July 2023
Is there any link between mortality from COVID-19 infection and QRS duration in healthy people?
Ramazan Gündüz 1, Songül Usalp 2, Bekir Serhat Yıldız 3
1 Department of Cardiology, Manisa City Hospital, Manisa, 2 Department of Cardiology, Sancaktepe Sehit Profesor Ilhan Varank Education and Research Hospital, Istanbul, 3 Department of Cardiology, Celal Bayar University, Manisa, Turkey
DOI: 10.4328/ACAM.21424 Received: 2022-10-02 Accepted: 2022-11-11 Published Online: 2023-05-29 Printed: 2023-07-01 Ann Clin Anal Med 2023;14(7):576-580
Corresponding Author: Songul Usalp, Department of Cardiology, Sancaktepe Sehit Profesor Ilhan Varank Education and Research Hospital, Namık Kemal Street, No:7, 34785, Sancaktepe, Istanbul, Turkey. E-mail: dr.songulusalp@hotmail.com P: +90 216 606 33 00 Corresponding Author ORCID ID: https://orcid.org/0000-0001-9572-5431
This study was approved by the Ethics Committee of Celal Bayar University, Faculty of Medicine as well as the Turkish Ministry of Health (Date: 2020-07-13, No: E.54208)
Aim: Cardiac involvement in COVID-19 infection is associated with in-hospital mortality and morbidity. This study aimed to evaluate the effects of COVID-19 infection on the heart in patients without any known chronic disease using electrocardiographic (ECG) parameters.
Material and Methods: The study included a total of 201 consecutive patients, including 150 survivors and 51 non-survivors, who were otherwise healthy and did not take any medication.
Results: The QRS duration, heart rate, troponin I, C-reactive protein (CRP), D-dimer and procalcitonin values were higher in the non-survivor group (p<0.05). Cox regression analysis showed that QRS duration [HR 1.038 (1.006–1.071), p=0.023], troponin I [HR 1.255 (1.045–1.506), p=0.035], CRP [HR 1.004 (1.002–1.007), p=0.001], and D-dimer [HR 1.000 (1.000–1.003), p=0.014] values were associated with a high mortality rate due to COVID-19. ROC analyses indicated that the cut-off value of QRS duration predictive of COVID-19 mortality was >85 ms [AUC: 0.615, 95% CI (0.519–0.711), p=0.014]. Kaplan-Meier survival analysis showed that a patient with QRS>85 ms had a higher in-hospital mortality rate at day 30.
Discussion: Patients with COVID-19 infection who were otherwise healthy and did not take any medication had a wide QRS duration and an increased risk of mortality during the first admission to the hospital. ECG may be useful for estimating COVID-19 mortality because of its quick and easy results.
Keywords: COVID-19, Heart, Electrocardiography, Mortality, Inflammation
Introduction
SARS-CoV-2 (COVID-19) remains an epidemic disease that emerged at the end of 2019 and is transmitted through the respiratory system, leading to acute respiratory distress syndrome, multiorgan failure and high mortality [1]. It is very fatal, especially in [5,6]. Electrocardiographic changes, such as ST-T segment, QRS voltage, QT and QTc interval, prolongation of AV conduction, and atrial or ventricular arrhythmias may be observed, indirectly reflecting the effects of COVID-19 on the myocardium [6,7]. Previous studies on cardiac involvement in COVID-19 infection included complex groups with chronic comorbid diseases. However, the presence of comorbid diseases, such as coronary artery disease (CAD), diabetes mellitus (DM), hypertension (HT), and chronic obstructive pulmonary disease (COPD), adversely affect the heart, leading to various ECG changes, and COVID-19 is more fatal in these patients [4-6].
Therefore, unlike previous studies, we aimed to investigate electrocardiographic parameters in patients who did not have a known chronic disease or did not use any medication and who were hospitalized for the first time due to COVID-19.
Material and Methods
This retrospective study included 3023 consecutive patients who presented to our hospital with a complaint of cough, fever and shortness of breath and were hospitalized for the first time with a diagnosis of COVID-19 infection between June 2020 and February 2021. Patients under the age of 18 years and over 65 years who were pregnant or puerperal and had a chronic disease, patiens with right or left bundle branch block (LBBB) on their ECG were excluded from the study. Among the remaining 837 patients, 201 patients with an admission ECG who did not use any medication due to COVID-19 or any other disease were included (Figure 1). Following the World Health Organization (WHO) guidelines, nasopharyngeal swab specimens were collected from all patients, and COVID-19 was detected using a reversetranscription-polymerase chain reaction (RT-PCR) assay test. All patients underwent thoracic computed tomography (TCT) scans to confirm the diagnosis. Demographic characteristics, laboratory parameters and clinical features on the admission of all patients were obtained from their medical records at our hospital. The highest level of troponin I was 0.02 ng/mL, C-reactive protein (CRP) was 10 mg/dL, procalcitonin was 0.05 ng/mL, ferritin was 150 ng/mL, and D-dimer was 250 ng/mL. All patients received favipiravir treatment for COVID-19 during their hospitalization and appropriate antibiotic therapy if they had concomitant pneumonia.
The primary endpoint of the study was death due to COVID-19, which was acute respiratory distress syndrome. The patients were divided into 2 groups: those who recovered after COVID-19 infection (survivor group) and those who died from respiratory failure due to COVID-19 (nonsurvivor group).
Electrocardiography
The ECGs of patients diagnosed with COVID-19 on the first day of admission to the hospital were obtained. All patients received a 12-lead ECG in the supine position (GE Marquette Mac 1200). Each ECG was taken at a paper speed of 25 mm/s, a gain of 10 mV, and a paper format of 3×4. ECGs were independently interpreted by two cardiologists. The QRS duration was defined as the time interval from the onset to the end of the QRS complex, and the QT interval was measured from the onset of the QRS complex to the end of the T-wave. The corrected QT (QTc) interval was measured using Bazett’s formula (cQT = QT ms / RRs) [8].
Follow-up
All patients were followed up from the first day of admission to the hospital until the day of discharge. The primary endpoint of the study was death due to COVID-19 infection.
Statistical analysis
Statistical analysis was performed using SPSS 20.0 (IBM Corporation, Armonk, NY, USA). Continuous variables were represented by mean ± standard deviation (SD) or median (minimum-maximum), categorical variables were expressed with n (number) and percentages (%). Normality assumptions were checked by the Shapiro-Wilk and Kolmogorov-Smirnov tests by the number of cases in the groups. Baseline characteristics of the COVID-19 patients were compared using the Student’s t-test for continuous variables, which were normally distributed and the Pearson’s χ2 test was used for categorical variables. Cox regression analyses were performed for the association between QRS duration, inflammatory parameters and mortality of COVID-19. Hazard ratios and their confidence intervals were reported for univariable and multivariable models. The Kaplan-Meier survival analysis was performed to estimate the cumulative 30-day risk of death when patients were stratified by QRS duration. The receiver operating characteristics curve analysis (ROC) was used to determine the optimal cut-off of the QRS duration in a prediction model for mortality of COVID-19. For all statistics, a two-tailed p-value below 0.05 was considered significant.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
A total of 201 consecutive patients diagnosed with COVID-19 were included in the study. The mean age of the patients was 42.8 ± 15.1 years in the survivor group (n=150) vs. 52.3 ± 10.3 years in the nonsurvivor group (n=51). There was no difference between the two groups in terms of sex, body mass index, smoking or duration of hospitalization. Oxygen saturation was lower in the nonsurvivor group (p<0.000) (Table 1).
In the non-survivor group, bilateral thoracic involvement (p=0.011), mechanical ventilation (p<0.000), days in the intensive care unit (p=0.005), serum glucose (p<0.000), creatinine (p=0.003), CRP (p<0.000), procalcitonin (p<0.000), D-dimer (p<0.000), ferritin (p=0.005), troponin I (p=0.026), white blood cell count (p<0.000) and neutrophil/lymphocyte ratio (p=0.001) were higher than in the survivor group. The heart rate (p<0.000), QRS duration (p=0.010), and QT interval (p=0.002) were higher in the non-survivor group (Figure 1). The results are shown in Table 1.
Univariable and multivariable Cox regression analyses were performed to define the risk (hazard ratio) of mortality associated with COVID-19. In multivariable Cox regression analysis, QRS duration [HR 1.038 (1.006–1. 071), p=0.023], troponin I elevation [HR 1.255 (1.045–1.506), p=0.035], CRP elevation [HR 1.004 (1.002–1.007), p=0.001], and D-dimer elevation [HR 1.000 (1.000–1.003), p=0.014] were associated with COVID-19 mortality (Table 2).
In the ROC analyses, the cutoff QRS duration to predict COVID-19 mortality was >85ms [AUC: 0.615, 95% CI (0.519–0.711), p = 0.014], with a sensitivity of 60% and a specificity of 62% (Figure 2). The Kaplan-Meier survival analysis showed that a patient with a QRS>85 ms had a higher in-hospital mortality rate at 30 days (Table 3, Figure 3).
Discussion
We found that the prolongation of QRS duration and increased inflammatory biomarkers were associated with mortality due to COVID-19 infection in healthy individuals. In addition, patients with a QRS>85 ms were found to have a high mortality rate due to COVID-19 infection.
Inflammatory parameters and high troponin levels are known to be associated with COVID-19 infection mortality, but the relationship between the prolongation of QRS and mortality has not been demonstrated in healthy individuals. Our study is the first to find that prolonged QRS duration was equally associated with increased mortality compared to other inflammatory biomarkers. The studies conducted thus far included many patients with various chronic diseases who thus received various medications, and numerous ECG parameters were found to be associated with COVID-19 mortality in these studies. Some studies have shown that both QRS and QT durations are associated with poor prognosis [4,9,10,11]. However, these patients were taking chloroquine and various other drugs. In contrast, patients with any chronic disease or taking any medication were excluded from our study. ECGs were taken before the initiation of treatment for COVID-19. Therefore, the bias was reduced in the ECG parameters included in the study.
Similar to our study, Lanza et al. evaluated the ECGs of COVID-19 patients admitted to the emergency department [9]. After a one-month follow-up, they found that QRS duration ≥110ms, LBBB, and the presence of any ECG abnormality were independent risk factors associated with mortality [9]. Similarly, a study by De Vita et al. in patients with and without COVID-19 who had acute infectious respiratory disease found that a wide QRS duration and LBBB were seriously associated with COVID-19-related mortality [10]. Poterucha et al. found that a wide QRS duration and a high troponin level were associated with mortality, along with other ECG changes [11]. These studies included patients with multiple chronic diseases, especially CAD; therefore, these results might have been unfavorable for those with heart disease. However, our patient population was homogeneous and treatment-naive when compared with other studies, and they did not use any drugs that could prolong the QRS duration.
The exact reason why patients with a wide QRS duration who were admitted to intensive care units due to COVID-19 had a higher mortality rate is unknown. There may be several explanations for the prolongation of QRS duration in patients with severe COVID-19 infection. First, COVID-19 may cause myocarditis by damaging the myocardium [12-14]. Inflammation of the cardiac muscles due to myocarditis may lead to cellular edema, thickened myocardial tissue, prolonged conduction through the myocardium and thus prolongation of the QRS duration. Another reason is that COVID-19 may lead to a systemic immune reaction [12,13]. In addition, COVID-19 may directly or indirectly affect the cardiac conduction system through immune mediators as a result of the activation of systemic inflammatory pathways, and thus, a wide QRS duration may cause intra- or interventricular conduction delay [3,7]. In our study, although the QRS durations were below the normal limits in the non-survivor group, the high mortality rate and higher troponin values in this group suggest that these patients might have presented with myocarditis [3,15,16]. Cardiac involvement of COVID-19 may be predicted indirectly by elevated troponin, BNP and electrocardiographic or echocardiographic parameters [14-16]. The mortality rate due to COVID-19 with myocardial damage reached almost 40% in one series [17]. The risk of mortality associated with acute cardiac injury was found to be more significant than that associated with age, DM, chronic pulmonary disease, and prior heart disease [18]. Although there is no definitive evidence showing the presence of COVID-19 in myocardial tissue in autopsy studies for myocarditis, RT-PCR analyses of heart tissue have detected the viral genome in 35% (n=7/20) of patients [14,19]. At the same time, cardiac hypertrophy and decreased ACE 2 levels were observed in these patients [19,20]. In our study, we could not make a definitive diagnosis of myocarditis, since no cardiac biopsy or cardiac MRI was performed in any patient. However, the elevation of troponin I along with other inflammatory biomarkers increases the possibility of myocarditis. Thus, severe myocarditis and associated QRS prolongation might have increased the mortality in patients.
Limitation
The most important limitation of our study was that it was a single-center, retrospective study, and the number of patients was limited. On the other hand, echocardiography could not be performed on all patients, and the diagnosis of myocarditis could not be confirmed by cardiac biopsy or cardiac MRI in any patient.
Conclusion
The prolongation of QRS duration was as significant as other inflammatory parameters and a possible independent risk factor to predict mortality due to COVID-19. ECG at the first admission of patients may provide insight into the prognosis of COVID-19. Compared to other examinations, easier and faster results obtained by ECG will be beneficial in this respect.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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Ramazan Gündüz, Songül Usalp, Bekir Serhat Yıldız. Is there any link between mortality from COVID-19 infection and QRS duration in healthy people? Ann Clin Anal Med 2023;14(7):576-580
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Effects of obesity center group intervention on eating disorders and maladaptive eating attitudes
Ayse Gokcen Gundogmus 1, Zeynep Tasyurek 1, Yasemin Kocyigit 1, Pelin Cibik Buyuk 2, Harun Karabacak 3, Sibel Orsel 1, Kadir Ozdel 1
1 Department of Psychiatry, Etlik City Hospital, 2 Department of Psychiatry, Ankara Ataturk Sanatoryum Training and Research Hospital, 3 Department of Surgery, Etlik City Hospital, Ankara, Turkey
DOI: 10.4328/ACAM.21597 Received: 2023-01-17 Accepted: 2023-03-27 Published Online: 2023-06-09 Printed: 2023-07-01 Ann Clin Anal Med 2023;14(7):581-585
Corresponding Author: Ayse Gokcen Gundogmus, Department of Psychiatry, Etlik City Hospital, 06010, Ankara, Turkey. E-mail: gokcengonen@gmail.com P: +90 532 740 50 33 Corresponding Author ORCID ID: https://orcid.org/0000-0002-1594-7542
This study was approved by the Ethics Committee of Ankara Diskapi Yildirim Beyazit Training and Research Hospital (Date: 2022-05-23, No: 138/15)
Aim: The inability to reach the desired results despite different treatments for obesity stresses the necessity of a multidisciplinary approach. Psychosocial interventions are one component in this regard, particularly fund of knowledge on the efficiency of cognitive behavioral therapy increases. This study investigated the efficiency of obesity center group interventions that included cognitive psycho-education programs.
Material and Methods: People admitted to the obesity center were included in the study and participated in 12-session programs within four months. The sessions included diet programs, physiotherapist interventions, and cognitive behavioral therapy-based psycho-education programs. A psychiatrist examined individuals before and after the program and evaluated them with self-report measures. Primary outcome measures included maladaptive eating behaviors and eating disorders, the secondary outcomes included depression, anxiety, body dissatisfaction levels, and efficiency of psycho-education.
Results: Individuals (n=68) lost weight after psycho-education, yet the change in the body mass index was not statistically significant. In the pre-intervention period, 66.17% of individuals had a psychiatric diagnosis, which significantly decreased to 39.70% in the post-intervention period. Individuals’ depression and anxiety scores significantly decreased (p=0.032; p=0.018, respectively), body satisfaction and restrained eating levels increased (p<0.001), while emotional and external eating behaviors decreased post-intervention (p<0.001).
Discussion: There was a decrease in general psychopathology, maladaptive eating behaviors, and eating disorders besides weight loss through interventions and a multidisciplinary approach in our center. Obesity is a growing and important public health concern, which should be handled through multidisciplinary approaches. Follow-up studies on the long-term efficacy of cognitive behavioral therapy-based approaches should be conducted.
Keywords: Obesity, Cognitive Behavioral Therapy, Psycho-Education, Eating Disorders, Depression
Introduction
Obesity causes various complications such as metabolic, cardiovascular and psychiatric complications and increases the risk of early death, osteoarthritis, cancer, stroke and dementia [1]. The etiology of obesity is multifactorial, and genetic, environmental and psychological factors play a role in its development [2, 3]. There is a growing literature regarding its relationship with diseases like depression and anxiety [4]. Besides, obesity has a relationship with some eating disorders such as binge eating and night eating, and maladaptive eating attitudes such as emotional eating and grazing [5-7]. All of these maladaptive eating attitudes not only cause obesity but also cause patients, who have lost weight due to medical treatments or obesity surgery, to gain weight or lose less weight than targeted during the follow-up period [4, 8].
Among the treatment options for obesity are lifestyle changes such as changing eating habits, diets, increase in physical activity, exercises as well as medication, surgical treatments and psychological interventions; and bariatric surgery is deemed the most effective treatment [2, 4]. The approach to the rehabilitation of obesity should be multi-disciplinary. Nursing services should be integrated with diet, physical/functional rehabilitation, psycho-education and rehabilitation [1, 9].
Among psychological interventions for obesity are psycho-education, behavioral therapy, cognitive behavioral therapy, and motivational therapy [2, 4]. Although recent behavioral therapies for obesity treatment have been effective in weight loss, they have been criticized because most of the individuals regain weight in the long term and treatments cannot be individualized, and it has been argued that cognitive behavioral therapy may be more effective [2, 10]. A comparison of group cognitive behavioral therapy, performed in addition to standard diet therapy, a physical activity program, and educational activities showed that the weight loss rate was higher in the cognitive behavioral therapy group [1]. Though there are positive research outcomes on the effectiveness of nutritional psycho-education, motivational therapy and cognitive behavioral therapy-based interventions in obesity treatment, there are also results showing that negative effects are observed, the effects are lost over time, or there is no effect at all [2, 3, 11, 12].
Our study primarily aimed to determine the effect of cognitive psycho-education, physical activity and diet treatment program created through a multi-disciplinary approach in the obesity center on eating disorders and maladaptive eating attitudes of individuals with obesity. The study secondarily investigated whether there was any change in depression, anxiety levels and body satisfaction of individuals. Our hypothesis has suggested that interventions reduce eating disorders, maladaptive eating attitudes, and mental symptoms and positively affect body satisfaction.
Material and Methods
Design and Setting
The study included individuals with obesity who admitted to the obesity center of Ankara Diskapi Yildirim Beyazit Training and Research Hospital, affiliated with the Health Sciences University of Turkey, between December 2020 and January 2022 to lose weight. The local ethics committee approved the study protocol (23.05.2022-138/15). A practitioner, general surgeon, dietitian, physical therapist, physiotherapist, psychiatrist, psychologist and endocrinologist worked together in a multi-disciplinary approach in the center. Each department made suggestions to the patients based on the examination results, started medical treatment if necessary and/or regulated their ongoing treatments.
Treatment Groups
Separate sessions were held by the psychologists, physical therapists and dietitians in the group work at the obesity center. In total, 12-session psycho-education was completed in four months. Dietitians taught healthy nutrition/diet and physical therapists taught patients appropriate exercises. The physical therapist taught exercises (strengthening, stretching, balance, active, active-assistive, passive, etc.) specific to the status of each patient.
Psycho-education groups may include up to 10-12 patients, and each session lasts 60-90 minutes. Group trainings are provided interactively using slides and motivational and cognitive behavioral techniques, minding verbal participation of each patient in every session. The content of psycho-education sessions is given in Figure 1.
Patients
All patients admitted to the center were invited to take part in the study, and forms were distributed to those who accepted after providing informed consent. The inclusion criteria were age between 18 and 65 years, body mass index (BMI) ≥30 and being literate. Those with mental disabilities (dementia, intellectual disability, etc.) or physical handicaps (having a vision-hearing problem that prevents interviews or filling out forms, etc.) were not included in the study. In addition, individuals with ongoing physical illnesses or ongoing medical treatment that could explain obesity were excluded. Individuals were required to have participated in at least nine sessions out of 12 to be considered to have completed the psycho-education program. Their height-weight measurement was done before and after the psycho-education program. Seventy-four individuals out of 93 met the criteria and were included in the study. The data of 68 individuals were included in the analysis due to the incomplete parts in the scale forms of the rest (Figure 2).
Measures
Structured Clinical Interview Tool (SCID-5-CV) was used to determine the presence of psychiatric diagnosis in individuals [13]. The socio-demographic data form included data about the participants’ age, sex, height, weight, education status. Weight measurement of the individuals was repeated after the group interventions were completed. Psycho-education information form was developed by psychiatrists and psychologists working at the obesity center in line with the content of the psycho-education program, consisting of 29 questions evaluating individuals’ knowledge about obesity, its causes and treatment options. The Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) are self-assessment scales that aim to measure the depression and anxiety levels [14, 15]. A higher score of Body Image Scale (BIS) shows higher level of body satisfaction [16]. Every item of the scale is related to an organ or region of the body (arm, leg, face, etc.) or function of the body (sexual activity level, etc.). The Dutch Eating Behavior Questionnaire (DEBQ) consists of three subscales that evaluate emotional eating behaviors, external eating behaviors and restricted eating behaviors [17]. The Turkish reliability and validity of all the scales were conducted [18-21] (Hovardaoglu, 1990, unpublished master’s thesis, University of Ankara).
Statistical Method
Experimental design was used with a single group pre-test and post-test. This design is practical although it is weaker compared to other designs, because it is difficult to find a second group in health practices in general. In the data analysis, descriptive statistical measures (frequency and percentages) and McNemar χ2 test were used for the pre- and post-training differences of individuals’ eating behaviors. For repeated measures of the scale scores, paired sample t-test was used. Normality tests (Kolmogorov-Smirnov and Shaphiro-Wilk) were used for the normality of the measuring tools. The data were analyzed using SPSS (v 25) software. For statistical significance level, 0.05 alpha was used.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
The study group consisted of 68 participants with obesity. The mean age of the participants was 43.81 (± 10.18), and 79.4% of them were female. Of them, 29.4% stated that they wanted bariatric surgery at the time of their admission to the center. Of them, 72.1% received high school and higher education.
Paired sample t-test was used for the BMI and weight loss of the individuals before and after the program (Table 1). After the program, individuals weighed less, and the difference was found to be significant (p<0.05). Their mean weight loss was found to be 5.72±12.54 kg. Also, their BMI values were lower, compared to the first assessment, yet the difference was not significant. According to the normality tests, the scales showed normal distribution, with the exception of depression and anxiety scores. Since there were 68 individuals in the study, the assumption of normality for gap analyses was not a source of concern. In this regard, parametric tests were used.
Forty-five participants had a psychiatric diagnosis or eating disorders according to DSM-V before the program. This number decreased to 27 after the psycho-education. There was a significant decrease in the diagnosis of binge eating, night eating and grazing after the program (Table 2).
Patients’ depression and anxiety levels decreased significantly after training and the change had a moderate effect size, while their body satisfaction scores increased with a large effect size (p<0.05). Considering the change in patients eating attitudes, their restrained eating attitude scores increased after the program, while their scores on emotional eating and external eating behaviors decreased. The determined differences were significant and all changes had a large effect size (p<0.05). The scores that individuals obtained from the information form at the end of the program were significantly increased and this difference had a moderate effect size (p<0.05) (Table 3).
Discussion
Our study aimed to evaluate the efficiency of multidisciplinary obesity center interventions. At the end of the program, individuals lost an average of 5.72±12.54 of weight (kg) and the effect size was large, but the change in BMI was not significant. Before the program, 66.17% of individuals had a psychiatric diagnosis according to DSM-V, which significantly decreased to 39.70% after the intervention. Furthermore, their depression and anxiety levels decreased and the changes had a moderate effect size. Their body satisfaction increased after the program and this change had a large effect size. Restrained eating levels of individuals increased, while their emotional and external eating attitudes decreased after the intervention. All changes determined on eating attitudes had a large effect size. Their knowledge about obesity after cognitive-based psycho-education partly increased.
Outcome measures of CBT studies focus on different areas such as changes in weight, in eating disorders, in eating attitudes, in psychopathology, and quality of life [11, 22]. While the majority of psychosocial interventions, including CBT detected no significant weight loss, there are also study results reporting weight loss with a longer-term personalized group CBT [4, 11]. The effect size on weight was small and the change was seen as a decrease as a result of our obesity center interventions consisting of a combination of cognitive-based psycho-education, physical activity program and diet treatment. It is not possible to know which factor(s) enable(s) weight loss because the interventions were multidisciplinary, as has been suggested in recent years [1, 9], and medical treatments are conducted concurrently in individuals who are in need.
Similar to the literature, our study found that after the group intervention, eating disorders (binge eating disorder, night eating) [5, 23], maladaptive eating attitudes (grazing, emotional eating, external eating), and depression and anxiety levels decreased [1, 4, 11, 12, 22, 24]. Depression and maladaptive eating attitudes such as grazing and emotional eating have negative effects on weight loss and focusing on emotion regulation interventions instead of diet is recommended in the treatment of emotional eating in particular [7, 8]. There are studies associating restrained eating attitude with more weight loss in follow-ups [11], and accordingly, our study has revealed that it increases through interventions [12, 24].
Our study found that body satisfaction after interventions turned out to be more positive. The literature showed that the shape and weight concerns of individuals with obesity decreased after CBT [12]. This change, detected in body satisfaction despite the slight weight change, can be related to the decrease in changes in eating attitudes and/or depression and anxiety levels as well as direct effects of the interventions.
One of the strengths of our study is that participation rates were high except the shutdown period due to COVID-19, although the treatment discontinuation rates in obesity were high [1]. Another strength is that our study not only used self-report measures, but also included clinician examinations.
Limitations
The lack of knowledge about medication given simultaneously and the inability to examine its impact are important limitations. In addition, a sample consisting of individuals in search for treatment only and obtaining the data from a single center prevent generalization of the results obtained. Evaluation of emotional eating and grazing made by the clinician is another limitation because it may have differences, as there are no clear diagnostic criteria. Furthermore, the fact that individual’s compliance with the diet and exercise programs and the effectiveness of these interventions has not been evaluated is another limitation of this study.
Conclusion
When we evaluate our study results with those of many other studies, they suggest that the effect of center group practices, which include cognitive behavioral group therapy, focuses mainly on depressive symptoms, anxiety symptoms, body satisfaction and eating attitudes, while their direct effects on weight change are more controversial. This, in a part, shows that it is difficult to associate psychosocial interventions directly with weight loss, but it is important to discuss psychosocial factors related to obesity. There is a need for follow-up studies regarding the long-term efficiency of the interventions [4].
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. Barrett S, Begg S, O’Halloran P, Kingsley M. Integrated motivational interviewing and cognitive behaviour therapy for lifestyle mediators of overweight and obesity in community-dwelling adults: a systematic review and meta-analyses. BMC Public Health. 2018;18(1):1160.
4. David LA, Sijercic I, Cassin SE. Preoperative and post-operative psychosocial interventions for bariatric surgery patients: A systematic review. Obes Rev. 2020;21(4):e12926.
5. McCuen-Wurst C, Ruggieri M, Allison KC. Disordered eating and obesity: associations between binge-eating disorder, night-eating syndrome, and weight-related comorbidities. Ann N Y Acad Sci. 2018;1411(1):96-105.
6. van Strien T. Causes of Emotional Eating and Matched Treatment of Obesity. Curr Diab Rep. 2018;18(6):35.
7. Heriseanu AI, Hay P, Corbit L, Touyz S. Grazing in adults with obesity and eating disorders: A systematic review of associated clinical features and meta-analysis of prevalence. Clin Psychol Rev. 2017;58:16-32.
8. Conceição EM, Utzinger LM, Pisetsky EM. Eating Disorders and Problematic Eating Behaviours Before and After Bariatric Surgery: Characterization, Assessment and Association with Treatment Outcomes. Eur Eat Disord Rev. 2015;23(6):417-25.
9. Capodaglio P, Donini LM, Petroni ML, Brunani A, Dalle Grave R, Di Flaviano CE, et al. Rehabilitation in obesity with comorbidities: a consensus document from experts of the Italian Society of Physical and Rehabilitation Medicine (SIMFER), the Italian Society of Obesity (SIO) and the Italian Society of Eating Disorders (SISDCA). Eat Weight Disord. 2014;19(3):383-6.
10. Dalle Grave R, Sartirana M, Calugi S. Personalized cognitive-behavioural therapy for obesity (CBT-OB): theory, strategies and procedures. Biopsychosoc Med. 2020;14:5.
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12. Abilés V, Rodríguez-Ruiz S, Abilés J, Obispo A, Gandara N, Luna V, et al. Effectiveness of cognitive-behavioral therapy in morbidity obese candidates for bariatric surgery with and without binge eating disorder. Nutr Hosp. 2013;28(5):1523-9.
13. First MB, Williams JB, Karg RS, Spitzer RL. User’s guide for the SCID-5-CV Structured Clinical Interview for DSM-5® disorders: Clinical version: American Psychiatric Publishing, Inc. 2016.p.1-176.
14. Beck AT, Ward C, Mendelson M, Mock J, Erbauch J. Beck depression inventory (BDI). Arch Gen Psychiatry. 1961;4:561–71.
15. Beck AT, Epstein N, Brown G, Steer R. An inventory for measuring clinical anxiety: Psychometric properties. J Consult Clin Psychol. 1988;56(6):893-7.
16. Secord PF, Jourard SM. The appraisal of body-cathexis: body-cathexis and the self. J Consult Psychol. 1953;17(5):343.
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22. Paul L, van der Heiden C, van Hoeken D, Deen M, Vlijm A, Klaassen RA, et al. Cognitive Behavioral Therapy Versus Usual Care Before Bariatric Surgery: One-Year Follow-Up Results of a Randomized Controlled Trial. Obes Surg. 2021;31(3):970-9.
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Ayse Gokcen Gundogmus, Zeynep Tasyurek, Yasemin Kocyigit, Pelin Cibik Buyuk, Harun Karabacak, Sibel Orsel, Kadir Ozdel. Effects of obesity center group ıntervention on eating disorders and maladaptive eating attitudes. Ann Clin Anal Med 2023;14(7):581-585
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The effect of endometrioma cystectomy on dysmenorrhea and noncyclic pelvic pain
Zercan Kalı 1, Fatma Tanılır Çagıran 2
1 Department of Gynecology and Obstetrics, Private Gözde Academy Hospital, Malatya, 2 Department of Gynecology and Obstetrics, Private Genesis Hospital, Diyarbakır, Turkey
DOI: 10.4328/ACAM.21600 Received: 2023-01-17 Accepted: 2023-04-29 Published Online: 2023-05-08 Printed: 2023-07-01 Ann Clin Anal Med 2023;14(7):586-589
Corresponding Author: Zercan Kalı, Department of Gynecology and Obstetrics, Private Gözde Akademi Hospital, Malatya, Turkey. E-mail: zercankali@gmail.com P: +90 530 223 96 30 Corresponding Author ORCID ID: https://orcid.org/0000-0002-7128-7550
This study was approved by the Ethics Committee of Diyarbakır Gazi Yaşargil Education and Research Hospital (Date: 2022-12-30, No: 280)
Aim: In this study, we aimed to evaluate the effect of endometrioma cystectomy on dysmenorrhea and noncyclic pelvic pain with a linear visual analog scale (VAS).
Material and Methods: Sixteen patients who were admitted with the diagnosis of symptomatic endometrioma and planned for endometrioma cystectomy were included in the study. Ten patients for whom cystectomy was decided due to non-endometriotic benign ovarian cysts were included in the control group. Pre- and postoperative VAS scores were recorded in the control group. Before the operation and in the first and third months of the postoperative period, patients with dysmenorrhea and noncyclic pelvic pain were asked to mark the perceived pain intensity on a 100 mm horizontal line. The area they marked was measured from the left edge with a ruler divided into 1 mm units and VAS scores were recorded.
Results: VAS values recorded to determine the severity of dysmenorrhea before endometrioma cystectomy decreased significantly in the first and third-month scorings after cystectomy. Similarly, VAS values recorded to evaluate noncyclic pelvic pain intensity before cystectomy decreased significantly in the first and third postoperative months. A more significant decrease was found in the VAS values recorded in the third month for both dysmenorrhea and noncyclic pelvic pain compared to the first month. Uni- or bilateral endometrioma did not significantly affect the decrease in VAS values. There were non-significant decreases in preoperative and postoperative VAS scores of the patients in the control group. There was no significant difference between the mean pain reductions for dysmenorrhea and noncyclic pelvic pain.
Discussion: Endometrioma cystectomy leads to a significant decrease in dysmenorrhea and noncyclic pelvic pain VAS scores. The decrease in VAS values becomes more evident as the postoperative period is prolonged.
Keywords: Endometrioma, Cystectomy, VAS, Pelvic Pain
Introduction
Endometriosis is defined as the placement of the endometrial gland and stroma outside the uterine cavity. Foci are mostly located in the pelvic peritoneum and adjacent organs. However, endometriotic foci can be located anywhere in the body and in distant organs. Endometrioma is one of the most common complications of endometriosis (15-45%) and is a fluid/blood-filled cystic formation in the ovaries. It is the most common cause of secondary dysmenorrhea in women of reproductive age and adolescents. Endometriosis/endometrioma is found in approximately two-thirds of women who undergo laparoscopy for chronic pelvic pain or dysmenorrhea. Endometriosis-induced CPP and dysmenorrhea do not fully respond to normal analgesics and oral contraceptives [1].
The formation of CPP and dysmenorrhea seen in endometrioma depends on the combined effect of many factors. Active endometriotic foci located in the peritoneum or adjacent pelvic organs cause both bleeding and inflammatory changes, as they contain estrogen receptors [2]. Iron in the blood in the foci causes oxidative stress and stimulates the synthesis of inflammatory molecules and prostaglandins [3]. Increasing prostaglandins stimulate the neurovascular tissues around the foci and trigger pain. Hemorrhages on the peritoneal surfaces potentiate the pain by compressing the adjacent nerve tissues. Chronic cyclic focal hemorrhages cause fibrosis in the peritoneum, causing tension and pain in the nerve fibers. An increase in angiogenesis and neural growth factor synthesis disrupts the innervation of the uterus, fallopian tubes, and ovaries, leading to chronic pain [4]. In clinical practice, endometrioma patients exhibit many different pain spectrums. In addition to dysmenorrhea and dyspareunia, many different forms of pain such as abdominal discomfort, low back pain, and heavy menstrual bleeding may occur [5]. Oral contraceptives and progesterone therapy are primarily used in medical treatment. For palliative purposes, nonsteroidal anti-inflammatory drugs can be tried [3]. GnRHa is the last-line drugs to be used for medical purposes. Endometrioma surgery may be required in cases that do not respond to medical treatment.
If the pain due to endometrioma does not decrease despite 6 months of medical treatment, surgery may be attempted. A 50% reduction in pain has been reported after endometrioma cystectomy [6,7]. The Linear visual analog scale (VAS) scoring is used in the objective evaluation of endometrioma-related dysmenorrhea and CPP. VAS is a form of measurement that correlates with acute pelvic pain. The VAS score consists of a non-graded 100 mm line ranging from zero pain to severe pain. The VAS score is measured with the help of a ruler with a 1 mm measuring interval [8,9]. This study was planned to compare VAS scores measured in the pre-and postoperative period in patients who underwent laparoscopic endometrioma cystectomy with the diagnosis of symptomatic endometrioma (subfertility, CPP, dysmenorrhea, etc.). VAS scores measured before surgery and in the first and third months after surgery were compared.
Material and Methods
Sixteen patients who were admitted with the diagnosis of symptomatic endometrioma and planned for endometrioma cystectomy were included in the study. Participants were selected from patients aged 20-35 years who applied to Gözde Akademi Hospital’s Gynaecology outpatient clinic with subfertility, pelvic pain, or dysmenorrhea and were subjected to endometriosis research. The diagnosis of endometrioma was made by gynecological examination and transvaginal ultrasonographic examination, taking into account the patient’s complaints. Transvaginal ultrasound has high diagnostic accuracy in the diagnosis of endometrioma. Endometrioma was diagnosed in the presence of unilocular ground glass-like cyst fluid in the USG examination. Pain during the examination was accepted as a finding supporting the diagnosis [10]. MR imaging was used in patients whose definitive diagnosis could not be made. In addition, serum CA-125 levels were also measured. Other causes of secondary dysmenorrhea other than endometrioma were investigated. Definitive diagnosis was made by visual examination during laparoscopy and pathological diagnosis of cyst material. Patients with high BMI values (>30 kg/m2), PCOS patients, those who had previous ovarian or pelvic surgery, and those who used hormonal therapy in the last 3 to 6 months were not included.
