May 2021
Can new anthropometric indices be used as a marker for the presence of metabolic syndrome?
Nur Demirbas, Ruhusen Kutlu
Department of Family Medicine, Meram Medical Faculty, Necmettin Erbakan University, Konya, Turkey
DOI: 10.4328/ACAM.20303 Received: 2020-08-10 Accepted: 2020-09-10 Published Online: 2020-09-21 Printed: 2021-05-01 Ann Clin Anal Med 2021;12(5):474-478
Corresponding Author: Nur Demirbas, Department of Family Medicine, Meram Medical Faculty, Necmettin Erbakan University, 42080 Konya/Turkey.
E-mail: ndemirbas76@hotmail.com P: +90 332 2236926 F: + 90 332 2236181 Corresponding Author ORCID ID: https://orcid.org/000-0002-4038-9386
Aim: Since traditional anthropometric measurements such as waist circumference (WC) and body mass index (BMI) can not adequately demonstrate muscle, fat mass, and body fat distribution, new indices have been developed taking into account the shape of the body. In this study, we aimed to investigate whether new anthropometric indices such as Rohrer Index (RI), Body Shape Index (BSI), and Body Roundness Index (BRI) can be used as markers for the presence of metabolic syndrome or not.
Materials and Methods: This study was performed on 1059 patients who met the inclusion criteria. Waist-to-height ratio (WHtR), BMI, BRI, BSI, RI were calcu- lated using the appropriate anthropometric measurements taken from the files of the participants.
Results: The prevalence of metabolic syndrome was 39.9% (n=423). There was a statistically significant relationship between BMI, WHtR, RI, BSI, BRI and gen- der, age, and metabolic syndrome (p<0.001). While there was a weak positive correlation between BSI and metabolic syndrome (r=0.182, p<0.001), there was a strong positive correlation between BRI and metabolic syndrome (r=0.610, p<0.001). The optimum cutting values for BMI, WHtR, and BRI were determined as 30.19 kg/m2, 0.59 cm and 5.24, respectively.
Discussion: BRI and WHtR were found to have a higher capacity to predict metabolic syndrome than other indices (BSI, RI, BMI), however, it was seen that it was not superior to BMI. Other anthropometric indices can be used as well as BMI and waist circumference for the prevention, early diagnosis, and detection of the metabolic syndrome risks in the primary health care centers.
Keywords: Metabolic syndrome; Obesity; Anthropometry; Adults; Primary health care
Introduction
Metabolic Syndrome (MetS) according to the Endocrine and Metabolism Association an increasingly common health problem in the world and in our country, is defined as a complex disease consisting of the collection of biochemical, physiological, clinical and metabolic factors that are associated with systemic disorders such as abdominal obesity, glucose intolerance or diabetes mellitus, dyslipidemia, hypertension and coronary artery disease (CAD). Genetic and environmental factors, age, obesity, physical inactivity, irregular eating habits and stress play an important role in the development of metabolic syndrome [1]. MetS exists in about one-third of the adult population in the world and in our country, and this frequency increases with age [2].
Visceral adiposity, known as central or abdominal obesity, is an important component of the metabolic syndrome. Abdominal obesity has been shown to be correlated with many pathophysiological conditions such as insulin resistance, impaired lipid metabolism and endothelial dysfunction [3-6]. According to the World Health Organization (WHO), in 2016, there were 1.9 billion overweight and 650 million obese adults around the world. The prevalence of obesity in the world almost tripled between 1975 and 2016. According to the results of the research conducted by the endocrine and metabolism association, Turkey was reported to have the highest prevalence of obesity in Europe, with a prevalence of 29.5%.
Body mass index (BMI=Weight(kg)/Height(m2)) which is an anthropometric measurement is a common, cheap and useful method used to define overweight and obesity. Other than BMI, waist circumference (WC), waist-to-height ratio (WHtR) and waist-hip ratio (WHpR) are also used to predict obesity and especially central obesity. However, the BMI does not provide information about muscle mass, fat mass and body fat distribution. Due to these limitations of direct measurements, the researchers have searched for new anthropometric indices to better identify diseases which cause obesity and metabolic syndrome. The body shape index (BSI) is a new anthropometric measurement recommended as a predictor of early obesity- related deaths, regardless of BMI. BSI is calculated using waist circumference, BMI, and height. Krakauer et al. (2012) revealed that BSI was more predictive of premature mortality than BMI or WC [7]. Body roundness index (BRI) is a measurement created by Thomas et al. (2013) which combines height and waist circumference to predict the percentage of body fat mass (FM%) and to assess the patient’s health status [8]. This index is derived to measure the height-independent body shape as an estimator of FM% and visceral adipose tissue (VAT). Researchers modeled the shape of the human body as an ellipse or an oval shape surrounding the body according to roundness. Thus, it can be applied as a visual aid to compare the body types and determine the position of the body type according to the reference range of healthy body roundness [8]. The waist-to-height ratio (WHtR) is a simple and effective anthropometric index [9], and it can be used equally to men and women to define central fat distribution in normal or overweight individuals with high metabolic risk, regardless of body weight and fat distribution. WHtR≥0.5 is considered as abdominal obesity [10]. While the BMI measures two-dimensional square plate of the body, and weight per square area, the Rohrer index (RI) is a three-dimensional cube of the body and measures the weight per cubic content. Therefore, RI takes into account the width and circumference of the person, unlike the measurement of BMI, and assumes that the width and circumference are proportional to the height of one [11].
We aimed to investigate whether new anthropometric indices, such as Rohrer Index (RI), Body Shape Index (BSI) and Body Roundness Index (BRI), can be used as a marker of the presence of metabolic syndrome or not.
Material and Methods
Place, type and universe of research
This study was planned to be conducted as a retrospective screening of the files of patients over 18 years of age who applied to the Family Practice outpatient clinic for any reason between the years of 2016-2018. Since the prevalence of metabolic syndrome and obesity was approximately 30% in our country, it was planned to enroll at least 450 patients in our study with a 5% error share and 95% confidence interval. Among 2000 patients who got examined and had files in our outpatient clinic between the years of 2016-2018, 1059 were included in the study by taking into consideration study exclusion criteria.
Ethical authorization of the study
Ethical approval was received from Necmettin Erbakan University, Meram Medical Faculty, Ethics Committee (Number: 2019/1807) before the study started. All participants provided electronic informed consent.
Data collection
Sociodemographic characteristics such as age, gender, marital status, educational levels were recorded. Smoking status and anthropometric measurements such as height, weight and waist circumference, systolic/diastolic blood pressures and the results of fasting blood glucose (FBG) and lipid parameters were measured.
Exclusion criteria
Those with a lack of information in the file, with congenital or acquired body anomalies, who have cancer, with a disease that affect blood glucose and lipid parameters and who use drugs for this, who have bone, endocrine and metabolic diseases, pregnant women and puerperants, those who receive medical or surgical obesity treatment and receive hypertension treatment and those under 18 years of age were excluded from the study. Anthropometric indices
Anthropometric indices were calculated by following formulas:
1. Waist to Height ratio (WHtR): Waist circumference (cm) / Height (cm);
2. Body Mass Index (BMI): Weight (kg) / Height2 (m);
3. Rohrer Index (RI): Weight (kg) / Height3 (m);
4. Body Shape Index (BSI): Waist circumference (cm)/ (BMI2/3*Height1/2(m));
5. Body roundness index (BRI):364,2-365,5√[1-(waist circumfer ence/2π)2/0,5*Height(m))2 ]
The diagnosis of metabolic syndrome
We used the most widely used and accepted criteria for the diagnosis of Metabolic Syndrome. According to this, three or more of the following findings are diagnosed as metabolic syndrome [12].
• Abdominal obesity (waist circumference: >102 cm for men, >88 cm for women);
• Hypertriglyceridemia (≥150 mg / dl);
• Low HDL (<50 mg/dl for men, <40 mg/dl for women);
• Hypertension ( ≥130/85 mmHg);
• Fasting blood glucose ≥100 mg/dl or Type 2 diabetes mellitus. Statistical analysis
When the findings of the study are evaluated, SPSS (Statistical Package for Social Sciences) for Windows 21.0 software program was used for statistical analyzes. Frequencies, mean, standard deviation, median, minimum and maximum values were calculated. The Chi-square test was used to compare categorical data. The appropriateness of the normal distribution of the quantitative data was evaluated with the Kolmogorov- Smirnov test. For non-parametric data, the Mann-Whitney U test was used in binary groups. The relationship between the groups was evaluated with the Spearman’s rank correlation test. The significance level was accepted as p<0.05. To compare the predictive ability and to determine the optimal cut-off values for multiple metabolic risk factors of obesity indices (ROC) analyzes were used. The cutoff points for each anthropometric indicator were identified using the Youden index.
Results
The mean age of patients in our study was 36.30±12.1 years, 68.1% (n=721) of them were female, 74.4% (n=788) were married, 36.1% (n=382) were university graduated, 26.1% (n=276) were officers and 26.6% (n=282) were smokers. The mean BMI of the participants was 30.20±7.2 kg/m2, while 52.3% (n=554) of them had BMI <30 kg/m2 normal/overweight and 47.7% (n=505) had BMI ≥ 30 kg/m2 obese. In this study, 41.1% (n=39) of men had waist circumference ≥102 cm and 66.4% (n=479) of women had a waist circumference >88 cm. Among the participants, 93.1% of men who were obese and 87.4% of women who were obese had wider waist circumference (p<0.001).
The mean WHtR of the participants was 0.58±0.1 (0.22- 1.09) and 79.7% (n=844) of them had abdominal obesity with WHtR≥0.5. The RI mean was 18.51±5.6 (8.46-117), BSI mean was 7.73±0.7 (2.46-10.92) and BRI mean was 5.18±2.2 (-0.44- 21.4). When we compared the anthropometric indices and genders, the mean values of BMI, WHtR, RI and BRI were higher in females than the males, while the mean BSI was higher in males (p<0.001).
When the age of the participants was compared with the anthropometric indices, the mean values of BMI, WHtR, RI, BSI and BRI were statistically significantly higher in the individuals over the age of 35 than those who were under the age of 35 years (p<0.001). The mean values of WHtR, RI and BRI were higher in the obese patients than those with normal/overweight patients, while the mean BSI was lower (p<0.001, p=0.016) (Table 1).
In our study, the prevalence of metabolic syndrome was found as 39.9% (n=423). The significant relationship between BMI, WHtR, RI, BSI, BRI and the existence of metabolic syndrome was found (p<0.001). Anthropometric indices were higher in patients with metabolic syndrome than in patients without metabolic syndrome (Table 2).
According to the Pearson correlation analysis between anthropometric indices, age and metabolic syndrome criteria, there was a positively poor correlation between BSI and metabolic syndrome ((r=0.181, p<0.001), while there was a moderate correlation between age and RI levels (r=0.351, r=0.452, p<0.001), and strong significant relationship between BMI, WHtR and BRI (r=0.537, r=0.619, r=0.610, p<0.001).
Roc analyzes were performed to compare the predictability of obesity indices. The area under the ROC curve in patients with metabolic syndrome (AUC) was 0.826 for BRI and WHtR, 0.790 for BMI, and 0.618 for BSI (Figure 1). The cut-off values, sensitivity and specificity of anthropometric indices according to the criteria of metabolic syndrome are shown in Table 3.
Discussion
According to the World Health Organization, BMI provides the most useful measurement of overweight and obesity. However, there is a need for new indices to predict adiposity, as it does not take into account body shape which changes by body fat, muscle mass, age and disease. In this study, we determined the relationship between these anthropometric measurements and metabolic syndrome.
While the mean values of BMI, WHtR, RI and BRI were higher in females than males, the mean value of BSI was higher in males. The mean values of BMI, WHtR, RI, BSI and BRI in those over the age of 35 were higher than those aged 35 years or younger and anthropometric index values were also increased with age. Similarly, Solak et al. found that BSI and WHtR values were higher in men than women and BMI and BRI values were statistically higher in women than men in their studies conducted with 288 patients in 2018 [13]. In this presented study, the frequency of the metabolic syndrome was found as 39.9% (35.9% in men and 40.2% in women). In a community- based multicenter study in our country, the prevalence of MetS was found to be as 28% in males, 39.6% in females and 33.9% in general [2]. Similar to our study, in Kutlu and Civi’s study, MetS frequency was 44.1% (49.0% in women and 31.2% in men). The prevalence of MetS in women was 2.11 times higher than in men [14]. In our region, the prevalence of MetS was observed to be higher than the country average due to the eating habits and lifestyle. In a study with 379 patients aged 40-65 years in China who were followed for 4,5 years, the prevalence of metabolic syndrome was found to be as 33.2% (37.8% in men and 23.9% in women) [15]. In another study conducted by Gülmez et al. in 2017, the prevalence of Met S was found to be 22.3%. They found that patients with MetS had significantly higher BMI, WC and neck circumference measurements than patients without MetS, and that neck circumference could be used as a valuable measurement method such as WC for MetS [16]. In our study, we found that the measurements of WC, WHtR, BMI, BSI and BRI were significantly higher in those with MetS than in those without MetS.
In our study, according to correlation analysis between age and metabolic syndrome criteria and anthropometric indices, there was a strong positive relationship with BMI, WHtR and BRI but a poor relationship with BSI was found. In the study by Zaid et al. which compared BSI and BRI for the capacity to assess the type and severity of dyslipidemia, they demonstrated that BRI was capable of predicting dyslipidemia, but not precede BMI and WC. On the other hand, BSI could not detect the presence or absence of dyslipidemia [17]. In a case-control study of 505 patients with and without diabetes mellitus, no significant correlation was found between HbA1c and FBG levels and anthropometric indices in patients with diabetes and they found that anthropometric indices have limited capacity and usefulness in monitoring diabetes and dyslipidemia [18]. In a study on 4395 people in Korea, both men and women showed a stronger correlation between WHtR and metabolic risk factors than BSI and found AUC values as 0.849 and 0.676, respectively. They found that WHtR had better predictive power for the metabolic syndrome [19]. In our study, compatible with the literature, the predictive values of BRI and WHtR for MetS (0,826-0,826) were found better than BMI, while the predictive values of BSI (0,618) were found very low. In a study which calculated BRI and BSI predictive values for overweight and obesity, BRI was found to have better predictive values for obesity than BSI [13]. In another study on 206 people selected according to MetS criteria, WC and WHtR were found to be better than BMI in predicting metabolic syndrome and it was reported that WHtR could be used in the diagnosis of MetS [20]. In a multicentre study with 1885 people followed for 3 years, followed by annual measurement of WC, BMI and WHtR and OGTT, WHTR value was found to be more successful than other measurements in prediabetes prediction [21].
In our study, the cut- off value for WC was 95.5 cm in women and 101.5 cm in men with MetS. According to data of the
Association of Endocrine and Metabolism of Turkey for the Turkish population, ≥100 cm in men and ≥90 cm in women is proposed as abdominal obesity criterion.
The study by Gu et al. conducted with 5685 people in 2018, showed that BMI, WC, and WHtR could similarly predict MetS in men (0.698 – 0.691 – 0.688) in men and MetS in women (0.676 – 0.666). The optimum cutting values of BMI, WC, and WHtR in the diagnosis of MetS in men were 24.1 kg/m2, 83.5 cm, and 0.51, respectively while these values were found to be 23.5 kg/ m2 and 77.5 cm in women [22]. In another study, the strongest predictor of MetS for men was BMI (0.770) and abdominal volume index (AVI) for women was (0.720). However, no significant difference was observed between WC and these two indices. In contrast, it was found that BSI did not adequately predict MetS in both genders [15].
In conclusion, we found that BMI, WHtR and BRI measurements predicted MetS more accurately than other anthropometric measurements in predicting metabolic syndrome. The most important limitation of the study was that the study was conducted in a tertiary health care facility, so it may not represent the community. To identify the relationship between obesity indices and metabolic risk factors, multi centers, bigger samplings and more comprehensive studies are needed. These anthropometric measurements are simple and easy, so these tests can be easily used in practice, especially in primary health care facilities.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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Evaluation of the knowledge level and attitude of physicians towards obstructive sleep apnea syndrome
Ayşe Sarıoğlu 1, Şamil Ecirli 2, Hayriye Şentürk 1, Selma Pekgör 1, Hülya Vatansev 3, Taha Tahir Bekçi 4
1 Department of Family Medicine, University of Health Science, Konya Training and Research Hospital, 2 Department of Internal Medicine, University of Health Science, Konya Training and Research Hospital, 3 Department of Chest Diseases, Meram Medical Faculty, Necmettin Erbakan University, 4 Department of Chest Diseases, University of Health Science, Konya Training and Research Hospital, Konya, Turkey
DOI: 10.4328/ACAM.20304 Received: 2020-08-11 Accepted: 2020-09-10 Published Online: 2020-09-21 Printed: 2021-05-01 Ann Clin Anal Med 2021;12(5):479-482
Corresponding Author: Selma Pekgör, University of Health Science, Konya Training and Research Hospital, Family Medicine Clinic, Konya, Turkey. E-mail: selmapekgor@outlook.com P: +90 3322210000/1803 Corresponding Author ORCID ID: https://orcid.org/0000-0001-9907-1842
Aim: The knowledge level and approach of physicians in Turkey to obstructive sleep apnea syndrome (OSAS) is unknown. The aim of this study is to evaluate the knowledge level and attitudes of physicians from various branches to OSAS.
