/0000-0002-9811-2726
This study was approved by the Ethics Committee of Aksaray University (Date: 2022-12-22, No: 157-SBKAEK)
Aim: The purpose of the study is to investigate the importance of hematological inflammatory parameters in predicting pregnancy loss in the first trimester.
Material and Methods: This study was conducted retrospectively between February and May 2022 in Aksaray University Training and Research Hospital, Obstetrics and gynecology outpatient clinic. Fifty-five of 110 patients diagnosed with first trimester pregnancy loss were included in the study. The control group consisted of 55 pregnant women with first trimester pregnancies.
Results: When the whole groups were compared, no statistically significant difference was observed in terms of hemoglobin, platelet, neutrophil, lymphocyte count, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), derived NLR ratio (dNLR), systemic inflammatory index (SII), systemic inflammatory response index (SIRI) and pan-immune-inflammation value (PIV).
Discussion: NLR, PLR, LMR, dNLR, SII, SIRI and PIV parameters were not associated with first trimester abortions. In this study, unlike previous studies, no hematological parameters, including the pan-immune-inflammation value, were found to have a role in predicting first trimester pregnancy loss.
Keywords: First-Trimester Abortion, Systemic Inflammatory Index, Systemic Inflammatory Response Index, Pan-Immune-Inflammation Value
Introduction
First trimester pregnancy loss (FPL) is the most common complication of early pregnancy, covering the first 12 weeks of pregnancy. 75% of all abortions occur before 16 weeks of gestation [1], of which 7.9% result in maternal death [2]. Many factors such as genetic anomalies, endocrinological disorders and immunological diseases have been associated with abortion [3]. Complications such as severe vaginal bleeding, endometrial damage, and infection can be observed during the FPL process. It may take time for women to realize that they have developed FPL because the symptoms are not specific. The diagnosis of FPL is difficult until confirming the dead fetus with ultrasound [4]. According to studies, it is clear that changes in maternal adaptive and immune response are important for a healthy pregnancy [5]. In recent studies, it has been suggested that the rates generally accepted as inflammation markers, neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), change in some conditions such as pregnancy-related complications, genital cancers, and infection [6-9].
Although many studies have stated that inflammation plays a key role in the pathophysiological mechanism of FPL, there are very few studies evaluating hematological parameters for this purpose. Bas et al. evaluated the hematological parameters for spontaneous abortions in the first and second trimesters [10]. Ardestani et al.’s study showed that NLR, MLR, PLR and derived NLR ratio (dNLR) levels were significantly higher in COVID-19 patients. In addition, NLR, LMR and dNLR were found to be significantly higher in those who died due to COVID-19 [11]. In the literature, studies have reported that it is possible to predict the development and severity of the diseases by looking at NLR and PLR levels [12,13].
Systemic inflammatory index (SII) and systemic inflammatory response index (SIRI) have started to be used in studies on cancers, acute pancreatitis, death prediction after coronary artery bypass surgery and other inflammatory processes [13-15]. However, pan-immune-inflammation value (PIV) is a new marker used specifically for cancers [16-19]; PIV in first-trimester pregnancy loss has never been studied before. A Complete blood count (CBC) is one of the first tests routinely requested after the presence of pregnancy is learned. In the present study, we purposed to evaluate parameters of the blood sera and inflammation indices obtained from these parameters, which is an easily accessible, inexpensive, and easily evaluated method for predicting first-trimester abortions.
Material and Methods
Purpose and Type of the Study
This retrospective study was conducted to evaluate CBC parameters in terms of whether there is a relationship between first trimester pregnancy loss and inflammation and to show whether pregnancy loss is predictable accordingly.
Sampling and participants
One hundred and ten pregnant women who applied to Aksaray University Training and Research Hospital, Gynecogy and Obstetrics Polyclinic between January 2022 and December 2022 and were diagnosed with first trimester pregnancy and met the criteria were included in this study. The present study included 55 patients with a diagnosis of first-trimester pregnancy loss and 55 patients with healthy pregnancies. The present study was approved by Aksaray University Local Ethics Committee (protocol number: 157-SBKAEK).