Ten patients for whom cystectomy was decided due to non-endometriotic benign ovarian cysts were considered as the control group. The cyst was removed using a four-port laparoscopy technique under general anesthesia. The content was aspirated from an incision made on the cyst and the cyst wall was removed with forceps. Bipolar cautery was used to control bleeding. Superficial peritoneal endometriotic foci were excised. Before the operation and in the first and third months of the postoperative period, patients with dysmenorrhea and noncyclic pelvic pain were asked to mark the perceived pain intensity on a 100 mm horizontal line. The area they marked was measured from the left edge with a ruler divided into 1 mm units and VAS scores were recorded. Pre- and postoperative VAS scores were recorded in the control group. Ethical approval for our study was obtained from Diyarbakır Gazi Yaşargil Education and Research Hospital on 30.12.2022 with protocol number 280.
Statistical analysis
Statistical Package for Social Sciences version 21.0 (SPSS, Chicago, IL, USA) was used for the analysis of all collected data. Whether the data were normally distributed was tested with Kolmogorov-Smirnov. Normally distributed data were analyzed with Student’s t-test, and abnormally distributed data were analyzed with the Mann-Whitney U test. The results were presented as mean+ SD, p<0.05 was accepted as statistically significant.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
The comparison of the preoperative and first and third postoperative month VAS scores of the patients in the endometrioma and control group is presented in Table 1. The cysts of all patients in the endometrioma and control groups were successfully removed. In the endometrioma group, foci located in the peritoneum and ligaments were also excised. No serious complication was detected during the surgical treatment of both groups. There was a significant decrease in CA125 values measured in the postoperative third month compared to preoperative values (41.4±5.22 IU/mL vs 27.3±7.40 IU/mL, p<0.01).
VAS values recorded to determine the severity of dysmenorrhea before endometrioma cystectomy decreased significantly in the first and third-month scorings after cystectomy. Similarly, VAS values recorded to evaluate noncyclic pelvic pain intensity before cystectomy decreased significantly in the first and third postoperative months. A more significant decrease was found in the VAS values recorded in the third month for both dysmenorrhea and noncyclic pelvic pain compared to the first month. Uni- or bilateral endometrioma did not significantly affect the decrease in VAS values. There were non-significant decreases in preoperative and postoperative VAS scores of the patients in the control group. There was no significant difference between the mean pain reductions for dysmenorrhea and noncyclic pelvic pain.
Discussion
Endometriosis occurs when endometrial tissue becomes functional by being implanted in any tissue under the influence of estrogen. The presence of a multifactorial etiology leads to the continuation of the problems related to its treatment. The main hormone that allows endometrial tissue to attach to the peritoneum and other organs is estrogen. During peritoneal involvement, pain due to bleeding and inflammation occurs. Although the aging of the foci reduces its activation in the chronic process, the picture of pain due to fibrosis and compression of the nerve fibers continues. Endometrioma is actually a serious ovarian complication of endometriosis [11,12]. It occurs after the interaction of foci in the peritoneum and ovarian surface epithelium. Endometriomas cause many different pain conditions such as subfertility, chronic pelvic pain, dysmenorrhea, and dyspareunia. In patients who do not respond to medical therapy, removal of foci and endometrioma may be required to reduce pain. However, surgery is not a definitive solution for pain. Since recurrence will be seen in most cases, the pain will start again [13].
Pain due to endometriosis shows individual differences. According to the pain threshold, patients describe pain is quite different ways. We analyzed the pre-and post-operative pain perception severity of patients who decided to have laparoscopic cystectomy due to the diagnosis of symptomatic endometrioma, using the VAS score. Some of these patients are the group of patients who apply with the complaint of infertility but also have concurrent pain. Some of them are patients who have difficulties in reaching the egg before IVF/ICSI. In summary, they are patients who have been given a surgical decision for more than one complaint. The fact that pain is subjective is the biggest difficulty in pain assessment. The VAS score is a non-objective scale used to evaluate different types of pain. When we looked at the VAS scores before and after endometrioma surgery, we found a significant decrease in the VAS score one month after the surgery. VAS scores three months after surgery were lower. The prolongation of the postoperative period led to a significant reduction in the pain felt. The decrease in the VAS score, which was determined as 81 and measured for dysmenorrhea in the preoperative period, to 34 in the first month and 22 in the third month, is an important evidence that endometrioma surgery reduces the severity of pain. Similarly, while the preoperative VAS score was 47 in the evaluation of noncyclic pelvic pain, it decreased to 9 in the first month and to 4 in the third month. Endometrioma cystectomy resulted in a reduction in CPP in addition to dysmenorrhea. Compared with the non-endometriotic cyst group, it was observed that the pain felt both preoperatively and post-operatively decreased more significantly in the endometrioma group. The pain felt by the patients in the control group may have been perceived as milder because it was mostly due to the compression effect of the cyst. In addition, the absence of intraperitoneal bleeding and inflammation in the control group may explain the difference in VAS scores between the groups.
The interpretation of the decrease in VAS scores after endometrioma cystectomy is quite complex. While some authors consider the VAS score to be a linear score, others consider it a ratio or ordinal [14]. We are closer to the group that accepts the VAS score as linear. The reduction in pain due to a decrease in the VAS score from 81 to 34 is two times less than the decrease from 81 to 22. This means a decrease of 60 in the late postoperative period versus a 50 percent decrease in the early postoperative period. The lower the VAS value, the more effective the surgical procedure.
Conclusion
As a result, the decision of surgery related to endometrioma pain should be left to the last stage. First, medical treatments should be tried, hormonal suppression should be done, and if no response is obtained, surgery should be started. Accompanying subfertility or adversely affecting daily performance strengthens the surgical option. Despite the limited number of cases, our study has clinical importance in terms of showing that endometrioma surgery significantly reduces VAS scores. It is obvious that there is a need for more comprehensive studies in which different scoring systems are used in combination.
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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5. Uludag SZ, Demirtas E, Sahin Y, Aygen EM. Dienogest reduces endometrioma volume and endometriosis-related pain symptoms. J Obstet Gynaecol. 2021; 41(8):1246-51.
6. Alkatout I, Mettler L, Beteta C, Hedderich J, Jonat W, Schollmeyer T, et al. Combined surgical and hormone therapy for endometriosis is the most effective treatment: prospective, randomized, controlled trial. J Minim Invasive Gynecol. 2013; 20(4): 473-81.
7. Sachedina A, Todd N. Dysmenorrhea, Endometriosis and Chronic Pelvic Pain in Adolescents. J Clin Res Pediatr Endocrinol. 2020; 12( 1):7-17.
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13. Kanellopoulos D, Karagianni D, Pergialiotis V, Nikiteas N, Lazaris AC, Iliopoulos D. Endometriosis and Subfertility: A Literature Review. Maedica (Bucur). 2022; 17(2):458-63.
14. Kheil MH, Sharara FI, Ayoubi JM, Rahman S, Moawad G. Endometrioma and assisted reproductive technology: a review. J Assist Reprod Genet. 2022; 39(2):283-90.
Download attachments:10.4328.ACAM.21600
Zercan Kalı, Fatma Tanılır Çagıran. The effect of endometrioma cystectomy on dysmenorrhea and noncyclic pelvic pain. Ann Clin Anal Med 2023;14(7):586-589
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Comparison of manual and target controlled methods for minimal-flow anesthesia with a laryngeal mask
Elif Aşıcı 1, Güvenç Doğan 2, Selçuk Kayır 2, Özgür Yağan 2
1 Department of Anesthesiology and Reanimation Clinic, Sandıklı State Hospital, Afyonkarahisar, 2 Department of Anesthesiology and Reanimation, Faculty of Medicine, Hitit University, Çorum, Turkey
DOI: 10.4328/ACAM.21635 Received: 2023-02-02 Accepted: 2023-04-29 Published Online: 2023-05-08 Printed: 2023-07-01 Ann Clin Anal Med 2023;14(7):590-594
Corresponding Author: Selçuk Kayır, Department of Anesthesiology and Reanimation, Faculty of Medicine, Hitit University, 19200, Çorum, Turkey. E-mail: drskayir@gmail.com P: +90 505 373 51 58 Corresponding Author ORCID ID: https://orcid.org/0000-0002-3176-7859
This study was approved by the Non-Interventional Research Ethics Committee of Hitit University Faculty of Medicine (Date: 2019-04-25, No: 2019/135)
Aim: Distribution of fresh gas flow and anesthetic agent in low- and minimal-flow anesthesia can be sustained manually by the anesthesiologist or using automatic settings on devices with the target-controlled method selection. The target-controlled method is a gas delivery mode, which automatically sets the fresh gas, anesthetic agent and oxygen distribution system without requiring additional manual settings to reach the targeted levels determined by the anesthesiologist for inhalation agent and oxygen values on the device. The aim of our study was to assess whether the target-controlled method may be more easily and reliably used compared to the manual-controlled method for minimal-flow anesthesia administration with a laryngeal mask.
Material and Methods: Our study included 82 patients with general anesthesia administration using a laryngeal mask for inguinal surgery under elective conditions. For minimal-flow anesthesia, the target- and manual-controlled methods were compared in terms of duration to reach minimal alveolar concentration (MAC) value 1, inhalation agent stability, gas consumption and the number of device interventions to ensure and sustain anesthetic stability.
Results: Target-controlled anesthesia displayed less variability in expirium sevoflurane concentration compared to manual control. In the manual-controlled group, the duration to reach the targeted MAC was significantly shorter compared to the target-controlled group (77 s vs. 120 s, p<0.001). The manual-controlled method required more interventions to the device to sustain the targeted oxygen and anesthetic agent concentrations compared to the target-controlled method (8 vs. 2, p<0.001). There was no significant difference between the groups in terms of sevoflurane consumption.
Discussion: In our study, the target-controlled method ensured adequate and stable anesthesia for short-duration cases with laryngeal mask use. Due to the ease of application and reduced number of device interventions required, we think the use of low- and minimal-flow anesthesia methods can be expanded.
Keywords: Target Control, End-Tidal Control, Manual Control, Minimal Flow, Low Flow
Introduction
The carrier gas amount in inhalation anesthesia determines the anesthesia rate, depth and consumption of inhaled gases [1]. Virtue [2] reported that the minimal flow, a type of low flow using a fresh gas flow of 0.5 L/min, was economic and safe. This method reduces the consumption of fresh anesthetic gases, thus, lowering costs, and with re-breathing it assists in preserving the temperature and humidity of inspiratory gas mixtures [1,3].
For low-flow anesthesia to provide safe and adequate anesthesia depth, it is necessary for anesthesiologists to continuously monitor patient follow-up parameters and to perform many interventions to the device. Some new-generation anesthesia devices have an advanced target-controlled (end-tidal control) gas delivery mode to make management of fresh gas flow and inhalation agents easier. In the target-controlled method, the device identifies the levels of oxygen and anesthetic gas concentrations in a sample of the exhalation gas mixture and performs automatic setting with the aim of reaching the targeted values. The anesthesiologist determines the target expirium oxygen percentage (EtO2) and expirium anesthetic agent concentration (EtAA) according to the patient’s needs and enters them into the anesthesia device. During the case, the anesthesia device monitors these parameters and automatically sets the gas distribution and total flow to obtain and preserve the targeted values. In the literature, studies comparing the target- and manual-controlled methods with endotracheal tube for airway showed the target-controlled method reduced the number of interventions to the device by the anesthesiologist to ensure safe anesthesia conditions [4-6].
The combination of low-flow anesthesia and laryngeal mask (LMA) was shown to involve a tolerable level of volume leaks due to the accurate insertion of the LMA and to provide safe anesthesia maintenance [7]. However, in the literature, we did not encounter any study about the use of the target-controlled method for anesthesia administration with LMA.
The hypothesis of our study is that the target-controlled method will be easier and more reliably applied compared to the manual-controlled method for minimal-flow anesthesia with LMA. To test our hypothesis, we aimed to compare these two methods using the same anesthesia device in terms of duration to reach target sevoflurane concentration, maintenance and adequacy of anesthetic depth and the number of device interventions to ensure stability.
Material and Methods
Our prospectively planned study was performed after receiving permission from Hitit University Faculty of Medicine Non-Interventional Research Ethics Committee (Date: 25.04.2019, No: 2019/135). The study included 82 patients with unilateral inguinal hernia surgery planned under elective conditions who provided written consent. Inclusion criteria were determined as American Society of Anesthesiologists (ASA) I-II physical risk status and age 18-75 years. Cases with chronic obstructive pulmonary disease, coronary artery disease, congestive heart failure, pronounced anemia, BMI >24 kg/cm2, heavy cigarette consumption, and chronic alcohol intake were excluded from the study. For the study, a GE Aisys CarestationTM anesthesia workstation (GE Healthcare, Madison, WI, USA) allowing the use of minimal-flow anesthesia was used.
Patients taken to the operating room were randomly assigned to one of 2 groups as Group M (minimal flow with the manual method) and Group H (minimal flow with the target-controlled method) using an internet-based software program (Research Randomizer, http://www.randomizer.org/).
In addition to routine monitoring (ECG, non-invasive blood pressure, SpO2), Entropy Easy Fit Sensor (Entropy™, GE Healthcare) monitoring was performed. Demographic data and vital signs were recorded. After registering the patient age and weight information into the anesthesia device, all cases were given preoxygenation for 3 min with 6 L/min 80% O2 – 20% air with a face mask. Then induction was completed with 20 mg lidocaine, 2.5 mg/kg propofol and 1 µg/kg fentanyl and an I-gel LMA appropriate to the patient’s weight was inserted. Patients with LMA not inserted due to patient or technical reasons were excluded from the study. Anesthesia maintenance was provided by an inhaled mixture comprising O2, medical air and sevoflurane, and IV remifentanil infusion (0.05-0.1 µg/kg/min). The opioid infusion dose was set by targeting a 40-60 entropy value interval showing adequate anesthesia depth during the operation. Patients were ventilated in volume-controlled mode with tidal volume 7 mL/kg, respiration rate 12/min, and positive expirium end pressure (PEEP) 5 cmH2O. EtCO2 value was targeted as 30 – 40 mmHg, with end-tidal O2 in the range of 35 – 40%.
Immediately after the LMA cycle connection in patients in Group M, total fresh gas flow (TGF) was set to 4 L/m, FiO2 50%, and vaporizer sevoflurane concentration 4%. The opening time for anesthetic gas was accepted as the initial time, and the duration, until minimal alveolar concentration (MAC) reached 1, was recorded. When MAC 1 was reached, the flow was lowered to 0.5 L/min to begin minimal flow, with FiO2 at 70% and sevoflurane concentration set to 5%. The necessary vaporizer settings and FiO2 settings were made to ensure MAC was 0.9-1.1 and EtO2 was 35 – 40%, and the number of device interventions was recorded.
For Group H patients, the EtAA concentration targeting the MAC 1 values calculated by the device according to patient age was chosen. Settings were TGF 4 L/min and EtO2 40%. The duration to reach MAC 1 value was recorded and then flow was lowered to 0.5 L/min. The anesthesiologist intervened with the device to hold the MAC value between 0.9 – 1.1, and the number of interventions was recorded.
With 15 minutes until the end of the surgical procedure, the anesthetic gases were stopped in both groups and the flow rate continued at 0.5 L/min. When subdermal suturing began, remifentanil infusion was discontinued. In Group M, the washout process began with manual settings (flow 10 L/min, FiO2 80%). In Group H, the washout process began with the end-tidal washout method, a feature of the target-controlled method (flow 10 L/min, FiO2 80%). When spontaneous respiration began, manual respiration continued and the LMA was removed when adequate tidal volume formed.
In our study, follow-up parameters were the duration to reach MAC 1, the number of interventions to the device, awakening time (duration from initiation of washout to eye opening), and gas consumption data obtained from the device (O2, air, sevoflurane). Other follow-up parameters comprised heart rate (HR), mean arterial pressure (MAP), SpO2, peak and mean airway pressure, compliance, FiO2, fractionated expiratory oxygen concentration (FeO2) and fractionated expiratory agent concentration (Fe agent) recorded in the 2nd, 5th, 10th, 15th and 30th minutes.
Patients with entropy value >60 in the intraoperative period were excluded from the study as sufficient anesthesia depth could not be induced. During follow-up, in case of balloon deflation and immobility due to leaks, the TGF rate was increased and the patient was excluded from the study. A fall of 25% or higher in MAP during the intraoperative and postoperative period was assessed as low hypotension. Patients with no response in spite of IV fluid support were administered 5 mg ephedrine IV. HR <50 beats/min was assessed as bradycardia and atropine 0.5 mg IV was administered. If complications like cough, hiccups, biting, desaturation, breath-holding and bronchospasm occurred, they were recorded and suitable interventions were made. Cases with operation duration exceeding 90 min were excluded from the study. Patients were monitored in terms of postoperative hemodynamic findings and complications in the recovery room.
Statistical analysis
In this study, statistical analyses were performed using the SPSS (Version 22.0, SPSS Inc., Chicago, IL, USA Hitit University License) program. Descriptive statistics are presented as mean ± standard deviation for continuous data with normal distribution, as median (min-max) for data without normal distribution and as numbers and percentages for categoric data. The normal distribution was investigated with the Kolmogorov-Smirnov and Shapiro-Wilk tests. When comparing the means from two independent sample groups for continuous variables, the independent groups t-test was used for data with a normal distribution and the Mann-Whitney U test for data without a normal distribution. Correlations between categoric variables were researched with the chi-square test or Fisher’s exact test linked to the amount of data in the cross-tab cells. The statistical significance level was assessed as p <0.05.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
Our study evaluated 111 patients for inclusion and was completed with 41 patients in two groups. The CONSORT flow diagram is presented in Figure 1.
In both groups, patient features and anesthesia durations were similar (Table 1). The duration to MAC 1 was 77 s in Group M and 120 s in Group H. The duration was significantly shorter in Group M (P <0.001). The maximum inspirium agent concentrations were 3.1 (2.1-3.9) in Group M and 2.7 (2.2-4.1) in Group H and this parameter was significantly high in Group M (P <0.05).
In-group assessment of expirium sevoflurane concentration found statistically significant differences in Group M at 2, 5, 10 and 15 minutes (P <0.001). In Group H, there were no significant differences (P =0.719). Comparisons between groups found significant differences in expirium sevoflurane concentrations in the 5th, 10th and 15th minutes (P 0.007, <0.001, <0.001, respectively, Table 2). The variation in expirium sevoflurane concentrations in both groups over time is presented in Figure 2.
The number of interventions to the device to reach and sustain the targeted O2 level and anesthetic agent concentration was 8 in Group M and 2 in Group H and the difference was statistically significant (P <0.001). The time to waking was 7.5 min in Group M and 6.9 min in Group H. There was no statistically significant difference in terms of waking durations between the groups (P =0.251).
In Group M, the oxygen and air consumption values were statistically significantly low compared to Group H (P <0.05, <0.01, respectively). In terms of sevoflurane consumption, there was no statistically significant difference between the groups (Table 2).
There were no statistically significant differences between the groups at all measurement times in terms of perioperative hemodynamic parameters, intraoperative airway pressure and complications.
Discussion
In our study comparing manual- and target-controlled methods for minimal flow administration with LMA, the target-controlled method provided a more stable anesthesia level. Additionally, the target-controlled method required less device interventions to reach and sustain the desired values.
In our study, the duration to reach MAC 1 in the manual-controlled group was significantly shorter compared to the target-controlled group (77 s vs. 120 s). In the literature, similar studies reported different results. A study by Potdar et al. [4] found that the duration to reach the targeted EtAA concentration of 1.5% was shorter in the target-controlled group (3 min vs. 13 min). Wetz et al. [2] found that the duration to reach the targeted EtAA concentration of 1.2-1.4% in minimal flow sevoflurane anesthesia was 275 s in the manual-controlled group and 178 s in the target-controlled group. The reason for the longer duration required to reach the targeted sevoflurane level with the manual method in these two studies may be the lack of use of high TGF at the start of inhalation anesthesia in their protocols. In our study protocol, we used high TGF initially to ensure adequate anesthesia depth for surgery in a shorter duration. In this process, maximum inspirium agent concentration values were 3.1% in Group M and 2.7% in Group H. In our study, the increase in maximum inspirium agent as a result of high TGF administration initially is consistent with the short duration to reach MAC 1 in the manual-controlled method.
Especially for low flow anesthesia, manually controlled anesthesia requires constant monitoring and numerous adjustments to the gas dosage by the anesthetist [9]. The duration allocated for manual control of anesthetic agents and O2 concentration may cause the anesthesiologist’s attention to be distracted from the patient. As the target-controlled method requires less monitoring and interventions, the workload is reduced, as shown in many studies in the literature [2,4,9,10]. In our study, consistent with the literature, the manual-controlled method requires a higher number of interventions to preserve the targeted intervals compared to the target-controlled method.
In spite of the lower number of interventions in the target-controlled group in our study, the expirium sevoflurane concentration showed less variation over time compared to the manual-controlled method. The target-controlled method was observed to ensure more stable anesthetic agent concentration compared to the manual-controlled method. In a study by Wetz et al. [2], they reported more stable expirium anesthetic agent levels in the target-controlled group. With the manual-controlled method, they found that the deviation percentage from the targeted value for the sevoflurane concentration was significantly higher at all measurement times.
Consistent with similar studies in the literature, there was no statistical difference observed in terms of waking durations for the groups in our study [6,9,10]. The lack of difference in waking duration is thought to be a result of similar patient characteristics, the same type of surgery and anesthetic methods.
According to the working principle of the target-controlled method, a fixed cycle pressure is provided at the end of expiration in the manual respiration bag. If this pressure reduces, TGF is automatically increased in response. If adequate cycle pressure cannot be provided in spite of the TGF increase, the target-controlled method is automatically ended [11]. In our study, adequate tidal volume did not form due to leak during the case for 2 patients in the manual-controlled group. The flow rate was increased as the bellows did not function and these patients were excluded from the study. In the target-controlled group, there was no patient excluded from the study due to leaks. As the target-controlled method preserved cycle air pressure by increasing TGF, we think no air leak at levels to disrupt ventilation formed in Group H in our study. In our study, no complications were encountered related to the target-controlled method applied with the end-tidal control module.
In our study, there were no statistically significant differences between the groups in terms of sevoflurane consumption. When we compared fresh gas consumption, the manual-controlled group was found to have significantly lower O2 and air consumption. The higher fresh gas consumption in the target-controlled method may be associated with the high TGF use initially and the short surgical duration. In a study by Wetz et al. [2] with similar results, they explained the substantially high sevoflurane consumption in the target-controlled method as a result of the target-controlled method’s use of high TGF. They proposed that this difference in consumption may reduce with longer anesthesia durations. Additionally, during the first 15 minutes of anesthesia in their study, the target-controlled method was found to have significantly higher O2 flow and they reported that this difference between the groups showed a reducing tendency in advancing time intervals. Due to the saturation phase of the anesthetic agent (washout stage), the target-controlled method may not have an anesthetic agent and fresh gas savings at pronounced levels during short-duration surgeries. As the anesthesia duration lengthens, a variety of studies reported that the anesthetic agent savings obtained with the target-controlled method will increase [6,12]. Comparison of anesthetic agent consumption remains limited due to differences in anesthetic devices used, TGA amounts, targeted anesthetic agent concentration and protocols applied.
One of the limitations of our study is that the comparison of anesthetic agent concentration or consumption information could only be assessed for a limited period of time between the groups because the mean surgical duration for cases in both groups was less than 1 hour. Another limitation is that the remifentanil dose administered was set according to intraoperative requirements and the dose received by each patient was different. However, all patients had adequate opioid dose set to keep entropy values in the 40-60 interval and attempts were made to minimize the effect of this dose difference on waking duration.
Conclusion
The main outcome of our study is that the target-controlled method may be safely used for minimal flow anesthesia in surgeries where LMA is chosen for airway control. Though the target-controlled method took longer to reach the desired sevoflurane concentration, it provided a more stable anesthetic agent concentration during inhalation anesthesia maintenance. Additionally, the target-controlled method required lower number of interventions to the device to sustain sevoflurane and EtO2 concentrations in the desired intervals. This largely simplified minimal flow anesthesia management and positively contributed to the patient monitoring process by saving the anesthesiologist from performing tiring, time-consuming and distracting tasks.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: This study is derived from a scientific research project funded by Hitit University Scientific Research Projects Unit (TIP19004.19) with the aim of obtaining an Entropy Easy Fit Sensor (Entropy™, GE Healthcare).
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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3. Hönemann C, Hagemann O, Doll D. Inhalational anaesthesia with low fresh gas flow. Indian J Anaesth. 2013;57(4):345-50.
4. Potdar MP, Kamat LL, Save MP. Cost efficiency of target-controlled inhalational anesthesia. J Anaesthesiol Clin Pharmacol. 2014;30(2):222-7.
5. Sieber TJ, Frei CW, Derighetti M, Feigenwinter P, Leibundgut D, Zbinden AM. Model-based automatic feedback control versus human control of end-tidal isoflurane concentration using low-flow anaesthesia. Br J Anaesth. 2000;85(6):818-25.
6. Lortat-Jacob B, Billard V, Buschke W, Servin F. Assessing the clinical or pharmaco-economical benefit of target controlled desflurane delivery in surgical patients using the Zeus anaesthesia machine. Anaesthesia. 2009;64(11):1229-35.
7. Hönemann CW, Hahnenkamp K, Möllhoff T, Baum JA. Minimal-flow anaesthesia with controlled ventilation: comparison between laryngeal mask airway and endotracheal tube. Eur J Anaesthesiol. 2001;18(7):458-66.
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Download attachments: 10.4328.ACAM.21635
Elif Aşıcı, Güvenç Doğan, Selçuk Kayır, Özgür Yağan. Comparison of manual and target controlled methods for minimal-flow anesthesia with a laryngeal mask. Ann Clin Anal Med 2023;14(7):590-594
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Transportation and shaping ability of 3 canal anatomy-friendly systems in curved root canals
Merve Babacan Özad 1, Ahter Şanal Çıkman 1, Taha Emre Köse 2, Banu Arıcıoğlu 3
1 Department of Endodontics, Faculty of Dentistry, Recep Tayyip Erdogan University, Rize, 2 Department of Oral and Maxillofacial Radiology, Faculty of Dentistry, Recep Tayyip Erdogan University, Rize, 3 Department of Endodontics, Faculty of Dentistry, İstanbul Medeniyet University, İstanbul, Turkey
DOI: 10.4328/ACAM.21659 Received: 2023-02-22 Accepted: 2023-04-29 Published Online: 2023-05-14 Printed: 2023-07-01 Ann Clin Anal Med 2023;14(7):595-599
Corresponding Author: Banu Arıcıoğlu, Department of Endodontics, Faculty of Dentistry, İstanbul Medeniyet University, İstanbul, Turkey. E-mail: banu.arc@gmail.com P: +90 216 830 38 03 Corresponding Author ORCID ID: https://orcid.org/0000-0002-1124-1905
This study was approved by the Ethics Committee of Medical Faculty of RTE University (Date: 2019-11-05, No: 2019/164)
Aim: In this study, we aimed to compare the shaping efficacy of the TruNatomy (TRN), XP-endo Shaper (XPS), and 2Shape (TS) NiTi rotary systems in terms of canal transportation, centering ratio, and removed dentin volume using cone beam computed tomography (CBCT).
Material and Methods: Sixty mesial root canals of mandibular first molar teeth with a curvature angle of 20-40° and curvature radius of 4-6 mm were allocated to three groups (n=20). Instrumentation was performed in compliance with the manufacturer’s instructions. CBCT images were taken in the same position before and after instrumentation. Canal transportation and the centering ratio were calculated at 3, 6, and 9-mm distances from the apex. Data were statistically analyzed.
Results: TS group had significantly higher transportation (P<0.05) and there was no significant difference between the TRN and XPS groups. In terms of centering ability, no significant difference was detected between the groups (P>0.05). The volume of removed dentin was significantly lower in the TRN group (P<0.05) and there was no significant difference between the XPS and TS groups.
Discussion: XPS and TRN groups showed less transportation than TS, whereas the centering ability was similar for all groups. In addition, the TRN group removed significantly less dentine, supporting the minimally invasive endodontic approach.
Keywords: Centering Ratio, Cone-Beam Computed Tomography, Root Canal Volume, Transportation, TruNatomy
Introduction
The objective of a successful root canal preparation is to remove the infected dentine, to prepare a sufficient space for effective irrigation, and to create a conical form for appropriate canal obturation, preserving the original canal anatomy [1]. However, the complex anatomy of the root canal makes it difficult to achieve ideal shaping, especially in curved canals [2]. Instrumentation procedures tend to deflect the root canal from its original axis and may lead to procedural errors, including lodging, zipping, strip perforation and transportation [3]. Therefore, with the improvement of thermomechanical production stages, more flexible NiTi rotary instruments that can provide better centering ability and preserve the original canal anatomy have been developed [4].
TruNatomy (TRN) (Dentsply Sirona, Ballaigues, Switzerland) is a new-generation heat-treated super elastic NiTi rotary system recently released on the market. Compared with traditional NiTi rotary instruments, the TRN has a smaller core structure and reduced shape memory characteristics. Each instrument has a regressive taper, which allows each instrument to maintain a maximum flute diameter of 0.8 mm [5].
XP-endo Shaper (XPS) (FKG Dentaire SA, La Chaux-de-Fonds, Switzerland) is a single-file system made of Max Wire alloy. This alloy is in the martensitic form at room temperature, and the phase transformation occurs at 35°C, thus it transforms into an austenitic form at body temperature, causing the file to become curved. This unique design preserves the three-dimensional configuration of the root canal anatomy, while allowing a gradual increase in the working area under the temperature effect [6].
The 2Shape (TS) (MicroMega, Besancon, France) is manufactured from T-Wire alloy. It has been reported that the use of T-wire alloy provides better shaping ability in curved canals [5].
In this study, it was aimed to compare the shaping ability of novel TruNatomy rotary system with a single instrument XP-endo Shaper and 2Shape rotary system consisting of 2 instruments. The null hypothesis is that there are no differences between TRN, XPS, and TS in terms of shaping efficacy in curved root canals.
Material and Methods
Local ethics committee approval was obtained from the Ethical Review Committee under the Research Foundation [removed for blind peer review] (No: 2019/164).
Sample Selection and Preparation
In this study, 60 mesial canals obtained from freshly extracted mandibular first molar teeth were used. The inclusion criteria for the study were as follows: the presence of 2 canals with a curvature angle of 20-40° (according to the Schneider method) [7], and a curvature radius of 4-6 mm (according to the Pruett method) [8], terminating with two separate foramina in the mesial root (type IV Vertucci canals); the absence of obstructions in the root canal; having initial apical diameter of 0.15 mm; completed root development; and no resorptions, cracks, or fractures in the root; and the presence of similar root lengths (17 ± 2 mm).
Tissue residues on the outer surface of the roots were removed using a periodontal curette. The teeth were kept in physiological saline at + 4°C during the study. Traditional access cavity was performed with an Endo-Z bur (Dentsply Maillefer, Ballaigues, Switzerland), and the mesial canals were explored with #10 K file (Dentsply Maillefer, Ballaigues, Switzerland). Working length was determined by subtracting 1 mm from the length at the time the file was first seen. To ensure standardization, the occlusal surfaces of the teeth were flattened under water cooling and the working length was fixed to 18 mm. The samples were embedded in acrylic blocks up to the level of the enamel-cement junction.
A fixed system was designed to obtain stable cone beam computed tomography (CBCT) images of the samples in the same position. The CBCT scans were obtained using a Planmeca system (Promax 3D Classic, Helsinki, Finland) with scanning parameters of 90 kV, 10 mA, 12 sec and 100 µm voxel size. The field of view (FOV) of the detector panel was 50×50 mm. The Planmeca Romexis Viewer software was used for processing the CBCT images. The obtained images were reconstructed with 0.1-mm section thickness. The curvature angles and radii of the samples were measured on the preoperative CBCT images and the selection of sample was made. The selected samples were divided into three groups with similar curvature angles and radii.
Root Canal Instrumentation
Before the instrumentation procedure, all samples were kept in a 37°C water bath for 30 minutes, and the irrigation solutions were also heated to 37°C to maintain the intracanal temperature during preparation. All instruments were used according to the manufacturer’s instructions in continuous rotation movement, using a VDW Gold endodontic motor (VDW GmbH, Munich, Germany) and each instrument was used in only two canals.
In the TRN group, respectively, Orifice Modifier (20/0.08), Glider (17 /0.02), Small (20/0.04), and Prime (26/0.04) files were used at 500 rpm and 1.5 Ncm settings. In the XPS group, a #15 K file was used to obtain a glide path before using the XPS file (30/0.04). Instrumentation was performed at 800 rpm and 1 Ncm settings. When the 30/0.04 gutta-percha fit the canal perfectly, instrumentation was finished. In the TS group, after establishing the glide path with a #15 K file, instrumentation was performed using a TS1 (25/0.04) and TS2 (25/0.06) at 300 rpm and 2 Ncm settings. In all groups, the root canals were irrigated with 2 mL of warmed NaOCl (2.5%), using a 30-G needle (KerrHawe SA, Bioggio, Switzerland) after each file change. The final irrigation was performed with 5 mL of NaOCl (2.5%) followed by 5 mL of distilled water.
CBCT Measurements
After instrumentation, postoperative CBCT scans were performed using the same parameters as in the initial imaging. Measurements were made at 3, 6, and 9-mm distances from the apex, considering the start and end points of the canal curvature. On preoperative and postoperative CBCT images, the shortest distance between the outer border of the root and the canal wall was measured from four different regions in axial sections by a single observer twice, 3 weeks apart, and the average values were recorded as the final data (Figure 1).
Transportation and centering ratios were determined using the formulas suggested by Gambill et al. [9]:
Transportation in the buccolingual direction = (B1-B2) – (L1-L2),
Transportation in the mesiodistal direction = (M1-M2) – (D1-D2)
Centering ratio in the buccolingual direction = (B1-B2) / (L1-L2) or (L1-L2) / (B1-B2),
Centering ratio in the mesiodistal direction = (M1-M2) / (D1-D2) or (D1-D2) / (M1-M2).
B1, L1, M1, and D1 indicate the shortest distance between the buccal, lingual, mesial, and distal borders of the root, and the canal wall before instrumentation and B2, L2, M2, and D2 indicate the shortest distances after instrumentation. According to these formulas, the result of 0 indicates that there is no canal transportation. Positive values indicate transportation towards buccal or mesial directions, and negative values indicate transportation towards lingual or distal directions. A centering ratio of 1 shows perfect centering. Any value other than 1 indicates that the canal is not centered. As the centering ratio gets closer to zero, the instrument’s centering ability decreases.
To determine the removed dentine volume, the CBCT images were transferred to the InVesalius program (version 3.1; Centro de Tecnologia da Informação Renato Archer, Campinas, SP, Brazil) and the root canal volumes were calculated by a single observer. The volume of removed dentine (mm3) was calculated by subtracting the preoperative volume of the root canal from the postoperative volume, referencing Hashem et al. [10] (Figure 2).
Statistical analysis
All data were analyzed using the SPSS (SPSS Inc., Chicago, IL) program. One-way ANOVA was used for normally distributed data and the Kruskal-Wallis test was used for non-normally distributed data in the comparison of transportation values and centering rates at different levels and in different directions according to the groups. One-way ANOVA was used for the comparison of the removed dentine volume by groups. P<0.05 was accepted to indicate statistical significance.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
According to the total mean transportation values, the TS group showed significantly higher transportation (P<0.05); the difference between the TRN and XPS groups was not significant. There was no significant difference between the groups at any level in the BL direction. In the MD direction, there was no significant difference between the groups at the 3-mm level, but at the 6-mm level, the TS group exhibited significantly more transportation than the TRN group, and at the 9-mm level, more than both the TRN and XPS groups (Table 1).
There was no significant difference between the groups at any level and direction in terms of centering ratio (P>0.05) (Table 2).
The volume of removed dentine in the TRN group was significantly lower compared with the others (P<0.05). The difference between the XPS and TS groups was not significant (Table 3).
Discussion
During instrumentation, it is aimed to achieve a conical form from apical to coronal, as well as to maintain the original anatomic configuration of the canal. NiTi rotary systems allow for easier and faster instrumentation besides preserving the original canal configuration, leading to considerably fewer procedural errors [4].
Extracted human teeth were used in our study because their in vitro reliability is closest to clinical conditions. In clinical conditions, the interference of the cervical dentine causes stress on files during canal instrumentation [11]. To mimic this condition, crowns were not removed in this study.
Although the small voxel size of Micro-CT is effective in evaluating shaping efficacy, such systems are expensive and require longer screening and reconstruction times compared with CBCT, which is an effective non-invasive imaging method to calculate the quantity of the removed dentine, canal transportation, and the canal centering ratio [10, 11].