Materials and Methods: In this cross-sectional analytical study, Obstructive Sleep Apnea Knowledge and Attitude (OSAKA) questionnaire was performed in order to measure knowledge levels and attitudes to OSAS. SPSS 22 package program was used for statistical analysis of data, p- value <0.05 was considered significant.
Results: Four hundred forty-four physicians (16 from fundamental sciences, 295 from internal branches, 99 from surgical branches and 34 general practi- tioners) participated in the study. The mean knowledge score was 11.41 ± 3.05 (0-18). The knowledge score of physicians aged 30 years and younger was significantly higher than those aged 31 years and older (p <0.001). There was a negative correlation between knowledge score and age of doctors (rs= -0.214, p <0.001). The level of knowledge of pulmonologists and ENT specialists was higher compared to physicians of other branches (p <0.05). No significant dif- ference was detected between the knowledge scores of academicians and non-academicians (p> 0.05). There was no correlation between knowledge scores and academic degrees (rs= -0.072, p = 0.188). It was observed that the knowledge level of physicians whose professional experience was 4 years or less was higher than that of those whose professional experience was 5 years or more (p = 0.001). A negative correlation was also detected between knowledge scores and professional experience (rs= -0.193, p <0.001).
Discussion: It was determined that physicians’ level of knowledge about OSAS was not sufficient and they felt insufficient about the management of OSAS patients. It would be appropriate to raise awareness of OSAS among practicing physicians within the scope of vocational training as well as in medical facul- ties and institutions providing specialist training.
Keywords: Obstructive sleep apnea; Knowledge; Attitudes; Physician; Questionnaire; OSAKA
Introduction
“Obstructive Sleep Apnea Syndrome” (OSAS) is the most severe form of sleep disorders with the highest prevalence in the community. OSAS is a syndrome characterized by recurrent partial or complete collapse of the upper respiratory tract during sleep [1]. If OSAS is not treated, it can lead to cardiovascular system diseases such as hypertension, heart failure, stroke, arrhythmia and cognitive disorders [2-4]. In a longitudinal study involving more than 10,000 participants, OSAS has been shown to be an independent risk factor for sudden cardiac death [5]. It has been reported that it causes serious loss of life and property by increasing the risk of traffic accidents and the rate of fatal accidents by causing daytime sleepiness [6,7].
OSAS is observed in approximately 2-4% of American adults [8,9]. In a meta-analysis examining 24 studies, the prevalence of OSAS ranged from 9% to 38%. The prevalence has been shown to increase with age and is more common in men and obese people. In recent years, the incidence of OSAS has increased along with obesity [10].
Although the prevalence of OSAS is so high and it causes serious morbidity and mortality, it is often not diagnosed and/ or treated. Young et al. reported that 82% of men and 93% of women with sleep apnea were undiagnosed. It has been reported in the conducted studies that the rate of referral of individuals at risk to higher levels for further examination is low [11-13]. The low level of knowledge and awareness of health workers in this regard may be an important factor. Since OSAS patients may apply to different clinics with very different complaints, the knowledge and awareness of physicians in all branches are of great importance for the early diagnosis and treatment of patients at risk. The aim of this study is to evaluate the knowledge levels and attitudes of physicians from different branches to OSAS.
Material and Methods
Our study was planned as a descriptive, cross-sectional study. Four hundred forty-four physicians working in Konya Training and Research Hospital, Necmettin Erbakan University Meram Medical Faculty Hospital, Selçuk University Medical Faculty Hospital and other health institutions in Konya city center were included in the study. No financial incentive was offered to complete the survey. Participants’ information such as age, gender, academic degree, post-graduation professional year and field of expertise were recorded. OSAKA (Obstructive Sleep Apnea Knowledge and Attitudes Questionnaire) questionnaire was applied in order to measure OSAS knowledge level and attitudes. OSAKA is a validated and reliable questionnaire used in various studies worldwide [14]. This questionnaire includes 18 knowledge level questions about the epidemiology, pathophysiology, symptoms, diagnosis and treatment of OSAS. The answers comprise of “right”, “wrong” and “do not know” options. The option “do not know” was regarded as the wrong answer. The five attitude questions in the second part are of the Likert type (Likert scale: 1 = not important … 5 = extremely important) and assess the importance of identifying patients with OSAS, with the first two assessing the importance of OSAS as a clinical disorder. The remaining three questions assess the self-confidence of doctors for the diagnosis and treatment of OSAS. The specialties of the participants were gathered under 8 titles which are evaluated under fundamental medical sciences: biochemistry, medical genetics, microbiology, and pathology. Under internal medicine sciences are emergency medicine, family medicine, dermatology, internal medicine, physical therapy and rehabilitation, pediatrics, psychiatry, public health, infectious diseases, cardiology, neurology, nuclear medicine, and radiology. Under surgical sciences are anesthesia, pediatric surgery, general surgery, thoracic surgery, ophthalmology, cardiovascular surgery, gynecology and obstetrics, neurosurgery, orthopedics, plastic surgery, and urology departments. Pulmonology and otorhinolaryngology (ENT) departments where the diagnosis and treatment of OSAS disease is performed, were evaluated in separate categories. Practitioners were also evaluated in a separate category. Statistical Analysis
The data obtained from the study were evaluated with SPSS 22.0 package program. Categorical variables were presented as frequency and percentage; while numerical variables were presented as mean±ss or (median, min, max). The Kolmogorov- Smirnov test was used to determine whether the continuous numerical variables fit the normal distribution. Variables were observed not to be consistent with normal distribution (p <0.05). Therefore, non-parametric test methods were preferred in our studies. The Mann-Whitney U-analysis method was used for the comparison of two groups and the Kruskal-Wallis analysis method was used for multiple group comparisons. Paired comparisons were made. Spearman’s Rho correlation analysis was used to determine the relationship between numerical variables. The Chi-Square analysis with Monte Carlo approach was used to determine the relationship between categorical variables and to determine independence status. A value of p<0.05 was considered statistically significant in all analyses.
Results
Among the participants, 44.8% were female and 55.2% were male. The mean age was 33.4 ± 7.82 (23-59) years. The average post-graduation professional experience was 8.8 ± 7.87 (1-36) years. While 4.7% of the participants were academicians, 95.3% were working as specialists or general practitioners; 3.6% of physicians are practicing in basic sciences, 64.0% in internal sciences, 19.6% in surgical sciences, 2.5% in pulmonology, 2.7% in ENT and 7.7% as a general practitioner (Table 1).
The mean knowledge score was 11.41 ± 3.05 (0-18). The mean knowledge score of women was 11.50±3.05 and the mean knowledge score of men was 11.33±3.06. There was no significant difference between the mean knowledge scores of men and women (p> 0.05). The mean number of correct answers of doctors aged 30 years and younger was significantly higher than those aged 31 years and older (p <0.001). There was no significant difference between the mean number of correct answers between the academicians and non-academicians (p> 0.05). It was observed that the knowledge level of physicians with professional experience of 4 years or less was higher than that of doctors with 5 years of professional experience or more (p = 0.001). The knowledge level of pulmonology and ENT doctors was higher than that of doctors of other branches (p <0.05) (Table 1).
There was a negative correlation between the number of correct answers and the age of doctors (rs= -0.214, p <0.001). Similarly, there was a negative correlation between the number of correct answers and professional experience (r).s= -0.193, p <0.001). There was no correlation between the number of correct answers and academic degrees of doctors (rs= -0.072, p = 0.188).
The first two attitude questions evaluated the attitudes of doctors towards the importance of OSAS in clinical practice, and this score was quite high. It was observed that up to 95% of the physicians were concerned about OSAS. The scores of the remaining three questions related to confidence in the diagnosis and treatment of OSAS were low; only 30% of physicians found their knowledge sufficient to deal with OSAS.
No significant difference was observed between attitude scores and age, professional experience, and other characteristics of the participants. There was a positive correlation between attitude scores and knowledge level (p <0.05) (Table 2).
Discussion
There are different studies in the literature that assess the level of knowledge and attitudes to sleep disorders or OSAS among physicians. However, most of them are performed between doctors of the single specialty area such as anesthesiologists and cardiologists or among newly graduated doctors [15-18]. Jokubauskas et al. conducted a study in which they surveyed dentists with a questionnaire they created [19]. In a study, a questionnaire was applied to medical students and physicians to measure the level of knowledge and attitude related to general sleep medicine [20]. There are also surveys conducted among primary care physicians that include questions about general sleep medicine [20-22]. Although Williams’ work is similar to ours, our study is the most extensive one in this field with 444 participants, involving all specialization groups including practitioners and academicians [23].
Similar to other studies, in our study, no difference was observed between gender and knowledge level [15-17, 23]. In our study, as in the first study in which OSAKA was developed, a negative correlation was found between age and professional year and knowledge level [14]. Similarly, Williams’ study showed that those with longer professional experience had lower levels of knowledge [23]. This may be due to the fact that the general medical knowledge of young physicians is up-to-date, and unused information of physicians who have been working in different fields for many years is forgotten. In Southwel’s and Wang’s studies, it was reported that there was no difference between age and professional year and level of knowledge [16,17]. This may be due to the fact that anesthesiologists and cardiologists encounter OSAS frequently in their daily practice and update their knowledge about OSAS. In addition, Wang’s study showed that those with a high professional title had a higher level of knowledge [16]. In our study, no significant difference was observed between academicians and non- academicians.
In our study, the average correct response rate of knowledge questions (63%) was similar to other studies conducted in recent years. The rate was found as 66% in a study of anesthetists, 62% in the study by Wang et al. and 60% in a study conducted in the primary care [15, 16].
In our study, it was seen that the level of knowledge of chest diseases and ENT specialists was higher compared to other fields. This result may be attributed to the fact that OSAS patients usually apply to the ENT or chest diseases department. While in Schotland’s study, the level of knowledge of internal medicine and family physicians was higher than that of pediatricians, no difference was observed in Williams’s study [14, 23].
OSAS remains a relatively poorly diagnosed condition in the general population. In addition, patients in primary care are not screened for OSAS, and comorbidities in high-risk patients fail to be identified [24]. In the studies performed, the rate of physicians referring patients for OSAS was found to be below the required level. In the study conducted by Raymond in primary care physicians, the rate of referral for evaluation of OSAS according to the symptoms was very low [22]. In our study, 30% of the doctors weren’t confident about identifying patients with OSAS risk, while 32% were undecided. Similarly, 32% of cardiologists reported that they were unsure about this [17]. In our study, similar to the literature, the level of knowledge of physicians about OSAS was found to be very low.
The findings of this study showed that the diagnosis and treatment of OSAS should be given more attention in medical faculties and institutions providing specialist education. We think that physicians working in different branches should update their knowledge about OSAS through both vocational retraining and personal efforts. This is very important for the early recognition of patients at risk for OSAS and prevention of comorbidities in primary care and different branches.
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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Ayşe Sarıoğlu, Şamil Ecirli, Hayriye Şentürk, Selma Pekgör, Hülya Vatansev, Taha Tahir Bekçi. Evaluation of the knowledge level and attitude of physicians towards obstructive sleep apnea syndrome. Ann Clin Anal Med 2021;12(5):479-482
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Correlation of chest CT and RT-PCR testing in coronavirus disease 2019 (COVID-19) in Turkey
Şenol Arslan 1, Orhan Delice 1, Mustafa Kahraman 2, Sibel İba Yılmaz 3, Mehtap Hülya Aslan 4
1 Department of Emergency Medicine, Erzurum Regional Training and Research Hospital, 2 Department of Radiology, Erzurum Regional Training and Research Hospital, 3 Department of Clinical Microbiology and Infectious Diseases, Erzurum Regional Training and Research Hospital, 4 Department of Microbiology, Erzurum Regional Training and Research Hospital, Erzurum, Turkey
DOI: 10.4328/ACAM.20310 Received: 2020-08-15 Accepted: 2020-09-14 Published Online: 2020-09-24 Printed: 2021-05-01 Ann Clin Anal Med 2021;12(5):483-487
Corresponding Author: Şenol Arslan, Erzurum Regional Training and Research Hospital, Department of Emergency Medicine, Erzurum, Turkey. E-mail: drsenolarslan@gmail.com P: +90 530 4164134 F: +90 ( 442 ) 232 50 25 Corresponding Author ORCID ID: https://orcid.org/0000-0002-6636-5307
Aim: Chest CT plays an important role in the treatment and diagnosis of COVID-19. It is important to remember that patients with RT-PCR test positive for COVID-19 infection may have normal chest CT.
Material and Methods: This study included patients who underwent RT-PCR and chest CT tests, as well as patients with suspected and confirmed COVID-19 positive cases according to the algorithm of the Institute of Science of Ministry of Health in Turkey were included in this study. The patients were divided into two groups as positive and negative according to RT-PCR results. These groups were divided into two subgroups: with CT findings compatible with COVID-19 and without them. When the RT-PCR test was taken as the gold standard, the specificity, sensitivity, PPV, NPV, and accuracy rates of chest CT were investigated in detecting COVID-19 infection.
Results: RT-PCR was positive in 192 patients and negative in 418 patients. The chest CT scan was positive in 43% (82/192) of 192 patients whose RT-PCR results were positive. Chest CT scan was positive in 25% (108/418) of 418 patients whose RT-PCR results were negative. In 31% of the patients (190/610), chest CT findings were positive for COVID-19. When RT-PCR results were taken as a reference, accuracy, specificity, and sensitivity values in terms of COVID-19 infection of chest CT were 44% (95% CI, 392/610 patients), 43% (95% CI, 82/192 patients), and 74% (95% CI, 310/418 patients) respectively.
Discussion: According to these data, we think that chest CT is not very successful in detecting patients infected with COVID-19, contrary to the literature. Clinicians should always be careful to identify patients with COVID-19 infection with normal thorax CT or negative RT-PCR testing.
Keywords: 2019-nCoV; RT-PCR; Computed tomography; Sensitivity; Specificity
Introduction
In December 2019, a series of “unknown viral pneumonia” cases were reported in Wuhan City, China [1]. The responsible pathogen has been described as the 2019 new coronavirus (2019-nCOV), and the World Health Organization (WHO) has named the associated pulmonary syndrome as Corona Virus Disease-2019 (COVID-19) [2]. Typical clinical signs are fever and cough, in addition to non-specific symptoms such as fatigue, shortness of breath, muscle pain, and headache [3].
It is important to detect infected patients early and keep them away from healthy individuals, because there are no specific vaccines and treatments for COVID-19. Social distancing is the most important strategy to save lives.
A reverse transcription-polymerase chain reaction (RT-PCR) test is required for the diagnosis of COVID-19. However, it takes a long time to obtain test results and produces a certain amount of false-negative results [4]. In a previous study, it was reported that the total positivity rate of RT-PCR for throat swab samples was between 30% and 60% in the first presentation [5]. In this case, RT-PCR with low sensitivity cannot quickly diagnose many of the COVID-19 patients, so these patients will not receive treatment in time. As a result, such patients will cause a rapid spread of the pandemic to a larger population, as the virus is highly contagious. Chest CT is relatively easy to use as a routine imaging tool for diagnosing pneumonia, and it is possible to diagnose pneumonia rapidly using CT. In some studies, it was noted that the RT-PCR test had limited sensitivity, but chest CT might show pulmonary abnormalities compatible with COVID-19 in patients whose RT-PCR results were negative [4, 6]. In the light of this information, it may be thought that chest CT will be useful for the diagnosis of COVID-19. In this study, we compared RT-PCR and chest CT test results in 610 patients suspected of COVID-19 to determine the value of chest CT compared to RT-PCR testing for diagnosis.
Material and Methods
Patient selection
Our study was a retrospective analysis, which was approved by the hospital ethics committee. Patients who applied to Erzurum Regional Training and Research Hospital of Saglik Bilimleri University for COVID-19 between 13 March 2020 and 15 May 2020 were evaluated. Written informed consent was obtained from the patients for the anonymized information to be published in this article. This study included patients who underwent both RT-PCR tests and chest CT and patients with probable and definitive COVID-19 positive cases according to the algorithm of the Institute of Science of Ministry of Health in Turkey were included in this study (Figure 1). RT-PCR results were obtained from the electronic medical records of the Ministry of Health’s Public Health Management System (PHMS). If a patient had more than one RT-PCR test, when any of the test results were found positive, the patient was considered to have been diagnosed with COVID-19. A repeated test was performed at intervals of 1 day or more in patients whose first RT-PCR test was negative.