Data collection tools
The demographic information of the patients included in the study (age, number of pregnancies, number of miscarriages) and CBC parameters obtained from the hospital automation system were evaluated. CBC values during routine scans were used. CBC parameters evaluation was performed using an automated blood analyzer. The diagnosis of FPL was made by clinical examination and ultrasound records. All patients were 6-12 weeks pregnant from the first day of their last menstrual period. FPL was defined as the monitoring of an intrauterine gestational sac with no fetal heartbeat but greater than 10 mm in diameter. The inclusion criteria were pregnant mothers between the ages of 18-40 years with gestational age between 6-12 weeks who had singleton pregnancies. Patients with any congenital uterine anomaly, cervical insufficiency, hydatiform mole or multiple pregnancies, large uterine fibroids, and known history of thrombophilia were excluded from the patients diagnosed with FPL. Blood samples from the antecubital veins of these women were obtained after admission to the hospital before any treatment was administered. A complete blood count was performed as a standard laboratory procedure. Hemogram parameters were recorded. NLR, PLR, LMR, dNLR (neutrophil count divided by the result of WBC count minus neutrophil count), SII (neutrophil x platelet/lymphocyte count), SIRI (neutrophil × monocyte/lymphocyte count), and PIV (neutrophil × platelet x monocyte/lymphocyte count) were calculated. Accessible data (age, number of pregnancies, number of miscarriages) and hemogram parameters of the patient and control groups were evaluated. No extra blood was drawn from the patients for the study.
Statistical analysis
IBM SPSS 22 statistical program was used for statistical analysis. Two independent groups were compared with Student’s t-test. Values that did not fit the normal distribution were compared using the Mann-Whitney U test. Statistically significant p-value was accepted as <0.05.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
The difference observed between those who had abortions and those who were healthy in terms of age, count of gravida and parity were not statistically significant (p=0.152, p=0.21, p=0.144) (Table 1). On the other hand, the number of abortions in FPL group was significantly higher than in the healthy group (p=0.04). A comparison of all parameters of the control and abortion groups are shown in Table 1.
Discussion
Most of the fetal deaths observed during pregnancy occur in the first trimester. Although many studies have stated that inflammation plays a key role in the pathophysiological mechanism of FPL, there are very few studies evaluating hematological parameters for this purpose. In the present study, we investigated CBC parameters, which are included in routine screening tests in the first trimester of pregnancy, between FPL and healthy control groups. Studies up to date have shown that high neutrophil count may be a marker of inflammation, infection, bleeding, tissue necrosis, stress-related conditions, and gestational diabetes mellitus [8,9]. In recent studies, neutrophil counts and NLR have been associated with several conditions such as HELLP syndrome, recurrent pregnancy loss, hyperemesis gravidarum, or spontaneous abortion, particularly in the first trimester [10,19,20]. In study of Bas et al., when compared with the control group, in the first and second trimester abortion groups, platelet volume, platelet-lymphocyte ratio levels decreased, and neutrophil, lymphocyte and NLR increased [10]. In this study, we detect no significant differences in neutrophil, platelet, and lymphocyte count, NLR, PLR, and SII ratios between FPL cases and the control group (p > 0.05) (Table 1). The different results of this study from previous studies can be explained by the fact that FPL has a much different pathogenesis; this also means that not all pregnancy products can trigger inflammatory responses to the same degree.
Recent studies have shown that NLR, PLR and dNLR indicate inflammation [11]. Murad et al.’s study on determining the prognostic predictive value of Body Mass Index (BMI), NLR, SIRI and BMI in patients with laryngeal squamous cell carcinoma, found that NLR≥ 2.02 + Low BMI or SIRI≥ 1160.85 + Low BMI increased the risk of death [13]. In this study, we found no correlation between FPL and hematologic parameters.
However, in this study, PIV, which is one of the newest markers, has been studied mostly in the field of cancer and was found to be significantly higher in worse overall survival [17-19, 22]. PIV has not been studied so far in women who had a first trimester abortion. Therefore, the present results have provided important information for the literature.
Clinically, it is unreasonable to expect a high degree of significance from the rates obtained, since the hematological conditions of the individuals before the diagnosis of FPL are not identical. In addition, disease progression may also move the hematological parameters in the direction opposite to that is expected. For example, deepening of thrombocytopenia with the development of disseminated intravascular coagulopathy may cause a decrease in LII. Conversely, with an increase in any systemic inflammation, there may be an increase in neutrophil count, with a corresponding decrease in lymphocyte count and thus an increase in SII. Therefore, it is possible to obtain different results in similar studies. As a matter of fact, in our study, unlike the literature, we showed that the inflammatory parameters of FPL were not significantly different compared to the control group.
Therefore, it is important to state that there was no statistically significant difference between the groups in our study in terms of age, gestational week, gravidity and parity. We may owe to the fact that the CBC parameters are not very different from each other, due to the excellent similarity of all demographic parameters except the health status of the pregnancy. However, the result should be supported by further prospective large-scale studies.
Conclusion
As a conclusion, we showed that there is no relationship between hematologic parameters and inflammatory indexes in FPL. The limitations of the study are that it is a single-center and small-scale study. However, despite these limitations, it is important because it is the first study to investigate the pan-immune-inflammatory value in first trimester abortions.
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.21626
Serife Ozlem Genc, Huseyin Erdal. Are pan-immune-inflammation value, systemic inflammatory response index and other hematologic inflammatory indexes clinically useful to predict first-trimester pregnancy loss? Ann Clin Anal Med 2023;14(5):473-477
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