In studies evaluating the quantity of transportation and centering ratios, there is no consensus on the measurement distances from the apex, and the fact that the maximum curvature points in all teeth will not be at the same level should be taken into account in ensuring standardization [12]. Therefore, in this study, the evaluation levels were decided as 3, 6, and 9 mm after determining between which levels the maximum curvature point was for each canal. Additionally, to obtain standard conditions in terms of canal curvature, besides the curvature angle, the radius of curvature was also taken into consideration and with curvature angles of 20-40° and radius of 4-6 mm were selected.
The apical diameter reached after instrumentation is also an important criterion in terms of standardization. The XPS file is a single-file system that has an ISO 15 tip size and 0.01 taper, and forms a canal with the apical size of ISO 30 and the taper of 0.04 at the end of the instrumentation procedure [13]. To ensure the final apical diameters of the samples were as close
as possible, in TRN and TS groups, TRN Prime (26/0.04) and TS2 (25/0.06) were used as final instruments, respectively.
It has been reported that the temperature in the root canal might affect the clinical performance of all types of NiTi instruments [14]. Therefore, in this study, all groups were kept in a warm bath at 37°C before being used and the intracanal temperature was maintained using irrigation solutions heated to 37 ° C to simulate clinical conditions and provide standardization between groups.
According to the findings of this study, the TRN navigated in the center of the canal, allowing for root canal instrumentation with minimal transportation, due to the improved flexibility and less shape memory due to the applied heat treatments [5]. In addition, the TRN removed significantly less dentine compared with the other groups in this study. This can be attributed to the working principle of the system, supporting minimally invasive root canal preparation. In consistence with our findings, in a micro-CT study by Perez Morales et al., they found that TRN had touched the least area on the canal surface compared with WaveOne Gold, Reciproc Blue, TruShape, IRace and XPS [15].
Wu et al. [16] showed that apical canal transportation of less than 0.3 mm would have a minimal effect on the prognosis of endodontic treatment. Although all rotary systems used in this study resulted in some transportation at all levels, the BL and MD transportation values were less than 0.3 mm in all groups. Although there was no significant difference between the BL transportation values at any level among the groups, significant differences were observed between MD transportation values at the 6 and 9-mm levels. This is a predictable result, considering that the canal structure is wider in the BL direction than in the MD direction, and the canal curvatures of the lower molars are seen more frequently in the MD direction. This is consistent with the results of similar studies [17,18].
According to the total transportation values, although the TS group resulted in significantly more transportation compared with the TRN and XPS groups, the difference between the TRN and XPS groups was not significant. Thus, the null hypothesis tested in the present study was rejected. Compatible with that study, the 0.06 taper of the final TS instrument compared with the 0.04 taper of the TRN and XPS groups may explain the significantly higher transportation values of the TS group in our study. In a micro-CT study, [19] comparing different systems in the mesiobuccal canals of maxillary molars with a curvature of 25-40°, TRN and XPS exhibited similar transportation and centering ability, which is consistent with the current study. Similarly, Pérez Morales et al. compared the shaping ability of different systems in mesial canals of mandibular molars using micro-CT and found no significant difference between the XPS and TRN groups [15].
In studies comparing the XPS and different NiTi rotary systems, it has been shown that the XPS displays lower transportation and better centering ability owing to the adaptive core technology [6]. In our study, XPS showed significantly less transportation compared with the TS group. This finding can be attributed to the adaptive core technology, which allows for the preservation of the original anatomy and curvature of the root canal. Besides, the booster-type tip design is also thought to help the instrument provide more central shaping.
In their study examining the shaping efficacy of TS and ProTaper Gold in the mandibular first molars using CBCT, Singh et al. [20] reported that the triple-helix cross-section design and the T-wire technology that improved the flexibility of the TS system allowed for overcoming the curvatures of the canals more effectively, resulting in less transportation and better centering ability. However, in our study, although the TS group showed similar centering ability with the other groups, this resulted in significantly higher transportation values compared to the other groups. Despite similar tooth samples and evaluation methods, these contradictory results between the two studies can be attributed to the difference in design and metallurgical properties of the systems with which the TS system was compared.
Investigating the shaping efficacy of new NiTi systems with different designs and kinematics is important in understanding how these differences affect clinical performance. Further clinical studies are required because in vitro studies do not fully reflect clinical performance.
Conclusion
Within the limitations of this study, centering abilities were similar for all groups, but the XPS and TRN groups showed significantly better performance compared with the TS group in terms of transportation. The TRN system removed significantly less dentine, supporting the minimally invasive root canal preparation.
Acknowledgment
We thank for Merve Babacan Özad dissertation.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: This study was supported by the Scientific Research Fund of RTE University in Rize/Turkey (Grand number: TDH-2020-1070)
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. De-Deus G, Barino B, Zamolyi RQ, Souza E, Júnior AF, Fidel, S et al. Suboptimal debridement quality produced by the single-file F2 ProTaper technique in oval-shaped canals. J Endod. 2010; 36(11):1897-900.
3. Oliveira MA, Venâncio JF, Raposo LH, Barbosa Júnior N, Biffi JC. Morphometric evaluation and planning of anticurvature filing in roots of maxillary and mandibular molars. Braz Oral Res. 2015;29:1-9.
4. Shen Y, Zhou HM, Zheng Y F, Peng B, Haapasalo M. Current challenges and concepts of the thermomechanical treatment of nickel-titanium instruments. J Endod. 2013;39(2):163-72.
5. Patil S, Alkahtani A, Bhandi S, Mashyakhy M, Alvarez M, Alroomy R, et al. Ultrasound Imaging versus Radiographs in Differentiating Periapical Lesions: A Systematic Review. Diagnostics (Basel). 2021;11(7):1208.
6. Öztürk BA, Ateş AA, Fişekçioğlu E. Cone-Beam Computed Tomographic Analysis of Shaping Ability of XP-endo Shaper and ProTaper Next in Large Root Canals. J Endod. 2020;46(3):437-43.
7. Silva EJ, Muniz BL, Pires F, Belladonna FG, Neves AA, Souza EM, et al. Comparison of canal transportation in simulated curved canals prepared with ProTaper Universal and ProTaper Gold systems. Restor Dent Endod. 2016;41(1):1-5.
8. Reddy Y P, Kavita S, Subbarao CV. Cyclic fatigue testing of three different rotary nickel titanium endodontic instruments in simulated curved canals – an in vitro sem analysis. J Clin Diagn Res. 2014;8(2):211-13.
9. Unno H, Ebihara A, Hirano K, Kasuga Y, Omori S, Nakatsukasa T, et al. Mechanical Properties and Root Canal Shaping Ability of a Nickel-Titanium Rotary System for Minimally Invasive Endodontic Treatment: A Comparative In Vitro Study. Materials (Basel). 2022;15(22):7929.
10. Hashem AAR, Ghoneim AG, Lutfy RA, Foda MY, Omar GAF. Geometric analysis of root canals prepared by four rotary NiTi shaping systems. J Endod. 2012; 38(7):996-1000.
11. Hartmann MSM, Barletta FB, Fontanella VRC, Vanni JR. Canal transportation after root canal instrumentation: a comparative study with computed tomography. J Endod. 2007;33(8):962-5.
12. Celik D, Tasdemir T, Er K. Comparative Study of 6 Rotary Nickel-Titanium Systems and Hand Instrumentation for Root Canal Preparation in Severely Curved Root Canals of Extracted Teeth. J Endod 2013;39(2):278-82.
13. Webber M, Piasecki L., Jussiani E.I, Andrello A.C, Dos Reis P. J, Azim K.A. Higher Speed and No Glide Path: A New Protocol to Increase the Efficiency of XP Shaper in Curved Canals-An In Vitro Study. J Endod 2020;46(1):103-9.
14. Grande NM, Plotino G, Silla E, Pedullà E, DeDeus G, Gambarini G. Environmental Temperature Drastically Affects Flexural Fatigue Resistance of Nickel-titanium Rotary Files. J Endod. 2017;43(7):1157-60.
15. Morales MDLNP, Sánchez JAG, Olivieri JG, Elmsmari F, Salmon P, Jaramillo DE. Micro-computed Tomographic Assessment and Comparative Study of the Shaping Ability of 6 Nickel-Titanium Files: An In Vitro Study. J Endod. 2021;47(5):812-19.
16. Wu MK, Fan B, Wesselink PR. Leakage along apical root fillings in curved root canals. Part I: effects of apical transportation on seal of root fillings. J Endod 2000;26(4):210-6.
17. Nathani TI, Nathani AI, Pawar AM, Khakiani MI, Ruiz XF, Olivieri JG. Canal Transportation and Centering Ability in Long Oval Canals: A Multidimentional Analysis. J Endod. 2019;45(10):1242-7.
18. Moghadam KN, Shahab S, Rostami G. Canal transportation and centering ability of twisted file and reciproc: a cone-beam computed tomography assessment. Iran Endod J. 2014;9(3):174.
19. Kabil E, Katić M, Anić I, Bago I. Micro-Computed Evaluation of Canal Transportation and Centering Ability of Five Rotary and Reciprocating Systems with Different Metallurgical Properties and Surface Treatments in Curved Root Canals. J Endod. 2021;47(3):477-84.
20. Singh S. Shaping Ability of Two-shape and ProTaper Gold Files by using Cone-beam Computed Tomography. J Contemp Dent Pract. 2019 1;20(3):330-4.
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Merve Babacan Özad, Ahter Şanal Çıkman, Taha Emre Köse, Banu Arıcıoğlu. Transportation and shaping ability of 3 canal anatomy-friendly systems in curved root canals. Ann Clin Anal Med 2023;14(7):595-599
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The SII index can predict mortality in the elderly in the emergency room
Sultan Özselçuk 1, Ramazan Güven 1 , Gülsüm Çalışkan Günay 2
1 Department of Emergency, Health Sciences University, Basaksehir Cam and Sakura City Hospital, Istanbul, 2 Department of Emergency, Antalya Atatürk Government Hospital, Antalya, Turkey
DOI: 10.4328/ACAM.21662 Received: 2023-03-20 Accepted: 2023-05-05 Published Online: 2023-05-11 Printed: 2023-07-01 Ann Clin Anal Med 2023;14(7):600-602
Corresponding Author: Sultan Özselçuk, Department of Emergency, Health Sciences University, Basaksehir Cam and Sakura City Hospital, Istanbul, Turkey. E-mail: sultanaozselcuk@hotmail.com P: +90 542 210 43 17 F: +90 212 960 60 00 Corresponding Author ORCID ID: https://orcid.org/0000-0002-2168-9818
This study was approved by the Ethics Committee of Basaksehir Cam and Sakura City Hospital (Date: 2021-05-05, No: 2021.04.27)
Aim: In this study, we aimed to predict mortality with systemic immune inflammation index in geriatric patients with a high quick sequential organ failure assessment score in the Emergency Room critical care unit.
Material and Methods: The study included 200 geriatric emergency room critical care patients with a quick sequential organ failure assessment of ≥ 2. The patients were divided into two groups: mortal and non-mortal. Diagnostic test performances of systemic immune inflammation index scoring were evaluated in the study using the mortality variable. The outcomes of the patients in the emergency department were evaluated. Statistical analyses were performed to compare the groups.
Results: The mean age was 76,8±7,0. The systemic immune inflammation index score was above 648, with 100% sensitivity and 31.9% specificity. Male patients had a significantly higher systemic immune inflation index than females (p=0.047; p<0.05). Mortality was higher in patients with a high index score (p=0.010; p<0.05). A weak positive correlation was found between the patients’ systemic immune inflammation index scores and Alanine Aminotransferase, Blood Urea Nitrogen, and creatinine values (r=0.164, r=0.182, and r=0.152, respectively). A weak negative correlation was found between the sodium value and the index score (r=-0.213).
Discussion: The systemic immune inflammation index can predict mortality in geriatric patients with a high quick sequential organ failure assessment score admitted to the emergency department. The index may be a more useful predictor of mortality in male patients than in female patients. There may be a relationship between the Alanine Aminotransferase, Blood Urea Nitrogen, and creatinine value changes in patients and the index.
Keywords: Geriatrics, Emergency Room, Sepsis, Inflammation
Introduction
A scoring guideline is very important in choosing which patients admitted to the emergency department will die, be discharged home, or be hospitalized. Scoring guides emergency physicians in terms of examination and treatment. Predicting the mortality of patients and early intervention are very important for saving patients’ lives.
Early diagnosis becomes more important, especially for patients in special groups having the red flag and with difficulties in diagnosis and treatment in the emergency room. One of these was the elderly patient group. It is necessary to move away from the classical patient approach, which complicates our work both at the point of diagnosis and at the point of treatment. A more personalized method should be followed, especially for patients aged ≥ 65 years. The response to sepsis may be suppressed by these drugs. Alternatively, the sepsis status of the patient may be noticed late owing to the effects of the drugs. There is a need for practical tools that do not delay the diagnosis of elderly patients and guide the diagnosis of intensive working emergency services.
Sepsis is a state of organ dysfunction caused by the dysregulated host response to infection. It is a critical condition leading to a high mortality rate and a significant worldwide health problem. Sepsis incidence increases with age, especially in very elderly patients (age ≥80 years), and mortality is also significantly higher in this population [1]. This high incidence and mortality could be explained by various reasons, such as multiple pre-existing comorbidities, reduced functional reserve, and abnormal immune system [2]. Sepsis diagnosis is also more difficult, given elderly patients’ vague symptoms and atypical clinical presentations. This poses an extreme challenge for emergency physicians in recognizing such patients early, especially those at a greater risk of adverse outcomes. Although the mortality rate due to sepsis is exceptionally high in geriatric patients, little is known about the predictive factors of this adverse outcome, and new predictors should be identified.
The Systemic immune inflammation (SII) index a novel inflammatory marker associated with the clinicopathological features and prognosis of several types of cancer, such as colorectal cancer, breast cancer, hepatocellular carcinoma, and PC [3]. The SII is calculated using the following formula: SII = platelet count × neutrophil count/lymphocyte count. Recent studies have used the index in different groups such as COVID-19 [4], coronary artery disease [5], acute pancreatitis [6], and aneurysmal subarachnoid hemorrhage [7]. This study aimed to use the systemic immune-inflammation index (SII index) to predict mortality in the elderly and very elderly patients with sepsis admitted to the emergency room (ER).
Material and Methods
After receiving the approval of the ethics committee, the study was started.
The study included elderly patients with sepsis and very elderly patients who were admitted to the ER department of Basaksehir Cam and Sakura City Hospital between May 1, 2021, and May 1, 2022. Patients aged ≥65 years were referred to as elderly, and those aged ≥85 years as very old. The quick sequential organ failure assessment (qSOFA) score was used to select patients with sepsis. Patients with a qSOFA score of ≥ 2 were included in the study.
In the study, we used Systemic Immune Inflammation Index (SII index) formula. SII index formula: (neutrophil count x lymphocyte count)/platelet count.
We took the patients’ blood sample results and noted the Complete Blood Count (CBC) to get neutrophil, lymphocyte and platelet counts.
Statistical analysis
The Statistical Package for the Social Sciences (SPSS) 25.0 package program was used for the statistical analysis of the data. Categorical measurements are summarized as numbers and percentages, and continuous measurements are presented as mean and standard deviation (median and minimum-maximum where appropriate). Chi-square and Fisher’s exact tests were used to compare categorical expressions. The Shapiro-Wilk test was used to determine whether the parameters in the study were normally distributed. The Mann-Whitney U test was used for parameters that did not show a normal distribution. The sensitivity and specificity values of the SII Index score were calculated based on the mortality variable of the patients included in the study, and the cut-off value was determined by examining the area under the receiver operating characteristic (ROC) curve. The statistical significance level was set as 0.05. Consent was obtained from all patients included in the study.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
The diagnostic test performance of SII index scoring, which was evaluated using the mortality variable in the study, is shown in Table 3. Accordingly, the SII index score was above 648, the SII index was 100%, and the specificity was 31.9% (Table 1).
The frequency of the female gender was higher in patients with a high SII index (p=0.047; p<0.005). Mortality was higher in patients with a high SII index (p=0.010; p<0.05). (Table 2)
A weak positive correlation was found between the patients’ SII index scores and ALT, BUN, and creatinine values (r=0,164; r=0,182; r=0,152). A weak negative correlation was found between the Na and SII index (r=-0.213) (Table 3).
Discussion
The recognition of sepsis and the prediction of mortality in elderly patients at risk is very important for diagnosis and early treatment initiation. The data obtained from these studies showed that the SII index score could predict mortality in elderly patients with 31.9% specificity and 100% sensitivity. Previous studies have shown different cut-off values (≥2207.53, ≥960, ≥2519.89± 2188.53, 694 [3] related to mortality [4,5,6,7,8]. In this study, an SII index value of ≥ 648 was found to be closely associated with mortality (p=0.038).
The SII was a better predictor of mortality in female patients. Corresponding data on this subject were not found in the literature. The SII index score was higher in mortality cases (p=0.010). These data can be used as a predictor of the SII index in estimating mortality in patients with sepsis aged ≥ 65 years admitted to the emergency department. Similar results are found in the literature, although the cut-off values vary in studies conducted in different fields.
Considering the blood test results, no correlation was found between the SII index and lactate levels. Further studies are required to investigate whether patients’ lactate levels do not increase despite sepsis, whether the lactate response develops slowly in elderly patients, or whether the SII index is more sensitive in predicting mortality. The results suggest that the increase in ALT, blood urea, and creatinine levels in elderly patients with sepsis may mean higher SII index scores and increased mortality; the opposite is also true. Further studies are required in this regard.
In light of the data, low blood Na values of elderly patients with sepsis admitted to the emergency department are associated with a higher SII index and increased mortality. A low SII index value of the patient indicates a higher Na value. Additional research is required to confirm these findings.
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. Rowe TA, McKoy J. Sepsis in Older Adults. Infect Dis Clin North Am. 2017;31(4):731-42.
2. Nasa P, Juneja D, Singh O. Severe sepsis and septic shock in the elderly: an overview. World J Crit Care Med. 2012;1(1):23-30.
3. Li X, Gu L, Chen Y, Chong Y, Wang X, Guo P, et al. Systemic immune-inflammation index is a promising non-invasive biomarker for predicting the survival of urinary system cancers: a systematic review and meta-analysis. Ann Med. 2021;53(1):1827-38.
4. Bilge M, Akıllı IK, Karaayvaz EB, Yesilova A, Kart Yasar K. Comparison of systemic immune-inflammation index (SII), early warning score (ANDC) and prognostic nutritional index (PNI) in hospitalized patients with malignancy, and their influence on mortality from COVID-19. Infect Agent Cancer. 2021;16(1):60.
5. Liu X, Guan G, Cui X, Liu Y, Liu Y, Luo F. Systemic Immune-Inflammation Index (SII) Can Be an Early Indicator for Predicting the Severity of Acute Pancreatitis: A Retrospective Study. Int J Gen Med. 2021;14:9483-9.
6. Candemir M, Kiziltunc E, Nurkoc S, Sahinarslan A. Relationship Between Systemic Immune-Inflammation Index (SII) and the Severity of Stable Coronary Artery Disease. Angiology. 2021;72(6):575-81.
7. Yun S, Yi HJ, Lee DH, Sung JH. Systemic Inflammation Response Index and Systemic Immune-inflammation Index for Predicting the Prognosis of Patients with Aneurysmal Subarachnoid Hemorrhage. J Stroke Cerebrovasc. 2021;30(8):e105861.
8. Yang Y, Wu CH, Hsu PF, Chen SC, Huang SS, Chan WL, et al. Systemic Immune-inflammation Index (SII index) predicted clinical outcome in patients with coronary artery disease. Eur J Clin Invest. 2020;50(5):e13230.
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Sultan Özselçuk, Ramazan Güven, Gülsüm Çalışkan Günay. The SII index can predict mortality in the elderly in the emergency room. Ann Clin Anal Med 2023;14(7):600-602
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The effect of intraoperative different oxygen concentrations on nausea and vomiting in morbidly obese patients undergoing laparoscopic bariatric surgery
Ramazan Akel, Aysun Yıldız Altun, Ahmet Deniz, Ahmet Aksu, İsmail Demirel, Azize Beştaş, Gülsüm Altuntaş, Esef Bolat
Department of Anesthesiology and Reanimation, Faculty of Medicine, Firat University, Elazig, Turkey
DOI: 10.4328/ACAM.21664 Received: 2023-03-02 Accepted: 2023-04-29 Published Online: 2023-06-10 Printed: 2023-07-01 Ann Clin Anal Med 2023;14(7):603-606
Corresponding Author: Esef Bolat, Department of Anesthesiology and Reanimation, Faculty of Medicine, Firat University, 23119, Elazig, Turkey. E-mail: esefbolat@gmail.com P: +90 505 681 65 06 F: +90 424 233 35 55 Corresponding Author ORCID ID: https://orcid.org/0000-0002-1678-0502
This study was approved by the Non-Invasive Research Ethics Committee of Firat University (Date: 2019-01-28, No: 308685)
Aim: Postoperative nausea and vomiting (PONV) is a common problem due to many factors, and is especially seen in the first two hours after the operation. In this study, we aimed to investigate the effect of different intraoperative oxygen concentrations on nausea and vomiting in morbidly obese patients.
Material and Methods: After the approval of the ethics committee, 206 patients who underwent laparoscopic bariatric surgery (LBS) in 2018 were included in the study by analyzing their files. The patients were divided into two groups according to the O₂ concentrations used. Those given 30% oxygen (n=87) were determined as GrupLO, and those given 70% oxygen (n=119) were determined as GrupHO. Demographic data of the patients, body mass index, ASA score, hemodynamic parameters and anesthetic agents used, Apfel score, visual analog scale (VAS) score, PONV score, and the amount of metoclopramide administered in the post- anesthetic care unit (PACU) were recorded.
Results: There was no significant difference between the groups in terms of demographic data and the anesthetic drugs used. PONV occurring in PACU was 66.66% (58/87) in Group LO and 44.53% (53/119) in Group HO. There was a statistically significant difference between the groups in the post-operative nausea-vomiting score (p<0.05). The amount of metoclopramide administered in PACU was lower in Group HO and it was statistically significant.
Discussion: In this study, we found that the frequency of PONV was higher in morbidly obese patients who underwent LBS, and intraoperative high oxygen concentrations reduced the incidence of PONV.
Keywords: Morbid Obesity, Intraoperative Oxygen Concentration, Postoperative Nausea-Vomiting, Laparoscopic Bariatric Surgery
Introduction
Postoperative nausea and vomiting (PONV) is a common problem due to many factors and is seen especially in the first two hours after the operation [1, 2]. It is controversial whether obesity is a risk factor for PONV. Although there are studies that indicate an increase or decrease in the incidence of PONV in patients with a relatively high body mass index (BMI) who go to surgery under general anesthesia, also some authors argue that there is no risk factor for PONV [3, 4, 5]. However, laparoscopic bariatric surgeries (LBS) are high-risk surgeries in terms of postoperative nausea-vomiting due to both increased intra-abdominal pressure and incisions affecting the vagus nerve, which is the afferent nerve of the nausea-vomiting pathway [6].
PONV, can cause aspiration in unconscious patients with inadequate laryngeal reflexes, leading to nosocomial infections, morbidity and mortality. In addition, it can increase hospital expenses by delaying the patient’s departure from the recovery room and discharge from the hospital [7, 8]. All these reasons lead to the search for solutions to prevent PONV.
In this study, it was aimed to investigate the effect of different intraoperative oxygen concentrations on PONV in morbidly obese patients who underwent LBS.
Material and Methods
In this study, the files and e-archive records of morbidly obese patients who had LBS in 2018 were examined. The study was approved by University Non-Invasive Research Ethics Committee (date: 28/01/2019, number 308685). Two hundred and six patients, whose data we could access completely, were included in the study. ASA IV patients were excluded from the study. The patients were divided into two groups as patients who received high oxygen (Group HO) and low oxygen (Group LO). Group LO (n=87) received 30% oxygen and Group HO (n=119) received 70% oxygen. Maquet Servo-i (Siemens, Germany) was used as the anesthesia machine, and the fresh gas flow was applied at 2 liters/minute. Patients’ ages, genders, BMIs, ASA scores, and oxygen saturations in the intra-operative and postanesthetic care unit (PACU) were enlisted. Intravenous and volatile anesthetics, opioid analgesics, muscle relaxant antagonists, post-operative VAS score, and antiemetic amount used in PACU were recorded.
PONV score: 1: No nausea-vomiting, 2: There is nausea, 3: There is retching, 4: There is vomiting
Apfel Score: 1-Female gender, 2-History of postoperative nausea-vomiting or motion sickness, 3-Non-smoking, and 4-Intraoperative or postoperative opioid use parameters were evaluated.
General anesthesia protocol was applied to all patients included in the study. All patients were given 2-3 mg/kg propofol based on lean body weight and 0.6 mg/kg rocuronium and 0.5 µg/kg remifentanil based on ideal body weight at induction. In the anesthesia maintenance, 0.01 – 0.1 µg/kg /min remifentanil infusion, sevoflurane and desflurane were used as inhalation anesthetics. For postoperative analgesia, 1.5 mg/kg tramadol or 0.5 mg/kg pethidine were given with 50 mg dexketoprofen intraoperatively.
Statistical analysis
Statistical analysis was performed using the Statistical Package for the Social Sciences 22.0 software. Data were expressed as “mean ± standard deviation”. In the comparison between groups, categorical variables were evaluated with the “chi-square test” and numerical variables were evaluated with the “independent sample t test”. Confidence interval was determined as 95% and a p-value less than 0.05 was considered statistically significant.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
There was no difference between the groups when age, gender, ASA, BMI, Apfel Score, duration of surgery and VAS at admission to PACU were evaluated (p>0.05) (Table 1). SaO2 values of the patients were over 90% at all measurement times and there was no statistically significant difference in terms of inhalation anesthetics, muscle relaxant antagonists and postoperative analgesic agents used in the groups (p>0.05).
Post-operative nausea-vomiting score is shown in Table 2 for both groups. There was a statistically significant difference between the groups (p<0.05). PONV that occurred in patients in the post-operative care unit was 66.66% (58/87) in Group LO and 44.53% (53/119) in Group HO, and it was statistically significant (p<0.05). When the amount of metoclopramide administered in PACU was compared between the groups, less rescue antiemetic was administered to Group HO. This difference was statistically significant (p<0.05) (Table 3).
Discussion
One of the most common complaints in patients undergoing surgical intervention under general anesthesia is PONV along with postoperative pain. Female gender, non-smoking status, history of PONV or motion sickness, and opioid usage are defined risk factors for PONV. General anesthesia administrations, volatile anesthetics and N2O, young age, duration of anesthesia, types of surgical methods are other risk factors [9]. Although the information about the frequency of PONV in obese patients is controversial, it has been reported to be high in bariatric surgeries [10]. Although it varies according to the anesthesia and surgery methods, there are studies reporting that the incidence of PONV reaches up to 98.7%. Therefore, antiemetic prophylaxis is recommended for these patient groups [11].
There is disagreement as to whether higher oxygen use would be beneficial as a strategy to reduce the risk of PONV. Different results were found in two meta-analyses at this point. Sungur et al. found it ineffective and Hovaguimian et al. found it effective in reducing the incidence of PONV [12, 13]. At the same time, Hovaguimian et al. stated that no side effects were observed in the lungs and surgical site infections were less common. In other studies, it has been reported that the incidence of PONV has decreased in abdominal and laparoscopic gynecological surgeries, but did not affect such surgeries as thyroidectomy and strabismus operations [14-17]. Greif et al. showed that high oxygen concentrations reduced the incidence of PONV in colon surgery [18]. As it is known, the three main pathophysiological mechanisms triggering PONV are the vestibulocochlear tract, the central chemoreceptor trigger zone, and the local gastrointestinal tract. Surgical stress reduces intestinal mobilization by reducing gastrointestinal blood flow, and surgical manipulations, although not global, may result in inadequate tissue perfusion in some gastrointestinal areas. Studies have reported that all these causes may affect the local gastrointestinal tract and high oxygen concentrations will reduce intestinal ischemia, thus can decrease the incidence of PONV.
Morbid obesity is a risk factor for increased intra-abdominal pressure. Increased intra-abdominal pressure leads to hypo-perfusion in the gastrointestinal tract [19]. Therefore, morbidly obese patients undergoing LBS may be more susceptible to nausea-vomiting by the local intestinal tract.
Administration of oxygen at high concentrations was thought to be associated with the development of atelectasis. But in a systematic review, Mattishent et al. declared that there was no increase in complications of high oxygen usage when compared the 80% and 30-35 % O2 [20]. Similarly, in a randomized controlled study, there was no difference between groups in terms of adverse effects when 80% O2 was used [21].
Limitations
There are some limitations of this study. The number of patients between the two groups was different because patients who had LBS in a certain time interval were included in the study. Due to the retrospective nature of the study, the anesthetic and analgesic drugs used could not be randomized between groups. Another limitation of the study is that only parameters in the PACU were evaluated and these parameters were not followed afterwards. This is due to the retrospective nature of the study. Further randomized controlled studies are needed to recommend the use of high O2 concentrations to prevent PONV in this patient group and LBS.
Conclusion
It is clear that the incidence of PONV depends on many factors. Although the mechanism of reducing PONV by intraoperative high O2 administration has not been clearly demonstrated, it may be due to preventing intestinal ischemia. In our study, we found that the incidence of PONV was high in morbidly obese patients who underwent LBS, and the use of intraoperative high O2 concentrations reduced the PONV.
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. Jin Z, Gan TJ, Bergese SD. Prevention and Treatment of Postoperative Nausea and Vomiting (PONV): A Review of Current Recommendations and Emerging Therapies. Ther Clin Risk Manag. 2020; 16: 1305-17.
2. Cavaye J, Dai B, Gurunathan K, Weir RM, Yerkovich S, Gurunathan U. NK1 receptor antagonists versus other antiemetics in the prevention of postoperative nausea and vomiting following laparoscopic surgical procedures: a systematic review and meta-analysis. J Anaesthesiol Clin Pharmacol. 2022; 38(1): 35-47.
3. Kwon YS, Choi, JW, Lee HS, Kim JH, Kim Y, Lee JJ. Effect of a Preoperative Proton Pump Inhibitor and Gastroesophageal Reflux Disease on Postoperative Nausea and Vomiting. J Clin Med. 2020; 9(3): 825.
4. Kranke P, Apfel C, Papenfuss T, Rauch S, Löbmann U, Rübsam B, et al. An increased body mass index is no risk factor for postoperative nausea and vomiting: A systematic review and results of original data Note. Acta Anaesthesiol Scand. 2001; 45(2): 160-6.
5. Jong HK, Mingi H, Young JK, Lee HS, Kwon YS, Lee JJ. Effect of Body Mass Index on Postoperative Nausea and Vomiting: Propensity Analysis. J Clin Med. 2020; 9(6): 1612.
6. Halliday TA, Sundqvist J, Hultin M, Walldén J. Post-operative nausea and vomiting in bariatric surgery patients: an observational study. Acta Anaesthesiol Scand 2017; 61(5): 471-9.
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8. Berg SM, Braehler MR. The Postanesthesia Care Unit. In: Gropper MA, editor. Miller’s Anesthesia. 9th ed. Philadelphia, PA: Elsevier; 2020.p.2586-613.
9. Stoops S, Kovac A. New insights into the pathophysiology and risk factors for PONV. Best Pract Res Clin Anaesthesiol. 2020; 34(4): 667-79.
10. Groene P, Eisenlohr J, Zeuzem C, Dudok S, Karcz K, Hofmann-Kiefer K. Postoperative Nausea and Vomiting in Bariatric Surgery in Comparison to Non-Bariatric Gastric Surgery. (Videosurgery and Other Miniinvasive Techniques.) 2019; 14(1): 90-5.
11. Ziemann-Gimmel P, Schumann R, English W, Morton J, Wadhwa A. Preventing Nausea and Vomiting After Bariatric Surgery: Is the Apfel Risk Prediction Score Enough to Guide Prophylaxis? Obes Surg. 2020; 30(10): 4138-40.
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Download attachments: 10.4328.ACAM.21664
Ramazan Akel, Aysun Yıldız Altun, Ahmet Deniz, Ahmet Aksu, İsmail Demirel, Azize Beştaş, Gülsüm Altuntaş, Esef Bolat. The effect of intraoperative different oxygen concentrations on nausea and vomiting in morbidly obese patients undergoing laparoscopic bariatric surgery. Ann Clin Anal Med 2023;14(7):603-606
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Course of minimal pleural effusions in non-small cell lung cancer
Suna Kavurgacı, Pınar Akın Kabalak, Derya Kızılgöz, Arife Yıldırım, Tilbe Saymaz, İlteriş Türk, Ülkü Yılmaz
Department of Interventional Pulmonology, Ankara Atatürk Sanatorium Training and Research Hospital, Ankara, Turkey
DOI: 10.4328/ACAM.21672 Received: 2023-03-06 Accepted: 2023-05-05 Published Online: 2023-05-26 Printed: 2023-07-01 Ann Clin Anal Med 2023;14(7):607-611
Corresponding Author: Suna Kavurgacı, Department of Interventional Pulmonology, Ankara Atatürk Sanatorium Training and Research Hospital, 06280, Kuscagiz, Keçiören, Ankara, Turkey. E-mail: suna.dr01@gmail.com P: +90 505 931 22 18 Corresponding Author ORCID ID: https://orcid.org/0000-0002-5856-4891
This study was approved by the Ethics Committee of Ankara Chest Diseases and Thoracic Surgery, Health Sciences University (Date: 2021-09-16, No: 5)
Aim: Patients with lung cancer may develop effusions at diagnosis or follow-up that can take three different forms: malignant pleural effusions (MPEs), paramalignant pleural effusions (PMPEs) and non-malignant effusions of known causes. Differentiating between MPE and PPE is crucial for the determination of appropriate patient management. This study examines the course of pleural effusions, and minimal pleural effusions in particular, that were detected at diagnosis and did not interfere with curative treatment during routine examinations following scheduled treatment.
Material and Methods: This retrospective study included Non-Small Cell Lung Cancer (NSCLC) patients with minimal pleural effusions who were scheduled for curative treatment (concurrent chemoradiotherapy [CRT] and surgery) between January 1, 2014 and December 31, 2020. The changes in pleural effusions at follow-up were assessed.
Results: At 3 months follow-up, there were six (6.3%) patients without follow-up and 14 (14.6%) patients who did not come for their follow-up appointments. Of the 76 patients with follow-up results, seven had increased pleural effusion quantities and 23 had decreased pleural effusion quantities, while the amount was similar in 46 patients. At 12 months follow-up, there were eight (8.3%) patients without follow-up, 13 (13.5%) patients who did not attend their follow-up appointments, and two (2.1%) patients who died. Of the 73 patients with follow-up data, 11 had increased pleural effusion quantities and 23 had decreased pleural effusion quantities, while the amount was similar in 39 patients.
Discussion: Patients without distant metastasis at diagnosis may be considered for curative treatment, which provides better survival, based on a careful assessment of the clinical and radiological variables of the minimal pleural effusions in such patients at diagnosis.
Keywords: Pleural Effusıon, Lung Cancer, Paramalignant
Introduction
Patients with lung cancer develop pleural effusions in varying amounts at diagnosis or at follow-up due to several etiologies.
Such effusions can take three forms [1]:
1. Malignant pleural effusions (MPEs): Identified during cytological examinations or from malignant cells in a parietal pleural biopsy.
2. Paramalignant pleural effusions (PMPEs): Pleural effusions resulting from malignancy. Malignant cells cannot be detected in the pleural fluid or tissue without direct pleural infiltration by tumor, and in such cases, the effusion accumulates due to secondary causes, such as bronchial obstruction, lymphatic obstruction or pulmonary embolism [2].
3. Non-malignant pleural effusions of known causes: Effusion develops as a result of congestive heart failure, chronic kidney failure or hypoalbuminemia.
PMPEs are detected in approximately 5% of patients with lung cancer, and are equally present in all pathohistological types of lung cancer, with an incidence of 5-10% in non-small cell lung cancer (NSCLC) and 6.5% in small cell lung cancer [3,4].
Differentiating between MPE and PPE is crucial for the determination of appropriate patient management, and should therefore be considered important
With the change from T4 to M1a in the seventh edition of the TNM classification, the accurate assessment of pleural effusion has become more important for tumor staging [5], although little is known about the epidemiological or prognostic implications of minimal pleural effusions in patients with lung cancer.
The present study examines the course of pleural effusions, especially minimal pleural effusions, which were detected at diagnosis and did to not interfere with curative treatment during routine examinations following scheduled treatment.
Material and Methods
This retrospective study included Non-Small Cell Lung Cancer (NSCLC) patients with minimal pleural effusions who were scheduled for curative treatment (concurrent chemoradiotherapy (CRT) and surgery) between January 1, 2014 and December 31, 2020. The patients’ demographic data, disease stage, pathological cell type, lesion characteristics (atelectasis, mediastinal and lymphovascular invasion), pleural effusion sampling status, location and biochemical characteristics of pleural effusion, Standard Uptake Value (SUV) of the pleural effusion on Positron Emission Tomography/Computed Tomography (PET/CT) and type of treatment administered (concurrent chemoradiotherapy and type of surgery) were obtained from the patient files.