The whole patient group underwent a CT scan without contrast within 5 days or less. If more than one chest CT scan was performed on one patient, care was taken to ensure the time interval between RT-PCR test and chest CT less than or equal to 5 days for comparison of diagnostic performance. Patients with a time interval of more than 5 days between both tests were excluded from the study. Atypical and typical chest CT findings were recorded according to chest CT characteristics which were previously described for COVID-19 [4, 5]. The patients were divided into two groups as positive and negative RT-PCR results. These groups were divided into two subgroups: with and without CT findings compatible with COVID-19 (Figure 2). When the RT-PCR test was taken as the gold standard, the specificity, sensitivity, accuracy, NPV, and PPV rates of chest CT in detecting COVID-19 infection were investigated.
Imaging protocol and analysis
All images were obtained in a supine position on a single BT (Aquilion 64, Toshiba, Japan) system. The main features of BT were as follows: matrix = 512 × 512, tube voltage = 120 kVp, pitch = 0.99 – 1.22 mm, automatic tube current modulation (30 – 70 mAs), field of view = 350 mm × 350 mm, slice thickness = 5 mm. All CT images were reconstructed to have a slice thickness of 1 mm. Chest CT images were examined by two radiologists who were blinded to RT-PCR results and had sufficient experience in chest CT interpretation. A decision was made as to whether CT findings were positive or negative. Both radiologists had sufficient information about the patients’ clinical symptoms (fever, dry cough, shortness of breath), and their epidemiological history. Radiologists described the features of chest CT. In addition, radiologists divided the patients into two groups, compatible or incompatible with the COVID-19 infection, by reviewing the chest CT images. Statistical Analysis
Statistical analyzes of the study were performed using the SPSS 23 version (SPSS Inc. Chicago, IL). Categorical variables are shown with frequency and percentage, continuous variables with mean and standard deviation. Negative predictive value, positive predictive value, accuracy, sensitivity and specificity results were calculated by probability ratio based on the RT- PCR result used as the reference (gold standard) in all data sets and subgroups. In the analysis, the confidence interval was determined as 95%. The performance of chest tomography in determining COVID-19 in different age groups and gender variables was also compared with the chi-square test. In the analysis, the degree of significance was taken as 0.05.
Results
General description:
Ten patients with a time interval of more than 5 between RT- PCR testing and chest CT were excluded from the study. The mean time interval between RT-PCR test and chest CT was determined as 1 day (time interval 0-5 days). The working flow diagram is shown in Figure 2. RT-PCR was positive in 192 patients and negative in 418 patients. In 31% of the patients (190/610), chest CT findings were positive for COVID-19. The main findings of chest CT scans of patients were ground-glass opacities (97% [185/190]) and consolidations (87% [166/190]) (Table 1). Chest CT scan was positive in 41% (80/192) of 192 patients whose RT-PCR results were positive. Chest CT scan was positive in 25% (108/418) of 418 patients whose RT-PCR results were negative.
Performance of Chest CT in the diagnosis of COVID-19:
One hundred ninety patients had positive chest CT findings. When RT-PCR results were taken as a reference, accuracy, sensitivity, and specificity values in terms of COVID-19 infection of chest CT were 44% (95% CI, 392/610 patients), 43% (95% CI, 82/192 patients), and 74% (95% CI, 310/418 patients), respectively. The performance of chest CT in the diagnosis of COVID-19 in age and gender groups is shown in Table 2.
When thorax CT was evaluated in the diagnosis of COVID-19, there was no significant difference between men and women in terms of accuracy, sensitivity, NPV, and PPV (p = 0.08, 0.08, 0.32, 0.94 and, respectively). However, the specificity of thorax CT was higher for men than for women, and this difference was significant (p = 0.04) (Table 3).
The sensitivity, NPV, and accuracy values of chest CT in patients over the age of 60 were higher than patients under the age of 60. This difference was also statistically significant (p = 0.000, 0.03, 0.000, respectively). There was no difference in specificity and PPV between <60 and ≥60 (p = 0.31, 0.36, respectively) (Table 3).
Patients with a negative first RT-PCR test and a positive RT- PCR in subsequent tests:
In our study, the first two RT-PCR test results were negative in three out of 33 patients (two-day test interval), and the third RT-PCR results were positive. Two of these patients had positive chest CT findings compatible with COVID-19. In 30 patients, the first RT-PCR test results were negative, and the second RT-PCR tests performed within two days were positive. Among these 30 patients, 17 had CT findings consistent with COVID-19.
Discussion
An increase in the number of infected patients during a pandemic is inevitable. As a result of this, there will be an unmet level of the RT-PCR kit which is necessary for the diagnosis of COVID-19. According to the algorithms, the RT-PCR test has an important place in the isolation of patients or the decision of hospitalization. Some studies show that RT-PCR has low sensitivity in detecting patients infected with COVID-19. There are a lot of reasons for low sensitivity, such as low viral load, poor nucleic acid detection technology, and inappropriate clinical sampling. In our study, the positivity rate of RT-PCR test for swab samples taken from the nose and throat regions was found to be 31% (95% CI), similar to the previous study by Yang et al (30 – 60%) [5].
Studies show that characteristic CT features of COVID-19 are ground-glass opacity, and multifocal pneumonic infiltrations [6, 7, 8]. In our study, the results of chest CT of the patients with COVID-19 were as follows: multiple lobes 73% (139/190), multiple lesions 69% (132/190), ground-glass opacity 97% (185/190), consolidation 87% (166 / 190), vascular dilatation 13% (24/190), and crazy-paving sign 29% (55/190). These findings were consistent with previous findings in the literature. Chest CT reveals many findings in COVID-19 patients as in our study. The severity and stage of the infection are shown as the reason why these findings are variable and varied [9]. However, these findings are not specific to COVID-19. They can be seen in other viral and atypical infections as well. Therefore, we cannot distinguish COVID-19 from other viral types of pneumonia, such as Severe Acute Respiratory Syndrome and Middle East Respiratory Syndrome, using chest CT [10, 11].
Some studies have shown that chest CT has a higher sensitivity than RT-PCR in detecting patients infected with COVID-19 [12]. According to this, it is thought that chest CT may be a more sensitive, practical, and fast method to diagnose and evaluate COVID-19, especially in the pandemic regions. When we take RT-PCR results as a reference in our 610 disease series, the accuracy, specificity, and sensitivity of chest CT in terms of COVID-19 infection are 44% (95% CI, 392/610 patients), 74% (95% CI, 310/418 patients) and 43% (95% CI, 82/192 patients), respectively. Our study has shown that chest CT is not sensitive enough for COVID-19.
In previous studies, conducted by Zhong et al and Tao et al, positive chest CT ratios were 76.4% and 97% in RT-PCR positive COVID-19 patients, respectively. In addition, Tao et al also demonstrated that more than 70% of patients with negative RT-PCR tests had typical chest CT findings compatible with COVID-19 [13, 14]. In our study, the rate of patients with chest CT findings among patients who were RT-PCR positive (true positive) was 41% (80/192). This may be due to the early diagnosis of these patients. The rate of patients with chest CT findings among patients who had negative RT-PCR results was 25% (108/418).
Unlike other previous studies, our study has shown that the false positive rate of CT is low. Our first goal is to isolate patients and implement appropriate treatment for the COVID-19 outbreak. Even some false positives of CT could be accepted to provide rapid control of the disease. However, our study has shown that CT has low performance in detecting true positives.
According to these data, we think that chest CT is not very successful in detecting patients infected with COVID-19, contrary to the literature. In the literature, there are studies showing that patients with RT-PCR positive COVID-19 infection may have a normal chest CT at admission [12, 14, 15]. When these studies and our study are evaluated together, it is concluded that the normal evaluation of chest CT cannot rule out the diagnosis of COVID-19, especially in patients who are symptomatic in the early period. Although the RT-PCR test has a false negative rate to some extent, the RT-PCR test remains the gold standard to make a definitive diagnosis of COVID-19. The conclusion we draw from our series is that chest CT may be a diagnostic aid rather than a diagnostic tool.
Conclusion
It is important to diagnose patients with COVID-19 at an early stage and isolate them from the community in terms of ending the pandemic. In addition, early diagnosis of these patients will decrease the mortality rates. However, neither RT-PCR nor chest CT can do this alone. Using the two tools together will make the job of clinicians seriously easier for us.
After all, the virus tests all of us. We need to figure out how good RT-PCR or thorax CT is to pass this test.
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.20310
Şenol Arslan, Orhan Delice, Mustafa Kahraman, Sibel İba Yılmaz, Mehtap Hülya Aslan. Correlation of chest CT and RT-PCR testing in coronavirus disease 2019 (COVID-19) in Turkey. Ann Clin Anal Med 2021;12(5):483-487
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This work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of the license, visit https://creativecommons.org/licenses/by-nc/4.0/
Comparison of the endovascular therapy with drug-coated balloon and bypass surgery for Trans-Atlantic Inter-Society Consensus II C and D femoropopliteal lesions
Sedat Ozcan 1, Emced Khalil 2
1 Department of Cardiovascular Surgery , School of Medicine, Canakkale Onsekiz Mart University, Çanakkale, 2 Department of Cardiovascular Surgery , School of Medicine, Ordu University Education and Research Hospital, Ordu, Turkey
DOI: 10.4328/ACAM.20312 Received: 2020-08-19 Accepted: 2020-09-19 Published Online: 2020-09-27 Printed: 2021-05-01 Ann Clin Anal Med 2021;12(5):488-493
Corresponding Author: Emced Khalil, Ordu University Education and Research Hospital Department of Cardiovascular Surgery, Ordu, Turkey. E-mail: emjedkhalil@gmail.com P: +90 5052401565 Corresponding Author ORCID ID: https://orcid.org/0000-0003-1050-2656
Aim: The optimal revascularization strategy with the greatest durability and the lowest morbidity in femoropopliteal artery occlusions still remains debated. This study aimed to compare 2-year follow up after endovascular therapy (EVT) and femoropopliteal bypass in subjects with TASC II C and D femoropopliteal artery occlusions.
Material and Methods: This study included 92 patients with extensive (TASC II C and D) de novo femoropopliteal occlusion who underwent EVT or femoropop- liteal bypass surgery. Drug coated balloons competent with target vessel diameter were used for PTA interventions.
Results: A total of 92 subjects with 92 limbs treated were included in the study. Fifty-one of the study subjects received EVT and 41 underwent femoropopliteal bypass surgery. The primary patency rate was higher in the femoropopliteal bypass group compared to the PTA group at 6th, 12th, and 24th -month follow-up studies.
Discusion: We compared the early and mid-term clinical outcomes of EVT and femoropopliteal bypass for TASC II C and D lesions of the femoropopliteal artery. We hypothesized that, given the superiority of drug-coated balloons compared to uncoated balloons in terms of postoperative outcomes, EVT with drug-coated balloons would provide superior primary patency compared to femoropopliteal bypass in subjects with complex femoropopliteal artery disease. However, our findings failed to demonstrate the superiority of EVT with drug-coated balloons over femoropopliteal bypass. This result supports the evidence derived from previous studies comparing the two treatment strategies for TASC II C and D lesions of the femoropopliteal artery. Our results indicate that postoperative ABI is also higher in subjects undergoing femoropopliteal bypass than those receiving EVT. Femoropopliteal bypass surgery provides a higher primary patency rate and a more significant improvement in ABI in subjects with TASC II C and D femoropopliteal artery occlusions with similar complication rates for the two treatment strategies.
Keywords: Femoropopliteal bypass; Endovascular; TASC
Introduction
Peripheral arterial disease (PAD) constitutes a significant healthcare problem [1]. About 25% of patients with symptoms of PAD require intervention and 5% progress to critical limb ischemia [2]. The risk of limb amputation and all-cause mortality has been shown to be increased in patients with critical limb ischemia [3]. Revascularization is critical in reducing mortality and morbidity [3].
The femoropopliteal region, which harbors the superficial femoral artery (SFA) and the popliteal artery, is particularly prone to atherosclerotic vascular disease due to the exposure to high dynamic forces of flexion, extension, shortening and torsion [4]. Vascular injury stemming from the cyclic deformation, strain caused by external forces, and cellular proliferation is considered to be responsible for the increased prevalence of PAD in the femoropopliteal region. Femoropopliteal bypass is the traditional first-line revascularization strategy for TASC II class D femoropopliteal disease, due to the lower patency rate with percutaneous transluminal angioplasty (PTA) in SFA stenosis compared to surgical revascularization [5]. On the other hand, recent advances in endovascular device technology, including hydrophilic guidewires, drug-coated balloons, and drug-eluting stents contain high success rates (exceeding 80– 90%) with endovascular therapy (EVT) in TASC II C/D lesions [6]. However, past studies comparing EVT with femoropopliteal bypass for TASC II C and D lesions have provided inconsistent results. Moreover, there are only a few studies comparing EVT with femoropopliteal bypass in the treatment of femoropopliteal disease. In general, the outcome achieved with bypass surgery is still better than that of PTA [7]. We hypothesized that EVT with drug-coated balloons could provide a primary patency rate comparable to femoropopliteal bypass surgery.
The purpose of this study was to compare the 2-year clinical outcomes of EVT and femoropopliteal bypass in subjects with TASC II C and D femoropopliteal artery occlusions.
Material and Methods
Study Group
This retrospective study included 92 patients with extensive (TASC II C and D) de novo femoropopliteal disease who underwent EVT or femoropopliteal bypass in Ordu University, Education and Research Hospital between March 2016 and March 2018. The ethic approval of the present the study was obtained from Ethical Committee of Ordu University, School of Medicine (Approval number: 2020/186). The indications for revascularization included intermittent claudication, resting pain, critical limb ischemia, wound infection, and tissue loss. All subjects were evaluated with duplex ultrasound and CT angiography subsequent to physical examination and ankle- brachial index (ABI) calculation. Limbs with significant stenosis requiring endarterectomy, limbs without at least one patent vessel up to the distal third of the leg, patients with occlusion of the tibioperoneal trunk, and subjects receiving hybrid therapy were excluded from the study. Data regarding demographic features, lesion characteristics and complications were collected and retrospectively evaluated. All participants provided written informed consent for the use of their data in this research.
Intervention
The optimal treatment strategy for each patient was chosen by the consensus of the cardiovascular team consisting of a cardiovascular surgeon, a cardiologist and a radiologist.
All femoropopliteal bypass surgeries were carried out under general anesthesia. Polytetrafluoroethylene (PTFE) grafts or saphenous vein grafts were used for femoropopliteal bypass surgeries. Autologous veins were the first choice for bypass grafting. The proximal anastomotic region was the common femoral artery or superficial femoral artery, and the distal anastomosis was located on the above-knee popliteal artery or below-knee popliteal artery.
All EVT interventions were performed in a standard manner by the same team. Following the local anesthesia of the groin, a 6 or 7F introducer was inserted into the ipsilateral common femoral artery. UF heparin bolus of 100U/kg was administered to all subjects undergoing PTA. An angled, tapered catheter and a hydrophilic guidewire were used to pass through the lesions. A wire escalation technique was used for crossing total occlusions. The subintimal technique was used only in cases where other techniques failed to pass through the lesion. DCBs matching the target vessel diameter were used for PTA interventions. Bail-out stenting was reserved for residual stenosis >30% and for flow-limiting dissections. A loading dose of 300 mg of clopidogrel was administered, followed by 75 mg daily for twelve weeks, in combination with aspirin and statin therapy on a long-term basis.
Follow-up was conducted by means of a clinical assessment, including ABI, and a duplex scan at 1, 6, 12, and 24 months. Primary patency, which was defined as a treated vessel that remained patent without restenosis or revascularization during follow-up, was recorded for each patient. A more- detailed medical examination and imaging were employed for any suspected complications. All complications including hematomas, pseudoaneurysm formation, wound infections, bleeding, and distal embolism were recorded during follow-up. The difference in primary patency rate between subjects undergoing EVT or femoropopliteal bypass was the primary outcome measure of the study. The differences in complication rate, ABI, and length of hospital stay between the groups were the secondary outcome measure.
Statistical analysis
All analyses were performed on Statistical Package for the Social Sciences (SPSS v21 Inc., Chicago, IL, USA). Data are given as mean ± standard deviation or median (minimum – maximum) for continuous variables according to the normality of distribution, and as frequency (percentage) for categorical variables. Categorical variables were evaluated using the Chi- square or Fisher’s exact tests. The Shapiro-Wilk test was used to determine whether variables were normally distributed. The independent samples t-test was used to analyze normally distributed variables, and the Mann-Whitney U test was used to analyze non-normally distributed variables. The change in ABI was analyzed with the Wilcoxon Signed Ranks test for repeated measurements. Between-groups comparison of the ankle- brachial index was performed by analyzing the differences between the repeated measurements, using the Mann- Whitney U test. Generalized estimating equations were used to compare primary patency rates between the groups. Repeated measurements of primary patency rate were analyzed with the Cochran’s Q test. Pairwise comparisons were performed with the Bonferroni correction method. Two tailed p-values of less than 0.05 were considered statistically significant.
Results
Patient and lesion characteristics
A total of 92 subjects with 92 limbs treated were included (mean age 65.87 ± 13.17 years, 87% males). Fifty-one of the study subjects received EVT and 41 underwent Femoropopliteal bypass surgery. Comparison of the demographic features of the study groups is presented in Table 1. Subjects receiving EVT were more likely to have Rutherford class 4 and 5 lesions, whereas subjects undergoing femoropopliteal bypass were more likely to have Rutherford class 3 and 4 lesions. The frequencies of TASC II C and D lesions were similar in the two groups. Diabetes was more frequent among subjects undergoing femoropopliteal bypass than in those receiving PTA (53.66% vs. 21.57%, p = 0.003). In contrast to diabetes, hypertension was more frequent among subjects receiving PTA than in those undergoing femoropopliteal bypass (58.82% vs. 24.39%, p = 0.002). Table 2 demonstrates the lesion characteristics. Lesion length was longer in subjects receiving PTA compared to those undergoing femoropopliteal bypass surgery (16 [4 – 50] cm vs. 12 [5 – 50] cm, p=0.022).
Surgery characteristics
Surgical features of the subjects undergoing femoropopliteal bypass are given in Table 3. Distal anastomosis point was above- knee in 25 subjects (60.98%) and below-knee in 16 subjects (39.02%). Autologous vein grafts were used in 75.61% of these subjects, while PTFE grafts were implemented in only 24.39% of the subjects undergoing surgery. Drug-coated balloons were used in all subjects. Bail-out stenting was employed in only 5 subjects (9.8%).
Outcomes
The primary patency rate was higher in the femoropopliteal bypass group compared to the PTA group at 6th, 12th, and 24th month follow-up (Figure 1). All groups displayed significant improvements in ABI in the post-procedural first month. However, the improvement in ABI was higher in the femoropopliteal bypass group compared to the PTA group (p = 0.008) (Figure 2). The median length of hospital stay in the PTA group was shorter compared to the femoropopliteal bypass group (2 [1 – 10] days vs. 5 [3 – 20] days, p < 0.001) (Figure 3). Four subjects receiving PTA (7.84%) and 2 subjects undergoing femoropopliteal bypass (4.88%) required amputation (p=0.689). No mortality was recorded during the follow-up.
Discussion
In this study, we compared the early and mid-term clinical outcomes of EVT and femoropopliteal bypass for TASC II C and D lesions of the femoropopliteal artery. Findings of the present study demonstrate that femoropopliteal bypass surgery provides a higher primary patency rate at early and mid-term follow-up in subjects with TASC II C and D femoropopliteal artery occlusions. The femoropopliteal bypass also leads to a more significant improvement in ABI compared to that achieved with EVT. Complication rates are similar in both treatment approaches. However, the length of hospital stay is significantly shorter in subjects receiving EVT compared to those undergoing femoropopliteal bypass surgery. Management of the occlusive lower extremity PAD is generally guided by the severity of the symptoms reported by the patients. Patients with mild to moderate symptoms are often assigned to conservative treatment, including smoking cessation, regular exercise, and regulation of cardiovascular risk factors [8, 9]. However, patients with critical limb ischemia are definite candidates for revascularization, since the timely restoration of adequate blood flow to the ischemic area is often critical for the salvation of the limb [10, 11]. Nevertheless, the optimal revascularization strategy with the greatest durability and the lowest morbidity still remains debated.
Recent developments in endovascular approach, supported by advanced endovascular technology and improved operator skills, have significantly extended the range of EVT use. Currently, an ‘endo-first’ strategy is considered the standard of care, particularly, for elderly and critically ill patients in many centers, even though the presence of comorbidities such as diabetes and chronic renal failure often complicates the success of EVT [12]. The European Society of Vascular Surgery (ESVS) guidelines recommend the use of the endovascular approach in the management of TASC II A and B PAD [3, 13]. Recent evidence has revealed that the clinical outcomes achieved with EVT under such anatomical conditions are comparable to those achieved with the surgical bypass. Moreover, EVT is more advantageous compared to surgical bypass in terms of healthcare costs and length of hospital stay [14]. However, whether EVT or surgical bypass provides better clinical outcomes in more complex arterial disease (TASC II C and D) is still controversial. In a retrospective analysis conducted by Gur and colleagues, EVT was shown to fail more frequently and alter the site of subsequent open treatment in TASC II C and D lesions compared to TASC A or B lesions [15].
There are limited studies comparing the endovascular and bypass surgery approaches in patients with TASC II C and D femoropopliteal occlusive disease. The majority of these studies indicate that the rates of primary patency are similar for the two approaches; however, perioperative complications are reported to be lower with EVT compared to femoropopliteal bypass [16, 17]. Some of the largest randomized clinical trials comparing the outcomes of bypass surgery and balloon angioplasty in patients with critical limb ischemia (among whom the majority of the target lesions were in the femoropopliteal artery), reported similar amputation- free survival and all-cause mortality for the two approaches [18]. Aihara et al. have shown in 1156 patients presenting with intermittent claudication that bypass surgery provides a higher primary patency rate than EVT in TASC II C and D femoropopliteal lesions [19]. However, the reported complication rate in that study was significantly lower in the EVT group than that of the bypass group. Recently, Okuno et al. have compared femoropopliteal bypass and the endovascular approach with self-expandable nitinol stents for TASC II C and D femoropopliteal lesions and found that a 3-year primary patency rate was significantly higher for femoropopliteal bypass than EVT [20]. The superiority of bypass surgery over EVT in complex femoropopliteal disease has been supported by other studies. Veraldi et al., in their retrospective study which included 80 limbs with TASC II D femoropopliteal lesions, showed that femoropopliteal bypass with polytetrafluoroethylene graft + Linton patch was superior to PTA ± bare metal stents in terms of primary patency at 6, 12 and 24 months [21]. However, PTA procedures included regular balloons in the aforementioned trials, and DCBs were not used in these studies. The present study is therefore unique in terms of using drug-coated balloons instead of regular balloons. Previous evidence with drug-coated balloons in femoropopliteal disease has shown promising efficacy of drug coated balloons, particularly with regard to late lumen loss and target lesion revascularization rates compared to angioplasty alone [22-25]. We hypothesized that, given the superiority of drug-coated balloons over uncoated balloons in terms of postoperative outcomes, EVT with drug-coated balloons would provide superior primary patency compared to femoropopliteal bypass in subjects with complex femoropopliteal artery disease. However, our findings failed to demonstrate the superiority of EVT with drug-coated balloons when over femoropopliteal bypass. This result supports the evidence derived from previous studies comparing the two treatment strategies for TASC II C and D lesions of the femoropopliteal artery. Our results indicate that postoperative ABI is also higher in subjects undergoing femoropopliteal bypass than those receiving EVT. The complication rate of the bypass group in this study was comparable to that of the EVT group. The only advantage of EVT over bypass surgery was the shorter length of hospital stay in subjects receiving EVT compared to those undergoing femoropopliteal bypass surgery.
With this in mind, we suggest that femoropopliteal bypass surgery is likely superior in the treatment of TASC II C and D lesions of the femoropopliteal artery, even if the EVT is performed with drug-coated balloons. In this context, we consider that EVT, even with drug-coated balloons, should be reserved for patients with significant comorbidities; whereas a bypass surgery should be offered for subjects who are more likely to have longer-term survival.
This study has some limitations that should be mentioned. Relatively small sample size and the retrospective, non- randomized study design are the major drawbacks. In addition, this study demonstrates single-center data. Lack of data concerning the healthcare costs for the two treatment strategies is also another limitation. However, implementation of autologous vein grafts in the majority of subjects undergoing femoropopliteal bypass, and utilization of drug-coated balloons rather than uncoated balloons in subjects receiving EVT are the strengths of the study.
Conclusion
Femoropopliteal bypass surgery provides a higher primary patency rate and a more significant improvement in ABI in subjects with TASC II C and D femoropopliteal artery occlusions. Complication rates are similar between the two treatment approaches. However, EVT provides shorter hospital stay compared to femoropopliteal bypass surgery. These findings suggest that femoropopliteal bypass surgery is likely in the treatment of TASC II C and D lesions of the femoropopliteal artery, even when DCBs are used in the EVT procedure.
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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Sedat Ozcan, Emced Khalil. Comparison of the endovascular therapy with drug- coated balloon and bypass surgery for Trans-Atlantic Inter-Society Consensus II C and D femoropopliteal lesions. Ann Clin Anal Med 2021;12(5):488-493
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A rare cause of chronic back pain: Elastofibroma dorsi
Hacer Boztepe Yesilcay, Sencan Akdag
Department of Thoracic Surgery, University of Healty Sciences, Antalya Education and Research Hospital, Antalya, Turkey
DOI: 10.4328/ACAM.20313 Received: 2020-08-19 Accepted: 2020-10-06 Published Online: 2020-10-10 Printed: 2021-05-01 Ann Clin Anal Med 2021;12(5):494-497
Corresponding Author: Hacer Boztepe Yesilcay, Department of Thoracic Surgery, University of Healty Sciences , Antalya Education and Research Hospital, 07100, Antalya, Turkey. E-mail: drhacer83@hotmail.com P: +90 5062529990 Corresponding Author ORCID ID: https://orcid.org/0000-0002-2150-7199
Aim: In this study, we aimed to retrospectively evaluate the symptoms, functions, and outcomes of patients who underwent surgery in our clinic for the diag- nosis of Elastofibroma dorsi between 2007 and 2019.
Material and Methods: A total of 19 patients operated on in our clinic for the diagnosis of Elastofibroma dorsi (ED) were evaluated in respect of demographic characteristics such as age and gender, symptoms, clinical findings, diagnostic and radiological features, surgical procedures, results of surgical treatments, and postoperative follow-up results.
Results: The patients comprised of 13 females and 6 males with the mean age of 55.7 years. The most common clinical complaint was swelling (53.3%). EDs were located on the right side in 7 cases, on the left side in 3, and bilaterally in 7. In all cases, the mass was > 5 cm in diameter. Complete surgical excision was applied using the muscle-sparing technique. All patients were followed up postoperatively, and there was no recurrence.
Discussion: ED should be considered in the differential diagnosis when middle-aged patients present with a mass in the scapular region and shoulder pain. Total excision is surgically sufficient in symptomatic patients.
Keywords: Elastofibroma dorsi; Shoulder pain; Chronic back pain
Introduction
Elastofibroma dorsi is a benign, rarely seen, slow-growing soft tissue lesion. First described by Jarvi and Saxen in 1961, the lesion is usually located at the inferior angle of the scapula, deep to the serratus anterior, and may be attached to the periosteum of the ribs [1]. Although the etiology is not clearly known [2], common symptoms are chronic back pain, stiffness, swelling, snapping of the scapula, and increased pain during shoulder movement. Non-invasive imaging methods such as ultrasonography, computed tomography, and magnetic resonance imaging are used in the diagnosis of elastofibroma dorsi [3]. Total excision is the best treatment to prevent relapses and relieve symptoms [4]. This paper, presents the experience of a single centre in the diagnosis and treatment of elastofibroma dorsi patients between 2007 and 2019.
Material and Methods
Approval for this study was granted by the Clinical Research Ethics Committee of Antalya Training and Research Hospital (decision no:1/8, dated: 9/01/2020). A retrospective review of 19 patients operated on for a diagnosis of elastofibroma dorsi in the period from 2007 to 2019 was carried out. The cases were evaluated in terms of age, gender, complaints, clinical findings, diagnostic and radiological features, surgical applications, surgical treatment results, and postoperative follow-up results. Radiological examinations were made using ultrasonography, thorax computed tomography (CT), and magnetic resonance imaging (MRI). In all cases, the mass diameter was measured on radiological evaluation. None of the cases were directly diagnosed by biopsy. With the pre- operative consent of the patients, surgical excision was applied in all cases using a transverse or parabolic incision at the inferior pole of the scapula. All operative samples were sent for histopathological evaluation and all cases were followed up for 6 months postoperatively.
Results
The cases comprised of 13 females (69%) and 6 males (31%) with the mean age of 55.7 years (range, 31-68 years). The most common clinical complaint was swelling (53.3%). Other complaints were chronic back pain (26.6%), snapping of the scapula (10%), and increased pain with shoulder movement (10%). The mean duration of symptoms was 20 months (range, 3 -96 months). The lesion was located in the subscapular region in all the patients; unilateral in 10 and bilateral in 9. Of the unilateral tumors, lesions were located on the left side in 3 cases and on the right in 7 (Table 1). Radiological examination with ultrasonography and thorax computed tomography (CT) was applied to all patients (Figure 1). Magnetic resonance imaging was applied in 7 cases that could not be evaluated adequately with thorax CT.
In all cases, total surgical excision of the lesion was performed using the muscle-sparing technique. A Hemovac drain was placed in the subscapular area and the layers were closed anatomically. The drain was then removed after 24-72 hours. All excised samples were sent for pathological examination. In the pathological examination, solid lesions with a yellow and white cross-section surface covered with fibrous capsule and containing adipose tissue were observed macroscopically (Figure 2). In the microscopic examination of hematoxylin- eosin-stained sections, mature adipocytes and elastic fibrils were seen to be stained positive with Van Gieson. Postoperative complications developed in 4 of the operated cases (21%); antibiotic allergy in 1 (5%) and seroma requiring needle aspiration in 3 (16%). The mean length of hospital stay was 4 days (range: 2 – 8 days) and the mean follow-up was 5 months (range: 3 months-2 years). No recurrence was observed during the follow-up period.
Discussion
Elastofibroma dorsi is a benign, unencapsulated, slow-growing soft tissue tumor that usually occurs in females, in the 5th and 6th decades of life. It was first described by Jarvi and Saxen in 1961 [1]. Although it is traditionally considered to be rare, in a series of 235 postmortems in patients older than 55 years, Jarvi and Lansimies showed changes in the subscapular thoracic fascia similar to elastofibroma in 24.4% of females (29/119) and in 11.2% of males (10/89) [5]. The age and gender of the patients in the current series were consistent with the literature. ED is often localized in the subscapular region, between the rhomboid and latissimus dorsi muscles and the sixth and eighth ribs. However, other localizations such as deltoid muscle, foot, greater trochanter, olecranon, cornea, stomach, greater omentum, ischial tuberosity, intraspinal space and chest wall have been reported in the literature [2,6,7].
ED is often unilateral and right-sided. Bilateral cases, which may be synchronous or asynchronous constitute approximately 10-60% [8]. In the current study, the lesion was located in the subscapular region in all the patients; unilateral in 10 (52.7%) and bilateral in 9 (47.3%). Of the 28 ED lesions, 16 were localized on the right side (57.1%). In patients with bilateral ED, the lesions were detected to be synchronous.
The pathogenesis of ED is not clear, and several hypotheses have been put forward. Repeated micro-injuries between the chest wall and the scapula, the source of excess elastin production, and collagen degeneration could play a role in the physiopathology of this rare lesion [9].
This view has been supported by the higher ED prevalence, particularly among individuals engaged in hard manual labour. However, the presence of elastofibromas in different locations and in patients who have never been involved in hard manual work has undermined this view. In the current study, 3 patients (15.7%) were manual labourers, and the remainder had no history of strenuous work or sporting activities.
In a study investigating genetic anomalies in ED cases, changes in DNA copy number were observed in tumor tissue, mainly in the chromosome Xq12-q22 and 19 regions [10]. In a cytogenetic study by Mc Comb et al., genetic instability was detected in chromosome number 1 and translocation in numbers 8-12, and it was stated that they may be neoplastic, not reactive, due to these clonal abnormalities. In the largest reported series of 170 patients with the lesion, a familial predisposition was suggested, as 32% had a positive family history of elastofibroma [8]. In the current study, none of the patients had a family history of ED. There are also opinions that ED may be due to reactive fibromatosis, degeneration due to vascular insufficiency, elastotic degeneration and enzyme defect [8].
Clinical findings are mostly related to the size of the lesion. They often grow slowly and are asymptomatic. As the lesion grows, swelling in the back develops with chronic back pain, increased pain with shoulder movements and snapping of the scapula [11]. In the current series, the most common clinical complaint was swelling (53.3%) and 26.6% of the cases reported chronic back pain.
Imaging modalities for diagnosis include ultrasonography, CT and MRI. Solivetti et al. reported that the use of diagnostic USG is an adequate and inexpensive method [12]. Kransdorf et al. reported that radiological evaluation with MRI or CT is compatible with histopathological evaluation [13]. MRI is considered the most important imaging modality. Malghem et al. reported that fibrous tissues within the mass have similar signal characteristics with the surrounding muscle tissues in the MRI examination, while fat tissue has higher signal characteristics than the mass, and these findings are pathognomic for the mass [14]. In the current study, the radiological examination was applied with ultrasonography and thorax CT to all patients. MRI was applied in 7 cases that could not be evaluated adequately by thorax CT. The radiological findings of the current series were compatible with the literature.