Minimal pleural effusion was defined as <10 mm thick effusion in the pleural space.
All patients with pleural effusions underwent thoracic ultrasound-guided thoracocentesis for diagnostic purposes if the effusion level was sufficient before initiating any treatment, and biochemical and cytological examinations were planned. Effusions were diagnosed as transudative or exudative based on Light’s criteria [2]. Samples of the pleural effusion materials were processed three times for cytological studies. The study included patients with small effusions that could not be detected by the thoracic US and that were not considered malignant clinically or radiologically, and patients with samples of effusion in whom malignant cells could not be identified.
The patients were followed up clinically and radiologically for disease progression and pleural effusion increase every three months for one year, and were questioned about symptoms (cough, dyspnea, pleuritic chest pain) that may develop secondary to increased pleural effusion. Especially at 3 months, when the first radiological follow-up after curative treatment was performed, and at 12 months, the change in the amount of pleural effusion (similar, increase, decrease) and the status of disease progression were recorded.
Patients with increased pleural effusions at follow-up were assessed for disease progression, malignancy in cytology (if fluid could be collected during the thoracic US), and for systemic diseases that might have caused such a fluid increase.
In patients with decreased pleural effusions at follow-up it was assessed whether the decrease was due to the treatment of the primary disease. If possible, the effusion was sampled and examined for malignancy in cytology. Follow-up was continued in patients with effusions that were too small to be sampled.
Patients with malignant pleural effusions, small cell lung carcinoma and malignant mesothelioma, and those with pleural effusions secondary to oligometastatic disease, chronic renal failure, heart failure, cachexia and hypoalbuminemia were excluded from the study.
This study was approved by the Ethics Committee of Ankara Chest Diseases and Thoracic Surgery, Health Sciences University (Date: 2021-09-16, No: 5)
Statistical Analysis
Data analyses were performed using IBM SPSS Statistics (Version 22.0. Armonk, NY: IBM Corp.). The normality of the distribution of continuous variables was ascertained from a Kolmogorov-Smirnov test, and Levene’s test was used to evaluate the homogeneity of variances. Unless otherwise specified, continuous data were described as mean±SD (minimum value-maximum value) for normal distributions, and as mean±SD and median (minimum value-maximum value) for skewed distributions. Categorical data were described as the number of cases (%). Categorical variables were compared using Pearson’s Chi-square test or Fisher’s exact test. A p-value of <0.05 was considered significant in all statistical analyses.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
A review was made of 615 patient files with early and locally advanced NSCLC between 2014 and 2020. After the exclusion criteria were applied, 96 patients with pleural effusions <10 mm at diagnosis were included in the study (Figure 1).
The study sample comprised 90 (93.8%) females and six (6.3%) males, with a mean age of 66.99±7.81 years within a range of 49–82 years. Of the total number, 50 (52.1%) patients had comorbidities (Table 1).
Considering the diagnoses of the patients, 57 (59.4%) had squamous cell carcinoma (SCC), 27 (28.1%) had adenocarcinoma, 10 (10.4%) had NOS (not otherwise specified) and two (2.1%) had adenosquamous cell carcinoma.
According to the stages, the patients had primarily locally advanced stages of the diseases (Table 2).
There was lymphovascular invasion in 4 (10.8%), mediastinal invasion in 12 (32.4%), atelectasis in 10 (27.0%), lymphovascular invasion + mediastinal invasion in 6 (16.2%) patients and mediastinal invasion + atelectasis in five (13.5%) patients.
Considering the location of the pleural fluid, it was ipsilateral to the mass in 84 (87.5%), contralateral in four (4.2%) and bilateral in eight (8.3%) patients.
Effusion sampling was performed through thoracic US in 38 (39.6%) patients. Among these patients, no pleural effusion could be collected in 11 (28.9%) due to the very small amount, while effusions were sampled in 27 (71%). The pleural effusion was transudative in one (2.6%) patient and exudative in 26 (68.4%) patients.
While there was no SUV uptake of pleural effusions on PET/CT in 72 (75.0%) patients, there was uptake in 24 (25.0%). The SUVmax ranged from 1.25 to 9.93 in patients with pleural effusion uptake on PET/CT, with a mean SUVmax of 2.92±1.85 and a median SUVmax of 2.34. An increase in effusion was identified only in one of the patients with SUV uptake on PET/CT at 3 months follow-up, but the disease was considered stable. At 12 months follow-up, an increase in effusion was identified in four patients, but the disease was considered stable.
Of all patients, 61 (63.45%) patients received chemoradiotherapy as the first-line therapy. Surgery was the first-line therapy in 35 (36.5%) patients, with lobectomy in 28 (80.0%) and pneumonectomy in seven (17.1%) patients.
Of those who underwent surgery, 25 (26.0%) received adjuvant chemotherapy and six (6.3%) received adjuvant chemoradiotherapy.
At 3 months follow-up, there were six (6.3%) patients without follow-up and 14 (14.6%) patients who did not come for their follow-up appointments. Of the 76 patients with follow-up data, seven had an increased amount of pleural effusion and 23 had a decreased amount of pleural effusion, while the amount was similar in 46 patients.
At 3 months follow-up, the rate of patients with decreased effusions was higher in patients who had surgery than in those who received CT, while the rates of patients with increased and similar effusions were lower, although there was no statistically significant difference between the groups (p>0.05) (Table 3).
At 3 months follow-up, the disease was stable in 55 (72.4%) and progressed in 21 (27.6%) patients.
At 12 months follow-up, eight (8.3%) patients were without follow-up, 13 (13.5%) patients did not attend their follow-up visits and two (2.1%) patients died. Of the 73 patients with follow-up data, 11 had increased pleural effusion amounts and 23 had decreased pleural effusion amounts, while the amount was similar in 39 patients.
The rate of patients with decreased effusion was higher in patients who had surgery than in those who received CT, while the rates of patients with increased and similar effusion were lower, although there was no statistically significant difference between the groups (p>0.05) At 12 months follow-up, the disease was stable in 55 (72.4%) and progressed in 21 (27.6%) patients.
The disease progressed in five of the seven patients with increased effusions at 3 months follow-up and in six of the seven patients with increased effusions at 12 months follow-up.
No malignant effusion was identified in the evaluations of patients with increased pleural effusions at follow-up.
Discussion
Pleural effusion is a common clinical presentation in patients with non-small cell lung cancer. Most effusions are malignant and indicate pleural metastases and unresectable disease, although some are potentially benign reactive fluid collection that do not interfere with curative surgery.
Our study addresses the importance/prognostic value of accurate characterization of minimal pleural effusions based on clinical and radiological variables in patients with non-small cell lung cancer who are candidates for curative therapy.
Thoracentesis is the initial diagnostic approach to characterize pleural effusions, although it is not recommended if the pleural effusion is minimal (<10 mm thick) on lateral decubitus radiographs or computed tomography (CT) scans [2,4,6]. While the cytological examination of pleural fluid is currently the least invasive and fastest approach to the diagnosis of malignancy, it is not always diagnostic, with a sensitivity in the 40–87% range [8]. In the present study, 38 (39.6%) patients underwent thoracentesis, while 58 patients did not due to a fluid amount of <10 mm, which is in line with the findings of previous studies [2,7]. Fluid could be sampled only in 27 (71%) of the patients who received thoracentesis.
Although we suggest that PET/CT, biochemical parameters and interventional methods are accurate diagnostic tools for distinguishing benign from malignant pleural effusion [9-12], our study focused more on the varying amounts of effusions during follow-up, rather than evaluating the course of minimal pleural effusions in cases where malignant pleural effusion was ruled out.
Our study re-assessed the presence of MPEs in patients with the progressed disease and increased pleural effusion at 3 months and 12 months of follow-up. Although most patients with malignant pleural effusions tend to have moderate-to-high effusion amounts, ranging from 500 to 2000 mL, none of our patients had effusions exceeding 1/3 of the hemithorax at follow-up. The malignant potential of pleural effusions was assessed by the thoracic US, sampling if the effusion amount was sufficient, questioning the presence of effusion-secondary symptoms and PET/CT. Clinical, radiological and cytological assessment revealed no malignant pleural effusion in any patient.
The radiological finding of a nodular pleural thickening of >1 cm and mediastinal involvement suggest malignant pleural thickening in malignant pleural effusions, although no such findings were observed in our patients at diagnosis.
Mediastinal or hilar bulky lymphadenopathy, atelectasis and lymphovascular invasion are known to be potential causes of pleural effusions in patients with lung cancer. In the present study sample, lymphovascular invasion was noted in four (10.8%) patients, mediastinal invasion in 12 (32.4%) patients, atelectasis in 10 (27.0%) patients, lymphovascular invasion+mediastinal invasion in six (16.2%) patients and mediastinal invasion+atelectasis in five (13.5%) patients. The increase in effusion in those with disease progression at 3 and 12 months was attributed to the development of lymphovascular invasion, mediastinal invasion and atelectasis.
Guidelines suggest [2,13] that clinical and radiological findings, as well as biochemical parameters, can aid in the diagnosis of MPEs and PPEs. In the present study PPEs were diagnosed primarily based on clinical and radiological findings, as the effusions of the patients could not be sampled due to the very small amounts.
Since malignant effusions prevent curative resection, it is important to differentiate between the benign and malignant forms in patients with potentially resectable non-small cell lung cancer [6].
The importance of this assessment is highlighted by our study that pleural effusions detected radiologically at diagnosis, although too small in amount for sampling, can be considered paramalignant after careful clinical and radiological assessment, especially in patients appropriate for curative treatment, thus providing the potential of having resectable disease and curative treatment.
The main limitation of this study is its retrospective design and sample size.
Although there is no similar study, our findings can be supported by similar studies with a larger number of patients.
Conclusion
We found that patients without distant metastasis at diagnosis may be considered for curative treatment, which provides better survival, based a careful assessment of the clinical and radiological variables of minimal pleural effusions in the patient at diagnosis.
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. Ak G, Metintas S, Taskın AN, Sener MU, Soyler Y, Yilmaz M, et al. Evaluation of Exudative Pleural Effusions: A Multicenter, Prospective, Observational Study. Lung . 2022;200(6):807-15.
5. Goldstraw P, Crowley J, Chansky K, Giroux DJ, Groome PA, Rami-Porta R, et al. The IASLC Lung Cancer Staging Project: Proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours. J Thorac Oncol. 2007;2(8):706-14
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7. Villena Garrido V, Ferrer Sancho J, Herna´ndez Blasco L, de Pablo Gafas A, Pe´rez Rodri´guez E, Rodri´guez Panadero F et al. Diagno´stico y tratamiento del derrame pleural. Arch Bronconeumol. 2006 ;42(7):349-72.
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Download attachments: 10.4328.ACAM.21672
Suna Kavurgacı, Pınar Akın Kabalak, Derya Kızılgöz, Arife Yıldırım, Tilbe Saymaz, İlteriş Türk, Ülkü Yılmaz. Course of minimal pleural effusions in non-small cell lung cancer. Ann Clin Anal Med 2023;14(7):607-611
Citations in Google Scholar: Google Scholar
Establishing the factors affecting treatment success in lung cancer cases presenting with malignant cavity
Derya Kızılgöz, Pınar Akın Kabalak, Suna Kavurgacı, Tuba İnal Cengiz, Ülkü Yılmaz
Department of Palliative Care Unit, Atatürk Chest Diseases and Thoracic Surgery Education and Research Hospital, Ankara, Turkey
DOI: 10.4328/ACAM.21675 Received: 2023-03-03 Accepted: 2023-05-05 Published Online: 2023-05-24 Printed: 2023-07-01 Ann Clin Anal Med 2023;14(7):612-615
Corresponding Author: Derya Kızılgöz, Department of Palliative Care Unit, Atatürk Chest Diseases and Thoracic Surgery Education and Research Hospital, 06280, Keçiören, Ankara, Turkey. E-mail: derya.ozaydin999@gmail.com P: +90 506 291 55 27 Corresponding Author ORCID ID: https://orcid.org/0000-0001-9304-216X
This study was approved by the Ethics Committee of Ankara Atatürk Chest Disease and Thoracic Surgery Training and Research Hospital (Date: 2019-11-14, No: 650)
Aim: Cavitation in lung cancer patients may affect the treatment process and that have the potential to lead to complications. Cavitation complications can be life-threatening. For this purpose, we investigated some clinical characteristics of lung cancer patients with cavitary lesions that we followed up in our clinic.
Materials and Methods: A retrospective examination was made of 54 patients who had been diagnosed with non-small cell lung cancer (NSCLC, squamous-cell lung carcinoma/non-small cell carcinoma) in the Ataturk Chest Diseases and Surgery Training & Research Hospital Palliative Care Unit between 2014 and 2018, and who had a radiological appearance of malignant cavity. The patients’ demographic data, weight loss ≥5%, hospitilation status and comorbidities predisposing to pulmonary infection, clinical problems (hemoptysis/ infection), treatment status ( completede/ incompleted) were recorded.
Results: In this study, 5% and over weight loss was statistically significantly higher the group that incompleted the treatment (p = 0.014). Completion of treatment was statistically significantly lower in hospitalized patients (p = 0.002). Albumin levels were found to be statistically significantly low in those who could not complete the treatment (p = 0.02).
Discussion: In conclusion, presenting with a cavitary lesion in lung cancer, frequently leads to hospitalization with infection/haemoptysis, and can have an adverse effect on the treatment process. This group of patients should be followed carefully in terms of complications, and care should be taken in terms of side effects of treatment.
Keywords: Lung Cancer, Malignant Cavity, Chemoradiotherapy
Introduction
Lung cancer is the leading cause of cancer-related death in the world [1]. The stage and pathological type of the tumor are among the main factors determining survival in non-small cell lung cancer; however, comorbidities predisposing to infections, the patient’s performance status and any weight loss affecting such status may also have an adverse effect on survival [2], and may negatively affect the treatment process. Cavitation, which also adversely affects the treatment process of patients, is radiologically detected at a rate of 10-20% at diagnosis in lung cancer patients, and is usually associated with ischemia or bronchial obstruction-related tumor necrosis [3]. Tumor cavitation presenting with cough, hemoptysis and recurrent pulmonary infection is common, especially in squamous-cell lung carcinoma, although it may occur with all pathological types of lung cancer [4]. Recurrent pulmonary infections due to treatment complications are common in lung cancer cases with cavitation [5]. Massive pulmonary hemoptysis may occur at a rate of up to 36% in squamous-cell lung carcinoma patients with cavitation [6]. Infection and/or hemoptysis can adversely affect the treatment of patients. Reductions in performance as a result of several complications associated with cavitary lesions in patients diagnosed with high-mortality lung cancer may lead to the suspension or discontinuation of treatment. In light of the above, in the present study, we determine the factors with a potentially adverse effect on the treatment process in patients who were pathologically diagnosed with squamous- and non-small cell lung carcinoma and with radiologically cavitary lesions, and also evaluate the treatment process in such patients.
Material and Methods
The study retrospectively examined 58 patients who were diagnosed with squamous-cell or non-small cell lung carcinoma in our hospital Palliative Care Unit and who had a radiological appearance of a malignant cavity between 2014 and 2018. Patients were staged according to the 8th TNM classification through an examination of computed thoracic tomography / 18F-fluorodeoxyglucose positron emission tomography scans. Patient files were examined, and the Eastern Cooperative Oncology Group (ECOG) performance statuses were recorded. Patients were reviewed in terms of chronic obstructive pulmonary disease (COPD) and diabetes mellitus (DM), as conditions with a predisposition to infection. Other examined variables included demographic data (age, gender, smoking status), cell types, stages, lesion regions, weight loss (5% weight loss in the last 3 months), laboratory findings (CRP, leukocyte, neutrophil and albumin levels), scheduled treatment, the status of hospitalization, reasons for hospitalization, status of culture growth and status scheduled treatment completion. Clinical conditions interfering with the treatment of patients and requiring hospitalization were classified under three (3) groups, the status of infection, the status of hemoptysis, and both. Treatment completion status was classified under two (2) groups based on the effect of such conditions on treatment. The first group consisted of patients who successfully completed the treatment; and the second group consisted of those who did not complete the treatment (treatment was delayed/never initiated/discontinued).
This study was approved by the Ethics Committee of Ankara Atatürk Chest Disease and Thoracic Surgery Training and Research Hospital (Date: 14.11.2019, No:650)
Statistical Analysis
Descriptive statistics were used for the demographic data of the study. When the patients were grouped according to the completion of the treatment, Student’s t-test was used for continuous data and Chi-square test were used for discrete data. P-value <0.05 was considered statistically significant.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
The mean age of the study participants was 63±8.1 years. Among the 54 patients, 52 (96.3%) were male and 2 (3.7%) were female. Weight loss was ≥5% in 37 (68.5%) patients, and not in 17 (31.5%) patients. Histopathologically, most patients had been diagnosed with squamous-cell carcinoma (n=48; 88.8%) and six patients (11.2%) had NOS. Most patients had early stage and local advanced disease (n=41). Lesions were located radiologically in the right upper lobe in 23 (42.6%) patients and in the left upper lobe in 16 (29.6%) patients. Mean CRP was 6.2±32.5, the white blood cell count was 10.0±4.2 and the mean neutrophil count was 6.7±3.5. Chronic obstructive pulmonary disease (COPD) and diabetes mellitus (DM) were detected in 23 and 6 patients, respectively. The distribution of treatments of the study population revealed that most underwent CRT with 35 (64.8%) cases, while 12 (22.2%) cases underwent CT. Treatment distribution is summarized in Table 1. Of the total, 37 patients were hospitalized during treatment. The reason for hospitalization was infection in 33 patients, hemoptysis in two patients, and both infection and hemoptysis in two patients. While initially planned treatment started smoothly in 31 patients, it was delayed in 15 patients, never performed in 5 patients, and was discontinued after starting treatment in 3 patients. While treatment was successfully completed in 28 patients, treatment was not completed in 26 patients. In the group that could not complete the treatment, weight loss of 5% and over was statistically significantly higher than in the group that completed the treatment (p = 0.014). There was no statistically significant difference between patients’ completion of treatment according to T staging (p> 0.05). There was no statistically significant difference between the presence of COPD and DM and completion of treatment in patients (p> 0.05). Completion of treatment was statistically significantly lower in hospitalized patients (p = 0.002). There was no statistically significant relationship between CRP, white blood cell, neutrophil levels and completion of treatment (p> 0.05). However, albumin levels were found to be statistically significantly low in those who could not complete the treatment (p = 0.02) (Table 2). There was no statistically significant difference between the location of the lesion and the completion of the treatment (p> 0.05).
Discussion
About 10-20% of lung cancer cases present with tumor cavitation radiologically, which is attributed to ischemia and/or tumor necrosis [3]. Previous studies have shown that lesions in cavitary lung cancer cases are often large and located at the periphery. Such tumors typically emerge with an increase in cough, sputum and infection parameters [5, 7]. The present study found that cavitary lesions tended to be located in the right upper lobe and left upper lobe, but did not establish any statistically significant association between lesion localization and the status of treatment completion (p>0.05). The increase in T stage compared to 8.TNM staging in lung cancer is an indication of poor prognosis, prognosis and survival [8]. In our study, no statistically significant difference was found between patients’ completion of treatment according to T staging (p> 0.05). This indicates that the size of the cavitary lesions of the patients did not contribute to the completion of the treatment.
Previous studies have reported that weight loss ≥5% is common in lung cancer patients with cavitary lesions, and that overall survival (OS), progression-free survival (PFS) and prognosis are poorer in patients with weight loss and anemia [9,10]. In lung cancer patients malnutrition is associated with a higher risk of developing complications and with mortality, sometimes lengthening the hospital stay [11]. In our study, it was found that the completion of the treatment was statistically significantly lower in patients with weight loss of 5% or more. Treatment termination was statistically significantly higher in patients with weight loss of 5% or more in patients who could start treatment (who started treatment smoothly and postponed treatment) compared to those who did not lose weight. The present study established the presence of weight loss ≥5% as a factor that may interfere both with the initiation and continuance of treatment. Studies have shown that hypoalbuminemia causes loss of appetite and fatigue, increases the side effects of chemotherapy and has a negative effect on the treatment process[12]. In our study, it was observed that patients with low albumin levels were statistically significantly higher in the group who could not complete the treatment. For this reason, it is important to provide nutritional support to this patient group starting from the diagnosis stage in the patient group with cavitary lesions, which are very difficult to manage.
Previous studies report that cavitary tumors lead to complications with infections that may be difficult to treat due to chemotherapy and/or radiotherapy [5]. These possible complications during treatment adversely affect the treatment process in cases of lung cancer with cavitary lesions, and sometimes cause problems with such high mortality rates that treatment cannot be completed. In such patients, immunosuppression related to chemo and/or radiotherapy causes a predisposition to infection, and resistant microbial agents may grow in the cultures. Furthermore, the reduced vascular blood supply in the cavity and turning into a growth medium complicates the treatment of infection in such patients, leading to an adverse effect on the treatment process. This results in a decrease in performance status and failure to complete treatment. The present study demonstrated that hospitalization with infections at the outset or during treatment was frequent in lung cancer cases with cavitary lesions, and negatively affected the treatment process in such patients.
In our study, it was observed that the hospitalization status of the hospitalized patients was statistically significantly lower. Due to its potential to interfere both with the initiation and termination of the treatment, patients with cavitary lesions should be monitored carefully, especially in terms of potential infections during the treatment process. In a previous study, poorer mean and overall survival rates and poorer prognosis were identified in cases of early cavitary lung cancer that had undergone a resection. The same study also identified wider vascular invasion and tumor size with cavitary tumors [13]. Poor prognosis and survival in lung cancer cases with cavitary lesions may be attributed to the tumor being radioresistant and aggressive [14], although the frequency of infections in such patients may adversely affect prognosis and survival. Related to this issue, a previous study identified frequent microbial growth in the transthoracic aspiration cultures of pyretic cancer patients with cavitary lesions [15]. In the present study, no statistically significant relationship was found among CRP, white blood cell, neutrophils and the status of completing the treatment (p>0.05). Additionally, there was no statistically significant association between the presence of COPD, which is a poor prognostic factor in lung cancer cases that is likely to have a negative effect on the treatment process, and the status of treatment completion. That said, treatment could be initiated without problem only in eight of the 23 patients diagnosed with COPD [16] (p>0.05), although this may be attributed to the low number of patients.
Conclusion
In conclusion, the presence of a cavitary lesion in lung cancer leads to frequent hospitalization with infections, and can potentially have an adverse effect on treatment. Weight loss and hypoalbuminemia have a negative effect on the process of completing treatment. In this regard, patients should be followed closely, treatment for infections with high mortality should be given early, nutritional support should be evaluated and patients with low performance status should be evaluated for follow-up with supportive treatment.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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2. Hoang T, Xu R, Schiller JH, Bonomi P, Johnson DH. Clinical model to predict survival in chemonaive patients with advanced non-small-cell lung cancer treated with third-generation chemotherapy regimens based on eastern cooperative oncology group data. J Clin Oncol. 2005; 23(1):175-83.
3. Chaudhuri MR. Primary pulmonary cavitating carcinomas. Thorax. 1973;28(3):354-66.
4. Dulmet-Brender E, Jaubert F, Huchon G. Exophytic endobronchial epidermoid carcinoma. Cancer.1986;57(7):1358-64.
5. Pentheroudakis G, Kostadima L, Fountzilas G, A Kalogera-Fountzila, G Klouvas, C Kalofonos, et al. Cavitating squamous cell lung carcinoma-distinct entity or not? Analysis of radiologic, histologic, and clinical features. Lung Cancer.2004;45(3):349-55.
6. Ito M, Niho S, Nihei K, Yoh K, Ohmatsu H, Ohe Y. Risk factors associated with fatal pulmonary hemorrhage in locally advanced non-small cell lung cancer treated with chemoradiotherapy. BMC Cancer.2012; 12:27.
7. Kolodziejski LS, Dyczek S, Duda K, Góralczyk J, Wysocki WM, Lobaziewicz W. Cavitated tumor as a clinical subentity in squamous cell lung cancer patients. Neoplasma. 2003;50(1):66-73.
8. Goldstraw P, Chansky K, Crowley J, Rami-Porta R, Asamura H, Eberhardt WEE, et al. The IASLC Lung Cancer Staging Project: Proposals for Revision of the TNM Stage Groupingsin the Forthcoming (Eighth) Edition of the TNM Classification for Lung Cancer. J Thorac Oncol. 2016;11(1):39-51.
9. Topkan E, Selek U, Ozdemir Y, Yildirim BA, Guler OC, Ciner F, et al. Incidence and Impact of Pretreatment Tumor Cavitation on Survival Outcomes of Stage III Squamous Cell Lung Cancer Patients Treated with Radical Concurrent Chemoradiation Therapy. Int J Radiat Oncol Biol Phys. 2018;101(5):1123-32.
10. Martin L, Birdsell L, MacDonald N, Reiman T, Clandinin MT, McCargar LJ, et al. Cancer cachexia in the age of obesity: skeletal muscle depletion is a powerful prognostic factor, independent of body mass index. J Clin Oncol. 2013;31(12):1539-47.
11. Vassallo JA, Barrios E. Weighted update of risk factors cancer. Locations and distribution of the disease in Uruguay incidence and mortality. Honorary commission for the fight against cancer. Uruguay. 2003;11-13.
12. Arrieta O, Ortega RMM, Villanueva-Rodríguez G, Serna-Thomé MG, Flores-Estrada D, Diaz-Romero C, et al. Association of nutritional status and serum albumin levels with development of toxicity in patients with advanced non-small cell lung cancer treated with paclitaxel-cisplatin chemotherapy: a prospective study. BMC Cancer. 2010;10:50.
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14. Brustugun OT. Hypoxia as a cause of treatment failure in non-small cell carcinoma of the lung. Semin Radiat Oncol. 2015;25(2):87-92.
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Derya Kızılgöz, Pınar Akın Kabalak, Suna Kavurgacı, Tuba İnal Cengiz, Ülkü Yılmaz. Establishing the factors affecting treatment success in lung cancer cases presenting with malignant cavity. Ann Clin Anal Med 2023;14(7):612-615
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Investigation of the relationship between femoral anteversion, pelvic inclination and spasticity in children with spastic diplegic cerebral palsy
Dilan Demirtas Karaoba, Busra Candiri, Burcu Talu
Department of Physiotherapy and Rehabilitation, Faculty of Health Sciences, Inonu University, Malatya, Turkey
DOI: 10.4328/ACAM.21681 Received: 2023-03-08 Accepted: 2023-05-05 Published Online: 2023-05-20 Printed: 2023-07-01 Ann Clin Anal Med 2023;14(7):616-620
Corresponding Author: Busra Candırı, Department of Physiotherapy and Rehabilitation, Faculty of Health Sciences, Inonu University, Malatya, Turkey. E-mail: busracandiri@gmail.com P: +90 507 378 07 17 Corresponding Author ORCID ID: https://orcid.org/0000-0001-7413-6371
This study was approved by the Clinical Research Ethics Committee of Inonu University (Date: 2018-02-27, No: 2018/5-5)
Aim: This research was planned to analyze the relationship between femoraloanteversion, pelvic inclination and spasticity in children with spasticodiplegic cerebral palsy.
Material and Methods: The study included 33 participants with spasticldiplegic cerebrallpalsy, aged 5-18 years (mean age 13.7 years [SD 3.1 years]; 15 girls, 18 boys), with GrosslMotor Function Classification Score 1 and 2. Femoralianteversion was evaluated with the Craig test. Pelvic inclination angle was measured using a specially designed caliper-like device and a mobile application (rotating sphere clinometer) with a phone placed on the device. Spasticity was evaluated using the Modified Ashworth Scale. The average spasticity values in the lower extremity hip flexor, adductor, internal rotator, knee flexor, plantar flexor and evertor muscles were calculated.
Results: A moderate positiveicorrelation was observed between the femoral anteversion angle and pelvic inclination angle (right: r=.373, p<.05; left: r=.412, p<.05) and between femoral anteversion angle and the mean value of lower extremity total spasticity (right: r= .361, p<.05, left: r= .368, p<.05). There was no significant relationship between the pelvic inclination angle and the mean value of lower extremity total spasticity (right: r=.208, p>.05; left: r=.302, p>.05).
Discussion: It was observed that an increase in lower extremity spasticity value may cause an increased femoralianteversion angle, while an increase in femoral anteversion may cause an increase in pelvic inclination angle.
Keywords: CP (Cerebral Palsy), Spasticity, Femoral, Biomechanical
Introduction
Cerebral Palsy (CP) is a chronic but non-progressive clinical picture that develops due to damage to the developing fetal or infant brain and causes various abnormalities in children [1]. Diplegic CP, which constitutes 32% of all CP and is the most common in premature infants, is characterized by spasticity in the pelvis and lower extremities and milder spasticity and incoordination in the upper extremities [2].
Children with cerebralopalsy (CP) have a normal skeletal structure at birth [3]. However, deformities may occur as a result of abnormal biomechanical loads due to spasticity. One of the important deformities seen in the hip joints ofochildren with CP is the increased Femoral Anteversion (FA) angle. The FA range is 30°-40° at birth and decreases to 15° by the age of 16. Due to the delay in walking, inability to stand upright, and continued hip flexion in children with CP, the iliofemoral ligament does not have a reducing effect on FA and an increased anteversion angle continues [4]. However, the etiology of increased FA in children with spastic CP is unclear. According to several previous studies , FA in children with CP may be functionally impacted by fetal positioning and hip adductor stiffness, but the results are conflicting [5]. In a study, it was shown that the moment created by the iliopsoas, rectus femoris, adductor brevis, medial hamstring muscles at certain degrees of hip flexion is the reason why flexion and internal rotation contracture are often seen together in spastic children. It was explained that internal rotationicontracture in the hip also limits the physiological decrease in FA [6]. Some studies have shown that increased FA is a cause of lower extremity deformities such as gait abnormalities, pelvic rotation, and anterior pelvic tilt, especially it is believed that the most important cause of bone deformities are abnormal muscle and joint strengths caused by the extra load on the bones [7]. In a study, it has been discovered that the pressure exerted on the hip of a spastic child created in the computerized mathematical model are six times greater than the pressure exerted on the hipiof a typical developing child [8]. Pelvic tilt is one of the biggest problems in children with spastic diplegia, as it transmits vertical forces to the pelvic spine and lower limbs as part of the kinetic chain. Increased pelvic anterior tilt is a common problem in children with CP and has been frequently described [9].
In light of this background, we consider that in the evaluation of the child with CP, a holistic approach to the child and a detailed biomechanical evaluation should be carried out, and thus, great gains can be achieved with small corrections in rehabilitation, therefore posture should be emphasized. Assuming that an increased FA angle has biomechanical effects on posture in children having spasticidiplegic CP, we think that especially increased FA and spasticity would cause anterior pelvic tilt in the pelvis. We assume that there would be biomechanical changes in the upper and lower extremities to compensate for this situation, but, to the best of our knowledge, there are none yet on this topic, according to a review of the literature. Therefore, this research was planned to examine the relationshipİbetween FA, pelvic inclination and spasticity in childrenİwith spastic diplegic CP.
Material and Methods
We conducted a multicenter, non-invasive and cross-sectional. The research was carried out with individuals attending SpeciallEducation and RehabilitationlCenters in Elazig and Malatya city centres. Study data were gathered from April to June of 2018. The research was examined and authorized by the EthicsiCommittee of local ClinicaliResearch (Approval number: 2018/5-5; Approval Date: 27.02.2018), and this study was carried out in accordance with the principles of the Declaration of Helsinki. The parents of the participants were informed about the study procedure before the study entry and an informed consent form was signed by both of sides indicating that they would willingly participate.
Children aged 5-18 (13.7±3.1) years, diagnosed with spastic diplegic CP, with GrossiMotor FunctioniClassification Score (GMFCS) 1 and 2, who had not undergone botox in the last 6 months, had not undergone any orthopedic surgery, and whose families gave informed consent were included in this study. Children who did not meet the inclusion criteria , children who did not want to participate voluntarily, and children of families who did not want their children to be included in the research were not included in the research. Individuals in institutions were chosen using a straightforward random selection procedure. All participants were registered..
Initially, 41 children with spastic diplegic CP were identified, and 5 children who did not meet the inclusion criteria were excluded. Afterwards, 3 more children who could not complete the evaluation parameters were excluded. Totally, 33 kids were included in our research (Figure1).
Assuming that the FA angle increased in 75% of the children with spastic diplegic CP with α=.05 and 1-β (power)=.80 in the power analysis performed before the study, it was calculated that at least 33 subjects should be included in the study [10]. The sample size was determined using the freely downloadable statistical program OpenEpi, version 3.
Test Procedure
Evaluation of the FA angle was done with the Craig test [11]. The patient was placed in the prone position, and the Craig test was carried out on the side of the hip that will not be tested. The hips were extendedand the knee on the side to be tested was in 90° flexion. The tester palpated the trochanter major with her left hand and internally rotated the hip with her right hand. The angleobetween the vertical plane and the tibia was calculaed by using a goniometer at the point where the trochanteric protrusion was most prominent [12].
Pelvic inclination angle was measured with the help of a device designed like a caliper and a public mobile application (Rotating Sphere Clinometer) that performs inclinometric measurements while the patient was standing. The short end of the caliper was kept to the anterior superior of the spina iliaca and the long end was held to the posterior superior of the spina iliaca, and a phone was placed on the device and the measurement was made in terms of angles with the mobile application (Rotating Sphere Clinometer) (Figure 2). In the studies, it was emphasized that the smartphone inclinometer is valid and reliable, in perfect agreement with the goniometer-based goldistandard for ROMimeasurement [13].
Spasticity was evaluated with the Modified Ashworth Scale, which is one of the methods that is easily used in practice. The Modified Ashworth Scale does not require equipment; It is easily and widely used in clinic. Scoring is done between 0-4 [14]. In our study, a total value for the lower extremity was calculated by taking the average of spasticity values in hip flexor, adductor, internal rotator, knee flexor, plantar flexor and evertor muscles in the evaluation of spasticity.
Statistical analysis
Quantitative data obtained from the research were analyzed utilizing the IBM SPSS Statistics 18 package program. The conformity of the variables to the normal distribution was examined using visual (histogram and probability graphs) and analytical methods (Shapiro-Wilk Test). Descriptive statistics (mean, standard deviation, frequency) were applied for the characterization of the patients. The relationship between FA, pelvic inclination and mean value of lower extremity total spasticity was evaluated with the Pearson correlation test. Correlation values (r ≥ 1.0 excellent correlation, 0.71–0.99 strong correlation, 0.30–0.70 moderate correlation, 0.01–0.29 weak correlation, 0.00 no linear correlation (neutral correlation)). P values below 0.05 were considered statistically significant.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
The study included 33 participants with spastic diplegic CP. The demographic characteristics of the individuals are summarized in Table1. The mean age of the children was 13.70±3.16; mean height was 147.5±21.09 cm; mean body weight was 45.73±14.73 kg; body mass index was 20.80±4.82. The mean FA, pelvic tilt, and lower extremity total spasticity values of the individuals are given in Table 2.
According to the correlation analysis conducted to examine the relation between FA, pelvic inclination and spasticity in children with spastic diplegic CP, a moderate positive correlation was found between femoral anteversion angle and pelvic inclination angle (right: r=0.373, p=0.032; left: r =0.412, p=0.017). There was also a moderate positive correlation between femoral anteversion and the mean value of lower extremity total spasticity (right: r=0.361, p=0.039; left: r= 0.368, p=0.035). There was no statistically significant relationship between the pelvic inclination angle and the mean value of lower extremity total spasticity (right: r= 0.208, p=0.244; left: r= 0.302, p=0.087) (Table 3).
Discussion
The study findings demonstrated that a moderate positive correlation was found between femoral anteversion angle and pelvic inclination angle, and between femoraloanteversion angle and loweroextremity total spasticity mean value. However, it was found that there was no direct significant relationship between the pelvic inclination angle and the mean value of lower extremity total spasticity.
In our study, we evaluated FA with the Craig test, since physical assessment, which is an indirect method in FA evaluation, is important for its practical use in clinical practice and to give an idea about rotational problems before imaging methods. At the same time, it was found that the pelvic inclination angle, which we evaluated using a caliper-like device and mobile application, which has practical use in the clinic, and the increase in FA and a tendency towards anterior pelvic tilt was observed. Studies in the literature support our conclusion. Akalan et al. demontstrated that an increase in FA may cause an increase in pelvic rotation and anterior pelvic tilt [15]. In a study comparing walking characteristics of children with and without neurological problems with increased FA, they showed that even without neurological problems, increased FA caused more complex problems such as anterior pelvic tilt, increased hip and knee flexion, apart from foot introversion [16].