Lipoma, neurofibroma, metastatic lesion, primary or metastatic sarcoma, fibrosarcoma, synovial sarcoma, and desmoid tumor should be considered in the differential diagnosis. Needle aspiration or incisional biopsy may be performed to eliminate the possibility of malignancy. However, excisional biopsy is often preferred, as a diagnostic radiological evaluation is usually sufficient [15,16]. No needle biopsies were performed in the current series.
Macroscopically, ED is a form of a non-encapsulated fibrous lesion of dirty white color with streaks of fat tissue. Some elastofibromas may have cystic degeneration. The typical histological appearance of the lesion is typical: large areas contain hyalinized collagenous stroma with small amount of fat tissue in between. In hypocellular collagenous stroma, fibrils and globules that show eosinophilic staining are striking. In sections stained with hematoxylin-eosin, fibrils and globules are important for determination of the location of the lesion and its diagnosis [4,9].
Elastofibroma dorsi is treated with total excision, but surgery is not recommended for asymptomatic lesions smaller than 5 cm [17-19]. In the current series, the mass in all cases was >5 cm in diameter, thus complete surgical excision was performed with the muscle-sparing technique that requires preparation of latissimus dorsi and serratus anterior muscle flaps.
The most common complications after surgical excision are hematoma or seroma. Therefore, after excision of the mass, the bleeding control should be performed cautiously [11]. In this study, hemovac drainage and a compression bandage were used to reduce these complications. Postoperative complications developed in four of the operated cases (21%); in one case (5%), antibiotic allergy was observed and in three cases (16%), seroma requiring needle aspiration was observed.
Local recurrence after total excision is rare and malignant transformation has not been reported. In the first recurrence, total surgical excision can provide cure, but in subsequent recurrence, total excision may not be performed [9]. In the current study cases, no recurrence was detected during the follow-up period.
In conclusion, ED should be considered in terms of differential diagnosis when middle-aged patients present with a mass in the scapular region and shoulder pain. Total excision is surgically sufficient in symptomatic patients.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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Rate of release in Turkish model cord blood banking: A single-center experience
Durmus Burgucu
Akdeniz University Teknokent Babylife Cord Blood Bank and Human Cell-Tissue Production Center, Antalya, Turkey
DOI: 10.4328/ACAM.20314 Received: 2020-08-20 Accepted: 2020-09-22 Published Online: 2020-09-27 Printed: 2021-05-01 Ann Clin Anal Med 2021;12(5):498-500
Corresponding Author: Durmuş Burgucu, Akdeniz University Teknokent Babylife Cord Blood Bank and Human Cell-Tissue Production Center, Akdeniz University, Campus, 07070, Antalya, Turkey. E-mail: dburgucu@akdeniz.edu.tr P: +90 242 226 16 80 F: +90 242 226 16 79 Corresponding Author ORCID ID: https://orcid.org/0000-0003-3980-982X
Aim: Cord blood has been successfully used since 1988 as a source of hematopoietic stem cells. Freezing and storing cord blood at −196°C and allowing it to be used when needed are the basis for cord blood banking applications. There are more than 100 banks in the world and 10 in Turkey. While the release rates of different centers in the world are known, data on the release rates of centers operating in Turkey have not yet been published. The aim of this study is to retrospectively evaluate the ratio of cord blood released with the purpose of hematopoietic stem cell transplantation and banking periods at a center engaged in Turkish Model Cord Blood Banking.
Materials and Methods: The study included the applicants of the Akdeniz University Technopark Babylife Cord Blood Bank and Human Cell-Tissue Production Center for cord blood banking services. In this cross-sectional retrospective study, data recorded in the Korddata data logging program between 01/01/2018 and 31/12/19 (over 24 months) were analyzed.
Results: In the first year, 726 units of cord blood were collected. Three units of the collected blood were released for transplantation purposes. In the second year, 709 units of cord blood were collected and 7 were released for transplantation. The release rate was 0.41% in the first year, which increased to 0.99% at the end of the second year.
Discussion: The Turkish Model Cord Blood Banking specific to our country is a mixed model in which private and public banking is performed together. In this study, for the first time in the literature, release rates from a center engaged in Turkish Model Cord Blood Banking have been published. Release rates for Turkey can be evaluated when other centers adopting similar models publish their data.
Keywords: Cord blood; Hematopoietic stem cell; Bone marrow Transplantation
Introduction
Cord blood has been successfully used since 1988 as a source of hematopoietic stem cells [1]. The first application and the following four different applications showed that cord blood can be processed and stored in a laboratory environment and can be banked in an evidence-based manner [2, 3]. After the initial data, it was predicted that the blood stored at −196°C could be used for bone marrow transplantation and cord blood banks could be established safely for this purpose and in 1993, the first cord blood bank was established in New York [4]. Subsequent data revealed that cord blood, received under appropriate conditions and frozen, can be stored for more than 20 years, preserving biological properties [5]. Cordbloodbankingmodelsaremainlydividedintotwo:public banking and private banks. There are more than 100 banks in the world and 10 in Turkey. In these banks, ~5 million units of cord blood are stored, including 800,000 public and 4 million private units [6]. The fundamentals of the banking model specific to Turkey were defined by the cord blood banking regulation published in 2005 and later passed to the literature as the “Turkish Model” [7, 8].
The main purpose of the Turkish Model is to ensure that private banks store cord blood to a certain amount (up to 25%) free of charge for transplantation to patients determined by the Ministry of Health for allogeneic use. Finding a source of hematopoietic stem cells to use for allogeneic purposes takes a certain amount of time. Data in the United States report it must be obtained from mobilized peripheral blood in a period of 3-4 months and an average of 12 days if it is to be obtained from cord blood. Cord blood banks provide significant advantages as they store products with ample shelf life that are quickly accessible [6]. While the release rates of different centers in the world are known, data on the release rates of centers operating in Turkey have not yet been published.
The aim of this study is to retrospectively evaluate the ratio of cord blood released with the purpose of hematopoietic stem cell transplantation and banking periods at a center engaged in Turkish Model Cord Blood Banking.
Material and Methods
This is a cross-sectional and retrospective study. The study included the applicants from the Akdeniz University Technopark Babylife Cord Blood Bank and Human Cell-Tissue Production Center for cord blood banking services. The release rates were calculated by detecting the number of released cord bloods only from this center for bone marrow transplantation between 01/01/2018 – 31/12/19. None of the centers operating in Turkey have published release rates so far. Data only from a single center were evaluated in this study. During the two years duration of the study, cord blood stored in the center and released for bone marrow transplantation was determined by evaluating the data in the product files and the Korddata data recording program. Approval from the clinical research ethics committee of Akdeniz University Faculty of Medicine with decision number 147, dated 21.02.2018 was obtained for this study.
Results
In this study, the products taken into permanent storage in the bank over a 2-year period and released for hematopoietic stem cell transplantation were evaluated. The study included the applicants from the Akdeniz University Technopark Babylife Cord Blood Bank and Human Cell-Tissue Production Center for cord blood banking services. In the first year, 726 units of cord blood were collected. Three units of the collected blood were released for transplantation purposes. In the second year, 709 units of cord blood were collected and 7 were released for transplantation. The first-year release rate was 0.41%, which increased to 0.99% at the end of the second year (Figure 1). Transplantations were performed for the following diseases: Thalassemia Major, Fanconi Aplastic Anemia, Immune Deficiency, Juvenile Myelomonocytic Leukemia, Congenital Neutropenia, and Acute Lymphoblastic Leukemia. In total, 10 units of cord blood were released for transplantation.
Discussion
Cord blood banking applications have an important place in hematopoietic stem cell transplantation. More than 40,000 units of cord blood have been successfully transplanted to date [6]. The aim of the globally accepted cord blood banking models is to create a pool for cord blood-based allogeneic hematopoietic stem cell transplantation. The allogeneic cord blood pool has an important place in allogenic transplantations. The amount of cord blood that must be kept in a bank to meet the needs or demands of the public varies depending on the population; accordingly, release rates also vary from bank to bank. According to the latest data, ~800,000 units of cord blood are stored in state-owned banks in the world, and the annual number of units released is 4100 [4]. On the other hand, more than 4 million units of cord blood are stored in private banks and 130 units are released annually. Also, some banks such as Mexico City, Besancon, and Tokyo report high release rates (10-16% of their inventory), although the number of cord blood units stored in these banks is unknown [6]. There are 10 banks operating in Turkey that are approved by the Ministry of
Health, but no data on release rates have yet been published. In the present study, products received and released over a 2-year period were evaluated. The release rates were calculated by detecting the number of released cord bloods only from this center for bone marrow transplantation between 01/01/2018 – 31/12/19. Data only from a single center (Akdeniz University Technopark Babylife Cord Blood Bank and Human Cell-Tissue Production Center) were evaluated in this study. During the two years duration of the study, cord blood stored in the center and released for bone marrow transplantation were determined by evaluating the data in the product files and the Korddata data recording program. It can be seen that the release rate of the bank examined is close to the release rates of state-owned banks around the world. However, the Turkish Model Cord Blood Banking practice is a mixed model in which both private and public banking is performed together. Therefore, the release rate is higher compared to the release rates of private banks around the world.
Conclusion:
In this study, for the first time in the literature, release rates from a center engaged in Turkish Model Cord Blood Banking have been published. Release rates for Turkey can be evaluated when other centers adopting similar models publish their data.
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. Broxmeyer HE, Douglas GW, Hangoc G, Cooper S, Bard J, English D, et al. Human umbilical cord blood as a potential source of transplantable hematopoietic stem/ progenitor cells.Proc Natl Acad Sci USA. 1989;86(10):3828–32.
2. Wagner JE, Broxmeyer HE, Byrd RL, Zehnbauer B, Schmeckpeper B, Shah N, et al. Transplantation of umbilical cord blood after myeloablative therapy: analysis of engraftment. Blood. 1992;79(7):1874–81.
3. Wagner JE, Kernan NA, Steinbuch M, Broxmeyer HE, Gluckman E. Allogeneic sibling umbilical cord blood transplantation in children with malignant and non- malignant disease. Lancet. 1995;346(8969):214–9.
4. Dessels C, Alessandrini M, Pepper MS. Factors influencing the umbilical cord blood stem cell industry. Stem Cells Transl Med. 2018;7(9):643–50.
5. Ballen K, Gluckman E, Broxmeyer HE. Umbilical cord blood transplantation: the first 25 years and beyond. Blood. 2013;122(4):491–8.
6. Mayani H, Wagner JE, Broxmeyer HE. Cord blood research, banking, and transplantation: achievements, challenges, and perspectives. Bone Marrow Transplant. 2020;55(1):48-61.
7. Brand A, Rebulla P, Engelfriet CP, Reesink HW, Beguin Y, Baudoux E, et al. Cord blood banking. Vox Sang. 2008;95(4):335-48.
8. Dessels C, Alessandrini M, Pepper MS. Factors Influencing the Umbilical Cord Blood Stem Cell Industry: An Evolving Treatment Landscape. Stem Cells Transl Med. 2018;7(9):643-50.
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Comparison of obstetric and infectious results among Syrian pregnant women
Şerif Aksin 1, Numan Çim 2, Cengiz Andan 1, Şeyhmus Tunç 1, Mehmet Rıfat Göklü 1
1 Department of Obstetrics and Gynecology, TC Ministry of Health, Health Sciences University, Gazi Yasargil Diyarbakır Training and Research Hospital, Diyarbakir, 2 Department of Obstetrics and Gynecology,Istanbul Bilim University Faculty of Medicine, Istanbul, Turkey
DOI: 10.4328/ACAM.20411 Received: 2020-11-24 Accepted: 2021-03-31 Published Online: 2021-04-16 Printed: 2021-05-01 Ann Clin Anal Med 2021;12(5):501-505
Corresponding Author: Şerif Aksin, TC Ministry of Health, Health Sciences University, Gazi Yaşargil Diyarbakır Training and Research Hospital, Obstetrics and Gynecology, Diyarbakir, Turkey. E-mail: serifaksin1@gmail.com P: +90 5052774937 Corresponding Author ORCID ID: https://orcid.org/0000-0002-1301-2508
Aim: We do not have enough information about the obstetric and fetal positions of migrant pregnant women.After the Syrian civil war in 2011, neighboring countries and Europe faced a wave of migration.The study aims at comparing the obstetric, fetal, and infectious outcomes of Turkish pregnant refugee women.
Material and Methods: A total of 810 Syrian and 810 Turkish pregnant women who gave birth between January 1, 2020 and August 1, 2020 were included in the study. The demographic characteristics, obstetric, fetal, neonatal, TORCH (Toxoplasma gondii, others, rubella virus, cytomegalovirus and herpes simplex virus), HBsAg, anti-HBs, anti-HCV, and anti-HIV seroprevalences, and laboratory results of the women were compared.
Results: Adolescent pregnancies were found to be higher among Syrian pregnant women (p<0.001). Normal birth rates were also higher in these women (p<0.001). The week of pregnancy at birth, age and Apgar scores were found to be lower compared to Turkish pregnancies (p<0.001). The rate of delivery below 2,500 grams was higher among Syrian women (p<0.001). Anti-HBs protection was not sufficient (p<0.05), and Toxoplasma gondii seropositivity seemed to be higher (p < 0.05). The rate of ARH + blood group in pregnant women from Syrian (28.5%) was lower than in Turkish pregnant women (34.9%) (p < 0.05).
Discussion: It was observed that the rate of adolescent pregnancy was higher in refugee pregnant women. Adolescent pregnancies are at risk in terms of ob- stetric and neonatal outcomes. Therefore, efforts to prevent these pregnancies should be made. Syrian pregnant refugee women should be protected against adverse perinatal and infectious situations.
Keywords: Syrian refugees; Pregnancy; Parturition; Infections
Introduction
According to the 1951 Refugee Convention of the United Nations, refugees are defined as “people who flee from their country of residence for various reasons with justifiable fear of persecution and believe that they will not be able to return to that country safely under the current conditions” [1]. Wars and natural disasters force populations around the world to migrate. Migration brings along many problems related to health, accommodation, nutrition, and safety [2].
According to the United National’s (UN) data dated January 12, 2017, there are 2,854,968 (58.2%) of the 4,904,021 registered Syrian refugees live in Turkey. A specially organized health care for Syrian refugees in Turkey was first established on April 29, 2011. Preventive health services are also provided to Syrian refugees [3].
Pregnant women may be exposed to many negative circumstances, such as situations that threaten their health, sexual abuse, exploitation, isolation, and a lack of social support [4]. Although accessing the health system in Turkey is not difficult, there may be problems stemming from different cultures and languages. Additional obstacles to healthcare access, including limited language proficiency, social isolation, poverty, mistrust of refugee women in healthcare providers, resistance to procedures, and communication problems, leave women vulnerable in such situations [5,6]. However, migrant women may have negative maternal-fetal, nutritional, and infectious risks [7].
The present study aims to investigate the obstetric, neonatal, and infectious statuses of Syrian pregnant migrant/refugee women in Turkey and to compare them to those of pregnant women in the country.
Material and Methods
Approval for the study was obtained from the Local Ethics Committee of the Gynecology and Obstetrics Department at Dr. Gazi Yaşargil Training and Research Hospital at Health Sciences University in Diyarbakır (Gazi Yasargil Training and Research Hospital Ethics Committee approval number: 2021-715). The study was carried out retrospectively with the hospital records of pregnant women who applied through the Ministry of Health at the Gynecology and Obstetrics Clinic of Saglik Bilimleri University’s Dr. Gazi Yaşargil Training and Research Hospital between January 1, 2020 and August 1, 2020. The cases included in the study consisted of migrant pregnant women who had migrated to Turkey due to the Syrian civil war and who did not reside in the country, and the same number of pregnant women living in the region where the hospital provides health services (Diyarbakır province and its surroundings), who applied to the clinic during the same period.
A retrospective screening was performed on the file records of the cases included in the study; only complete file records were included in the study group. A total of 15 Syrian migrants and 10 pregnant women from Turkey were excluded from the study due to missing data in their files. The records of 810 pregnant Syrian migrant women were included in the archive scanning carried out in accordance with the specified criteria. The control group consisted of 810 Turkish pregnant women who applied to the hospital in the same year as the
Syrian migrant pregnant women. The age, gravida, caesarean section number, blood type, hemogram, biochemistry values, HBsAg, anti-HBs, anti-HCV, and anti-HIV results obtained by the enzyme-linked immunosorbent Assay (ELISA) method, TORCH results, ultrasonographic fetal biometric parameters, weeks of pregnancy, birth weight of babies, first- and fifth- minute Apgar scores, delivery types, caesarean diagnoses, fetal complications, and obstetric complications of the cases were compared. Only cases with fetal birth weight >500 grams were included in the study.