Most researchers and clinicians attribute that children with CP acquire bone malformations as a result of a muscular imbalance brought on by muscle spasticity. However, there is no consensus about the muscles that cause this illness. According to certain theories, an overactive Psoas drags the lesser trochanter forward, torsion is caused on the proximal femur by the internal rotators contracting, and the greater trochanter loses stimulation as a result of the adductors’ spasticity [3]. Hip displacement has been attributed to abnormal forces produced by the hip adductor muscles, followed by the influence of the iliopsoas and hamstrings [17]. These abnormal forces were thought to induce numerous abnormalideformities of the femur and hip, including excessive FA and coxa valga, resulting in hip displacementiand dislocation. It is thought that hip flexor tension, hip rotator imbalance, adductor muscles, tight hamstring and weak abductors are among the elements affectingiFA [18]. However, controversial results have also been reported. In a study, no relationship was found between FA and hypertonicity of hipiadductor and hamstringimuscles [19]. In another research, no significant difference was found between FA grade and ankle plantar flexors, knee flexors, and hip flexors, but a strong correlation was found between FA grade and hip adductors [In another research, no significant difference was found between FA grade and ankle plantar flexors, knee flexors, and hip flexors, but a strong correlation was found between FA grade and hip adductors. available at: https://tez.yok.gov.tr/UlusalTezMerkezi/tezSorguSonucYeni.jsp]. Shefelbine et al. stated that hip flexors and hip adductors had an effect on the FA angle [3]. Arnold et al. showed in their study that adductors do not significantly contribute to excessive internal rotation of the hip [20]. As stated in studies on this subject, the effect of hip flexor and adductor spasticity on FA is still a question mark. Factors affecting FA should be studied further. Different results may be due to validation problems and validation bias in clinical evaluation studies of goniometry to measure FA. In addition, accurate correct results may not have been obtained because the weight-bearing position was not used. In light of this information in the literature, a moderate correlation was found between FA and the mean value of lower extremity total spasticity in the data we obtained in our study. We think that this relationship may be secondary to the prevention of natural derotation of the femur due to spasticity and muscle imbalance, and to the non-stretching of the anterior capsule due to the child’s general spasticity.
There are not many studies in the literature on the relationship between pelvic inclination angle and spasticity, but different results have been shown. It has been hypothesized that rectus and psoas spasticity cause increased anterior pelvic tilt [21]. Ja Young Choi et al. in their study on 30 children with spastic CP, showed that higher dynamic spasticity of the hamstring is associated with greater posterior pelvic tilt [22]. In our study, no significant relationship was found between the pelvic inclination angle and the mean value of lower extremity total spasticity. If the severity of spasticity does not cause an increase in the femoral anteversion angle, it is possible to interpret this situation as that there may not be an increase in the pelvic inclination angle. At the same time, it is not always easy to determine the effect of any effect on other subjects, as in the biomechanical effects of spasticity in children with complex neurological problems such as CP. Due to the time-consuming and costly objective evaluation parameters, subjective parameters are used in the clinic, which do not take much time and are low in cost, but with high validity and reliability. However, these parameters are often incomplete in evaluating functional quality in CP. In order to exclude the limitation in terms of this inclination angle, application was used as a relatively objective method in our study. In addition, although the evaluation criteria and parameters used in the studies reveal objective results, no method can clearly reveal muscle spasticity. We assume that this may be the cause of the various study outcomes.
Limitation
Our study has some limitations. First of all, it is influenced by the sample size. More generalizable results will come after scanning with bigger samples. In addition, more research needs to compare test results test results in kids with various types of CP.
Conclusion
It was observed that the increase in the mean value of lower extremity total spasticity may cause an increase in the FA angle, in this case, an increase in the pelvic inclination angle. However, it was not found that the mean value of lower extremity total spasticity may not have a direct effect on the pelvic inclination angle without causing an increase in the femoral anteversion angle. In the evaluation of the child with CP, we think that a holistic approach to the child and detailed biomechanical evaluation can be made, and thus, with small corrections in rehabilitation, great gains can be achieved.
Since our research is the first study to examine the relationship between FA, pelvic inclination and spasticity in children with CP, a new perspective can be gained on this subject, which has not been clarified to a large extent in the literature.
Acknowledgment
We thanks to Havva Adli for helped us in data collection and we would like to thank all the participants who agreed to participate in the study.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
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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Dilan Demirtas Karaoba, Busra Candiri, Burcu Talu. Investigation of the relationship between femoral anteversion, pelvic inclination and spasticity in children with spastic diplegic cerebral palsy. Ann Clin Anal Med 2023;14(7):616-620
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Undergoing surgery in the pandemic: A qualitative study
Dilay Hacıdursunoğlu Erbaş, Betül İlbey Koç, Sevda Suçeken, Fatma Eti Aslan
Department of Nursing, Faculty of Health Sciences, Bahçeşehir University, Istanbul, Turkey
DOI: 10.4328/ACAM.21682 Received: 2023-03-08 Accepted: 2023-05-05 Published Online: 2023-05-19 Printed: 2023-07-01 Ann Clin Anal Med 2023;14(7):621-624
Corresponding Author: Dilay Hacıdursunoğlu Erbaş, Department of Nursing, Faculty of Health Sciences, Bahçeşehir University, 34353, Beşiktaş, Istanbul, Turkey. E-mail: dhacidursunoglu@gmail.com P: +90 506 863 90 44 Corresponding Author ORCID ID: https://orcid.org/0000-0002-1151-0765
This study was approved by the Ethics Committee of Sancaktepe Şehit Prof. Dr. İlhan Varank Training and Research Hospital (Date: 2021-10-27, No: 2021-202)
Aim: The aim of the study was to understand the experiences of patients with a negative COVID-19 test who underwent elective surgery during the pandemic and thus contribute to patient-focused care.
Material and Methods: The study was carried out with patients who had elective surgery under regional anesthesia. Study data were collected with a patient information form and a semi-structured interview form. To analyze the data, patients’ answers to the semi-structured questionnaire were brought together under themes relevant to the purpose and grouped and evaluated using the content analysis method.
Results: The study was conducted with 13 patients, of whom eight were women, 10 were married, and six had their first surgery. Two themes and eight sub-themes were determined after the analysis of the data. The themes were experienced emotional states and access to treatment.
Discussion: In the literature, it has been stated that the anxiety of the patients who underwent surgery is high. In the COVID-19 pandemic, problems related to the pandemic such as the prolongation of the treatment period, uncertainty and visitor restriction were added to this anxiety. Since the number of qualitative studies on how patients who underwent surgery during the pandemic period perceive and experience the surgical process is limited, our study is a study that provides information on this subject. In this process, patients’ concerns are increasing and this issue should be emphasized in patient-centered care.
Keywords: Surgery, Human Experimentation, COVID-19, Pandemic, Qualitative Research
Introduction
Surgery is a special experience associated with anxiety and reduced control. According to the data of the General Directorate of Health Services of the Ministry of Health, a total of 4,704.094 patients underwent surgery in Turkey in 2021 [available at: https://sbsgm.saglik.gov.tr/Eklenti/40566/0/health-statistics-yearbook-2019pdf.pdf].
In this process, patients experience anxiety for a number of reasons such as being unfamiliar with the hospital environment, possible complications, and fear of the unknown. In their meta-analysis, Abate et al. (2020) found that the prevalence of preoperative anxiety was 48% in surgical patients and that patients with fear of complications had four times higher preoperative anxiety.
It is known that many major pandemics have been recorded since the existence of humanity [2]. After the black plague, cholera, Spanish flu, and swine flu, the most recent worldwide pandemic was the COVID-19 pandemic [3]. Getting the disease and being hospitalized, as well as disallowing patient relatives in hospitals and companions or visitors in the clinics due to the pandemic were factors that caused stress in patients (available at: https://www.who.int/teams/mental-health-and-substance-use/mental-health-and-covid-19) [4, 5]. Preoperative anxiety levels increased in patients undergoing elective surgery during the COVID-19 pandemic. In their study with neurosurgery patients scheduled to undergo elective surgery, Doglietto et al. (2020) found that the strongest factor associated with anxiety in patients was the risk of being infected with COVID-19 disease.
How do patients who have a negative COVID-19 test and have to undergo surgery during the pandemic process feel? The answer to this question will help identify patients’ needs, thus allowing for a better quality of care. A limited number of studies were found in the literature with patients with negative COVID-19 tests. For this reason, the study was conducted to understand the operating room experiences of patients with negative COVID-19 test who underwent elective surgery and thus contribute to the literature.
Material and Methods
This study was carried out in Istanbul to understand the operating room experiences of patients using the qualitative interpretative phenomenological design [7, 8]. The conduct of the study was based on the Qualitative Research Reporting Consolidated Criteria Checklist (COREQ) [9].
Sample selection
There is no limitation on the number of samples in studies with the qualitative phenomenological design [8]. The criterion sampling method was used in this study. Sampling criteria in the study were patients operated electively with regional anesthesia, 18 years of age and older, oriented and able to answer questions, had a negative COVID-19 test, and agreed to participate in the study.
Ethical Approval Statement
Institutional permission and ethics committee approval for the research were obtained with the decision no. 2021-202 on October 27, 2021. The patients who participated in the study were informed about the study, and their consent was obtained by explaining that their voices would be recorded with a tape recorder, and that the information provided would be kept confidential and would not be used for any other purpose. Accordingly, the participants were coded as “H” to express “patient [hasta in Turkish]” and each participant was given numbers next to the code, for example H1, H2, H3.
Data Collection
The patient information form includes four open-ended questions on participants’ age, gender, marital status, and the number of surgeries they have had.
Semi-structured interview form included six questions about hospital stays and surgeries during the pandemic period.
During the interview, a voice recorder was used to record the interviews. The interviews were held in the patient rooms in the hospital. Each interview lasted an average of 30 minutes.
Data Analysis
Patient responses to the semi-structured questionnaire were coded in line with the purpose by the researchers. Researchers compared and classified the various codes according to their differences and similarities. Patients’ answers were brought together under the determined themes and evaluated using the content analysis method.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
Thirteen patients with an age range of 34-73 years participated in the study. Eight of them were women, 10 were married, and six had their first surgery.
Two themes and eight sub-themes were obtained in the study (Table 1).
Theme 1. Experienced emotional states
Sub-theme 1: Fear of being sick with COVID-19
Most of the patients stated that they were afraid of contracting COVID-19 disease during the operation and did not feel safe. One of them expressed his feelings as follows: “I was so afraid that I even quit smoking, and I have been smoking for 20 years, believe me. I am very afraid that I will catch the virus in the hospital” (H10).
Sub-theme 2: Fear of having COVID-19 and infecting their relatives
Regarding patients’ fears, patients, especially those living with an elderly family member were afraid of infecting them. A remarkable example was from a patient who lived with his mother and father: “My parents are old. Now I’m very careful not to catch COVID-19 in the hospital and infect my family” (H6).
Sub-theme 3: Fear of the unknown
Patients, especially those who had not previously had COVID-19 disease, seemed to have a serious fear of the unknown. The statement of a 53-year-old patient was a notable example “I have had stomach aches for a long time. I want to have this surgery as soon as possible, but I do not know what will happen if I get COVID from the hospital, if my surgery is delayed” (H11).
Sub-theme 4: Fear of death
One patient’s statement was as follows: “We hear a lot of deaths on the news. They say that especially those who have diseases die. I also have high blood pressure, so I am afraid of dying if I get COVID” (H4).
Sub-theme 5: Not feeling safe
The majority of patients stated that hospitals are risky areas for COVID-19 disease and therefore they do not feel safe. One patient commented, “I do not feel safe at all because I do not know who may have COVID” (H3).
Sub-theme 6: Submission
One patient said, “I was hospitalized again last month. The nurses told me how important it is to wash my hands, I never take off my mask anyway. That is why I am not afraid, we will get what is in our destiny” (H9).
Theme2. Access to treatment
Sub-theme 1: Conveniences
A patient said, “I am a teacher, I am together with many children at school. I think I would have been sick already because it was crowded at school. I am very happy to have my surgery now, it is easy to make an appointment right now.” (H5).
Sub-theme 2: Challenges
A patient stated the difficulties she had in accessing treatment during the COVID-19 pandemic as follows: “Because my doctor has COVID-19, the patients he was going to operate piled up and we had to postpone my surgery a little. Actually, I was going to have surgery earlier.” (H8).
Discussion
Abrupt postponement of elective surgeries, fear of contracting COVID-19 disease during hospital visits, the predicted increase in postoperative morbidity in COVID-19 patients undergoing surgery are described as factors that increase concern and anxiety in patients awaiting and undergoing surgery during the pandemic [6, 10, 11, 12].
Balkaya et al (2021) determined in their study that patients who were concerned about being infected with COVID-19 disease during hospitalization had higher anxiety scores than those who did not have such concerns. In the study of Moveman et al. (2021) determined in their study that 61% of the patients were worried about contracting the COVID-19 disease, especially during admission to the operating room and waiting areas. Işıklı et al. (2023) found in their study that patients’ fear of COVID-19 disease was close to moderate. In our study, similar to the literature, the majority of patients stated that they were afraid of surgery and did not feel safe in the COVID-19 pandemic. Most of these fears were caused by the need for prolonged hospitalization, the unknowns about the process, staying away from their relatives, the risk of infecting family members with COVID-19 disease. Besides, they experienced the fear of death, especially those with chronic diseases and elderly patients.
Three of the patients did not have any negative reports of fear of getting sick since they had the COVID-19 disease previously. A study in the literature on the emotional state and fears of patients scheduled for elective surgery during the COVID-19 pandemic reported that 55% of the patients were afraid of contracting COVID-19 disease during hospitalization. In addition, a previous infection due to COVID-19 disease has been associated with reduced fear of COVID-19 disease [10].
The study by Gültekin et al (2021) determined that 72.3% of the patients did not receive any information about the rates of COVID-19 disease among patients and staff, the tests performed in the hospital where they were treated, or the precautions taken. In the study by Keskin et al. (2021), patients who reported that they could not get enough information about the surgical processes, and who were concerned that the treatment could not be completed, had higher levels of fear. In our study, the majority of the patients stated that they did not think that they had enough information about the COVID-19 disease measures taken in the hospital, so they were worried and afraid.
In the study by Keskin et al. (2021), patients experienced a moderate fear of the pandemic, and 16.1% of the patients postponed their follow-up dates at least once due to this fear. In access to treatment theme, some of the patients stated that having surgery in the COVID-19 pandemic had some conveniences, whereas some others mentioned difficulties. As conveniences, they said that it would be easier for them to access treatment because other patients were afraid of going to the hospital. However, there were also patients who noted that disruptions could occur in the planned surgical treatments, and their surgeries were postponed to a later date because of the healthcare workers who had COVID-19.
Strengths and limitations
These results cannot be generalized to all patients as the study was conducted in a single institution and a qualitative design was used. The strength of the study was that it examined how patients who underwent surgery during the pandemic period perceived and experienced the process. The results indicated that patients’ anxiety increased in this process and that this issue should be emphasized in patient-centred care.
Conclusion and Suggestions
There are quantitative studies in the literature on the concern and anxiety experienced by patients undergoing elective surgery related to COVID-19 disease. We think that our qualitative study on the subject will contribute to understanding and interpreting the experiences of patients with negative COVID-19 tests undergoing elective surgery. We believe that healthcare professionals should identify patients’ fears of surgery and COVID-19 disease and support them accordingly.
Acknowledgment
Thank you to patients who kindly volunteering to participate in our research.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: During this study, the authors received no financial support from any pharmaceutical company that has a direct connection to the research topic, a company that provides and/or manufactures medical instruments, equipment and materials, or any commercial company. During the evaluation process of the study, no material and/or moral support, which may adversely affect the decision to be made about the study, was received.
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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7. Erdoğan S, Nahcivan N, Esin MN, editors. Hemşirelikte araştırma süreç uygulama ve kritik (Research process, practice and critical in nursing). İstanbul: Nobel Kitabevi; 2017. p.131-64.
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Download attachments: 10.4328.ACAM.21682
Dilay Hacıdursunoğlu Erbaş, Betül İlbey Koç, Sevda Suçeken, Fatma Eti Aslan. Undergoing surgery in the pandemic: A qualitative study. Ann Clin Anal Med 2023;14(7):621-624
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Comparison between pre- and post operative effects of ıntravenous anesthetic drugs on leukocytes: A clinical diagnostic study
Kamal Jalal Rashid 1, Safa Bakr Karim 1, Muhammed Babakir-Mina 2
1 Department of Anesthesia, 2 Department of Medical Laboratory, College of Health and Medical Technology, Sulaimani Polytechnic University, Sulaimani, Iraq
DOI: 10.4328/ACAM.21683 Received: 2023-03-10 Accepted: 2023-05-05 Published Online: 2023-05-19 Printed: 2023-07-01 Ann Clin Anal Med 2023;14(7):625-629
Corresponding Author: Kamal Jalal Rashid, Department of Anesthesia, College of Health and Medical Technology, Sulaimani, Iraq. E-mail: kamal.rashid@spu.edu.iq P: +90 964 7725 219 634 Corresponding Author ORCID ID: https://orcid.org/0000-0003-4850-2715
This study was approved by the Ethics Committee of College of Health and Medical Technology, Sulaimani Polytechnic University (Date: 2021-08-03, No: CH 00085)
Aim: The leukocytes were affected by anesthesia and intravenous anesthetics. The purpose of this research was to examine the impact of these medicines preoperatively to evaluate the effects of intravenous anesthesia and anesthesia method on leukocytes, which are substantial immune system cells.
Material and Methods: One hundred participants who were recovering from surgery between November 2021 and March 2022 were the subject of the prognostic research. Before induction, a participant’s blood was drawn, and six hours following the procedure, a further blood specimen was collected. For all specimens, complete blood count (CBC) tests were performed to determine leukocyte levels before and after surgery.
Results: In general, the mean neutrophil counts rose after surgery, whereas the mean lymphocyte, monocyte, eosinophil, and basophil counts declined. Leukocytes are more affected by general anesthesia than by other types of anesthesia. With the exception of pentothal, all hypnotic anesthetic medications affected the level of leukocytes. Individuals who received analgesics had a clear impact on leukocytes compared with those without analgesia. Moreover, leukocyte alterations for muscle relaxant have been observed; this resulted in lower cell, lymphocytes, monocytes, eosinophils and basophils levels but higher neutrophils counts. Most intravenous anesthesia showed substantial alterations when measured by neutrophil and lymphocyte count (p<0.05).
Discussion: All analgesics, hypnotics, and muscle relaxants, with the exception of pentothal, may reduce lymphocytes, particularly cells. An increase in neutrophil levels could occur when intravenous anesthetics are given postoperatively.
Keywords: Anesthetic Drugs, General Anesthesia, Leukocytes, Pentothal, Propofol
Introduction
Anesthesia is the procedure of administering medicines to a person in order to keep them from pain during surgery or other medical care. The drug may be delivered using a variety of different techniques, including injection, topical lotion, eye drops, skin patches, and sprays. During medical treatments, these medications protect the body from experiencing any loss of sensation or consciousness. One of the most common types of pain medication, known as General Anesthesia (GA), induces forgetfulness and analgesic in patients, regardless of the temporary blindness of the muscles after administration of medications [1].
Sufficient depression of the neurological system, brought about by known GA, is necessary in order to perform intensive, factor involves issues or concerns treatments such as surgical procedures [2].
Intravenous (IV), inhalation, intravenous sedation, opiates, and antimitotic medicines are the five main types of anesthetic drugs. Every person in the group has their own set of disadvantages when it comes to accomplishing the main objective of general anesthesia [3].
The beginning of modern intravenous anesthetics may be traced back to the introduction of Pentothal into the field of anaesthetic therapy. Nowadays, Propofol is the intravenous anesthetic used in clinical settings most frequently. Also at low dosages, Propofol may provide a sedative or antiemetic action, which is one of the drug’s many advantages [4].
Anxiolysis, the induction of memory, and feeling drowsiness are the most common clinical applications of Midazolam. The most recent addition to the antidepressant family, Remimazolam, has an exceptionally brief term of action as a result of its rapid elimination via plasma esterases [4].
Analgesia was attained by the use of Ketamine. That was the very first-time medical anesthetic used this technique. Additionally, Fentanyl was the first created as an intravenous anesthetic; nonetheless, its most strong hypnotic analgesia has become of concern [5]. Both atracurium and rocuronium are examples of non-depolarizing muscle relaxants that are administered during anesthesia and have a transitional or rapid onset of action [6].
Leukocytes includes, Granulocytes (neutrophils, eosinophils, and basophils) and non-granulocyte (monocytes and lymphocytes) that are components of the immune system, which help the human body to invade or resist infection and other diseases [7, 8].
The purpose of the prescription of hypnotic medicines preoperatively is to generate sedation, which affects the hematological and immunological systems, particularly leukocytes [9].
The immune system is made up of a complex structure of molecules, and lymphocytes are one of them that function together to safeguard the body from hazardous microorganisms. They have a capacity to immediately distinguish every disease and infectious cell in addition to remembering them. Allergy, predisposing factors, and inflammatory disorders may all be produced by immune response imbalances [10].
Throughout the course of breakthroughs in fundamental research as well as enhancements in laboratory activities, such as tissue culture and procedures for the segregation of tissues, several types of general anesthetic have been demonstrated to possess the ability to reduce the immune response’s activity. Anesthesia-induced immunosuppression,, which involves conformational changes in lymphocytes and suppression of natural killer cells, is particularly problematic for individuals with the majority of neoplasms [11].
According to the examination of the effect of anesthesia method on post-operative natural killer T cells, no differences were found between some of the spinal anesthesia crew and the minimal invasive GA crew [12].
Material and Methods
People who had recently undergone surgical procedures were the subjects of this retrospective clinical investigation. Consent after receiving appropriate information was obtained from every patient. From November 2021 to March 2022 we gathered data from a variety of facilities, including Shar Medical Center and Sulaimani Surgery Center.
The study was approved by the Research Ethics Committee of the College of Health and Medical Technology, Sulaimani Polytechnic University (Research study code CH 00085). Informed consent was obtained from all the subjects.
The 100 patients in this research, whose ages varied from 5 to 80, were randomly selected. Patients undergoing general anesthesia were given intravenous infusions of Propofol (2-3 mg/kg) or Pentothal (2-3 mg/kg) for initiation, and they were given either Fentanyl (0.5-2 g/kg) and or Ketamine (0.1-0.3 mg/kg) as analgesia. Medicaments and onset and development were given intravenously to participants. After anesthesia was administered, either rocuronium (0.6-1.2 mg/kg) or atracurium (0.5 mg/kg) was given as a muscle relaxant.
Participants who were about to receive spinal anesthesia were positioned so that they sit or lie on their side. Intrathecally, ten to fifteen milligrams of Bupivacaine and fifteen micrograms of Fentanyl were injected.
In addition, because of the lengthy nature of the surgery, other participants were given a combination of general anesthesia and spinal anesthesia for sleep with sedation [Midazolam (0.05-0.08)].
Blood was obtained to collect samples for examination prior to the procedure. The first findings were acquired during the day procedure, thirty minutes before the induction of anesthesia; the second blood sample was taken six hours after the operation.
An implantable catheter was placed into a vein in the participant’s forearm vein, and 5 milliliters (ml) of blood was collected from the midline of the cubital, cephalic, and basilic veins. The blood was then placed in an EDTA tube. Blood samples were used to obtain a CBC (complete blood count) test on a Colter-Medonic M51 machine with serial number (TF11041924093).
Inclusion criteria :, all participants had a normal white blood cell count before surgery and were healthy.
Exclusion criteria: individuals under the age of 5 and those who with abnormal white blood cell count were excluded from the study.
Analytical evaluations and information management were carried out using the Statistical Package for the Social Sciences (SPSS) version 22. The Chi-square test (χ2) was utilized for contrasting the categories. The work of establishing the relationship between the mean and the variables was carried out using the (ANOVA) test and the independent sample test. A statistically significant interaction between the factors was considered to exist if the P-value was much less than 0.05.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
A total of 100 participants were included in the research, including 36 male and 64 female individuals. The age range of the majority of the instances, which accounted for 55%, was 20-40 years.
Before the surgery, mean eosinophil levels were 66.75, but they increased to 81.08 after operation, the difference was 14.33. Lymphocytes count before the operation was 26.47, however this number dropped to 14.98 after the operation. Before the operation, the number of monocytes was 4.06, however, this number dropped to 2.64 after surgery. Before the procedure, eosinophils counts were 2.15; after the procedure, they dropped to 0.93. (Figure 1).
The mean level of lymphocytes in people undergoing GA was 26.01 prior to surgery but decreased to 14.14 as a result of GA. Before the surgery, the mean for those handled with SA was 27.60; nevertheless, after the operation, it was 26.05. For patient populations in both SA and GA, the mean level also dramatically decreased. Regarding neutrophils, mean levels increased during surgery for participants who had GA, and SA+GA, 67.04 to 78.08 and 60.4 to 72.9, respectively; however, for those who underwent SA, smaller increases were found from 74.95 to 77.85. The p – value for such changes was less than 0.001, making them statistically significant for both lymphocytes and neutrophils (Figure 2).
The mean level of lymphocytes in participants who were given Propofol, Midazolam, and Marcaine during surgery was 26.52, 37.30, and 28.65; however, after surgery, these numbers dropped to 13.81, 31.70, and 18.15, accordingly. But the standard deviation increased from 13.55 to 19.85 for those who were given Pentothal. When it comes to neutrophils, the mean significantly improved following surgery for individuals who were given Propofol and Marcaine, with ranges of 66.35 to 82.47 and 65.97 to 77.86, respectively. The mean level, however, dropped after the procedure from 83.35 to 75.00 among individuals who were given Pentothal. The p – value for such changes was less than 0.001 for both lymphocytes and neutrophils, indicating that they were statically important (Table 1).
Based on the results that we obtained, the levels of lymphocytes, monocytes, eosinophils, and basophils all fell after the surgery at various rates; however, the levels of neutrophils rose after the operation in all individuals. Before and after the operation, the correlation between lymphocytes and analgesics was found to be significant (p-value <0.001), as well as the relationship between monocytes and neutrophils (neutrophil p-value = 0.02) and (monocyte p-value = 0.01); however, the p-value for eosinophils and basophils revealed that the validity was not significant (eosinophils=0.09; basophils=0.8). On the other hand, those who did not get analgesics showed any appreciable changes in the median frequencies for all leukocytes (Table 2).
With regard to muscle relaxant, the levels of lymphocytes, monocytes, eosinophils, and Basophils reduced after the operation; however, the levels of neutrophils rose. Even so, there were no significant changes for eosinophils and basophils (p=0.6 and p=0.9), despite substantial correlations between lymphocytes and neutrophils with muscle relaxants before and after the operation (p-value 0.05) (Table-3).
Discussion
According to the findings of this particular research, the count of lymphocytes before operations was considered to be acceptable; nevertheless, the number dropped to pathological levels following anesthesia. It follows that anesthesia medications may have an effect on the cells in question. This finding is consistent with other previous studies, which suggested that anesthesia medicines may have an effect on the leukocytes and lower the count of lymphocytes after surgery.
Patients who receive general anesthesia or combined spinal and general anesthesia have a more significant reduction in their lymphocytosis after surgery as a result of spinal anesthesia. On the other hand, patients receiving local anesthesia do not experience any transition in their white blood cell count. In contrast, following surgery, the number of neutrophils in the blood of those who had general anesthesia, spinal anaesthesia, or both spinal and general anesthesia has been shown to increase. A significant relationship between these characteristics was revealed. This suggests that anesthetics have a negative impact on the immune system, and more research is recommended to confirm this impact. In addition, both clinical and experimental research have shown that anesthesia has the potential to negatively affect immunity [13-15]. When more than one type of anesthesia is combined with operations, there are a large number of variables that might contribute to a disruption in immune system. These variables include general disorders, the length of the operation, illness that is also implicated, as well as anesthesia medicines and procedures [16]. In general, anesthesia has the effect of suppressing the immune system [17].
These changes may occur as a reaction to the action of various hormones; additionally, lead to decline in monocyte, eosinophil and Basophils counts. After the operation, patients who have been administered complete intravenous anesthetics showed a decrease in their lymphocytosis at every observation period examined [15].
When the levels of leukocytes prior to and after anesthesia were analyzed, the researchers found that the use of hypnotics was related to a change in the level of lymphocytes. This result indicates or probably may be due to a decrease in the number of cells. It may also have to do with how the medications respond to different doses. Prior research concluded that the release of stromal hormonal and mediators could be responsible for the activation of the neuroendocrine system that occurs after anesthesia and surgical procedures [18, 19]. In addition, leukopenia may develop as a consequence of the administration of anesthetic as a result of a variety of hormones, cytokines, and acute-phase reactants, the death of cells, or inhibition of the mortality of lymphocytes [20]. In contrast to this, there was no change in the total number of leukocytes in patients sedated with Propofol and Fentanyl [17].
According to the outcome of this investigation, the frequency of neutrophils reaches its peak six hours after surgical intervention. Because of this, any anomalous substances that are interred into the human body and then come into contact with the macrophage and invade the drugs because they recognized those drugs as abnormal foreign bodies resulting in the elevation in the levels of neutrophils. Likewise, medicines have the potential to signify a foreign body and cause an interchange in the number of monocytes. Previous results have been quite close to being consistent with this finding [21]. It has been shown that the use of Propofol reduces the number of neutrophils, but the use of Pentothal and Midazolam led to an increase in macrophages [21]. The results of this study are consistent with those of the earlier research.
As a result, researchers compared the levels of monocytes before the procedure to the frequencies of monocytes after the surgery, and the research revealed that the various analgesics had an effect on the level of WBCs in the majority of instances. In addition, the level of all leucocytes except for neutrophils grew after the surgery. This is significant for two reasons: mainly, macrophages (neutrophils) are regarded very first lines of strong protection against infections, and secondly, granulocyte have the capacity to safeguard patients from bacterial infections [14]. In many circumstances, a required and natural response of the body to an infection is a rise in the percentage of granulocyte (neutrophils). This increase in the number of macrophages is a required biological response [22]. According to the findings of our research, neutrophilic granulocytes and the enormous inflow of those cells into the circulation, along with leukocytes, cause depletion [23]. Additionally, Jafarzadeh and colleagues found that ketamine and fentanyl affect the immune system [9], and our research found comparable results. This result may have been influenced by the participants’ ages, the duration of the procedures, or the sorts of operations. On the different side, there was only a minor percentage of an increase in the rates of leukocytes in individuals who did not get the analgesics (these participants underwent surgery under spinal anesthesia). Perhaps this is due to the method or type of treatment that was performed. Yet, some writers indicated that the anesthesia approach was associated with less change in the counts of leukocytes than with operation stress [15].
In regard to muscle relaxants, the level of (lymphocytes, monocytes, eosinophils and basophils) all reduced after the surgery, although the number of neutrophils has increased, and substantial variations are revealed between them. This shift most likely occurred as a result of the real effect that those medications had on monocytes, as well as the increased presence of pharmaceuticals that occurred as a result of those drugs being physically administered into the bloodstream. Prior research has reached the same result [15]. In addition, Sangwan and his colleagues came to the same opinion [24]. Nevertheless, the lymphocyte count changed less in individuals who were given general anesthesia instead of muscle relaxant (those under spinal anesthesia). This suggests that there were no suppressive impacts since they have never used intravenous anesthetics to induce anesthesia in these patients [24].
Conclusion
Individuals who have general anesthesia get a higher risk of having a reduction in their neutrophil count compared to individuals who get spinal anesthesia. Compared to other hypnosis and anesthesia medications, the efficiency of propofol and Marcaine in lowering cell counts is much higher. All analgesics and muscle relaxants that have been taken have the potential to produce inflammatory cell fractions, especially lymphocytes. Moreover, with the exception of Pentothal involving a specific, all anaesthetic medications have the potential to increase the number of neutrophil cells within the human organism.
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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Kamal Jalal Rashid, Safa Bakr Karim, Muhammed Babakir-Mina. Comparison between pre- and post operative effects of ıntravenous anesthetic drugs on leukocytes: A clinical diagnostic study. Ann Clin Anal Med 2023;14(7):625-629
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The relationship between vitamin C and oxidative status in periodontitis: A case-control study
Elif Emiroğlu 1, Tülin Çakır 2, Meral Yüksel 3, Fatma Esra Güneş 4, Ali Çekici 2, Berna Karakoyun 5
1 Department of Nutrition and Dietetics, Faculty of Health Sciences, Istinye University, 2 Department of Periodontology, Faculty of Dentistry, Istanbul University, 3 Department of Medical Laboratory, Vocational School of Health Related Services, Marmara University, 4 Department of Nutrition and Dietetics, Faculty of Health Sciences, Istanbul Medeniyet University, 5 Department of Physiology, Hamidiye School of Medicine, University of Health Sciences, Istanbul, Turkey
DOI: 10.4328/ACAM.21693 Received: 2023-03-15 Accepted: 2023-05-05 Published Online: 2023-05-19 Printed: 2023-07-01 Ann Clin Anal Med 2023;14(7):630-634
Corresponding Author: Berna Karakoyun, Department of Physiology, Hamidiye School of Medicine, University of Health Sciences, Istanbul, Turkey. E-mail: bernakarakoyun@gmail.com P: +90 533 267 96 72 Corresponding Author ORCID ID: https://orcid.org/0000-0003-0929-4239
This study was approved by the Clinical Research Ethics Committee of Marmara University, Faculty of Medicine (Date: 2017-01-06, No: 09.2017.035)
Aim: A co-factor for reactions including collagen hydroxylation, vitamin C prevents oxidative damage to DNA and proteins and may be associated with oxidative stress in periodontitis. This study was designed to test the hypothesis that vitamin C is inversely related to oxidative stress markers in individuals with periodontitis.
Material and Methods: This study was conducted with 25 individuals with periodontitis and 24 individuals without periodontitis. Vitamin C intake of participants was determined using a valid food frequency questionnaire, and plasma ascorbic acid levels of participants were measured using high-performance liquid chromatography. Total antioxidant status and total oxidant status were measured in serum and saliva samples, and the oxidative stress index was calculated. Lucigenin-enhanced chemiluminescence assays determined superoxide radicals in saliva.
Results: Vitamin C intake in patients with periodontitis was found to be lower than in the control group (124.68 mg/d and 176.71 mg/d, p=0.003, respectively). The plasma ascorbic acid levels and total oxidant status (p=0.03,r=-0.42) and superoxide radical levels (p=0.01,r=-0.53) were inversely correlated in patients with periodontitis.
Discussion: Dietary vitamin C intake in patients with periodontitis was lower than in healthy individuals; vitamin C intake may be inversely related to oxidative stress which is the underlying cause of periodontitis.
Keywords: Periodontitis, Antioxidants, Oxidative stress, Vitamin C, Periodontal disease
Introduction
Periodontal diseases which may cause periodontal tissue destruction, alveolar bone loss and infection are microbial and inflammatory conditions [1]. It is accepted that the main etiologic factor of periodontal diseases is the microbial agents in dental plaque. However, the pathogenesis and etiology of this disease are determined in addition by age, gender, low socioeconomic status, obesity, genetics, tobacco and alcohol use, endocrine disorders, neurologic status, local factors related to teeth, nutritional status and oxidative stress [2, 3]. Though many diseases are associated with oxidative stress, it remains unclear whether oxidative stress is the cause or the result of periodontitis. To prevent or treat oxidative stress related to periodontitis, factors that may cause free radical formation such as smoking, alcohol, ultraviolet light and extreme heat should be avoided and consumption of antioxidant nutrients such as selenium, vitamin E and vitamin C should be increased [4].
Vitamin C has antioxidant effects on free radicals and inhibits their negative effects on the body, sweeping them up and preventing oxidative damage to lipids and proteins. Vitamin C is involved in synthesizing intercellular materials such as collagen fibers in connective tissue and the bone-tooth matrix and plays a role in regulating the immune system. Because of these functions, low vitamin C concentration in the serum and/or plasma may contribute to risk factors of periodontitis [5-7].
This study hypothesizes that there are inverse relationships between vitamin C and oxidative stress markers in individuals with periodontitis and evaluates the relationships between vitamin C intake, plasma ascorbic acid levels (PAAL) and parameters related to oxidative stress in individuals with periodontitis.
Material and Methods
This study is a case-control study. The sample size was determined as 24 for both study and control groups (p = 0.05, power 80%). Forty-nine individuals (control group n=24, periodontitis group n=25) aged 18 to 65 participated in this study.
All participants were informed about the study and approved the consent form. Ethical approval for this study was obtained from the Marmara University Faculty of Medicine’s Clinical Research Ethics Committee (Protocol no: 09.2017.035).
The exclusion criteria included:
– Periodontal treatment within 6 months of the study
– Tooth extraction within 2 weeks of the study
– Any systemic disease
– Vitamin C supplement use within 3 months of the study
– Antibiotic use within 6 months of the study
– Alcohol or tobacco use
– Pregnancy or lactation
Periodontal Evaluation
In all groups, periodontal status was evaluated with plaque index (PI) and gingival index (GI); in addition, clinical attachment level (CAL) and probing pocket depth (PPD) were measured. Cases, where participants showed bleeding on probing (BP), were documented. All periodontal measurements were performed by one individual using the Williams periodontal probe (Hu-Friedy, USA). All clinical measurements were made from 6 points of teeth (mesiobuccal, buccal, distobuccal, distolingual, lingual, and mesiolingual). The mean PI/GI/PPD/CAL/BP of the individuals was obtained by taking the average of these values.
PI, plaque index, determines the thickness of the plaque extending along the gingival margin; to see the plaque, the teeth are air-dried and the plaque is not stained. GI, gingival index, evaluates the gingiva; the probe tip is moved around the gingival edge for 30 seconds and inflammation, bleeding and color are evaluated. CAL, clinical attachment level, measures the distance from the cementum boundary to the bottom of the pocket. PPD, probing pocket depth, measures the distance from the free gingival margin to the base of the pocket; the periodontal probe should be held parallel to the long axis of the tooth, advanced by applying a slight force and stopped when it encounters resistance. BP, bleeding on probing, is evaluated according to whether there is bleeding in the regions after measuring the periodontal pocket size.
Determination of Vitamin C Intake
A valid food frequency questionnaire was developed to evaluate the dietary vitamin C intake among healthy Turkish adults. This was used by a dietitian to determine the vitamin C intake of study participants [8]. Average daily consumption, of foods were calculated using the frequency of consumption and the amounts consumed at one time. The Vitamin C content of foods was obtained from the ‘United States Department of Agriculture’, ‘Turkish Food Composition Database’ and the ‘BeBiS Nutrition Information System 7.1’ (Pasifik Company, Turkey). Daily vitamin C intake levels are expressed as mg/day.
Sample Collection and Preparation
Plasma: Blood samples were collected in 10 ml lithium heparin tubes in the morning (8:00-9:00 am) after an overnight fast and before periodontal examination and were centrifuged for 10 minutes at 3000 rpm at 4°C.
Serum: Blood samples collected in dry tubes were centrifuged for 10 minutes at 3000 rpm at 4°C and serum samples were stored at -80 °C until analysis.
Saliva: Individuals spit in sterile specimen containers after fasting for 12 hours and before periodontal examination and samples were stored at -20 °C until analysis.
Determination of Plasma Ascorbic Acid Level (PAAL)
A private laboratory determined ascorbic acid in plasma using high-performance liquid chromatography on the day of the sample collection. PAAL values were reported as mg/L.
Evaluation of Total Antioxidant Status (TAS) and Total Oxidant Status (TOS) in Serum and Saliva
Serum and saliva TAS and TOS levels were measured by the Erel method using TAS/TOS assay kits (Rel Assay Diagnostics). TAS units are mmol Trolox Eqv./L and TOS units are µmol H2O2 Eqv./L. Oxidative Stress Index (OSI) units are AU (arbitrary unit) calculated with the formula OSI = [TOS (µmol H2O2 Eqv./L) / TAS (µmol Trolox Eqv./L)] × 100 [9, 10].
Analysis of Superoxide Radicals in Saliva
The superoxide radical in saliva samples was measured by chemiluminescence. Lucigenin reacts with superoxide radicals to produce light, which is then measured for 5 min using a luminometer (Berthold EG & G Minilumat LB 9509, Bad Wildbad, Germany). Lucigenin probes (Final 0.2 mmol/L) were added to saliva samples containing phosphate buffered saline (pH 7.8) and results were expressed as area under the curve of relative light unit (rlu).
Statistical Analysis
Statistical analysis was performed using statistical software packages (IBM SPSS Statistics, version 22.0). The normality of distribution was determined by the Shapiro-Wilk test. Numbers and percentage values were shown for categorical variables, and differences between groups were analyzed. Quantitative data reported included median, mean rank, 25th percentile and 75th percentile values. The Mann-Whitney U test was applied to compare the median values between groups. The Spearman correlation test was used for the correlations between quantitative values. A value of p<0.05 was considered significant.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
In this case-control study evaluating the relationship between vitamin C and oxidative status in periodontitis, PAAL, vitamin C intake, serum and saliva TAS, TOS, OSI values, saliva superoxide radical levels and periodontal evaluation results of patients with periodontitis were compared to healthy individuals. The mean age of the control group was 39.08±9.99 (29-62) years, while the mean age of the periodontitis group was 42.52±7.66 years (31-55). There were 13 women (54%) and 11 men (46%) in the control group and 13 women (52%) and 12 men (48%) in the periodontitis group. There were no significant differences between the mean age and gender distribution of the participants in the two groups (p=0.06 and p=0.88, respectively).
Data on the periodontal parameters of individuals were evaluated. In the control group, the number of missing teeth, PI, GI, PPD, CAL and BP were lower than the periodontitis group (statistically significant for all parameters) (Table 1).
The vitamin C intake, PAAL, serum and saliva TAS, TOS, OSI levels and saliva superoxide radical levels of groups were compared. The dietary vitamin C intake was higher in the control group (p=0.003) and the superoxide radical level was higher in the periodontitis group (p=0.001). No statistically significant difference was found between the groups in other parameters (Table 2).
Weak/very weak correlations were found between vitamin C intake and oxidative status and periodontal parameters of participants with periodontitis, but none of these were significant. Significant negative correlations were found between vitamin C intake and superoxide radical level (r=-0.34; p=0.02) and most of the periodontal parameters when all participants were considered together (Table 3).
The Spearman correlation test was used to investigate the relationships between PAAL and parameters related to the oxidative status of individuals and periodontal parameters. In patients with periodontitis, there was a significant negative correlation between PAAL and serum TOS level (r=-0.42; p=0.03) and a negative and moderate correlation between superoxide radical level and PAAL (r=-0.53; p=0.01) (Table 3).
Discussion
Vitamin C affects oxidative stress, collagen synthesis, and the immune system, and is thought to play a role in the formation and development of periodontitis, which is characterized by oxidative stress, inflammation and periodontal tissue destruction. This study points to the fact that vitamin C intake is lower in individuals with periodontitis than in healthy individuals, and underscores the relationship between vitamin C and serum TOS and saliva superoxide radical levels in individuals with periodontitis.
Our study found dietary vitamin C intakes of the periodontitis group to be significantly lower than the control group; previous studies on this subject differ. Nishida et al. found a relationship between vitamin C intake level and periodontal diseases, while a different study found no relationship between vitamin B1 and vitamin C intake and risk of periodontitis despite finding a positive relationship between vitamin B2 and vitamin A intake and the risk of periodontitis [11, 12]. Our study showed that PAAL of individuals with periodontitis was lower than in healthy individuals (but not significant). Another recent study has shown that vitamin C, vitamin E and reduced GSH levels in plasma, erythrocyte and gingival tissues of individuals with periodontitis are significantly lower than in healthy individuals [13]. Munday et al.’s 2020 study showed that six of 20 people with periodontitis had vitamin C levels below the target range; Isola et al. showed that individuals with periodontitis had lower levels of saliva and serum vitamin C than in the control group [14, 15]. Kuzmanova et al. reported that plasma vitamin C levels significantly lower in individuals with periodontitis compared to controls (8.3 and 11.3 mg/L respectively; p<0.05). But there was no difference between the dietary vitamin C intake of the groups [16].
In periodontal disease, the measurement of antioxidant, oxidant
or reactive oxygen metabolites (ROM) levels in saliva is considered more accurate than in serum because many factors affect the systemic oxidative status [4]. To assess the oxidative status of participants in this study, TAS, TOS and OSI were measured in saliva and serum and superoxide radicals were measured in saliva. Baltacıoğlu and colleagues showed that serum and saliva TOS and OSI values of individuals with periodontitis were significantly higher and total antioxidant capacity lower than healthy individuals; they argued that OSI value could be used as a marker for periodontal diseases [17]. In other study, similarly, serum TAS values of individuals with periodontitis were found to be significantly lower than healthy individuals [18]. Some studies evaluating oxidative status in periodontitis measured ROM in serum or saliva. Our study measured the level of ROM in saliva samples by chemiluminescence. Our study found higher superoxide radical levels in the group with periodontitis than in the control group (p=0.001) and found significant correlations between PAAL and superoxide radical levels in individuals with periodontitis. Canakci et al. found that ROM production and activity in the saliva increased and antioxidant activity decreased during periodontal inflammation [19, 20]. Acquier et al. showed significantly higher ROM levels in the saliva of individuals with chronic and aggressive periodontitis than controls and a positive correlation between ROM level and some clinical indexes (CAL and PPD) [21]. In our study, the correlation between PAAL and superoxide radical levels supports the role of vitamin C in the formation mechanism of periodontitis.
A systematic review of the relationship between periodontal disease and vitamin C (2019) reported that low vitamin C intake or low blood ascorbic acid levels increased the severity of the disease and worsened its prognosis [22]. Amaliya et al. showed a negative correlation between plasma vitamin C levels and CAL and reported that vitamin C could affect the severity of periodontal destruction [23]. In a study of individuals aged 70 years and over, a negative relationship between serum vitamin C levels and CAL was shown [24]. In our study, weak/moderate, negative, and significant correlations were found between vitamin C intake and PI, GI, PPD, CAL, BP.
According to the findings of our study, vitamin C intake is lower in individuals with periodontitis than in healthy individuals, but there is no significant difference between the OSI, TAS, TOS values of the two groups. Despite this, the fact that dietary vitamin C intake is associated with many periodontal parameters suggests that this vitamin may also be effective against periodontitis due to functions (neutrophil extracellular trap formation, inflammation, collagen synthesis etc.) other than antioxidant activity [25].
Methodological limitations of this study included PAAL measurement. Since PAAL was affected more by short-term vitamin C intake than leukocyte ascorbic acid, ascorbic acid measurement was preferred in leukocytes rather than plasma. Also, if there had been more patients in the study, significance might have increased and/or different relationships might have been found.
Conclusion
In conclusion, this study found that individuals with periodontitis have a lower intake of vitamin C and found relationships between plasma vitamin C levels and oxidative status and some periodontal parameters. Well-designed, long-term, longitudinal studies are needed to evaluate the effectiveness of vitamin C supplements and/or dietary interventions to support periodontal treatment.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: This work was supported by Marmara University Research Fund (SAG-C-YLP-120417-0149) (https://bapko.marmara.edu.tr/).
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.21693
Elif Emiroğlu, Tülin Çakır, Meral Yüksel, Fatma Esra Güneş, Ali Çekici, Berna Karakoyun. The relationship between vitamin C and oxidative status in periodontitis: A case-control study. Ann Clin Anal Med 2023;14(7):630-634
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Coping with stress, psychological resilience and psychiatric symptoms in migraine patients
Burcu Sırlıer Emir 1, Sevler Yıldız 2, Aslı Kazgan Kılıçaslan 3, Serpil Doğan 4, Osman Kurt 5, Kerim Uğur 6
1 Department of Psychiatry, Clinic of Psychiatry, Elazığ Fethi Sekin City Hospital, Elazığ, 2 Department of Psychiatry, Clinic of Psychiatry, Binali Yıldırım University, Erzincan, 3 Department of Psychiatry, Clinic of Psychiatry, Bozok University, Yozgat, 4 Department of Neurology, Clinic of Neurology, Elazığ Fethi Sekin City Hospital, Elazığ, 5 Department of Public Health, Adıyaman Provincial Health Directorate, Adıyaman, 6 Department of Psychiatry, Clinic of Psychiatry, Malatya Turgut Özal University, Malatya, Türkiye
DOI: 10.4328/ACAM.21700 Received: 2023-03-23 Accepted: 2023-05-17 Published Online: 2023-05-30 Printed: 2023-07-01 Ann Clin Anal Med 2023;14(7):635-639
Corresponding Author: Burcu Sırlıer Emir, Department of Psychiatry, Clinic of Psychiatry, Elazığ Fethi Sekin City Hospital, 23100, Elazığ, Türkiye. E-mail: bsirlier@hotmail.com P: +90 424 606 60 00 F: +90 424 238 76 58 Corresponding Author ORCID ID: https://orcid.org/0000-0002-3389-5790
This study was approved by the Ethics Committee of Fırat University (Date: 2022-02-24, No: 2022/03-28)
Aim: Migraine is a prevalent chronic disease with unknown etiopathogenesis that affects the quality of life. In the present study, we aimed to investigate anxiety, depression, coping with stress and psychological resilience of migraine patients.
Material and Methods: The study was conducted with 40 patients and 40 healthy individuals. The study data were collected with a sociodemographic and clinical data form, Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Psychological Resilience Scale for Adults (RSA), and Inventory of Coping Strategies (ICS).
Results: It was determined that the RSA-structural resilience, RSA-social competence, BDI, BAI, ICS-optimism and ICS-social support scores of the patients were significantly higher when compared to the control group, RSA-self-perception, RSA-future perception, RSA-familial conformity, RSA-social resources, RSA-total and ICS-safe approach scores were significantly lower in the patient group when compared to the controls. There were positive correlations between the number of migraine attacks and RSA-future perception, RSA-familial conformity, RSA-social resources and RSA-total scores of the patients; There was a significant negative correlation between the number of migraine attacks and ICS-optimism scores.
Discussion: The incidence of anxiety and depression was significantly higher and psychological resilience was significantly lower in the patients when compared to the control group. It could be suggested that patients could prefer ineffective coping strategies and their psychological resilience could be low. The determination of the psychiatric complications associated with migraine could alter treatment interventions, and thus, the prognosis.
Keywords: Migraine; Depression, Anxiety, Resilience, Coping with Stress
Introduction
Migraine is a significant public health issue that could lead to functional and labor losses [1]. Although its etiology is not completely known, genetic and environmental factors are known to affect its incidence [2]. The increase has been associated with the frequency of anxiety disorders and depression. Anxiety and depression could be induced by severe and frequent migraine attacks, they could also trigger migraine; therefore, there is a bidirectional correlation between these factors [3].
Stress is the most significant trigger of migraine, and most individuals experience their first attack under stress, and most severe attacks were observed during stressful periods [4]. It has also been demonstrated that stress can lead to chronic migraine [3]. The assumption that migraine occurs not only due to stress, but also due to the lack of adaptation to stress, was proposed earlier, and recent studies have supported this assumption [5]. The perception of danger or threat could lead to a struggle to eliminate the danger, called coping with stress [6]. Studies have associated recurrent migraine attacks with maladaptive coping strategies [7].
Individuals sometimes surrender to stress, while sometimes they could struggle to overcome it. The coping strength of individuals who adapt quickly and easily to adversity is called psychological resilience [8]. Psychological resilience could play a key role in the prognosis of the disease, as well as its progression [9].
We considered that depression, anxiety, psychological resilience, and coping mechanisms are significant parameters in migraine, which affect the prognosis of the disease, quality of life and treatment. Thus, the present study aimed to investigate anxiety and depression, psychological resilience, coping levels and correlations between these factors in migraine patients.
Material and Methods
The study was approved by the Fırat University ethics committee (No: 2022/03-28). The study was conducted at Elazığ Fethi Sekin City Hospital Hospital, Neurology Clinic between March 2022 and September 2022. The study was conducted with 40 tension headache patients who presented to the Neurology outpatient clinic at Elazığ Fethi Sekin City Hospital and were diagnosed by a neurologist based on the International Headache Society (HIS, 2004) diagnostic criteria, and 40 healthy individuals who met the study criteria. The participants were interviewed by a psychiatrist for about 30 minutes with a structured interview form based on DSM-5, and those with psychiatric comorbidities to psychotic disorders were also included in the study. The study data were collected with a Sociodemographic data form, Beck Depression Inventory, Beck Anxiety Inventory, Psychological Resilience Scale for Adults, and Inventory of Coping Strategies.
Patients, who were 18-65 years old, diagnosed with migraine, without a known metabolic disease, physical pathology, or any other neurological disease, were included in the study.
Data Collection Instruments
Sociodemographic Data Form: It was developed by the authors based on the data requirements of the current study. It included demographic data such as age, marital status, education level, place of residence, employment, income level, and clinical evaluation questions such as anamnesis details, smoking or alcohol use.
Beck Depression Inventory (BDI): The validity and reliability of the study in Turkish were determined by Hisli [10] and the cut-off point was determined as 17.
Beck Anxiety Inventory (BAI): The validity and reliability of the study in Turkish were determined by Ulusoy et al. [11]
Psychological Resilience Scale for Adults (RSA): The scale was developed by Friborg et al. [12] and includes ‘self-perception’ and ‘future perception’, ‘structural resilience, social competence’, ‘familial adaptation,’ and ‘social resources’ dimensions. In the present study, the Chronbach alpha was determined as 0.86.
Inventory of Coping Strategies (ICS): It was developed by Folkman and Lazarus [13] in 1980. The scale includes 30 items and 5 sub-dimensions. The reliability of the scale was determined as high since the Cronbach Alpha coefficient was 0.70.
Data analysis
The study data were analyzed on SPSS version 22 software (Statistical Package for Social Sciences; SPSS Inc., Chicago, IL). In the study, descriptive categorical data are presented as counts and percentages, and continuous data are presented as means and standard deviations (Mean ± SD). Intra-group categorical data were compared with Chi-square analysis (Pearson Chi-square). The normal distribution of the continuous variables was determined with the Kolmogorov-Smirnov test. Paired group data were compared with the Mann-Whitney U-test. Spearman’s correlation test was employed to determine the correlation between continuous variables. The statistical significance was accepted as p<0.05.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
The study was conducted with 80 participants (40 patients and 40 controls). Eighty percent of the patient group were female and 20% were male, 77.5% of the control group were female and 22.5% were male. There was no significant difference between the gender of the groups (p=0.785). The mean age of the patients was 33.3±10.0 years and the mean age of the control group was 32.4±9.8 years, and there was no significant difference between the mean age of the groups (p=0.654). The employment rate (12.5%) was significantly lower in the patient group when compared to the control group (42.5%) (p=0.003). Migraine incidence in the family members of the patients (77.5%) was significantly higher when compared to the control group (17.5%) (p<0.001) (Table 1).
The RSA-structural resilience (p<0.001), A-social competence (p<0.001), BDI (p<0.001), BAI (p<0.001), ICS-optimism (p=0.001) and ICS-social support (p<0.001) scores of the patients were significantly higher when compared to the control group. RSA-self-perception (p=0.013), RSA-future perception (p<0.001), RSA-familial adaptation (p=0.005), RSA-social resources (p<0.001), RSA-total (p<0.001) in the patient group) and ICS-safe approach (p=0.002) scores of the patients were significantly lower compared to the control group (Table 2).
There were positive significant correlations between the number of migraine attacks and RSA-future perception, RSA-familial adaptation, RSA-social resources, and RSA-total scores of the migraine patients, while there was a negative significant correlation between the number of migraine attacks and the RSA-optimism score. A positive and significant correlation was determined between the time of diagnosis and RSA-despair score (Table 3).
Discussion
Although it was assumed that genetic and neurobiological factors were responsible for the correlation between migraine and depression, certain studies have focused on stress, a risk factor for both [14]. Depression and anxiety disorders are comorbid psychiatric diseases that are frequently observed in migraine patients, leading to a decrease in quality of life, resistance to treatment, and further drug use [3]. High anxiety and depression levels were identified in the present study, demonstrating the significance of the early diagnosis of psychiatric comorbidities in the prevention of the chronic disease [15]. Thus, further comprehensive pharmacological or non-pharmacological treatments of migraine and psychiatric comorbidities should be considered.
In our study, the incidence of migraine was significantly higher in the family members of the patients, suggesting familial transmission. In the literature, early onset disease and higher disability levels were reported in patients with a family history of migraine [16]. Also, the low employment rate reported in our study supported the loss of labor due to the disease.
Coping strategies balance stress and migraine. Günel et al. [7] reported that migraine patients sought less social support and were more optimistic about coping. The optimism observed among the migraine patients in the present study was consistent with that study; however, our patients sought more social support. We found that the self-confidence of the patients was low, suggesting that the acceptance of and coping with migraine pain was inadequate [17]. There is a negative correlation between self-confidence and perceived stress, and based on the present study findings, it could be suggested that perceived stress was high in migraine patients. We determined a positive and significant correlation between the time of diagnosis and ICS-despair scores. In a study conducted with multiple sclerosis patients, a chronic neurological disease, a positive correlation was reported between depression and anxiety in multiple sclerosis patients who adopted the despair approach [18].
Although several studies have been conducted on migraine, its etiopathology still remains unclear, and has been quite difficult to determine its triggers [19]. Recent studies have focused on psychological factors as well as physiological factors in migraine incidence and resistance. Perceived stress, a significant psychological factor, was associated with the incidence of migraine attacks [20]. Stress is a key risk factor not only for the attack incidence, but also the decrease in response to treatment and chronicity of episodic migraine [3,21]. It should be noted that daily life events rather than major events have been associated with decreased functionality [20]. This finding indicates the significance of perception not the event in migraine.
In the study, it was determined that RSA self-perception, RSA future perception, RSA familial adaptation, RSA social resources, and RSA total scores were lower in migraine patients when compared to the control group. Self-perception is the self-knowledge of individuals and associated with self-discipline and neurotic personality traits. It is expected that individuals with high self-discipline and low neuroticism would have high resilience due to their self-perception [22]. It demonstrates strong social relations, and it was suggested that seeking social support predicts psychological resilience in migraine [21]. Future perception refers to the views of the individual about the future, and familial adaptation refers to the support provided by family members, and the present study findings indicated negative views about the future and more maladaptive familial conditions among migraine patients [23].
Improving resilience could be a solution when interventions against stress are not possible. Where acceptance and commitment therapy (ACT) has been applied as a behavioral approach in migraine patients, it was reported that ACT improved psychological resilience, and the patients could cope with stress more easily [24]. In a study conducted by Martin et al. [25], behavioral interventions such as exposure, desensitization and learning to cope were employed, and learning to cope was found to be the most effective method.
Limitations
The limitations of the study included its cross-sectional nature and the employment of self-report scales. The strengths of the study were the inclusion of only migraine patients and exclusion of other diseases characterized by headaches, and the employment of multidimensional scales. It could be suggested that interventions that aim at coping with stress and psychological resilience, as emphasized in our study, could be beneficial.
Conclusion
In conclusion, patients suffered from high anxiety and depression levels, and exhibited low resilience. It could be suggested that patients employed ineffective coping strategies when coping with pain and their psychological resilience levels were low. Due to the prevalence of concomitant psychiatric disorders in migraine, early post-diagnostic psychiatric evaluation is important. We hope that since it could change the prognosis and treatment of comorbidities, future studies should be conducted with larger sample sizes to investigate the correlation between these factors, and the findings of the present study would shed light on future 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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Download attachments: 10.4328.ACAM.21700
Burcu Sırlıer Emir, Sevler Yıldız, Aslı Kazgan Kılıçaslan, Serpil Doğan, Osman Kurt, Kerim Uğur. Coping with stress, psychological resilience and psychiatric symptoms in migraine patients. Ann Clin Anal Med 2023;14(7):635-639
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The prognostic role of Gustave Roussy Immune Score (GRIm-Score) in metastatic lung adenocarcinoma patients treated with chemotherapy
Yasemin Söyler, Ayperi Öztürk
Department of Interventional Pulmonology, Ankara Ataturk Sanatorium Training and Research Hospital, Ankara, Turkey
DOI: 10.4328/ACAM.21701 Received: 2023-03-24 Accepted: 2023-05-17 Published Online: 2023-05-27 Printed: 2023-07-01 Ann Clin Anal Med 2023;14(7):640-645
Corresponding Author: Yasemin Söyler, Department of Interventional Pulmonology, Ankara Ataturk Sanatorium Training and Research Hospital, 06280, Keçiören, Ankara, Turkey. E-mail: dryaseminsoyler@gmail.com P: +90 535 843 07 36 F: +90 312 355 21 35 Corresponding Author ORCID ID: https://orcid.org/0000-0002-0507-0767
This study was approved by the Ethics Committee of Ankara Ataturk Sanatorium Research and Training Hospital (Date: 2023-02-22, No: 2012-KAEK-15/2657)
Aim: The Gustave Roussy Immune Score (GRIm-Score) in metastatic lung adenocarcinoma, based on the neutrophil-lymphocyte ratio, albumin and lactate dehydrogenase levels, divides patients into high and low-risk groups. In this study, we aimed to determine the prognostic role of GRIm-score in metastatic lung adenocarcinoma (LA) patients treated with chemotherapy.
Material and Methods: This was a retrospective, observational single-centre study. Patients who had metastatic LA (January 2018 – December 2018) were divided into two groups according to GRIm-score. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Cox regression analyses were performed to determine the risk factors independently associated with PFS and OS.
Results: Sixty patients [low-risk (n = 45), high-risk (n = 15)] were included in the study. The two groups had similar demographic characteristics and tumor features. In the low-risk and high-risk groups, the median PFS was 7.07 (95%CI: 5.79 – 8.34) and 4.53 (95%CI: 2.97 – 6.08) months (p = 0.009), respectively, and the median OS was 12.20 (95%CI: 8.70 – 15.69) and 7.70 (95%CI: 2.94 – 12.45) months (p = 0.03), respectively. The PFS and OS of the high-risk group were significantly worse than that of the low-risk group. Multivariate Cox regression analysis revealed that a high GRIM score was an independent risk factor for worse PFS (HR: 2.11; 95%CI: 1.13 – 3.95; p = 0.01) and OS (HR 1.87, 95% CI: 1.02 – 3.44, p = 0.04).
Discussion: GRIM score can be a guide in predicting the survival of metastatic LA patients treated with chemotherapy and can be used as a simple and easily accessible marker.
Keywords: Adenocarcinoma, Gustave-Roussy-Immune (GRIm)-Score, Lactate Hehydrogenase (LDH), Lung Cancer, Neutrophil-Lymphocyte Ratio (NLR)
Introduction
Non-small cell lung cancer (NSCLC) is one of the most frequent cancers and the leading cause of cancer-related deaths worldwide in recent years [1]. Lung adenocarcinoma is the most predominant subtype of NSCLC and its incidence is increasing. Most patients with lung adenocarcinoma are diagnosed in an advanced stage and the prognosis is poor [2]. Over the past decades, treatment options, including targeted therapy and immunotherapy, have ushered in a new era of anti-cancer treatment. Cytotoxic systemic chemotherapy also remains an important treatment for metastatic lung adenocarcinoma. Although major improvements have been made in lung cancer treatments, patient selection and assessment of the prognosis should be considered for more appropriate management strategies [3]. However, the identification of prognostic factors for poor outcomes among metastatic lung adenocarcinoma patients is still an important unmet need.
The Gustave Roussy Immune-score (GRIm-score) was first identified by Bigot et al in 2017 for better patient selection in phase I clinical trials for immunotherapies [4]. GRIM-score, based on the combination of neutrophil-to-lymphocyte ratio (NLR), serum albumin (Alb) and lactate dehydrogenase (LDH), all of which have been demonstrated to be potent prognostic markers reflecting host systemic immune-nutritional status, categorizes patients into different prognostic risk groups [5-7]. For NSCLC, several studies have reported that GRIm-score can be used as a prognostic marker for immunotherapy or surgery [5,7]. Moreover, the prognostic value of GRIm-Score also has been confirmed in various cancers [8,9]. However, as far as we know, little is known about whether the high GRIm-score is associated with poor outcomes in metastatic lung adenocarcinoma patients treated with chemotherapy. Therefore, the purpose of the current study was to evaluate the prognostic role of GRIm-score in metastatic lung adenocarcinoma patients treated with chemotherapy.
Material and Methods
Patients
We retrospectively investigated patients aged older than 18 years with metastatic lung adenocarcinoma who were treated with chemotherapy (± palliative radiotherapy if indicated) as first-line treatment according to the guidelines at our institution between January 2018 and December 2018 [10]. Patients were staged based on the 8th edition TNM staging system proposed by the International Association for the Study of Lung Cancer (IASLC) [11]. The exclusion criteria were: (1) a history of other malignant tumours; (2) recent clinical evidence of acute infection, inflammatory diseases, autoimmune diseases or trauma; (3) incomplete first-line anti-cancer therapy (due to death, low-performance status or self-refusal etc.) and (4) absence of clinical information (laboratory or radiological) or loss of follow-up (Figure 1).
Clinical characteristics included demographic data (age, sex, smoking comorbidity), tumor features (date of diagnosis, metastatic sites, number of metastatic sites, date of progression and death) and laboratory tests within 1 week of the initiation of anti-cancer treatment were recorded from our hospital’s electronic medical record system or patients’ files. GRIm-Score was calculated based on NLR, serum lactate dehydrogenase and serum albumin for each patient as follows: Patients were assigned 1 point if they had NLR > 6, LDH > upper limit normal (Our hospital’s upper limit of normal (ULN) LDH is 247 U/L) or albumin < 3.5 g/dL, for a total of 3 points. GRIm-Score 0-1 was considered low risk and 2-3 was considered high risk.
Primary survival outcomes were determined as progression-free survival (PFS) and overall survival (OS). PFS was considered as time (months) from the first treatment until radiological progression or death due to any cause /last follow-up (censored at last follow-up for patients alive and without progression), whichever occurred first [7]. OS was considered as the time (months) from the date of diagnosis of SCLC until the date of death from any cause or the last date of follow-up. Patients who were still alive and still did not show progression were censored at the final follow-up. The cut-off date for follow-up was March 1, 2023.
The study was approved by the ethics committee of Ankara Atatürk Sanatorium Training and Research Hospital Clinical Research Ethics Committee (Decision no:2012-KAEK-15/2657 Date:22.02.2023) and performed in accordance with the Good Clinical Practice guidelines and assent specific to our country. The Declaration of Helsinki and its subsequent revisions were followed. As this study was retrospective, an informed consent form was waived.
Statistical Analysis
Categorical data were expressed as a number of cases (%) and compared using the Chi-square test or Fisher exact test. The normality of the distribution of continuous variables was evaluated by the Kolmogorov-Smirnov test. Continuous data were given as mean ± standard deviation (SD) for normal distributions and were compared using Student’s t-test for two independent groups. Continuous data were presented as medians and interquartile ranges (IQR) for skewed distributions and were compared using the Mann–Whitney test for two independent groups. The median follow-up duration was calculated using the reverse Kaplan-Meier method. OS and PFS were estimated using the Kaplan-Meier method and compared using the log-rank test. Cox proportional hazard regression model analysis was performed to identify risk factors independently associated with OS and PFS, and presented with the hazard ratios (HRs) and 95% confidence interval (95% CI). All significant variables, which were identified using the univariate Cox regression analysis (p < 0.1), were included in the multivariate Cox regression analysis. A p-value of < 0.05 was considered statistically significant. IBM Corp. Released 2017. IBM SPSS Statistics for Windows, Version 25.0. Armonk, NY: IBM Corp. was used for statistical analyses.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
Patient Characteristics
Sixty (11 (18.3%) females, 49 (81.7%) males, mean age 62.4 ± 8.6]) patients with metastatic lung adenocarcinoma were enrolled on the study. Most of the patients (n = 51, 85%) had a history of smoking and approximately half of the entire study population (n = 29, 48.3%) had at least one comorbidity. Twenty-five (41.7%) patients had multiple metastatic sites (≥ 2 sides) and the most metastasis site was pleura/malign pleural effusion (n = 33, 55%), followed by bone (n = 21, 35%) and contralateral lungs (n = 15, 25%).
While 45 (75%) patients were in the low-risk group, 15 (25%) were in the high-risk group according to the GRIm-score. The demographic data (age, sex, smoking comorbidity) and tumour features (number and location of metastasis) were similar between the two groups. Regarding laboratory parameters, the high-risk group had significantly higher levels of neutrophil (6.2 (3.74) vs 5.2 (2.79), p = 0.02), LDH (274 (20.7) vs 207 (9.4), p = 0.001) and NLR (6.15 (0.68) vs 2.81 (0.24), p = 0.002) and lower levels of lymphocytes (1.44 ± 0.72 vs 1.92 ± 0.57, p = 0.01) and albumin (29.4 ± 0.43 vs 37.8 ± 0.48, p < 0.001) than those in the low-risk group. The remaining laboratory parameters (white blood cells, platelets, hemoglobin) were similar between the two groups (Table 1).
High GRIm-score was associated with worse PFS and OS
All patients, except one, progressed and died at the time of the last follow-up. The median PFS and OS of the entire population were 6.70 (95%CI: 5.86 – 7.53) and 10.03 (95%CI: 6.39 – 13.66) months, respectively. In the low-risk and high-risk groups, the median PFS was 7.07 (95%CI: 5.79 – 8.34) and 4.53 (95%CI: 2.97 – 6.08) months (p = 0.009), respectively (Figure 2a), and the median OS was 12.20 (95%CI: 8.70 – 15.69) and 7.70 (95%CI: 2.94 -12.45) months (p = 0.03), respectively (Figure 2b). The PFS and OS of the high-risk group were significantly worse than that of the low-risk group.
GRIm-score was an independent prognostic factor for PFS and OS
Univariate Cox regression analysis revealed that GRIm high-risk (HR: 2.25; 95%CI: 1.20 -4.19; p = 0.01) and presence of other metastases (HR: 0.53; 95%CI: 0.27 – 1.05; p = 0.007) were related to worse PFS. Multivariate Cox regression analysis indicated that only GRIm high risk (HR: 2.11; 95%CI: 1.13 -3.95; p = 0.01) was an independent risk factor for worse PFS (Table 2). Univariate Cox regression analysis also demonstrated that the presence of bone metastasis (HR: 1.64; 95%CI: 0.95 -2.83; p = 0.07) and GRIm high-risk (HR: 1.87; 95%CI: 1.02 – 3.42; p = 0.04) were associated with worse OS. GRIm high-risk (HR 1.87, 95% CI: 1.02- 3.44, p = 0.04) was only an independent prognostic factor for worse OS on multivariate Cox regression (Table 3).
Discussion
In the current study, we demonstrated the prognostic role of GRIm-score in metastatic lung adenocarcinoma. Our results revealed that GRIm-score independently predicts the prognosis and high GRIm-score is associated with poor outcomes in metastatic lung adenocarcinoma patients treated with chemotherapy.
Until today, it has been well established that biomarkers of systemic inflammation/nutritional status, including NLR, albumin and LDH, are associated with outcomes in NSCLC patients. Prior studies have concluded that systemic inflammatory response and nutritional status have a substantial impact on the occurrence, development, and metastasis of patients with lung cancer [12,13]. Gu et al. reported NLR to be potentially a useful biomarker to predict the poor prognosis for NSCLC, suggesting that NLR could reflect the imbalance of pro- and anti-tumour activity of the hosts in respect of inflammatory response [14]. Similarly, NLR has also been found to be a prognostic maker in NSCLC patients treated with immunotherapy or NSCLC patients receiving adjuvant chemotherapy [15,16]. Serum albumin has also been proven to be closely associated with the advance and prognosis of cancer. As one of the negative acute phase reactants, albumin levels can reflect the inflammatory status. It can also present nutritional status, which can indicate disease severity, disease progression and prognosis [17,18]. In systemic reviews, low serum albumin level has been identified as a significant indicator of poor prognosis in patients with NSCLC [19,20]. LDH plays an important role in tumour metabolism through the regulation of anaerobic glycolysis, which is closely related to tumour cell proliferation. This enzyme also promotes tumour survival by inhibiting apoptosis and preventing necrosis in an anoxic environment [21]. Most studies have demonstrated that higher pretreatment LDH level was associated with worse OS in NSCLC patients [22-24].
Considering that the GRIm-score is a novel nutritional and inflammatory-based prognostic score and consists of NLR, albumin and LDH, it may also be a useful marker. GRIm-score using these parameters was first established by Bigot et al in ICT phase I trials population. They found that patients with a high GRIm-score had an inferior OS than patients with a low GRIm-score [4]. This score has also been studied in various cancers. For instance, the high GRIm-score group showed worse OS and disease-free survival compared with those in the low GRIm-score group in colorectal cancer patients and esophageal squamous cell carcinoma patients [9,25]. Furthermore, Lenci et al. reported no association between GRImT1 (GRIm-score at 45 days since treatment initiation), GRIm∆ (GRIm-score difference between baseline and at 45 days since treatment initiation) and patient outcomes in advanced NSCLC patients treated with first-line chemotherapy, while a significant association was found in patients treated with pembrolizumab [7]. As far as we know, there was only one study that evaluated GRIm-score in lung adenocarcinoma patients treated with chemotherapy. This study conducted by Minami et al. demonstrated that the PFS and OS of low-score groups were significantly longer than those of high-score groups in wild-type EGFR adenocarcinoma [6]. Consistent with their results, the PFS and OS of the high-risk group were significantly worse than that of the low-risk group in our study. Furthermore, Minami et al. revealed that a high GRIm-score was an independent poor prognostic factor of OS of first-line cytotoxic chemotherapy [6]. Our study confirmed this result and also supported the usefulness of GRIm-score as a promising and useful pretreatment prognostic maker for this population.