Statistical analysis
The data were transferred to the IBM SPSS 23 program using a computer and evaluated by statistical analyzes. Before the statistical analyzes, checks were carried out to ensure that there was no data entry error and that the parameters were within the expected range. Normality assumptions of continuous variables were analyzed using the Kolmogorov- Smirnov test. The significance level was accepted as p<0.05 in all analyzes. The Mann-Whitney test was used to compare continuous variables that did not show a normal distribution with two-level variables. The relationships between categorical variables were analyzed using the Chi-square/Fisher’s exact analysis. The significance level was accepted as p<0.05 in all analyzes.
Results
In this study, the first group was composed of Syrian migrant pregnant women (810 cases), while the second group was composed of Turkish pregnant women (810 cases). Ages, gravidas, Apgar scores, fetal head circumferences, and height values of the Syrian pregnant women included in the study (Group 1) were significantly lower than those of the Turkish pregnant women (Group 2) (p<0.001). These findings are presented in Table 1.
Mean aspartataminotransferaz (AST) and alaninaminotransferaz (ALT) values of the pregnant women in Group 1 were significantly lower than the values for those in Group 2 (p<0.05). The hemogram and blood biochemistry values of the cases in the study are shown in Table1.The blood types of the cases are presented in Table1. The most common blood type in Group1 was 0 Rh+, while the least common blood type was AB Rh-. In Group 2, the most common blood type was A Rh+, while the least common blood type was AB Rh-. The rate of ARH + blood group in pregnant women from Syrian (28.5%) was lower than that of Turkish pregnant women (34.9%) ( p < 0.05).
When the anti-HBs results were compared, anti-HBs positivity was found to be statistically significantly higher in the cases in the second group (p < 0,05). Anti T. gondi IgM and IgG positivity were 18% and 4% and 56% and 26%, respectively (p<0.05). The obstetric results of the cases are shown in Table 2. Adolescent pregnancy rates were higher in Group 1 compared to Group 2 (p<0.001). The number of first pregnancies was higher in Group 1 (p<0.001). When the mode of delivery was examined, 67.2% of the pregnant women had a vaginal delivery (72.5% in Group 1 and 61.9% in Group 2), and 32.8% had a caesarean section (27.5% in group 1 and 38.1% in group 2; p<0.001). When the birth weights of the babies were examined, it was observed that 9.7% of the babies were below 2,500 grams (12.8% in Group 1 and 6.8% in Group 2), while 90.3% were above 2,500 grams (87.2% in Group 1 and 93.2% in Group 2; p<0.001).
The caesarean section indications of the cases are shown in Table 2. In the Syrian immigrant pregnant women (Group1), the most frequent causes of caesarean section were head- pelvis incompatibility and previous uterine surgery (59.2%), and the least frequent causes wereumbilical cord prolapse and fetal presentation anomaly (0.9%). In Turkish pregnant women (Group-2), it was observed that caesarean operation was performed mostly because of previous uterine surgery (62.7%) and fetal distress, and lessoften because of cord prolapse (0.2%). Complications occurring in the pregnancies are presented in Table 2.
Discussion
Migrations have occurred around the world for centuries due to natural disasters, wars, or other reasons. People migrate to countries with better conditions than those in which they live, hoping to find better opportunities. The migrant pregnant women in the present study were citizens of other countries who emigrated due to war. Citizens who migrate to another country without permission benefit from fewer health insurance expenses than the country’s citizens. As a result, they may not have access to services such as preventive health and prenatal follow-up, and this may cause negative reproductive results [8,9].
In the present study, the mean age of pregnant Syrian migrant women was lower than that in the control group (25.94±6.53 and 28.47±6.94, respectively; p<0.001). The gravida average of the pregnant Syrian migrants was lower than that of pregnant women in the control group (1.70±1.38 and 3.39±2.50, respectively; p<0.001). In a study by Mumtaz et al. examining pregnancy, childbirth, and postpartum care of migrant women who had recently arrived in Canada compared to Canadian women, the mean age of pregnant Canadian migrant women was lower than that of the control group. The gravida numbers were similar in both groups [10].
When the type of delivery was examined in both groups, the rate of normal birth was higher in the Syrian group. There was no difference in cesarean rates between the groups. When cesarean operation indications were examined, head-pelvis incompatibility and previous uterine surgery rates were high in the group of pregnant Syrian women. In the group of Turkish pregnant women, however, the rates of previous uterine surgery and cesarean operations performed due to fetal distress were found to be high. Normal birth rates were high in the group of Syrian women. Kıyak et al. and Güngör et al. found similar birth rates in their studies [11,12]. Cesarean section rates were also found to be high in a study conducted among Syrian refugee women in Lebanon [13].
In a meta-analysis of 76 studies comparing cesarean rates in migrant and non-migrant women in industrialized countries of the West, it was reported that women who migrated from sub-Saharan Africa, Somalia, and South Africa gave birth by caesarean more than women in the developed countries. Further, Eastern European and Vietnamese women had lower caesarean rates, and North African, West Asian, and Latin American women had an emergency caesarean section. It was also found that communication barriers, low socio-economic status, poor maternal health, cephalopelvic mismatch (CPD), gestational diabetes/high BMI, and lack of prenatal care were the most common risk factors for caesarean in migrant women [14].
In the Syrian migrant pregnant group, infants’ first- and fifth- minute Apgar scores were found to be lower than in women in the Turkish pregnant group, which is similar to other findings in the literature (p <0.05). Age, gravida, Apgar score, fetal head circumference, and height were found to be significantly lower in the group of Syrian pregnant women than in the group of Turkish pregnant women (group 2; p<0.001). A total of 9.7% of babies had a birth weight of <2500 grams (12.8% in group 1 and 6.8% in group 2). Low infant birth weight in the subgroup analysis may have been caused by the specific problems faced by migrant women, such as feeding and war trauma.
In a study that investigated the health status of pregnant refugee women in Sweden between 2014 and 2017, Liu et al. found that refugee women had a higher risk of poor pre-pregnancy general health status, gestational diabetes, and serious anal sphincter damage. In addition, the rates of stillbirth, low birth weight, and small birth rate compared to gestational age were higher for the refugee women. Further, neonatal Apgar scores at birth were lower than those of Swedish-born women, and the rates of adverse infant outcomes were higher [15].
HBsAg positivity and negativity rates were similar in the pregnant women; the HBsAg positivity rate was 2.6% (p = 0.255). When the anti-HBs results were compared, anti-HBs positivity was found to be statistically significantly higher in the cases in the second group (p < 0.05)
In their study examining the seroprevalence of HBsAg positivity in native and migrant pregnant women in Taiwan, Lin et al. found that the HBsAg positivity rate was 12.4% for all of the women. Taiwanese women and migrants from China and Cambodia had high rates of HBsAg positivity, while Thai women had the lowest HBsAg positivity rate. Lin et al. reported that HBsAg positivity rates showed a statistically significant difference between local and migrant pregnant women (p<0.001). They also reported that HBsAg positivity in native pregnant women decreased linearly over the years (1996–2015) with the implementation of the hepatitis B vaccine program in their country, but that HBsAg positivity did not show a significant decreasing trend in pregnant migrant women [16].
In the present study, no significant difference was found between Turkish and Syrian pregnant women in terms of anti-Rubella IgM and IgG positivity and anti-CMV IgM and IgG positivity (p=0.704 and 0.986, respectively). Anti T. gondi IgM and IgG positivity rates were 18% and 4% for the Syrian women, and 56% and 26% for the Turkish women. The difference between the groups was found to be significant (p<0.05).
In another study, Sampedro et al. found a higher rate of seroprevalence of Toxoplasma in pregnant migrant women compared to non-migrants. The overall prevalence of anti- rubella immunization was 97.3%. They also found the lowest prevalence in Sub-Saharan and North African women (88% versus 89%). In their study, the prevalence of HBsAg in migrants was higher compared to that of Spanish women (2.6% versus 0.4%), and they reported that this rate was particularly high among Eastern European (6.9%) and Asian pregnant women (8.1%) [17]. In their study investigating the rubella immunization status in migrant and Canadian pregnant women in Toronto, McElroy et al. found that around 93% of Canadian women were immune to rubella. They also found that the lowest rubella immunity rates were in pregnant women born in North Africa and the Middle East (87.1%), as well as in China and the South Pacific (91.5%) [18].
Our study shows that the Syrian population has a higher Toxoplasma seropositivity compared to Turkish citizens. Similarly, eating habits and accommodation and hygiene problems causedby migration can affect seropositivity. Knowing of TORCH infections of Syrian migrants, who frequently migrate to Europe and other countries, may enable proactive approaches of health systems in providing prenatal care for Syrian pregnant women who have been integrated into Europe. Racape et al. reported that negative perinatal outcomes were not always correlated and that high levels of socio-cultural and economic activity in immigrant groups prevented negative perinatal outcomes [19.20]. In another study, Gagnon et al. found that risks such as low birth weight, preterm delivery, perinatal mortality, and congenital anomalies among immigrant pregnant women were similar in countries with strong integration policies, and more negative consequences had been found in European countries with weak integration policies [21]. The American College of Obstetrics and Gynecology (ACOG) advocates the removal of all existing barriers to universal health care for all pregnant women regardless of their migration status [22].
The limitations of this study are that it was conducted retrospectively, and the educational levels, vaccination statuses, and socio-economic statuses of the Syrian pregnant women could not be evaluated.
Conclusion
It was observed that the rate of adolescent pregnancy was higher in refugee pregnant women. Adolescent pregnancies are at risk in terms of obstetric and neonatal outcomes. Therefore, efforts to prevent these pregnancies should be made. Also, there should be a plan for providing more supportive health care services for Syrian refugee pregnant women who are vulnerable to infectious agents and have negative obstetric outcomes.
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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The relationship between nutritional status and heart rate variability in elderly patients
Hatice Tolunay 1, Ozge Kurmus 2, Suat Gormel 1, Serkan Asil 1, Salim Yasar 1, Erkan Yildirim 1, Yalcin Gokoglan 1, Hasan Kutsi Kabul 1
1 Department of Cardiology, Gulhane Training and Research Hospital, 2 Department of Cardiology, Ufuk University Faculty of Medicine, Ankara, Turkey
DOI: 10.4328/ACAM.20441 Received: 2020-12-16 Accepted: 2021-01-15 Published Online: 2021-01-26 Printed: 2021-05-01 Ann Clin Anal Med 2021;12(5):506-511
Corresponding Author: Hatice Tolunay, Gulhane Training and Research Hospital, Department of Cardiology, General Dr. Tevfik Sağlam Street, No: 1 Etlik, 06010, Ankara, Turkey. E-mail: drhaticearslan@gmail.com P: +90 5052563112 Corresponding Author ORCID ID: https://orcid.org/0000-0002-9407-3395
Aim: Malnutrition is a common health problem in elderly patients. Prognostic nutritional index (PNI) and geriatric nutritional risk index (GNRI) are two easily- calculable indexes developed as indicators of nutritional status, showing prognosis relationships with some diseases. We planned a study to define the relationship between PNI, GNRI, which indicates nutritional status and is also a criterion of frailty, and heart rate variability (HRV), which is a cardiovascular risk marker.
Material and Methods: A total of 96 patients over 65 years of age who had no known chronic disease other than controlled hypertension and regulated diabe- tes and who underwent rhythm holter monitoring were evaluated. Framingham risk scores (FRS), PNI, GNRI of the patients were calculated. HRV parameters were recorded.
Results: The root mean square of successive differences (rMSSD) (p:0.02) and percentage of adjacent RR intervals with a difference of duration >50ms (pNN50) (p:0.035) were significantly lower in the patient group with low PNI. HRV frequency domain parameters, low-frequency/high-frequency (LF/HF) (p:0.048) and total power (TP) (p:0.044) were significantly higher in the patient group with low PNI. There was no significant relationship between GNRI and HRV parameters.
Discussion: PNI is a simple indicator of decreased HRV and increased cardiac risk in elderly patients. PNI is more valuable than GNRI in predicting increased cardiac risk related to HRV in elderly patients. The results of our study support the effect of adequate nutrition on cardiac autonomic modulation in the elderly and confirm that nutrition in this age group is a correctable cardiac risk factor.
Keywords: Elderly patient; Nutritional status; Serum albumin; Heart rate; Rhythm holter
Introduction
Physiological changes, acute and chronic diseases that occur with aging adversely affect nutrition. In old age, the incidence of chronic diseases and malignancies increases and cognitive abilities decrease. Malnutrition is common as a result of psychological problems and care problems [1]. Knowing how aging and malnutrition affect the cardiovascular system structurally and functionally may provide the opportunity to prevent or reduce the risk of developing cardiovascular disease in elderly patients.
Heart rate variability, defined as cyclic changes in sinus velocity over time, is a method used to evaluate the autonomic function of the heart, providing information about sympathetic- parasympathetic balance. Reduced HRV is evaluated as a determinant of increased risk for cardiovascular disease and mortality [2]. It has been found that low parasympathetic activity is a marker for poor prognosis in patients with acute coronary syndrome without ST elevation [3].
PNI has been associated with different inflammatory processes in several studies. The relation of PNI with acute heart failure, cardiac surgeries, some cancers and survival and mortality has been demonstrated in previous studies [4,5].
The GNRI is a nutritional index developed to provide information about the severity of malnutrition and mortality in hospitalized elderly patients [6]. There are studies showing that it is a prognosis marker in heart failure [7,8].
In our study, elderly patient group without chronic diseases except for controlled hypertension and regulated diabetes mellitus was evaluated. Old age is an important risk factor for cardiac diseases. It is important for preventive medicine to evaluate the cardiac effects of nutrition before chronic diseases develop. We planned a study to evaluate the relationship between PNI and GNRI, which indicates nutritional status, and HRV, which is a cardiac risk marker, in partially healthy patients over 65 years of age.
Material and Methods
All patients over the age of 65 who applied to the cardiology clinic of Gulhane Training and Research Hospital between June 2019 and June 2020 with complaints of palpitations and who underwent rhythm holter monitoring were evaluated. Patients with a diagnosis of coronary artery disease, heart failure, chronic liver, kidney disease and cancer, those taking medications that may affect rhythm, those with acute or chronic infections, those with rheumatological disease, those without serum albumin and lymphocyte data, and those without height and weight data, uncontrolled hypertension and insulin users with complicated diabetes and active smokers, patients with atrial and ventricular arrhythmias were excluded from the study. Ninety-six patients out of 1225 holter records who met the inclusion criteria were included in the study. The study was compliant with the Helsinki Declaration and was approved by the local ethics review committee.
Biochemical analysis and nutritional status evaluation
The initial demographic and clinical variables of the study population were recorded from the data in the hospital database. Serum creatinine, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride and hemoglobin values were recorded at the hospital admission. The FRS of the patients was calculated according to age, gender, total cholesterol level, HDL cholesterol level, and systolic blood pressure. According to the FRS, patients were divided into 3 categories as high, medium and low risk. Patients with a 10-year adverse event risk > 20% were considered high-risk, 10-20% were considered medium- risk, and <10% were considered low risk [9]. Body mass index (BMI) was calculated using the formula: body mass index = body weight / (height) 2.
Prognostic Nutritional Index
PNI was calculated on the basis of admission data as follows: 10 x serum albumin (g/ dl) + 0.005 x total lymphocyte count (per mm3) from the report of Onodera et al. A PNI value ≥ 50 is defined as normal, <50, as mild- moderate malnutrition [5]. Geriatric Nutritional Risk Index
In this study, GNRI was calculated from serum albumin and BMI by examining the data during outpatient clinic examination [6]. Calculation of GNRI
GNRI= 14.89 × serum albumin (g/dL) + 41.7 × BMI/22
When the BMI / 22 of the patient is greater than 1, the BMI / 22 is calculated as 1.
Since the stable elderly patient group was evaluated in our study, the number of patients that could be considered moderate and severe malnutrition was low and the patients were divided into 2 groups with GNRI <100 and ≥ 100.
Holter rhythm analysis
Twenty-four -hour Holter electrocardiography data were evaluated using a 5-lead Holter device (Northeast Monitoring, Inc. DR181 Holter Recorder, 3-channel Holter) to evaluate heart rate variability. HRV parameters were automatically determined with the holter data processing program. HRV time and frequency domain parameters determined by the automatic analysis method were recorded from the existing holter records of all patients [10].
Statistical analysis
Data analyses were performed using SPSS for Windows, version 22.0 (SPSS Inc., Chicago, IL, United States). Whether the distribution of continuous variables was normal or not was determined using the Kolmogorov- Smirnov test. Levene’s test was used for the evaluation of homogeneity of variances. Unless specified otherwise, continuous data were described as mean ± SD for normal distributions, and median (minimum statistical analysis differences in normally distributed variables between two independent groups were compared using Student’s t- test; the Mann-Whitney U test was applied for comparisons of the not normally distributed data. While the differences in normally distributed variables among more than two independent groups were analyzed using One-Way ANOVA, otherwise, the Kruskal- Wallis test was applied for comparisons of the not normally distributed data. Categorical variables were compared using Pearson’s chi-square test or Fisher’s exact test, and p- value <0.05 as was accepted as a significant level for all statistical analyzes.