Conclusion
The present study indicates that the GRIm score is an independent prognostic factor of poor outcomes for metastatic lung adenocarcinoma patients treated with chemotherapy. Additional prospective randomized clinical trials are required to comprehensively inquire into the prognostic role of the GRIm 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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2. Imai H, Kishikawa T, Minemura H, Yamada Y, Ibe T, Yamaguchi O, et al. Pretreatment Glasgow prognostic score predicts survival among patients with high PD-L1 expression administered first-line pembrolizumab monotherapy for non-small cell lung cancer. Cancer Med. 2021;10(20):6971-84.
3. Howlader N, Goncalo F, Mooradian M, Meza R, Kong CY, Cronin KA, et al. The effect of advances in lung-cancer treatment on population mortality. N Engl J med. 2022;383(7):640-9.
4. Bigot F, Castanon E, Baldini C, Hollebecque A, Carmona A, Postel-Viany S, et al. Prospective validation of a prognostic score for patients in immunotherapy phase I trials: The Gustave Roussy Immune Score (GRIm-Score). Eur J Cancer. 2017;84:212-8.
5. Li SJ, Zhao L, Wang HY, Zhou HN, Ju J, Du H, et al. Gustave Roussy Immune Score based on a three-category risk assessment scale serves as a novel and effective prognostic indicator for surgically resectable early-stage non-small-cell lung cancer: A propensity score matching retrospective cohort study. Int J Surg. 2020;84:25-40.
6. Minami S, Ihara S, Komuta K. Gustave Roussy Immune Score is a prognostic factor for chemotherapy-naive pulmonary adenocarcinoma with wild-type epidermal growth factor receptor. World J Oncol. 2019;10(1):55-61.
7. Lenci E, Cantini L, Pecci F, Cognigni V, Agostinellii V, Mentrasti G, et al. The Gustave Roussy Immune (Grim)-score variation is an early-on-treatment biomarker of outcome in advanced non-small cell lung cancer (NSCLC) patients treated with first-line pembrolizumab. J Clin Med. 2021;10(5):1005.
8. Minami S, Ihara S, Ikuta S, Komuta K. Gustave Roussy Immune Score and Royal Marsden Hospital Prognostic Score Are Biomarkers of Immune- Checkpoint Inhibitor for Non-Small Cell Lung Cancer. World J Oncol. 2019;10(2):90-100.
9. Feng JF, Wang L, Yang X, Chen S. Gustave Roussy Immune score (GRIm-Score) is a prognostic marker in patients with resectable esophageal squamous cell carcinoma. J Cancer. 2020;11(6):1334-40.
10. Ettinger DS, Wood DE, Aisner DL, Akerley W, Bauman JR, Bharat A, et al. Non-Small Cell Lung Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2022;20(5):497-530.
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12. Sánchez-Lara K, Turcott JG, Juárez E, Guevara P, Núñez-Valencia C, Oñate-Ocaña LF, et al. Association of nutrition parameters including bioelectrical impedance and systemic inflammatory response with quality of life and prognosis in patients with advanced non-small-cell lung cancer: a prospective study. Nutr Cancer. 2012;64(4):526-34.
13. Mitsuyoshi T, Matsuo Y, Itou H, Shintani T, Iizuka Y, Kim YH, et al. Evaluation of a prognostic scoring system based on the systemic inflammatory and nutritional status of patients with locally advanced non-small-cell lung cancer treated with chemoradiotherapy. J Radiat Res. 2018;59(1):50-7.
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Yasemin Söyler, Ayperi Öztürk. The prognostic role of gustave roussy immune (GRIm)-score in metastatic lung adenocarcinoma patients treated with chemotherapy. Ann Clin Anal Med 2023;14(7):640-645
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The effect of coronary artery bypass graft operations on serum asprosin values
Hüseyin Kafadar 1, Cengiz Güven 2
1 Department of Forensic Medicine, Faculty of Medicine, Harran University, Sanliurfa, 2 Department of Cardiovascular Surgery, Faculty of Medicine, Adiyaman University, Adıyaman, Turkey
DOI: 10.4328/ACAM.21708 Received: 2023-03-30 Accepted: 2023-05-17 Published Online: 2023-05-28 Printed: 2023-07-01 Ann Clin Anal Med 2023;14(7):646-650
Corresponding Author: Hüseyin Kafadar, Department of Forensic Medicine, Faculty of Medicine, Harran University, Sanliurfa, Turkey. E-mail: dr.hkafadar@gmail.com P: +90 506 909 11 66 Corresponding Author ORCID ID: https://orcid.org/0000-0002-6844-7517
This study was approved by the Non-Invasive Clinical Research Ethics Committee of Adıyaman University, Faculty of Medicine (Date: 2019-03-20, No: 2019/2-4)
Aim: The main purpose of this study was to investigate the effects of coronary artery bypass graft operations (CABGO) on serum asprosin levels.
Material and Methods: Twenty-five patients who underwent CABGO with the diagnosis of coronary artery disease (CAD) were included in the study. The patients were divided into three groups according to the study time: preoperative (preop), postoperative day 1 (postop1), and postoperative day 7 (postop7). The effects of the operation on asprosin levels were discussed in light of the literature data by evaluating fasting plasma asprosin levels for at least 8 hours in all three groups.
Results: There were 13 men and 12 women in the study group with a mean age of 64.4±9.9 years. It was found that the asprosin levels that were measured in the postop1 and postop7 groups were significantly higher than in the preop group (P<0.001). When the factors that affected the asprosin hormone levels at different times were examined, it was found that only the gender factor was significant (P=0.013). Although a significant increase was observed in postop7 and postop1 when compared to the preop value in both genders, a decrease was detected in postop7 when compared to postop1; and although this decrease was statistically significant in women (P=0.010), it was not significant in men (P=0650).
Discussion: In CABGO patients, increased serum asprosin levels are detected in the early postoperative period. This increase was more significant in women, which may be because of the protective effects of asprosin, which also has antioxidant features.
Keywords: Asprosin, Coronary Artery Disease, Coronary Artery Bypass, Graft
Introduction
A new glycogenic adipokine was identified in 2016 by Romero et al. This hormone, which is encoded by two exons of the Fibrillin 1 gene, is secreted by White Adipose Tissue and regulates hepatic glucose secretion during fasting [1].
This hormone also stimulates the hypothalamic nutrition center, and causes appetite stimulation and fat storage [2]. The Fibrillin 1 gene, which is the source of asprosin, was isolated in various organs e.g. the heart, lung, and kidney. Studies also showed that pancreatic β cells can secrete asprosin under hyperlipidemic conditions [1,3].
Asprosin shows a functional contrast to insulin. Although low glucose levels increase its production, it is inhibited in the nutritional state. It was reported that the injection of recombinant asprosin caused a sudden glucose peak and hyperinsulinemia in experimental studies. Some clinical and experimental studies also showed that it is cardioprotective, and provides significant improvements in left ventricular ejection fraction contributing to wound healing [4,5].
This hormone that has a long history was accepted as a potential biomarker for abnormal glycolipid metabolic disorders e.g. obesity and Type 2 Diabetes. However, serum asprosin levels were not investigated in patients who were operated on for CAD. The purpose of the study was to investigate the effects of the operation on the asprosin levels in patients who undergo CABGO.
Material and Methods
This study was approved by Adıyaman University, Faculty of Medicine, Non-Invasive Clinical Research Ethics Committee (Decision Date: 20/03/2019; Decision Number: 2019/2-4).
The study was designed as a prospective self-match study. Written consent forms were obtained from all participants, and a total of 25 patients were included in the study between February 2019 and June 2019. Patients with a Body Mass Index (BMI) ≥30, diabetic, hyperlipidemic, liver failure, pancreatic acute-chronic disease, and acute infections were excluded from the study. Those who died in the first week were not included in the study. The patients were divided into three groups according to the study time as preoperative (preop), postoperative day 1 (postop1), and postoperative day 7 (postop7). At least 8 hours of fasting venous blood samples were taken from all three groups, and were centrifuged for 10 minutes at 1200gX3000rpm, then were separated and stored at -80°C until the analysis day. After the samples were taken from 25 patients at three different times (preop, postop1 and postop7), asprosin values were evaluated with the Homo Sapiens Asprosin Elisa Kit -SEA332Hu (26603 W. Fernhurst Dr., Unit 2201, Katy. TX77494, USA). The effects of Coronary Artery Bypass Graft Operation on FPA values were investigated by comparing the preop, postop day 1, postop day 7 and fasting daily plasma asprosin (FPA) values of the patients. Also, the relationship between asprosin and gender were evaluated by comparing the FPA values in each group and between the groups according to gender. Effects of age, BMI, Total Cholesterol (TC), Total Glyceride (TG), High-Density Lipoprotein-cholesterol (HDL), Low-Density Lipoprotein-cholesterol (LDL), and the number of bypassed vessels (CABGOx) on the FPA value were also investigated.
Statistical analyses
Mean±standard deviation was given as a descriptive value for quantitative variables and the number of patients (percentages) for qualitative variables. The distribution of the variables was checked with the Kolmogorov-Smirnov Test. The relations between the variables were evaluated with Pearson’s Correlation Analysis. The Wilcoxon Test was used for repeated measurement analyses, and the Independent Simple T-Test was used for independent variables. The factors affecting the changes in Asprosin hormone were analyzed by using the Univariate Linear Regression Analysis. The IBM SPSS Statistics 22 was used for statistical analysis, and the statistical significance level was taken as 0.05.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
A total of 25 patients (12 female, 13 male) were included in the study. The mean age was 64.4±9.9 years. The preparative demographic data of the patients are shown in Table 1.
Firstly, data were evaluated without considering gender and other independent variables to detect the effects of the operation on the FPA levels. The FPA value (12.27±3.48) that was measured for postop1 was found to be significantly higher than the preoperative FPA value (8.12±2.80) (P<0.001). The FPA value that was measured at postoperative 7 (11.50±2.92) was significantly higher than the preoperative FPA value (p=0.002). However, although the FPA value at postop7 (11.50±2.92) was lower than the postop1 value (12.27±3.48), which was not statistically significant (p=0.112) (Table 2).
The relationship between variables and preoperative FPA level was examined by Pearson’s Correlation Analysis. A positive correlation was detected between gender, BMI, TC, TG, and CABGOx. This relation was particularly strong for gender and CABGOX [r(23)=0.731, P<0.001, r(23)=0.825, P<0.001, respectively].
Multivariate Linear Regression Analysis was made to examine the effects of the preoperative dependent variable on the independent variables of gender, BMI, TC, TG, and CABGOx. As a result of the analysis, the significant regression model, F(5.19)= 24.19, P<0.001, and 86% of the variance in the dependent variable (R2adjusted=0.864) were confirmed with the independent variables. Preoperative FPA value for gender (ß= 0.403, t(19)=2.24, P=0.037, pr2=0.25), BMI (ß= 0.354, t(19)=2.09, P=0.05, pr2=0.187), and CABGOx (ß= 0.389, t(19)=2.34, P=0.031, pr2=0.223) were found. In this respect, a positive correlation was detected. However, the relationship between preoperative FPA and TC (β= -0.17, t(19)=-0.153 P=0.88, pr2=0.001), and TG (β= 0.122, t(19)=0.078, P=0.447, pr2=0.031) was not significant (Table 3).
The scatter plot of the Multiple Regression Analysis between the variables with preoperative FPA is summarized in Figure 1.
Risk factors that affected changes in Asprosin hormone with respect to time were examined with the Univariate Linear Regression Analysis, and only the gender variable was found to be significant. In this context, the fact that the gender was female instead of male increased the change in the FPA hormone by 1.857 units. Also, it has been observed that gender alone explained 23.9% of the change in the FPA hormone.
According to gender, the preop and postop 1st-day FPA values were higher in women on day 2 (P<0.001), and the difference between the genders was not significant on the postoperative day 7 (P=0.051). According to gender, there was a statistically significant increase in postop1 and postop7 in women when compared to pre-op values, and a significant decrease in postop7 compared to postop1 (P=0.002, P=0.002, P=0.010, respectively). Among the groups, postop1 and postop7 were significantly higher in males than preop values (P<0.001). Although there were decreases in postop7 in men when compared to postop1, and this was not statistically significant (P=0.650) (Table 2). The distribution of repeated measurements of the FPA hormone according to gender is summarized in Figure 2.
Discussion
To the best of our knowledge, our study is the first one in the literature to examine FPA levels in patients with operated Coronary Artery Disease. In our study, it was observed that the FPA levels increased in the early postoperative first week in patients with CABGO and the diagnosis of CAD. It was shown in our study that FPA values were increased in the early postoperative period compared to the preoperative period in patients with CABGO, regardless of the variables. This increase was especially significant on the first postoperative day. It was also observed that there were significant increases on postoperative day 7 compared to the preoperative period. However, it was also observed that there was a slight decrease in postop7 compared to postop1 in the entire patient population. Although this decrease was significant in females, it was not at statistically significant levels in males. Another important finding of our study was that preoperative FPA values had a positive relation with the number of diseased arteries in CAD. A similar relation was also detected between BMI and female gender, which is consistent with the literature data. A positive and linear relation was detected between the female gender and BMI and FPA.
Asprosin is a peptide glycogenic hormone, which stimulates glucose release from the liver by affecting OLFR734 receptors. This effect is limited to hepatic glucose production, independent of insulin levels. In normal healthy individuals, the normal FPA level in women was between 4.02 ± 0.49 nmol/L, and 5.94 ± 3.04 nmol/L in men [6].
The levels decrease in the presence of high insulin and glucose levels (in the case of satiety). In the first years after its discovery, it was shown in previous studies that the target organ was the liver. However, in studies conducted later, the asprosin receptor (OLFR734) was expressed outside the liver, in kidney cells, adipose tissues, olfactory nerves, testicular cells, and muscle tissues [7].
Asprosin levels have a circadian rhythm. Studies conducted on humans and experimental animals have shown that although its levels increase at night (in case of fasting), they decrease after a meal. It has been shown to increase appetite by crossing the blood-brain barrier in rodents [4,8].
Although its levels increase in obesity, insulin resistance, Type-1 and Type-2 diabetic patients, anorexia nervosa, gestational diabetes, and preeclampsia, its levels have been shown to decrease in neonatal progeroid syndrome, anorectic oncological patients, acromegaly, and streptozocin-induced diabetic mice [4].
A clinical study (in addition to animal experiments) that reported direct relations between serum asprosin and coronary artery stenosis in people with acute coronary syndrome with unstable angina pectoris showed that there was a significant and positive relation in this respect, and asprosin may be the first biochemical marker to predict severity [9,10].
In our study, it was shown that there is a positive and linear relationship between preoperative asprosin levels and female gender, BMI, TC, and TG. In other words, CADs that have high TC, TG, BMI, and female gender showed high preoperative asprosin levels. These results were in agreement with the literature data. Also, the number of bypassed coronary arteries was associated with higher preoperative asprosin levels.
A systemic inflammatory response occurs in cardiac surgeries that are carried out with extracorporeal circulation. Ischemia-reperfusion injury, contact of blood with non-endothelial circuits, cellular traumas because of surgical manipulations, oxidative stress, activation of the complement, and coagulation cascade are the causes of this inflammatory response. All these results might end up in cellular, and then, organ damage [11]. It was found in the literature review that the cardioprotective effect of asprosin was demonstrated in a study that investigated the effects of mesenchymal stromal cells previously treated with asprosin on the myocardium. It has also been shown to act by preventing H2O2-mediated apoptosis [12].
It was observed in the present study that the FPA levels increased in the first week in patients who underwent CABGO compared to the preoperative period, which was more significant on the first postoperative day. This is likely to be associated with the cardiac protective effects of asprosin, which has anti-inflammatory features. However, further studies are required to support this hypothesis. This increase in asprosin was higher in women than in men, which seems difficult to explain with the findings of our study. New studies that will be supported by a larger patient population and experimental studies will better shed light on the many mysteries of asprosin.
Study limitations
The main limitations of this study are the small number of patients, the use of single hospital data in the study. The limited number of studies in the literature on the cardioprotective effects of asprosin can be counted among the limitations of the study.
Conclusion
As a conclusion, an increase was detected in FPA values in the first week in operated CAD. Although this increase showed a decrease in the measurements after one week, it was still higher than the preoperative period. Based on the data obtained from the literature review we believe that this increase can be associated with the antioxidant cardioprotective effects of FPA. However, more extensive and experimental studies are needed to prove this.
The present study had several limitations. The first was the low patient population. The second was that only 3 measurements were made in the patients. We believe that controlled and experimental studies may provide more precise results to examine the protective effects of PFA against the negative cardiac effects of extracorporeal circulation with daily serial measurements.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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2. Duerrschmid C, He Y, Wang C, Li C, Bournat JC, Romere C, et al. Asprosin is a centrally acting orexigenic hormone. Nat Med. 2017;23(12):1444-53. DOI: 10.1038/nm.4432.
3. Li E, Shan H, Chen L, Long A, Zhang Y, Liu Y, et al. OLFR734 Mediates Glucose Metabolism as a Receptor of Asprosin. Cell Metab. 2019;30(2):319-28. DOI: 10.1016/j.cmet.2019.05.022.
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5. Donma MM, Donma O. Asprosin: Possible target in connection with ghrelin and cytokine network expression in the post-burn treatment. Med Hypotheses. 2018;118:163-8. DOI: 10.1016/j.mehy.2018.07.008.
6. Wiecek M, Szymura J, Maciejczyk M, Kantorowicz M, Szygula Z. Acute anaerobic exercise affects the secretion of asprosin, irisin, and other cytokines – a comparison between sexes. Front Physiol. 2018;9:1782. DOI: 10.3389/fphys.2018.01782.
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Download attachments: 10.4328.ACAM.21708
Hüseyin Kafadar, Cengiz Güven. The effect of coronary artery bypass graft operations on serum asprosin values. Ann Clin Anal Med 2023;14(7):646-650
Citations in Google Scholar: Google Scholar
Evaluation of maternal serum galectin-9 levels in pregnancies with the threat of preterm birth
Savaş Özdemir 1, Fatih Şahin 1, Gül Özel Doğan 2, Özlem Baytekin 3
1 Department of Obstetrics and Gynecology, Prof. Dr. Cemil Taşçıoğlu City Hospital, 2 Department of Obstetrics and Gynecology, Şişli Hamidiye Etfal Hospital, 3 Department of Biochemistry, Şişli Hamidiye Etfal Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.21720 Received: 2023-04-09 Accepted: 2023-05-17 Published Online: 2023-06-07 Printed: 2023-07-01 Ann Clin Anal Med 2023;14(7):651-654
Corresponding Author: Fatih Şahin, Department of Obstetrics and Gynecology, Prof. Dr. Cemil Taşçıoğlu City Hospital, Sisli, Istanbul, Turkey. E-mail: fatih_sahin67@hotmail.com P: +90 544 743 01 67 Corresponding Author ORCID ID: https://orcid.org/0000-0002-1621-5896
This study was approved by the Ethics Committee of Istanbul Health Sciences University, Şişli Hamidiye Etfal Training and Research Hospital (Date: 2021-10-11, No: 354)
Aim: Galectins expressed in various locations in the maternal-fetal interface play a role primarily in immunomodulation, embryo implantation, trophoblast invasion, and angiogenesis, which are early pregnancy events. Therefore, they are responsible for the physiological and healthy course of pregnancy. We aimed to evaluate the usability of the Galectin-9 (Gal-9) marker in predicting the risk of preterm birth.
Material and Methods: This prospective study included 40 singleton pregnancies (20-37 weeks) with threatened preterm labor and 40 healthy pregnancies without obstetric complications. The maternal Galectin-9 levels in serum were measured.
Results: No statistically significant difference was found in terms of maternal Galectin-9 levels between the preterm labor and control groups (p=0.758). In pregnancies with threatened preterm labor, white blood cell (WBC) levels were found to be statistically lower than in the control group (p=0.046). There was a significant positive correlation between systolic blood pressure level and WBC level (p=0.015). A statistically significant negative correlation was found between the WBC level and the Galectin-9 level (p=0.007).
Discussion: There is no relationship between maternal Galectin-9 level and threatened preterm labor in complicated pregnancies.
Keywords: Galectin-9, Preterm Labor, Immune Modulation
Introduction
Preterm birth remains an unresolved health problem, accounting for about 10% of live births worldwide. Due to vulnerable body surfaces, immature immunity, and a variety of injurious exposures, preterm infants are predisposed to sepsis particularly in the first 4 weeks of life. This is a continuous challenge to clinicians who are involved in the care of preterm infants, since sepsis and persistent inflammation are considered crucial mediators for mortality and the development of long-term morbidities [1]. Therefore, there is an urgent need to identify risk factors and biomarkers aiming at the prevention and early treatment of sepsis.
Galectins are a family of beta-galactoside-binding proteins that are non-classically secreted and have recently received considerable attention in the spatio-temporal regulation of surface ‘signal lattice’ organization, membrane dynamics, cell-adhesion and disease therapeutics. Galectin-9 is a unique member of this family, with two non-homologous carbohydrate recognition domains connected by a linker peptide sequence of variable lengths, resulting in the generation of isoforms with distinct properties and functions in both physiological and pathological settings, such as during development, immune reactions, neoplastic transformations and metastasis [2]. Galectins, a protein group commonly found in mammals, regulate various fundamental biological processes [3]. Until today, 13 subtypes have been identified in humans [4]. The biological functions vary among subtypes depending on the presence of a suitable ligand and even local concentrations, thus creating functional diversity [5]. Galectins expressed in various locations in the materno-fetal region are mainly involved in early pregnancy events such as immune modulation, embryonic implantation, trophoblast invasion, and angiogenesis [6]. Therefore, they are responsible for the physiological and healthy course of pregnancy. Due to their immunomodulatory functions, galectins act as a shield preventing the rejection of the semi-allogeneic fetus, and as a result, they also contribute to the continuation of pregnancy by preventing its termination. Although galectin interactions during gestation are well characterized, potential outcomes of these interactions in the context of preterm birth are poorly defined.
In this study, we aimed to evaluate the usability of the Galectin-9 biomarker in predicting the risk of preterm labor.
Material and Methods
The study was carried out with the permission of ‘Istanbul Health Sciences University Şişli Hamidiye Etfal Training and Research Hospital’ Clinical Research Ethics Committee (Date: 11.10.2021, Decision No: 354). All procedures were carried out in accordance with the ethical rules and the principles of the Declaration of Helsinki.
This prospective study included pregnant women between the ages of 18-40 years who were admitted with indications of preterm labor between November 1, 2021 and May 1, 2022 at the Istanbul Health Sciences University Şişli Hamidiye Etfal Training and Research Hospital Obstetrics and Gynecology Clinic. The study also included a control group of healthy pregnant women who presented for routine clinic visits and had no uterine contractions. Pregnant women with membrane rupture, hypertension, multiple pregnancies, diabetes, thyroid diseases, chronic diseases, body mass index over 30 kg/m2, preeclampsia, intrauterine growth retardation, or fetal anomalies were not included in the study. Preterm labor is defined as regular uterine contractions accompanied by cervical dilation (>3 cm) or cervical length of less than 20 mm between 20 weeks and 36 weeks 6 days of gestation, based on the last menstrual period and ultrasound findings. Pregnant women diagnosed with preterm labor were admitted to the hospital. IV fluid therapy was administered, and routine laboratory tests, including complete blood count, biochemistry, urinalysis, coagulometer, urine culture, cervical culture, and vaginal culture tests were performed. Women with a gestational age of 34 weeks or less were given tocolytic and corticosteroid therapy. Informed written consent was obtained from pregnant women admitted with preterm labor for whom we collected blood samples to investigate the Galectin-9 biomarker, in addition to routine tests. Each patient provided a onetime 10 mL sample of the whole blood collected into a K2EDTA tube for further testing. Each sample was centrifuged for 10 min at 2500 rpm and the collected serum was stored at −80 °C until analysis. The serum concentration of galectin-9 was assayed in duplicate using an enzyme-linked immunoassay (ELISA) kit according to the manufacturer’s protocol. All patient records were recorded on case report forms.
Statistical Analysis
A power analysis was performed in advance using G*Power version 3.1.9.7 to determine the minimum sample size required to test the study hypothesis [7]. Results indicated that the required sample size to achieve 80% power for detecting a medium effect, at a significance criterion of α = .05, was N = 80 for [One way ANOVA]. SPSS 15.0 for Windows program was used for statistical analysis. Descriptive statistics were presented as numbers and percentages for categorical variables and as mean, standard deviation, minimum, maximum, and median for numerical variables. Ratios in independent groups were compared with the Chi-square test. Comparisons of numerical variables in independent two groups were performed with the Student t-test when the normal distribution condition was met, and with the Mann-Whitney U test when the condition was not met. Relationships between numerical variables were examined using Spearman’s Correlation Analysis as the parametric test condition was not met. The statistical alpha significance level was accepted as p<0.05.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
The mean parity of patients with non-stress test (NST +) who are at risk of preterm birth was found statistically lower compared to the control group (NST -) (p=0.046). Cervical length (CX) was found significantly lower in pregnant women at risk of preterm birth (p<0.001). The mean white blood cell (WBC) count in NST + pregnant women was found statistically lower compared to the control group (NST -) (p=0.046). Fever was statistically higher in pregnant women at risk of preterm birth compared to the control group (p=0.042). Diastolic blood pressure was found significantly higher in NST + pregnant women (p=0.005). The mean hemoglobin (HB) levels in NST + pregnant women were found statistically higher compared to the control group (p=0.049).
There was no statistically significant difference between the mean Galectin-9 levels of the preterm birth at risk and control groups (p=0.758). The findings are summarized in Table 1.
Culture results, antibiotic, tocolytic, and corticosteroid usage in patients at risk of preterm birth with a positive non-stress test (NST +) are summarized in Table 2.
A significant positive correlation was found between Galectin-9 levels and systolic blood pressure (p=0.015). A significant negative correlation was found between white blood cell (WBC) levels and Galectin-9 (p=0.007). The findings are summarized in Table 3.
Discussion
The aim of this study was to investigate the maternal serum levels of galectin-9 in pregnancies at risk of preterm birth. There are studies in the literature on galectin and adverse pregnancy outcomes; in a study conducted, Galectin-1 (Gal-1) levels were found to be low in pregnant women with preterm prelabor rupture of membranes (pPROM), but no significant relationship was observed with maternal serum levels of Galectin-9 [8].
Until now, little has been known about Galectin-9 (Gal-9), and there are limited data on its full function and properties. Galectin-9 is expressed not only by the endometrium, but also by trophoblasts, stromal cells in the decidua, endothelial cells of the placenta, and several types of immune cells [9,10]. Similar to Gal-1, in a murine model, Gal-9 participates in processes that are involved in the local anti-inflammatory environment, enabling implantation and early fetal development [11]. Additionally, Gal-9 is responsible for the suppression of uterine natural killer (NK) cells via secretion in endometrial stromal cells [9]. However, although a similar role for Gal-9 has been proposed in human pregnancy, the available data are based only on a mouse model [8]. As pregnancy progresses, the expression and concentration of Gal-9 in the mother’s blood increase, making it another galectin that is likely to be very important in maintaining pregnancy [12]. Regarding the available data on pregnancy complications, several studies have found an association between low Gal-9 expression and spontaneous miscarriages [9]. Similarly, there are studies linking low Gal-9 and recurrent pregnancy loss [13]. It has been suggested that the abnormal Tim-3/Gal-9 pathway, due to the immunomodulatory effect of Gal-9, may contribute to preeclampsia [14]. Interestingly, some studies have shown that serum levels of Gal-9 are higher in women carrying a male fetus compared to a female fetus [15]. In our study, there was no significant difference in Gal-9 levels between pregnant women at risk of premature birth and the control group.
The limitations of this study include a small number of participants and being conducted at a single center. Additionally, examination of the placenta and fetal membranes may provide value for future studies. However, to investigate Gal-9 levels as potential, promising clinical markers for the prediction of preterm labor, further clinical studies on larger groups are required.
Conclusion
There is no relationship between maternal galectin-9 levels and preterm labor risk in pregnant women.
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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3. Bao B, Kellman BP, Chiang AWT, Zhang Y, Sorrentino JT, York AK, et al. Correcting for sparsity and interdependence in glycomics by accounting for glycan biosynthesis. Nat Commun. 2021; 12(1): 4988.
4. Fuselier C, Dumoulin A, Paré A, Nehmé R, Ajarrag S, Granger Joly de Boissel P, et al. Placental Galectins in Cancer: Why We Should Pay More Attention. Cells. 2023; 12(3): 437.
5. Mariño KV, Cagnoni AJ, Croci DO, Rabinovich GA. Targeting galectin-driven regulatory circuits in cancer and fibrosis. Nat Rev Drug Discov. 2023; 22(4): 295-316.
6. Hu G, Wu J, Gu H, Deng X, Xu W, Feng S, et al. Galectin-3-centered paracrine network mediates cardiac inflammation and fibrosis upon β-adrenergic insult. Sci China Life Sci. 2022; DOI:10.1007/s11427-022-2189-x
7. Faul F, Erdfelder E, Lang AG, Buchner A. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007; 39(2): 175-91.
8. Boroń DG, Świetlicki A, Potograbski M, Kurzawińska G, Wirstlein P, Boroń D, et al. Galectin-1 and Galectin-9 Concentration in Maternal Serum: Implications in Pregnancies Complicated with Preterm Prelabor Rupture of Membranes. J Clin Med. 2022; 11(21): 6330.
9. Heusschen R, Freitag N, Tirado-González I, Barrientos G, Moschansky P, Muñoz-Fernández R, et al. Profiling Lgals9 splice variant expression at the fetal-maternal interface: implications in normal and pathological human pregnancy. Biol Reprod. 2013; 25; 88(1): 22.
10. Li Y, Feng J, Geng S, Geng S, Wei H, Chen G, et al. The N- and C-terminal carbohydrate recognition domains of galectin-9 contribute differently to its multiple functions in innate immunity and adaptive immunity. Mol Immunol. 2011; 48(4): 670-7.
11. Nikzad H, Haddad Kashani H, Kabir-Salmani M, Akimoto Y, Iwashita M. Expression of galectin-8 on human endometrium: Molecular and cellular aspects. Iran J Reprod Med. 2013; 11(1): 65-70.
12. Meggyes M, Miko E, Polgar B, Bogar B, Farkas B, Illes Z, et al. Peripheral blood TIM-3 positive NK and CD8+ T cells throughout pregnancy: TIM-3/galectin-9 interaction and its possible role during pregnancy. PLoS One. 2014; 20; 9(3): e92371.
13. Wyatt MA, Baumgarten SC, Weaver AL, Van Oort CC, Fedyshyn B, Ruano R, et al. Evaluating Markers of Immune Tolerance and Angiogenesis in Maternal Blood for an Association with Risk of Pregnancy Loss. J Clin Med. 2021; 10(16): 3579.
14. Hao H, He M, Li J, Zhou Y, Dang J, Li F, et al. Upregulation of the Tim-3/Gal-9 pathway and correlation with the development of preeclampsia. Eur J Obstet Gynecol Reprod Biol. 2015; 194: 85-91.
15. Enninga EAL, Harrington SM, Creedon DJ, Ruano R, Markovic SN, Dong H, et al. Immune checkpoint molecules soluble program death ligand 1 and galectin-9 are increased in pregnancy. Am J Reprod Immunol. 2018; 79(2): 12795.
Download attachments: 10.4328.ACAM.21720
Savaş Özdemir, Fatih Şahin, Gül Özel Doğan, Özlem Baytekin. Evaluation of maternal serum galectin-9 levels in pregnancies with the threat of preterm birth. Ann Clin Anal Med 2023;14(7):651-654
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Relationship between respiratory problems and vitamin D levels in very low birth weight infants
Handan Hakyemez Toptan, Nilgun Karadag, Sevilay Topcuoglu, Emre Dincer, Abdulhamit Tuten, Selahattin Akar, Tulin Gokmen Yildirim, Elif Ozalkaya, Guner Karatekin, Fahri Ovali
Department of Neonatology, University of Health Sciences, Zeynep Kamil Maternity and Children’s Disease Health Training and Research Center, Istanbul, Turkey
DOI: 10.4328/ACAM.21727 Received: 2023-04-14 Accepted: 2023-05-17 Published Online: 2023-05-30 Printed: 2023-07-01 Ann Clin Anal Med 2023;14(7):655-659
Corresponding Author: Handan Hakyemez Toptan, Department of Neonatology, University of Health Sciences, Zeynep Kamil Maternity and Children’s Disease Health Training and Research Center, 34668, Üsküdar, Istanbul, Turkey. E-mail: mdhandanhakyemez@gmail.com P: +90 532 318 46 56 Corresponding Author ORCID ID: https://orcid.org/0000-0002-6966-8514
This study was approved by the Ethics Committee of Zeynep Kamil Maternity and Children Training and Research Hospital (Date: 2016-11-25, No: 158)
Aim: The impact of vitamin D on the developing lungs and respiratory diseases in early life is increasingly attracting the attention of neonatologists. This study aimed to investigate the association between vitamin D [25 (OHD)] levels and respiratory problems in blood in infants with very low birth weight (VLBW).
Material and Methods: Sixty-six infants with VLBW were divided into two groups: those with a vitamin D level less than 20 ng/mL (Group 1) and infants with a vitamin D level equal to or greater than 20 ng/mL (Group 2). Infants’ demographic data such as birth weight, gender, maternal age, gestational week, mode of delivery, and durations of mechanical ventilation, and length of stay in the hospital, mortality status, and BPD status were recorded.
Results: The median birth weight was 995.00 (min-max: 565-1500) g. The median gestational age was 28 (23-32) weeks and the median maternal age was 32 (21-46) years. All infants (n=66;100%) developed respiratory distress syndrome. A significant relationship was found between the severity of respiratory distress syndrome (RDS) and vitamin D deficiency in infants with VLBW (r = 0.898, p = 0.001). There was a significant correlation between the duration of hospitalization and 25 (OH) D levels within the first 24 hours (p = 0.001).
Discussion: Low 25 (OH) D levels in infants with VLBW were correlated with early-onset sepsis, severity of RDS, and duration of hospitalization. There was no significant correlation between vitamin D levels and PDA and BPD.
Keywords: 25-hydroxy D Vitamin, Respiratory Distress Syndrome, Bronchopulmonary Dysplasia, Very Low Birth Weight
Introduction
Vitamin D (25 [OH] D) is a steroid hormone, which functions primarily in the development of a healthy skeleton and in the regulation and maintenance of body levels of calcium levels [1]. The importance of 25 (OH) D in newborns has been increasingly better understood in the last few years [2]. Furthermore, vitamin D seems to play a crucial role in the regulation of lung development in the fetus, lung maturation and cellular growth [3]. Therefore, the impact of 25 (OH) D on developing neonatal lungs and respiratory diseases in early life is increasingly attracting the attention of neonatologists.
Maternal 25 (OH) D deficiency increases the risk of developing gestational diabetes mellitus, preeclampsia, intrauterine growth restriction and premature delivery [4]. These, in turn, trigger preterm delivery and preterm infants are at a greater risk of developing vitamin D deficiency. Vitamin D levels of the infant reflect the maternal levels. Since placental transfer is the primary source of vitamin D for the developing fetus, this means that maternal 25 (OH) D deficiency reflects vitamin D deficiency in a newborn [5]. Vitamin D deficiency has been correlated with various respiratory problems, including neonatal sepsis and respiratory system infections [6]. Studies have associated low 25OHD levels at birth with subsequent respiratory infections, such as respiratory syncytial virus [7]. There are also studies reporting that the prevalence of asthma is higher among preterm infants with low levels of 25OHD [8].
Very low birth weight (VLBW) infants are defined as infants born with a birth weight < 1500 g. These infants tend to develop several diseases, including respiratory problems. The majority of VLBW infants have respiratory distress syndrome. Bronchopulmonary dysplasia (BPD) was defined for the first time in 1967 by Northway in premature infants with respiratory distress syndrome (RDS) after prolonged ventilator support [9]. Some studies have reported that BPD remains the most common long-term complication of VLBW despite the use of minimally invasive strategies of respiratory support, prenatal steroids, and exogenous surfactants [10]. However, whether vitamin D deficiency is associated with BPD in VLBW infants is controversial and its potential contribution to BPD is not clear [11]. This study aimed to investigate the association between vitamin D [25 (OHD)] levels in the blood and respiratory problems in infants with VLBW.
Material and Methods
This study was designed as a prospective cross-sectional study.
In total, the study included 66 infants with VLBW in a range of
565 and 1500 g who were followed-up in our neonatal intensive
care unit (NICU) between 2016 and 2017. Infants receiving vitamin D before enrollment, those with congenital anomalies and infants with a history of maternal immunosuppressant therapy in the antenatal period were excluded from the study. Serum 25 (OH) D levels were measured on the postnatal 1st day, 28th day and 36th gestational week. The infants were divided into two groups: those with a vitamin D level less than 20 ng/mL (Group 1) and those with a vitamin D level equal to or greater than 20 ng/mL (Group 2).
Infants’ demographic data such as birth weight, gender, maternal age, gestational week, mode of delivery, durations of mechanical ventilation, and length of stay in the hospital, mortality status, BPD status, surfactant use, number of times of receiving surfactant, antenatal steroids use, sepsis, pneumonia, oligohydramnios, 1st and 5th minutes Apgar scores, and CPAP status were recorded. In addition, the presence of oligohydramnios and preeclampsia was also recorded.
All infants included in the study received surfactant therapy. In infants in whom extubation could not be achieved immediately, synchronized intermittent mandatory ventilation (SIMV) was the primary mode of ventilation, providing a tidal volume with inspiratory time of 0.35 to 0.38 seconds, respiratory rates of 40 to 60 breaths/minute, and a positive end-expiratory pressure (PEEP) of 5-6 cm H2O. When a PIP of 15 cmH2O, PEEP of 4 -5 cmH2O, respiratory rate (RR) of 15 per minute and a FiO2 value ≤30% were obtained, patients were extubated to receive nasal CPAP.
The presence of patent ductus arteriosus (PDA) was evaluated through echocardiography in all infants included in the study on the 3rd day of life. If hemodynamically significant PDA was diagnosed, ibuprofen was given as pharmacologic treatment.
The associations between the levels of 25 (OH) D and respiratory disorders, including BPD, surfactant requirement, cPAP status, PDA status, length of hospital stay and mortality were investigated.
Blood samples of all patients were collected at the time of admission, on the 28th day and in the 36th gestational week during routine blood sampling. Plasmas of the blood samples were separated and kept at −80 °C until analysis. A High-Performance Liquid Chromatography (HPLC) System (Shimadzu LC-20AT model) was used to determine the levels of 25 (OH)D.
Ethical Considerations
Ethics Committee approval for the study was obtained from the local ethics committe of the Zeynep Kamil Maternity and Children Training and Research Hospital (Date: 2016-11-25, No: 158). Written informed consent was taken from the parents before the participation of their neonates in the study. The study was performed in accordance with the Declaration of Helsinki revised in 2013.
Statistical Analysis
Data obtained in this study were statistically analyzed using the SPSS version 21.0 (SPSS, Statistical Package for Social Sciences, IBM Inc., Armonk, USA). The normality of the variables was tested using the Kolmogorov-Smirnov method and expressed as a mean±standard deviation or median (IQR) as appropriate. Qualitative variables are expressed as percentages and frequencies, normally distributed continuous variables as means (standard deviations, SD) and non-normally distributed variables as medians (interquartile range [IQR] p25-p75). Pearson’s correlation was used to evaluate the correlations between 25 OH vitamin D and other variables. The Chi-square test was performed for categorical variables. P- values <0.05 were considered statistically significant.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
This study included a total of 66 infants followed-up and treated in our NICU. The median birth weight was 995.00 (min-max: 565-1500) g. The median gestational age was 28 (23-32) weeks and the median maternal age was 32 (21-46) years. Of all infants, 30 (45.45%) were male and 36 (54.55%) were female. Table 1 shows antenatal and demographic data of the infants.
The median 25 (OH) D level on the 1st day was 4.95 (3.90-10.53) ng/ml, and the median 25 (OH) D on the 26th day or at discharge was 15.5 (7.5-37.8) ng/ml. The distribution of patients according to 25 (OH) D is shown in Figure 1.
There was no significant difference between infants with 25 (OH) D <20 and ≥20 ng/mL between the two measurement times (p=0.083). All infants (n=66;100%) developed respiratory distress syndrome. Sixteen (24.24%) developed BPD, while 24 (36.36%) infants developed PDA and 20 (30.30%) developed pneumonia. Preeclampsia was observed in 19 (28.79%) and oligohydramnios in 6 (9.09%) mothers. Early sepsis was observed in 23 (34.85%) infants and late sepsis in 28 (42.42%) infants. Surfactants were required in 54 (81.82%) patients and steroids in 32 (48.48%) patients. The median duration of mechanical ventilation was 2 (0-8.50) days. The median duration of transit to enteral feeding was 14.50 (8.0-22.25) days. The median duration of hospitalization was 41.50 (26.5-68.0) days. Mortality occurred in 11 (16.67%) infants (Figure 2).
In the correlation analysis, a significant correlation was found between vitamin D deficiency and the severity of RDS in infants with VLBW (r = 0.898, p = 0.001). There was a significant correlation between low 25 (OH) D levels (<20 ng/mL) measured on the first day and sepsis (r=-0.557, p=0.003). However, there was no statistically significant correlation between low 25 (OH) D levels (<20 ng/mL) measured on the 28th day or at discharge and late sepsis (r=0.97, p=.094). No significant relationship was observed between BPD and 25(OH) D levels (p>0.05). No statistically significant correlation was observed between low levels of 25 (OH) D (<20 ng/mL) measured on the first day and PDA (p=0.887). Similarly, no statistically significant correlation was observed between low 25 (OH) D levels (<20 ng/mL) measured on the 28th day and PDA (p=0.615). A significant correlation was found between the duration of hospitalization and the levels of 25 (OH) D in the first 24 hours (p = 0.001). No correlation was observed between 25 (OH) D levels in the first 24 hours and mortality (r = 0.492, p = 0.931).
Discussion
There is increasing global interest regarding the role of vitamin D in health and disease. Vitamin D is known to play a role in human pulmonary function [12]. Studies have shown that patients with lung diseases often have low Vitamin D serum levels. Epidemiological data indicate that low levels of serum Vitamin D are associated with impaired pulmonary function, increased incidence of inflammatory, infectious or neoplastic diseases [13]. Vitamin D deficiency in blood has also been associated with increased incidence of respiratory tract infections during infancy [14]. Wide biological effects of Vitamin D, suggest that the deficiency of vitamin D during the fetal and neonatal periods may have long-lasting health consequences [15]. It has also been shown that low blood levels of Vitamin D are associated with an increased risk of respiratory problems [16]. In the present study, we evaluated the effects of Vitamin D deficiency on respiratory problems in low-birth-weight infants.
Neonatal RDS is a common cause of respiratory distress in newborns that present within hours after birth. RDS primarily affects preterm infants [17]. Critical factors playing a role in the pathogenesis of neonatal RDS include surfactant deficiency and pulmonary immaturity. In the present study, 54/66 infants required surfactant therapy. In our study, all VLBW infants had respiratory distress syndrome. In addition, a significant relationship was found between the severity of RDS and deficiency of vitamin D in infants with VLBW (r = 0.898, p = 0.001). Dogan et al. showed that vitamin D deficiency was an independent factor for the development of RDS in premature infants [18].
Neonatal sepsis is defined as a systemic condition originating from bacterial, viral or fungal causes and is associated with hemodynamic changes and clinical findings causing severe morbidity and mortality [19]. While early-onset sepsis describes cases presenting manifestations within the first 72 hours of life, late-onset sepsis describes cases diagnosed after the first seven days [20]. Low vitamin D levels that are generally common in the neonatal population have been found to be significantly higher in neonates with sepsis [21]. In the present study, there was a significant correlation between low 25 (OH) D levels (<20 ng/mL) measured on the first day and sepsis (r=-0.557, p=0.003). However, there was no statistically significant correlation between low 25 (OH) D levels (<20 ng/mL) measured on the 28th day or at discharge and late sepsis (r=0.97, p=.094). We think that the difference in late sepsis may be due to the effect of surfactant supplementation, which was initiated from the first day of life in our study.
BPD is a chronic pulmonary disorder that primarily affects preterm infants. The new BPD definition differs from the first and is characterized by pulmonary vascular dysplasia or hypoplasia and alveolar simplification rather than scarring and fibrosis of the lungs [22]. Potential contribution of Vitamin D deficiency to BPD is unknown. Joung et al found no correlation between 25(OH) D levels and the development of BPD [11]. In our study also no significant relationship was observed between BPD and the levels of 25(OH) D (p>0.05). Furthermore, in a meta-analysis and systematic review, including eight studies, the authors concluded that the vitamin D levels at the time of birth, reflecting maternal and fetal vitamin D status during pregnancy, was significantly correlated with the incidence of BPD. However, no information was given about the later measurements of vitamin D levels [23].
A patent ductus arteriosus occurs commonly in preterm infants, especially in those with respiratory distress syndrome. In our study, PDA occurred in 36.36% (24/66) of VLBW infants. Studies have proposed that severe RDS justifies a controlled trial of very early closure of the PDA in the very low-birth-weight infant with severe RDS [24]. In a study by Kim et al., PDA occurred in 48.4% of VLBW infants [25]. In our study, PDA was observed in 24 (36.4%) of VLBW infants. We could not find a significant difference between Vitamin D deficiency and PDA.
In the present study, a significant correlation was observed between hospitalization duration and the levels of 25 (OH) D in the first 24 hours (p = 0.001). No correlation was observed between 25 (OH) D levels in the first 24 hours and mortality (r = 0.492, p = 0.931).
Study Limitations
The main limitations of this study include its single-center design and relatively small number of patients. In addition, a control group with term infants could be created. Finally, we could not compare maternal and neonatal vitamin D levels. However, given the limited number of existing data in the literature and the need for further studies, we believe that our results will guide for future more comprehensive studies.
Conclusion
The results of this study revealed that low 25 (OH) D levels in infants with VLBW were correlated with early-onset sepsis, severity of RDS, and duration of hospitalization. There was no statistically significant correlation between the levels of vitamin D and BPD and PDA. However, there is a need for further comprehensive studies with larger series to better enlighten these correlations.
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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16. Camargo CA Jr, Ingham T, Wickens K, Thadhani R, Silvers KM, Epton MJ, et al. Cord-blood 25-hydroxyvitamin D levels and risk of respiratory infection, wheezing, and asthma. Pediatrics. 2011;127(1):e180-7.
17. Yadav S, Lee B, Kamity R. Neonatal Respiratory Distress Syndrome. Treasure Island (FL): StatPearls Publishing; 2021.
18. Dogan P, Ozkan H, Koksal N, Bagci O, Varal IG. Vitamin D deficiency and its effect on respiratory distress syndrome in premature infants: results from a prospective study in a tertiary care centre. Afr Health Sci. 2020;20(1):437-43.
19. Ozmeral Odabasi I, Bulbul A. Neonatal Sepsis. Med Bull Sisli Etfal Hosp. 2020;54(2):142-58.
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Handan Hakyemez Toptan, Nilgun Karadag, Sevilay Topcuoglu, Emre Dincer, Abdulhamit Tuten, Selahattin Akar, Tulin Gokmen Yildirim, Elif Ozalkaya, Guner Karatekin, Fahri Ovali. Relationship between respiratory problems and vitamin D levels in very low birth weight infants. Ann Clin Anal Med 2023;14(7):655-659
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Microbiology and antimicrobial resistance in pediatric acute rhinosinusitis with acute otitis media
Khanh Van Nguyen Thi 1, Hong Anh Le 1, Quoc Chinh Do Hoang 2, Quang Minh Le Tran 3, 4
1 Department of Medical Examination, National Otolaryngology Hospital of Vietnam, Hanoi, 2 Department of Otolaryngology, Graduate Student of Hanoi Medical University, Hanoi, 3 Department of Otolaryngology, Ear Nose Throat hospital, Ho Chi Minh City, 4 Department of Otorhinolaryngology, Pham Ngoc Thach University of Medicine, Ho Chi Minh City, Vietnam
DOI: 10.4328/ACAM.21733 Received: 2023-04-18 Accepted: 2023-05-26 Published Online: 2023-06-25 Printed: 2023-07-01 Ann Clin Anal Med 2023;14(7):660-663
Corresponding Author: Quang Minh Le Tran, Department of Otorhinolaryngology, Pham Ngoc Thach University of Medicine, Ho Chi Minh City, Vietnam. E-mail: dr_minhle@yahoo.com P: +8490 399 11 51 Corresponding Author ORCID ID: https://orcid.org/0009-0005-3832-9930
This study was approved by the Ethics Committee of National Otolaryngology Hospital of Vietnam (Date: 2022-01-17, No: 021022/NOH)
Aim: This study aimed to describe organisms cultured from pediatric acute rhinosinusitis (ARS) with otitis media (OM), as well as current resistance patterns of pathogens.
Material and Methods: The study was conducted from February to October 2022. Children with acute rhinosinusitis and acute otitis media underwent endoscopic-guided cultures at National Otorhinolaryngology Hospital of Vietnam to obtain pathogens and for analysis of antibiotic resistance.
Results: The total of 72 cultures were obtained from 72 children with acute rhinosinusitis and otitis media under the age of 6 years. Gram-negative bacteria were isolated in 48.6% and Gram-positive bacteria in 37.5% of patients. Susceptibility rates of H. influenzae were 100.0% to meropenem and piperacillin/tazobactam; 55.6% to amoxicillin/ clavulanic acid. Resistance rates of H. influenzae were 100.0% to both cefuroxime and co-trimoxazole. Susceptibility rates of S. pneumoniae were 100.0% to levofloxacin, moxifloxacin, vancomycin, tigecycline, rifampicin and linezolid. Resistance rates of S. pneumoniae were 100.0% to erythromycin, 93.3% to tetracycline and 86.7 to clindamycin. Susceptibility rates of M. catarrhalis were 100.0% to meropenem, ceftazidime, ciprofloxacin, levofloxacin, gentamycin and doxycycline. Resistance rates of M. catarrhalis were 100.0% to co-trimoxazole, 87.5% to azithromycin.
Discussion: This study highlights that H influenzae, S. pneumoniae, M. catarrhalis, and S. aureus are the major bacteria found in pediatric acute rhinosinusitis with acute otitis media. Because of different patterns of antibiotic resistance, a targeted antibiotic treatment according to culture sensitivity studies is needed for more effective therapy.
Keywords: Microbiology, Antimicrobial Resistance, Rhinosinusitis, Otitis Media
Introduction
Rhinosinusitis is defined by the inflammation of the nasal cavity mucosa and sinuses mucosa, which may or may not include bone lesions [1]. It is commonly infective in origin and usually results from simple viral rhinosinusitis (the common cold) [2]. This primary infection has the effects of reducing ciliary function, causing edema of the nasal mucosa and sinus ostia, and increasing nasal secretions. These stagnant secretions within the sinuses may become secondarily infected with bacteria, commonly Streptococcus or Haemophilus. Certain conditions may predispose to sinusitis. These include any condition that blocks the ostia of the sinuses, such as nasal polyps, or conditions that interfere with airflow through the nose, for example, a deviated septum. The roots of the upper teeth often project into the maxillary sinus, and thus dental infections can also lead to sinusitis [2-4].
Otitis media (OM) is the most common diagnosis for medical visits in preschool-age children and the most frequent indication for outpatient antibiotic use in the USA and the world, with estimated annual public health costs totaling US$ 2.8 billion annually [5-7]. OM is characterized by signs and symptoms of middle-ear effusion (MEE), defined as fluid collection in the middle ear. It may also include otorrhea (drainage of fluid from the middle ear), which occurs after perforation of the tympanic membrane or through ventilation tubes placed previously. OM can be classified as acute otitis media (AOM), otitis media with effusion (OME), recurrent AOM, and chronic suppurative OM (CSOM). Each has a separate basis in its best course of treatment. AOM is defined by the presence of middle-ear inflammation and fluid of sudden onset and often presents with constitutional symptoms consistent with infection, such as fever and pain [8]
Although the bacteriology of pediatric chronic rhinosinusitis appears to be well established, research on current bacterial resistance patterns is limited. Numerous studies have been conducted to characterize antibiotic resistance in rhinosinusitis recently, either via endoscopic middle meatus sampling or intraoperative biopsy. The subjects of these studies, however, are mainly adults, and pediatric patients are seldom included. Furthermore, large-scale surveillance examining antimicrobial susceptibility of upper respiratory pathogens reveals an ongoing evolution and geographic variation in bacterial resistance, which highlights the need for updated data on antimicrobial susceptibility in different regions and countries [9].
Material and Methods
A prospective study was conducted from February to October 2022 at the National Otorhinolaryngology Hospital in Hanoi, Vietnam. This study was approved by the Ethics Committee of the hospital (IRB number 021022/NOH). Consent was obtained from all participants in this study.
Patients were included if they were under 6 years of age and presented with typical symptoms of acute rhinosinusitis (purulent nasal drainage/postnasal discharge and nasal congestion) and acute otitis media lasting less than 12 weeks. Ear, nose, and throat examination was carefully conducted, and purulent discharge was collected via the endoscopic middle meatus for bacterial cultivation.
Samples from the sinus were sent to the microbiologic laboratory within 1 hour. In the microbiology laboratory, aerobic specimens were plated on blood agar plate and chocolate agar, and cultured for 24 hours at 35°C. Potentially pathogenic organisms that grew on culture were identified and reported semi-quantitatively using standard techniques. Analysis of the patterns of antimicrobial resistance was conducted for specific antibiotics according to different aerobic bacteria.
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
The study included 72 patients (48 males, 24 females) diagnosed with acute rhinosinusitis and acute otitis media. The study group consisted of patients of both sexes with ages ranging from 0 to 5 years. This group of patients was divided into two groups according to the age criterion: from 0 to 2 years old (42 patients, 58.3%); from 3 to 5 years old (30 patients, 41.7%).
Culture results showed that 13.9% (10 cultures) of aspirates yielded normal upper airway flora or no growth at all. Gram-negative bacteria were isolated in 48.6% (35/72) and Gram-positive bacteria in 37.5% (27/72) of patients. Polymicrobial growth (more than one isolate per culture) was noted in 0% of the cultures. The analysis of culture results is shown in Table 1.
This study analyzed the resistance of Haemophilus influenza, Streptococcus pneumonia, and Moraxella catarrhalis to major antibiotics (Table 2). The resistance rate of S. pneumoniae isolates and the resistance rate of M. catarrhalis isolates are shown in Table 3.
Susceptibility rates of M. catarrhalis were 100.0% (8/8) to meropenem, ceftazidime, ciprofloxacin, levofloxacin, gentamycin and doxycycline. Resistance rates of M. catarrhalis were 100.0% (8/8) for co-trimoxazole, 87.5% (7/8) for azithromycin.
Discussion
The higher rate of positive bacterial cultures can be explained by the fact that in this study, the cases were mainly located in the provinces and rural areas, where the use of older generation antibiotics was not effective in killing bacteria. Some negative culture results may be due to the fact that patients have been using strong and prolonged antibiotics prior to admission to central hospitals. Other possible causes of negative cultures are the role of anaerobic bacteria.
Overall, the most common bacteria isolated were Heamophilus influenzae (37.5%) followed by Streptococcus pneumoniae (20.8%), Moraxella catarrhalis (11.1%), Staphylococcus aureus (9.7%). Less common bacteria were Streptococcus mitis and Kocuria rosea (1.4%). Subgroup analysis revealed that 69.4% of bacterial isolates were pathogens commonly implicated in acute bacterial rhinosinusitis (Haemophilus influenza, Streptococcus pneumonia, and Moraxella catarrhalis). Several recent studies by other authors have also shown similar results that Haemophilus influenza, Streptococcus pneumonia, and Moraxella catarrhalis are still the three most common bateria in acute rhinosinusitis [10-14].
Susceptibility rates of H. influenzae were 100.0% (27/27) to meropenem and piperacillin/tazobactam; 92.6% (25/27) to ciprofloxacin and levofloxacin; 55.6% (15/27) to amoxicillin/ clavulanic acid. Resistance rates of H. influenzae were 100.0% (27/27) to both cefuroxime and co-trimoxazole. C.-H. Hsin et al showed that the susceptibility rates of H. influenzae were 100.0% to ciprofloxacin and cefuroxime. This means that in Vietnam, the resistance rates of H. influenzae to cefuroxime is almost very high compared to other countries [9].
Susceptibility rates of S. pneumoniae were 100.0% (15/15) to levofloxacin, moxifloxacin, vancomycin, tigecycline, rifampicin and linezolid. Resistance rates of S. pneumoniae were 100.0% (15/15) to erythromycin, 93.3% (14/15) to tetracycline and 86.7 (13/15) to clindamycin.
Susceptibility rates of M. catarrhalis were 100.0% (8/8) to meropenem, ceftazidime, ciprofloxacin, levofloxacin, gentamycin and doxycycline. Resistance rates of M. catarrhalis were 100.0% (8/8) to co-trimoxazole, 87.5% (7/8) for azithromycin.
Conclusion
This study shows that H influenzae, S. pneumoniae, M. catarrhalis, and S. aureus are the major bacteria found in pediatric acute rhinosinusitis with acute otitis media. The study also revealed a different pattern of antibiotic resistance compared with previous studies performed in children. When prescribing antimicrobial therapy for children with acute rhinosinusitis, current patterns of antibiotic resistance should be considered, which may vary according to different geographic areas. For rhinosinusitis recalcitrant to empirical antibiotics, targeted antibiotic treatment according to culture sensitivity studies is needed for more effective therapy.
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. Kardos P, Malek FA. Common Cold – an Umbrella Term for Acute Infections of Nose, Throat, Larynx and Bronchi. Pneumologie. 2017; 71(4): 221-6.
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4. Qadri H, Andrabi DZ, Nemade SV, Shinde KJ, Naik C, Yeolekar A, et al. Medical Graduate’s Basic Knowledge and Clinical Skills Assessment in Otorhinolaryngology Post Internship. Indian J Otolaryngol Head Neck Surg. 2019; 71(Suppl. 1): S162-6.
5. Lewis AT, Backous D, Choi BY, Jaramillo R, Kong K, Lenarz T, et al. Healthcare consumption among subjects with otitis media undergoing middle ear surgery-analysis of cost drivers. Eur Arch Otorhinolaryngol. 2023; 280(1): 175-81.
6. Noorbakhsh KA, Liu H, Kurs-Lasky M, Smith KJ, Hoberman A, Shaikh N. Cost-effectiveness of management strategies in recurrent acute otitis media. J Pediatr. 2023; 256:11-17.e2.
7. van Uum RT, Venekamp RP, Pasmans CTB, de Wit GA, Sjoukes A, van der Pol AC, et al. Cost of childhood acute otitis media in primary care in the Netherlands: economic analysis alongside a cluster randomised controlled trial. BMC Health Serv Res. 2021; 21(1): 193.
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10. Brook I. Acute sinusitis in children. Pediatr Clin North Am. 2013; 60(2): 409-24.
11. DeMuri G , Wald ER. Acute bacterial sinusitis in children. Pediatr Rev. 2013; 34(10): 429-37; quiz 437.
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13. Leung AKC, Wong AHC. Acute Otitis Media in Children. Recent Pat Inflamm Allergy Drug Discov. 2017; 11(1): 32-40.
14. Sawada S, Matsubara S. Microbiology of Acute Maxillary Sinusitis in Children. Laryngoscope. 2021; 131(10): E2705-11.
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Khanh Van Nguyen Thi, Hong Anh Le, Quoc Chinh Do Hoang, Quang Minh Le Tran. Microbiology and antimicrobial resistance in pediatric acute rhinosinusitis with acute otitis media. Ann Clin Anal Med 2023;14(7):660-663
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Applicability and results of surgical treatment of chronic anal fissures in the polyclinic
Hakan Demir
Department of General Surgery, Sakarya University Training and Research Hospital, Sakarya, Turkey
DOI: 10.4328/ACAM.21754 Received: 2023-05-11 Accepted: 2023-06-16 Published Online: 2023-06-25 Printed: 2023-07-01 Ann Clin Anal Med 2023;14(7):664-667
Corresponding Author: Hakan Demir, Department of Sakarya University Training and Research Hospital General Surgery, Sakarya, Turkey. E-mail: hakan-demir06@hotmail.com P: +90 532 464 19 54 Corresponding Author ORCID ID: https://orcid.org/0000-0001-5973-4605
This study was approved by the Ethics Committee of Sakarya University (Date: 2023-05-02, No: E-71522473-050.01.04-241695_141)
Aim: As a result of the experience gained, it has been revealed that 90% of proctological procedures can be done with local anesthesia on an outpatient basis, patients do not need to stay in the hospital for days and recovery can be followed up on an outpatient basis.
Material and Method: Research cases were operated by a single physician. In the study, 209 outpatients were operated in the outpatient clinic and 6 patients were operated in the general operating room.
Results: In the research, 209 outpatients operated in the outpatient clinic and 6 patients operated in the general operating room were included. Of the patients operated on in the outpatient clinic, 124 were women and 85 were men. The recovery rate was 90.4% and the recurrence rate was 9.6% in those operated in the outpatient clinic.
While the median monetary value of the cases operated on in the outpatient clinic was 429.41 TL (40.89 USD), it was 1373 TL (130.76 USD) in the general operating room group (p 0.002).
Discussion: Performing uncomplicated proctological cases in the local operating room in order to use the general operating room more effectively supports our study in terms of both institutional profitability and surgical treatment results.
Keywords: Outpatient, Chronic Anal Fissure, Lateral Internal Sphincterotomy
Introduction
Anal fissures are ruptures of the anoderm. A lifetime incidence of anal fissures is predicted to be 11%, affects men and women equally, and can be seen at any age [1]. Symptomatologically, fissures below six weeks are called acute, and those over six weeks are called chronic anal fissures. Anal fissures cause pain, itching and bleeding. This reduces the quality of life of those suffering from the disease. The exact etiology of primary anal fissures is unknown. The initiating factor is thought to be anoderm trauma due to overstretching, especially from hard or large stools, local irritation from diarrhea, anorectal surgery, and anoreceptive sex [2].
In addition, constipation and hard bowel movements are reported in only 13% of patients with fissures. In most patients with anal fissures, the event that causes the fissures to become chronic is hypertonicity and hypertrophy of the internal anal sphincter as a result of increased resting pressures of the anal canal and internal sphincter [2,3].
Secondary fissures may develop as a result of previous anal surgery, inflammatory bowel disease, granulomatous disorders (for example, tuberculosis, sarcoidosis), infections (for example, human immunodeficiency virus, syphilis), chemotherapy or malignancy [4,5].
Most fissures occur in the posterior midline (90%). Anterior midline fissures constitute approximately 10-25% of fissures detected in women and 1-8% of fissures detected in men. Anterior and posterior midline fissures may occur simultaneously in approximately 3% of cases. Sometimes the fissure sites may be atypically located outside the antero-posterior line. Anterior fissures occur in young female patients who have injury or dysfunction of the external anal sphincter due to childbirth [6].
Although acute anal fissures respond to medical treatment at a high rate, when chronic fissures develop, they are more difficult to heal and respond to conservative treatment on average 50%. [6,7] Therefore, there is a need for the adoption of surgical treatment options.
The increase in oncological and complicated cases causes long waiting times for hospitalizations and delays in treatment. Compared to other proctological cases, surgical treatment of chronic anal fissures is more successful in terms of recovery and patient satisfaction. Modern local anesthetic agents provide serious benefits in practice. Therefore, it seems possible to treat a certain part of proctological diseases on an outpatient basis [8].
The primary purpose of this retrospective study is to report the results of sphincterotomy performed under local anesthesia in outpatient settings in patients with chronic anal fissures. The secondary aim is to compare the results of complicated cases in terms of recurrence and cost, in order not to occupy the general operating room.
Material and Methods
After the approval of Sakarya University Ethics Committee (Date: 02/05/2023; No: E-71522473-050.01.04-241695_141), patients who were operated for chronic anal fissure between January 2018 and March 2023 were retrospectively analyzed.The study patients were operated by a single surgeon. I and II scores of the American Society of Anesthesiologists (ASA) were preferred. Patients who were within 30-60 minutes of arriving at the hospital on an emergency basis and were psycho-socially ready for local surgery were included.
Patients were operated in the jack-knife position in the outpatient clinic, and in the lithotomy position in the general operating room. During the operation, lateral internal sphincterotomy or controlled sphincterotomy was performed by numbing the fissures first and then the operation field (usually at 9 o’clock position) with prilocaine.
The patients were discharged after thirty minutes of observation after surgery. Controls were made in the first, second and third months. In cases with complicated anal stenosis and a contralateral sphincterotomy, the control of the patients was extended to six months. The patients who were operated on in both operating rooms were asked about their recovery status, recurrence, complications, incontinence, satisfaction, and whether they had any problems, and the data were recorded. The surgery prices of the patients and the savings of the institution (i.e profitability ratios) were calculated by considering the price application notification of the Ministry of Health of the Republic of Turkey. It is stated in both Turkish liras and American dollars on the basis of international annual exchange rates.
Only chronic anal fissures and atypical chronic anal fissures that caused anal stenosis were included in this study. Acute anal fissures and chronic anal fissures associated with hemorrhoidal disease were excluded.
Statistical analysis
We performed descriptive analyses to provide information on the general characteristics of the study population. The Kolmogorov-Smirnov test was used to evaluate whether the distributions of numerical variables were normal. Accordingly, the Mann-Whitney U test was used to compare the numeric variables between groups. The numeric variables were presented as median (minimum-maximum). Categorical variables were compared using the Chi-Square test. Categorical variables were presented as number and percentage. A p-value <0.05 was considered significant. Analyses were performed using SPSS statistical software (IBM SPSS Statistics, Version 25.0. Armonk, NY: IBM Corp.)
Ethical Approval
Ethics Committee approval for the study was obtained.
Results
Comparisons made in terms of demographic, clinical and cost characteristics of the cases between the group treated in the operating room and the group treated in the outpatient clinic are shown in Table 1.
The research included 209 outpatients operated in the outpatient clinic and 6 patients operated in the general operating room. One hundred twenty-four of the patients who were operated on in the outpatient clinic were women and 85 were men. The mean age was 38 years in the outpatient clinic and 43 years in the inpatients. There was no significant difference between the exposure times (p 0.539).
In terms of fissure types, the typical ones were mostly performed in the outpatient clinic, while the atypical ones were performed in the general operating room. The difference was found to be statistically significant (p 0.015).
In terms of etiology, constipation in patients operated on in the outpatient clinic and diarrhea in patients operated on in the general operating room had a significant difference (p<0.01)
There was no significant difference in terms of pain, bleeding and itching in both groups (p0.669, p1.0, p1.0). The recovery rate was 90.4% and the recurrence rate was 9.6% in those operated in the outpatient clinic.
In the general operating room group (4/6), 66.7% were operated mostly in cases of recurrence, delayed recovery, or anal stenosis. It was observed that more complicated cases were performed in the general operating room, making a significant difference compared to those performed in the outpatient clinic (p0.002).
While the mean follow-up period of the patients operated in the outpatient clinic was 30 months, the follow-up period of the patients operated in the general operating room was 11 months. No significant difference was found between them (p 0.105).
The median monetary value of the cases operated on in the outpatient clinic was 429.41 TL (313.90-1002.47 TL), 40.89 USD, while it was 1373 TL (357.85-1373 TL) and 130.76 USD in the general operating room group (p 0.002).
The median cost of the materials used was 26 TL (23-29 TL) (2.47 USD) in the outpatient clinic, and 923 TL (864-982 TL) (87.90 USD) for the materials, surgical set and anesthesia application in the general operating room. Relatively, the hospital’s profitability rates were higher in the outpatient clinic.
Fecal contamination and minimal incontinence were observed in one patient in the general operating room group. In the outpatient group, one patient reported fecal contamination and five patients reported gas incontinence (6/209) 2.8%. At the 6th month of follow-ups, minimal incontinence complaints were absent in both groups. While patient satisfaction rates were 91% in the local anesthesia group in the early period, the satisfaction with recovery increased to 98% at the end of the third month. In the early period, the highest rate of dissatisfaction was associated with pain.
Discussion
Experiences have shown that 90% of proctological diseases can be performed on an outpatient basis with local anesthesia, with anal diseases there is no need to stay in the hospital for days, and recovery can be followed up on an outpatient basis [9].
In chronic anal fissures, the most effective surgical treatment of choice is lateral internal sphincterotomy (LIS). It maintains its gold standard feature. It is offered as a first-line treatment option according to the application parameters of the American Society of Colon and Rectal Surgeons. However, complete or partial closure of the sphincter predisposes to sphincter dysfunction, which may manifest as gas, fluid, or fecal incontinence in varying degrees [10].
Due to concerns about impaired continence after sphincterotomy, several modifications of the LIS have been developed over the last two decades and terms such as “customized” or “controlled” LIS have been introduced. The extent of sphincterotomy is determined as the percentage of sphincter division or the length of the distance above or below the dentate line. As might be expected, more sphincter division is associated with a higher incidence of impaired continence [11].
In our study, prilocaine was injected into the fissure line first in the local operating room. After the patient’s pain was relieved, complete relaxation of the anus was achieved. With resolution of anal spasm, fissure depth, type and number were observed. The amount of sphincterotomy was adjusted by obtaining preliminary information about the performance of the anus. We adopt that with careful patient selection, the incontinence rate will decrease further. Numerous studies have been conducted to examine the effect of this on outcomes.
In a 2013 meta-analysis by Garg et al. [10], they showed that the overall rate of continence disorder may be as high as 5-14%, despite some recent studies. Al-Thoubaity et al. [12] found a low incontinence rate of 0.4% in their study.
Davies et al. [13], focusing specifically on postoperative incontinence and investigating long-term outcomes after lateral anal sphincterotomy, reported a success rate of 92% in postoperative fissure healing, while two (5.6%) patients reported prolonged objective and symptomatic incontinence.
In our study, fecal contamination and minimal incontinence were observed in one patient in the general operating room group. In the outpatient group, two patients reported fecal contamination and five patients reported gas incontinence (7/209) 0.03%. At the 6th month follow-up, there were no minimal incontinence complaints in both groups. While patient satisfaction rates were 91% in the local anesthesia group in the early period, the satisfaction with recovery increased to 98% at the end of the third month. In the early period, the highest rate of dissatisfaction was associated with pain.
Sphincterotomy can be done with an open or closed technique. An open LIS is defined by Eisenhammer, a closed LIS by Notoras. It is performed by entering the intersphincteric region with a small incision from the anoderm edge and suspending the internal sphincter. In controlled sphincterotomy, the distal part of the sphincter is partially cut with a scalpel No. 11 based on the perianal skin.
Cho et al. [11] recommended adjusting the exact length of the sphincterotomy to the length of the anal fissure. Controlled lateral sphincterotomy technique was observed to protect the anal sphincter more.
Mentese et al. [14] in a randomized, prospective study compared the use of anal calibrators. They reported that controlled sphincterotomy provided faster relief in pain, and significantly lower early postoperative continence impairment and treatment failure.
In our study, controlled sphincterotomy was performed in 26 (12.4%) patients in the outpatient group and in 1 (16.7%) patient in the general operating room group. Considering the relaxation capacity of the anus, it was left for the second session or contralateral sphincterotomy could be performed if necessary.
In 2015, Liang et al [15] stated that the healing rate of the fissure was 98% in the treatment of recurrent chronic anal fissure after surgical treatment. They presented the results of a prospective study designed to indicate that only 4% of cases required a contralateral, lateral internal sphincterotomy. They showed that it can be applied in the treatment of recurrent chronic fissures with minimal risk of incontinence.
In our case series, contralateral sphincterotomy was performed in 0.028% of outpatients (6/209) because their anal fissures did not heal. All recovered in the third month of follow-up.
We observed that the amount of savings achieved by the institution in terms of local currency (TL) and foreign currency (USD) was medianly significant in the group treated in the outpatient clinic compared to the group treated in the operating room. According to the price application communiqué of the Ministry of Health of the Republic of Turkey, the median price of anal fissure surgery for five years (considering the international average exchange rate) was 429.41 TL, (313.90-1002.47 TL) (40.89 USD). In the general operating room group, it was 1373 TL (357.85-1373 TL) (130.76 USD).
The average institutional profitability per case is 450 TL (42.85 USD) in the operating room, and 403.41 TL (38.42 USD) in the outpatient clinics.
These results concluded that it is more reasonable to perform surgery in the outpatient clinic, given the workload of the operating room.
In the study by Nahas et al. [16], although the price policies for surgery differ from country to country, the cost of surgery for a one-day hospitalized patient is USD 570.00 and for outpatient treatment USD 390.00.
Conclusion
Today, with the excellent analgesia provided by local anesthetics in outpatients, its applicability and success rates have increased a lot. The increase in complicated cases and malignant patients has led to the need to allocate a general operating room for these cases. To use the general operating room more effectively, uncomplicated proctological cases should be performed in the local operating room. This study supports the positive outcome of outpatient surgical treatment.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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