Results
The laboratory data of the patients and analysis results of HRV time and frequency domain parameters are summarized in Table 1. The mean age of the patients was 72.05 ± 4.89 years and 48 (50.0%) were male. The number of patients with hypertension was 64 (66.7%), the number of patients with diabetes was 32 (33.3%). There were 35 (36.5%) patients with GNRI <100 and 48 (50%) patients with PNI <50.
Albumin (p<0.001), triglyceride (p:0.014), hemoglobin (p:0.023), lymphocyte (p<0.001), and GNRI (p<0.001) values were significantly higher in patients with high PNI than in those with low levels. RMSSD (p:0.02) and pNN50 (p:0.035) were significantly lower in the patient group with low PNI. Among the HRV frequency domain parameters, LF / HF (p:0.048) and TP (p:0.044) were significantly higher in the patient group with low PNI. There was no significant relationship between other HRV parameters and PNI (Table 2).
While the mean age of those with high GNRI was statistically significantly lower, albumin (p <0.001), hemoglobin (p<0.001), lymphocyte (p:0.006) and PNI (p<0.001) were statistically significantly higher. There was no significant relationship between GNRI and HRV time and frequency domain parameters. There is a statistically significant difference among FRS risk groups in terms of age, gender, hemoglobin, HDL, PNI, LF, TP, LF / HF ratio. PNI was lowest in patients with high FRS (P:0.045). LF was highest in patients with high FRS (p:0.040). Also, LF/ Continuous variables are expressed as either mean± standard deviation (SD) or median (min- max). Continuous variables were compared with Student’s t-test or Mann-Whitney U test . Statistically significant p-values are in bold.
HF: high frequency; LF: low frequency; VLF: very low frequency; pNN50: percentage of adja- cent RR intervals with a difference of duration >50 ms; rMSSD: root mean square of differ- ences between adjacent normal RR intervals, expressed in ms; SDNN: standard deviation of all normal RR intervals, expressed in milliseconds; SDANN: standard deviation of the average NN intervals in 5 minute recordings during the study period.
HF ratio was highest in patients with high FRS (p<0.001). TP was lowest in patients with high FRS (p:0.025). Comparison of demographic and clinical data, nutritional indexes and HRV parameters with low-medium-high FRS groups are summarized in Table 3.
Discussion
The present study showed that the HRV time- domain parameters, rMSSD and pNN50 were significantly lower and the HRV frequency domain parameters, LF/HF and TP were significantly higher in the patient group with low PNI. The findings of this study suggest that nutritional status is associated with sympathovagal balance in the elderly.
The autonomic nervous system is involved in nutritional control through the posterolateral hypothalamus and in cardiovascular control with the dorsomedial hypothalamus [11]. Sympathovagal balance disorders and malnutrition in elderly patients are two important geriatric syndromes. In elderly individuals, malnutrition has many causes, including gastrointestinal motility and changes in hormone secretion that underlie aging anorexia. Hypoalbuminemia is the result of inflammation and inadequate protein and calorie intake in people with chronic disease [12]. While the decrease in albumin in acute events is mostly associated with inflammation, in chronic events it may be due to both inflammation and malnutrition [13].
Similar to other systems in the human body, the nervous system experiences a functional decline with aging. These changes have been described in the somatic and autonomic components of the nervous system. HRV reflects this balance between sympathetic and parasympathetic activity [14]. Pagani et al. suggested that the ratio of LF to HF can be used to measure the changing relationship between sympathetic and parasympathetic nerve activities, that is, sympathovagal balance in both health and disease. Increases in LF/HF reflect the transition to sympathetic dominance and are a tool for assessing cardiovascular autonomic regulation [15].
According to a meta-analysis, anorexia has been reported to play a role in the etiopathogenesis of autonomic dysfunction [16]. There are studies showing increased sympathetic modulation of the autonomic nervous system in malnutrition [17-19]. There are studies supporting that malnutrition in the critical developmental period in children can lead to autonomic imbalance through morphological changes [20,21]. Our study has confirmed that malnutrition in the critical destruction stage can lead to autonomic imbalance in the elderly, as well as during the construction phase in children. As a result, an imbalance in the autonomic nervous system with aging may cause nutritional deficiency, and nutritional deficiency may adversely affect the sympathovagal balance with increased sympathetic activity. PNI was initially defined as an indicator of immunonutritional status based on serum albumin level and lymphocyte count. In the study evaluating the effect of PNI on in-hospital and long-term mortality in patients with STEMI, patients with lower PNI values had 7.9 times more rehospitalization and 6.4 times higher mortality compared to patients with higher PNI [22]. Candeloro et al.’s study found that low PNI values were associated with short-term and long-term mortality in elderly patients hospitalized for acute decompensated heart failure [7]. In a meta-analysis examining the prognostic value of the GNRI score in heart failure, it was found that the low GNRI score independently predicted all-cause mortality and major cardiovascular events in elderly patients with heart failure [8]. There are insufficient data in the literature evaluating the relationship between PNI, GNRI and HRV in elderly patients where nutritional status is important. Our study is important in terms of examining the cardiac effects of nutritional status, which is important in terms of prognosis in different diseases in elderly patients and comparing two nutritional and cardiac prognostic markers.
In our retrospective study, it was observed that those with low PNI had significantly lower HRV in the geriatric age group without chronic disease except for controlled hypertension and regulated diabetes. The RMSSD duration and pNN50 value, which were independent of diurnal changes and other effects and reflected parasympathetic tone, were significantly lower in the group with low PNI than the group with high. There was no significant relationship between GNRI and HRV parameters. When patients were grouped according to FRS, a significant difference was found between the low-medium-high risk groups in terms of the LF / HF ratio, which is assumed to be an indicator of sympathovagal balance. In addition, a significant positive correlation was observed between LF, which is an important indicator for evaluating sympathetic activity, and FRS. Thiese are data proving that increased cardiac risk is related to increased sympathetic tone in patients with high-risk scores.
In addition, in patients over 65 years of age, poor protein and malnutrition in the stage before the development of complicated chronic diseases are associated with higher cardiac sympathetic activity, which may be associated with increased cardiovascular morbidity and mortality through HRV time and frequency domain variables. The relationship between late stage chronic diseases and nutritional indexes has been proven in previous studies, and studies evaluating the importance of nutritional indexes in stable elderly patients are insufficient. Therefore, in terms of preventive medicine, the importance of protein- based correct and adequate nutrition should be emphasized in addition to lipid-poor nutrition recommendations for the elderly patient group, even if they do not have a chronic disease. Limitations
Our study has some limitations. The study has a cross-sectional and retrospective design, so we do not have data showing the prognostic value of PNI in elderly patients. The relationship and prognostic significance between HRV and PNI in stable hypertensive and diabetic elderly patients can be clarified with prospective studies with larger patient populations.
Conclusion
This study showed that PNI was associated with HRV in the stable elderly patient group. Also, it was found that patients with high FRS have lower PNI values. The PNI calculated from serum albumin concentration and total lymphocyte count is a
simple and objective indicator of nutrition, and our findings are important in terms of proving the cardiac importance of correct and high-quality nutrition for elderly patients.
Acknowledgment
We would like to thank Ahmet Arslan for his assistance in retrospective screening of holter rhythm data.
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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Hatice Tolunay, Ozge Kurmus, Suat Gormel, Serkan Asil, Salim Yasar, Erkan Yildirim, Yalcin Gokoglan, Hasan Kutsi Kabul. The relationship between nutritional status and heart rate variability in elderly patients. Ann Clin Anal Med 2021;12(5):506-511
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Characteristics and outcomes of acute appendicitis cases during the COVID-19 pandemic
Murat Başer, Mehmet Kağan Katar
Department of General Surgery, Yozgat Bozok University, Faculty of Medicine, Yozgat, Turkey
DOI: 10.4328/ACAM.20483 Received: 2021-01-13 Accepted: 2021-02-15 Published Online: 2021-04-16 Printed: 2021-05-01 Ann Clin Anal Med 2021;12(5):512-516
Corresponding Author: Murat Başer, Yozgat Bozok University, Faculty of Medicine, General Surgery Department, Yozgat, 66100, Turkey. E-mail: muratbaser66@hotmail.com P: +90 505 759 17 22 F: +90 354 217 10 72 Corresponding Author ORCID ID: https://orcid.org/0000-0002-3568-2713
Aim: Our aim in this study was to investigate the effects of the COVID-19 pandemic on acute appendicitis (AA) cases.
Material and Methods: This study was designed as a single-center, retrospective, and observational study. The patients were divided into three groups relative to the date of the first COVID-19 case in Turkey, which was March 10, 2020 (Group A: before the pandemic; Group B: pandemic period; Group C: the same period one year before the pandemic). A total of 413 patients were included in the study.
Results: In terms of treatment modality, the rate of open appendectomy was significantly higher in Group B (p<0.001). Rates of conversion to open surgery, as well as rates of complicated appendicitis were also significantly higher in Group B (p=0.027, p=0.024, respectively). While there was no difference between the groups in terms of preoperative hospitalization duration (p=0.102), it was found that the duration of symptoms, operation time, and postoperative length of hospital stay were significantly higher in Group B (p<0.001, p=0.011, p=0.001, respectively). In addition, the complication rate in group B (8.9%) was also significantly higher than in the other two groups (p=0.023).
Discussion: We found that the rate of open surgery, the rate of conversion of laparoscopic surgery to open surgery, complication rates, mean operation time, and postoperative hospital stay were significantly higher in AA patients that underwent surgery during the COVID-19 pandemic period. We believe that the main reason for this negative outcome is the late admission of the patients to the hospital.
Keywords: Acute appendicitis; COVID-19; Pandemic; Outcomes
Introduction
The novel virus, which first appeared in Wuhan, China in December 2019, was named “severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)” by the International Committee on Taxonomy of Viruses, and on February 11, 2020, the emerging clinical syndrome was defined as COVID-19 by the World Health Organization (WHO) (https://www.who.int/dg/speeches/detail/ who-director-general-s-remarks-at-the-media-briefing-on- 2019-ncov-on-11-february-2020). Since that date, COVID-19 has spread very rapidly around the world. On March 11, 2020, the World Health Organization (WHO) declared the infection a pandemic. In Turkey, early measures, such as international travel restrictions, held off the emergence of the first COVID-19 case, which was eventually detected on March 10, 2020, a later date compared to many countries. Since this date, the Turkish Ministry of Health has undertaken a series of measures, such as the closure of schools at all levels, closure of universities, curfews for citizens over 65 and under 18 years old, and the conversion of many hospitals into pandemic response centers. Despite these measures, the number of infected people within the first month of the epidemic exceeded 47,000, the number of new cases per day toped 4,700 and the total number of deaths surpassed 1,000. These numbers prompted the Ministry of Health to take new and more aggressive measures, such as restricting travel in and out of many regions, as well as curfews for all citizens in many provinces. In addition to these measures, it has been emphasized on news outlets and many social media platforms that hospitals should not be visited unless absolutely necessary.
Acute appendicitis (AA) continues to be one of the most common causes of acute abdominal pain in the emergency department and requires rapid surgical intervention. The overall incidence of AA in the USA has been reported to be 9 out of 10,000, and the lifetime risk is around 7% [1]. Although it has been shown that conservative treatment can be applied in some selected cases, appendectomy is still considered the gold standard in AA treatment [2, 3].
While the vast majority of the published literature on COVID-19 focuses on disease transmission characteristics, pathogenesis, treatment options, and patient outcomes, the impact of the pandemic on other areas of medicine and recommendations for solutions have not yet been adequately investigated. Our aim in this study was to investigate the impact of the COVID-19 pandemic on AA cases that are frequently encountered in emergency abdominal surgery practice. We also elaborated on changes that can be made to address these issues.
Material and Methods
Ethics committee approval was obtained from the Clinical Research Ethics Committee of our university before initiation of the study. This study was designed as a single-center, retrospective, and observational study and was carried out in accordance with the Declaration of Helsinki.
Patients
Based on the date of March 10, 2020, when the first COVID-19 case was detected in Turkey, the data of patients treated in our hospital between December 10, 2019 – June 10, 2020 and
March 10, 2019 – June 10, 2019, were retrospectively analyzed from the hospital data record system. The inclusion criteria for the study were radiological or intraoperative diagnosis of AA, age over 18 years, and access to all medical data records. The exclusion criteria for the study were pregnancy and the application of additional interventional procedures (such as oophorectomy) during the appendectomy. A total of 413 patients were included in the study. A flow chart of the study population is presented in Figure 1.
The patients were divided into 3 groups based on the March 10, 2020 date. Patients treated for AA in the 3-month period before this date (December 10, 2019 – 10 March 2020) were included in Group A. Patients treated for AA in the 3-month period after this date (March 10, 2020 – June 10, 2020) were included in Group B, and the patients treated for AA between the same dates 1 year ago (March 10, 2019 – 10 June 2019) were included in Group C.
Data Collection and Definitions
Patients’ sociodemographic data, the surgical technique applied (open or laparoscopic), intra-operative findings (operation time, uncomplicated appendicitis, or complicated appendicitis), postoperative complications, mortality, and postoperative length of hospital stay were evaluated. Simple, focal or suppurative appendicitis was considered uncomplicated appendicitis, while gangrenous, perforated appendicitis, and periappendiceal abscess were considered complicated appendicitis. Perforation was evaluated based on intraoperative findings. In equivocal cases, perforation was assessed using the patient’s pathology report. Complications occurring within 30 days after the patient’s first discharge were accepted as postoperative complications. The time when the patients first reported nausea, vomiting, dyspepsia, epigastric pain, or any other abdominal pain was defined as the time of symptom onset. The time between the onset of symptoms and admission to the hospital was defined as the symptomatic time, while the time between admission and the start of surgery was designated as the preoperative hospitalization time. If the symptom onset time was fully recorded, the symptomatic time was calculated based on this record. In cases where an approximate time was given, it was defined as follows: if symptoms began in the morning, the symptom onset time was set to 7 a.m., and if the symptoms began in the evening, the symptom onset time was set as 7 p.m. Statistical Analyses SPSS 22.0 (Statistical Package for Social Sciences, IBM Inc., Chicago, IL, USA) was used for statistical analysis of the data. Continuous variables were expressed as mean ± standard deviation. The Kolmogorov-Smirnov test was applied to test the normality of the distribution. The Chi-square or Fisher’s exact tests were used to compare groups related to categorical variables. When comparing the two groups, the Student-t test was used for parametric data, while the Mann-Whitney U test was used for non-parametric data. Age, symptomatic time, preoperative hospitalization time, operation time, and postoperative length of hospital stay were compared with a Kruskal-Wallis one-way analysis of variance, followed by a Mann-Whitney post hoc test. A p -value of less than 0.05 was considered statistically significant.
Results
There were no significant differences between the groups in terms of age and gender (p=0.313, p=0.245, respectively). Similarly, there were also no significant differences between the groups in terms of medical comorbidities. The patient demographic data are shown in Table 1.
Evaluation in terms of treatment modality showed that the rate of open appendectomy in Group B was significantly higher as compared to the other two groups (p<0.001). In addition, the conversion from laparoscopic surgery to open surgery occurred in 4 (3.6%) patients in Group A, 11 (12.1%) patients in Group B, and 5 (4.3%) patients in Group C. This conversion rate was significantly higher in Group B (p=0.027). Data on treatment approach modalities and rates of conversion of laparoscopic surgery to open surgery are given in Table 2. Moreover, the rates of complicated appendicitis were significantly higher in Group B compared to the other two groups (p=0.024) (Table 2). There was a significant difference between the groups in terms of symptomatic duration, and post hoc analysis indicated that the symptomatic duration was significantly higher in Group B (p<0.001), while no significant difference was detected between Groups A and C (p=0.477). On the other hand, no significant differences were found between the groups in terms of preoperative hospitalization time (p=0.102). However, it was determined that there was a significant difference between the groups in terms of operation time (p=0.011). The post hoc analysis indicated that the operation time in Group B was significantly longer compared to Groups A and C (p=0.045, p=0.021, respectively). In addition, there was a significant difference between the groups in postoperative length of hospital stay (p=0.001). The post hoc analysis showed that the mean postoperative length of hospital stay in Group B, with an average of 2.07 days, was significantly higher compared to Groups A and C (p=0.024, p=0.001, respectively). Complications developed in the postoperative period occurred in 3 (2.4%) patients in Group A, 13 (8.9%) in Group B, and 4 (3%) in Group C, and the rate of complications in Group B was significantly higher than the other two groups (p=0.023). In addition, among the patients included in our study, the only mortality occurred in one patient in Group B. Data on complications are given in Table 2.
Discussion
The number of AA cases during the pandemic in our study was similar to those of the pre-pandemic period and the same period last year. The population of our city is approximately 450,000 people, and there are two hospitals, including ours, with similar capacities. During the pandemic, the other hospital was designated as a treatment center for patients infected with COVID-19 (AA cases were not treated in the other hospital during this time). Considering this detail, it can be interpreted that number of AA cases has actually decreased . Some studies in the literature have also reported a decrease in the incidence of AA during the COVID -19 pandemic [4, 5]. However, a better assessment could have been carried out by including the number of AA cases from the other hospital before the pandemic and same period last year.
We found that open surgery rates during the pandemic period were higher compared to other periods. This preference for open surgery may be due to the higher rates of complicated appendicitis during the pandemic period compared to other periods in our study. Moreover, in patients diagnosed with complicated appendicitis in the preoperative period, concerns of possible insufficient drainage and debridement during laparoscopic surgery might have affected the surgeon’s choice of operation technique. Similarly, we think that high rates of complicated appendicitis during the pandemic period also impacted the rates of conversion of laparoscopic surgery to open surgery during this period. While our rate of conversion to open surgery in non-pandemic periods was similar to the studies in the literature, this rate was higher during the pandemic period [6, 7]. Moreover, we also found that the mean operation time during the pandemic period was longer compared to the other periods. This might be because of the high rates of complicated appendicitis, which may lead to a technically difficult procedure and thus prolong the operation. Moreover, surgeons might have taken more time to be more careful due to the concern of contamination.
While our complication rates in the non-pandemic period were similar to studies in the literature, the rate of complications was higher during the pandemic period [8, 9]. The high level of postoperative wound infection and pneumonia during this period is noteworthy. In addition, the only mortality among our cases occurred during the pandemic period. We think that the high rate of complicated appendicitis during this period explains the high complication rates.
On the other hand, the mean postoperative length of hospital stay in the non-pandemic period was consistent with the studies in the literature, while during the pandemic period it was higher [10, 11]. We think that the high rate of complications in the postoperative period may have led to the longer duration of postoperative hospital stay during the pandemic period.
In our study, adverse conditions during the pandemic period, such as a high rate of open surgery, a high rate of conversion to open surgery, a high complication rate, longer operation time, and the prolonged postoperative length of hospital stay are actually combined in one denominator, which is the high rate of complicated appendicitis. In a study conducted by Kim JW et al. that included 1753 patients, it was reported that the increase in the time between the onset of AA symptoms and admission to the hospital was a risk factor for the development of perforation and complications [12]. Another study also suggests that late admission to the hospital caused complicated cases and made acute appendicitis management more difficult during the pandemic period, which was already a troubling period [13]. Indeed, in our study, we also found that the mean time between the onset of AA symptoms and admission to the hospital during the pandemic period was longer than in non-pandemic periods. At this point, it may be thought that a similar result may occur if the time elapsed between the hospital admission and the start of the operation is prolonged. However, in our study, the similarity between the mean time between the hospital admission and the time of surgery onset in the pandemic period and the non- pandemic periods eliminates this possibility. Therefore, we believe that late hospitalization of patients served as the basis for the negative consequences that occurred in AA patients during the pandemic period.
One of the reasons for patients’ late arrival to the hospital after the onset of AA symptoms may have been the patients’ anxiety and worry about the transmission of COVID-19 from patient- to-patient in the emergency department. Indeed, studies have shown that hospitals create high-risk environments for the transmission of respiratory diseases during epidemics [14-16]. We think that due to this concern, patients refrained from going to the hospital during the initial period of symptom onset and came to the hospital only when symptoms worsened. However, prospective studies on this subject need to be carried out in order to reach a definitive judgment. Another reason for late admission to the hospital might have been the complete curfew that was implemented for 3-4 days on certain days of the week in the first 3 months of the pandemic. This curfew might have caused the patients to delay going to the hospital. In addition, we are of the opinion that the perception of “not going to hospitals unless absolutely necessary” that was emphasized on many platforms, especially on social media, resulted in the late admission of patients to the hospital.
During the pandemic period, patients delayed coming to the hospital for various reasons. However, in order to prevent this late application to the hospitals, the question of “what could be done during the pandemic period?” should be emphasized. We believe that our health systems should be reviewed to include more guidance. Curfews and travel restrictions succeeded in preventing the aggressive spread of the disease in Turkey. Since hospitals are risky environments in terms of contamination during epidemic periods, we believe that healthcare systems need to provide adequate technical equipment and be able to reach affected patients at home, rather than waiting for them to come to the hospitals. For example, many delayed cases could be avoided by establishing a communication network where patients with any symptoms could call or consult via a phone application and then, if necessary, have their first examination at their own location or home.
The limitations of the study are the retrospective design and the fact that it was conducted in a single center.
Conclusions
In this study, we found that rates of open surgery, conversion of laparoscopic surgery to open surgery, complications, mean operation time, and mean postoperative length of hospital stay were higher in AA patients treated during the pandemic period compared to non-pandemic periods. We believe that the main reason for this negative outlook is patients’ late admission to the hospital. In this regard, we believe that a re-evaluation of the health system is needed so that during pandemics, such as COVID-19, health care professionals are still able to reach patients with symptoms at home by establishing a communication network instead of waiting for their arrival at the hospital.
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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Effect of red cell distribution width (RDW) on short-term mortality and morbidity in patients with acute coronary syndrome
Haydar Karahan
Department of Emergency Medicine, Ministry of Health Mardin Province Nusaybin State Hospital, Mardin, Turkey
DOI: 10.4328/ACAM.20540 Received: 2021-02-13 Accepted: 2021-04-09 Published Online: 2021-04-18 Printed: 2021-05-01 Ann Clin Anal Med 2021;12(5):517-521
Corresponding Author: Haydar Karahan, Department of Emergency Medicine, Ministry of Health Mardin Province Nusaybin State Hospital, Mardin, Turkey. E-mail: haydarkarahan@hotmail.com P: +90 532 135 87 36 Corresponding Author ORCID ID: https://orcid.org/0000-0002-5114-5969
Aim: Previous studies in the literature have shown that high RDW values are significantly associated with coronary artery disease (CAD), heart failure, and peripheral artery disease. The prognostic value of RDW for CAD in the preliminary period was discussed in the limited literature. In this study, it was aimed to investigate the relationship between red cell distribution width (RDW) and the mortality and morbidity of acute coronary syndrome (ACS) in a 1-year follow-up.
Material and Methods: This study had a retrospective design. It enrolled patients who had their first ACS. Age, sex distribution and the levels of RDW, low- density lipoprotein (LDL), and high-density lipoprotein (HDL) were determined. Mortality rates by the first month and the first year were determined. The 1-year rates of recurrent ACS, percutaneous coronary intervention (PCI), and heart failure were also recorded.
Results: The data of 132 patients were analyzed. The survival rate was 85.6% (n=113) at 1 month and 74.2% (n=98) at 1 year. RDW was significantly lower in patients who survived at 1 month and 1 year (p<0.001 and p=0.004, respectively). In the 1-year follow-up, RDW was significantly higher in patients who had ACS, who underwent PCI, and who developed heart failure (p=0.021, 0.001, and 0.001, respectively). A significant increase of 11.5% was found in 1-year mortality for RDW levels above 14.1% (Hazard ratio=3.24, 95% CI: 1.58-6.66; p=0.001).
Discussion: The RDW level is a simple, fast, and reliable parameter in deciding the prognosis of patients with ACS admitted to the emergency department.
Keywords: Red cell distribution width; RDW; Coronary artery disease; Mortality; Morbidity
Introduction
Red cell distribution width-standard deviation (RDW-SD, fL) and red cell distribution width-variation coefficient (RDW-CV, %) are considered markers of anisocytosis and routinely reported in automatic complete blood counts to make a differential diagnosis of anemia [1,2]. RDW is positively correlated with age and hemoglobin level [3]. Previous studies in the literature have shown that high RDW values are significantly associated with coronary artery disease (CAD), heart failure, and peripheral artery disease [4,5]. Recent studies have described a relationship between RDW and mortality in acute myocardial infarction (AMI) [6,7]. Azab et al. found that patients with RDW >14% had a significantly higher 4-year mortality than patients with RDW <14%. (30% vs 7%, respectively; p<0.0001) [4]. Nagula et al. found a positive correlation between high RDW level and the AMI severity and calculated that RDW above a threshold value of 14.3% had a sensitivity of 58.9% and a specificity of 84.8% for CAD on coronary angiography (CAG) [8]. Poludasu et al. found a 4-year survival rate of 70% in patients with RDW >15.7 and 85% in patients with RDW <13.3%, with the difference being statistically significant (p<0.001) [9]. In the present study, we aimed to investigate the relationship between RDW at admission and 1-year mortality and morbidity in patients with acute coronary syndrome.
Material and Methods
This study was retrospectively designed and enrolled patients who were diagnosed with AMI in the emergency department of a secondary state hospital and referred for CAG between 2016 and 2020. The study data were obtained from patient files and archive records. The study included patients older than 18 years of age with objective evidence of AMI, whose 1-year medical records after the initial diagnosis were available. Patients with a previous history of AMI, PAG, coronary artery bypass surgery, end-stage renal disease, cancer, thalassemia, or bleeding diathesis were excluded. Patients with age older than 85 years, clinical evidence of active infection, active or chronic inflammatory or autoimmune disease, steroid use, and anemia were also excluded. Age, gender distribution, admission RDW, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) levels were determined. The rates of survival and recurrent ACS, CAG intervention, and heart failure at 1 month and 1 year were also recorded. The patients were divided into two groups below and above the median values of RDW, HDL, and LDL levels.
Continuous variables were expressed as mean ± standard deviation (SD), and categorical variables as percentages. Student’s t-test or analysis of variance was used to compare parametric continuous variables; Mann-Whitney U-test or Kruskal-Wallis test was used to compare nonparametric continuous variables. The χ2 test was used to compare categorical variables. ROC analysis was used to determine a clinical threshold value for RDW values. Multivariate logistic regression analysis was used to determined variables associated with mortality. Survival analysis was performed using Kaplan- Meier curves. SPSS 22.0 program (IBM Corp., Armonk, NY, USA) was used for all statistical analyses. This study was performed in compliance with the 1964 Helsinki Declaration and its
subsequent amendments. Ethics committee approval for the study was obtained from the affiliated institution (No:459; Date:15.08.2020).
Results
Medical records of 239 patients were reviewed and data of 132 patients meeting the inclusion criteria were included in the final analysis. The mean age of the patients was 66.4±10.2 years. The number of females was 60 (45.5%) and the number of males was 72 (54.5%). ACS occurred in the form of STEMI in 24 (18.2%) patients and NON-STEMI in 108 (81.8%) patients. The survival rate was 85.6% (n=113) at 1 month and 74.2% (n=98) at 1 year. The study findings are summarized in Table 1 and Table 2.
The RDW was 14.9±0.6% in patients who died and 13.9±1.1% in those who survived by 1 month (p <0.001; 95% CI: 0.6-1.3). The RDW was 13.9±1.1% in survivors at 1 year and 14.6±0.8% in patients who died from ACS, with the difference being statistically significant (p= 0.004; 95% CI:0.2-1.0). The RDW was 15.2±0.6% in patients who developed heart failure by 1 year after ACS and 14.0±1.1% in those who did not develop heart failure, with the difference being statistically significant (p=0.00; 95% CI:0.3-2.0). The relationship of other parameters with mortality and morbidity, and the t-test statistics are shown in Table 3.
In our study, the median value of RDW was 14.1%. According to the Kaplan-Meier survival analysis, 1-year survival was statistically higher in patients with RDW ≥14.1% (Log-rank test p=0.001, Figure 1). Strikingly, the mortality rate was 9 times higher in patients with RDW above the median value of 14.1% by 1 month after ACS (Odds ratio (OR)=9.09, 95% CI: 2.4-33.2, p<0.001). According to the Cox regression analysis, a significant increase of 11.5% was found in 1-year mortality for higher RDW levels (Hazard ratio: HR=3.24, 95% CI: 1.58-6.66; p = 0.001).
According to the ROC analysis, the cut-off value of 14.2% for RDW had a sensitivity of 67.6% and a specificity of 64.3% for 1-year mortality following ACS (AUC: 0.710, 95% CI: 0.620- 0.800, Figure 2A). The cut-off value of 13.9% for RDW had a sensitivity of 56.7% and a specificity of 58.8% for recurrent ACS by 1 year (AUC: 0.662, 95% CI: 0.560-0.163, Figure 2B). The cut-off value of 14.7% for RDW had a sensitivity of 66.7% and a specificity of 69.1% for undergoing CAG by 1 year (AUC: 0.821, 95% CI: 0.723-0.919, Figure 3a). The cut-off value of 14.7% for RDW had a sensitivity of 75.1% and a specificity of 69.4% for the development of heart failure (AUC: 0.792, 95% CI: 0.692-0.892, Figure 3b).
Discussion
This study showed a relationship between high RDW values and ACS-related mortality, recurrent ACS, the development of new- onset heart failure, and CAG intervention in the early post-ACS period. Especially in the very early period after ACS, mortality was significantly higher on average by 9 times (OR) among patients with an RDW value above the median value of 14.1%. RDW reflects variability in the size of peripheral erythrocytes and is based on the width of the volume distribution curve, with larger values showing greater variability (anisocytosis). RDW is altered by the levels of iron, B12, or folate, or hemolysis [6,10,11].
In the Tromsø Study, which started with 25,612 participants in 1994-1995, a 13% increase in the ACS risk was found for each 1% increase in RDW at the end of 15.8 years of follow-up (HR=1.13) [12]. Cemin et al. showed that RDW was a significant marker for ACS among 1971 patients admitted to the emergency department with chest pain [13]. In that study, they found that a cut-off value of 13.7% for RDW had a sensitivity of 75% and a specificity of 52% for the presence of ACS (AUC: 0.610). Felker et al. reported that a higher RDW level was a strong and independent marker of morbidity and mortality in patients with chronic heart failure [14]. Van Kimmenade et al. found a significant 1.03-fold increase in mortality risk for each 1% increase in RDW during the 1-year follow-up period in patients with acute heart failure (p=0.04) [15]. In addition, a significant relationship has been shown between high RDW level and cardiovascular death and hospitalizations due to heart failure [16-18].
In a prospective study involving 310 patients presenting with ACS, Akın et al. found high RDW level to be a significant risk factor for CAD severity (OR=1.16, p=0.021) [19]. Gül et al. found a cardiovascular mortality rate of 18% in the high RDW group and 12% in the low RDW group at a follow-up of 3 years (p<0.001) [20]. In addition, they reported a 6-month mortality rate of 9.5% in the high RDW group and 1.9% in the low RDW group (p=0.002). Similarly, the 6-month and 3-year rates for recurrent ACS were significantly higher in the high-RDW group than in the low-RDW group (27.4% versus 13.7%; p=0.03, and 10.7% versus 6%; p <0.001, respectively). Similarly, we categorized our patients into two groups as those with RDW≤ 14 and those with RDW>14. We demonstrated that the rate of hospitalization due to heart failure was 16.8% in the high-RDW group and 7.9% in the low-RDW group by 3 years (p=0.020). Furthermore, our ROC analysis found that an RDW value of 14% was a significant cut-off value for 3-year cardiovascular death (AUC: 0.70, sensitivity 60%, specificity 72.5%) [20]. Wang et al. found that the rates of mortality and heart failure among 1604 patients were significantly higher in the high-RDW group by 1 month after ACS (OR=2.1 p<0.001 and OR=2.1, p<0.001, respectively) [21]. In 2506 patients who underwent CAG for STEMI, Uyarel et al. found an in-hospital mortality rate of 7.6% in the high-RDW group (mean 16.1±1.6%) and 3.6% in the low- RDW group (mean 13.4±0.8%) (p<0.001) [22]. In that study, where the RDW median value was taken as 14.8%, the rates of cardiovascular mortality (11.4% versus 4.4%), recurrent ACS (10.2% versus 7.8%), and heart failure (11.1% versus 7%) were significantly higher in the high-RDW group at a mean follow-up of 21 months (p <0.001, p=0.080, and p=0.003, respectively). In this study, an 83% increase in long-term mortality was found for high RDW levels, thus RDW level was an independent risk factor (HR=1.831).
In our study, an average of 9-fold mortality increase was found for high RDW levels at a follow-up of 1 month (Odds ratio (OR)=9.09, 95% CI: 2.4-33.2). Similarly, a high RDW level was found to be an independent risk factor for 1-year mortality (HR=3.24%, 95CI: 1.58-6.66). Furthermore, in accordance with the literature, a high RDW level was found to be a significant risk factor for the development of ACS, CAG intervention, and heart failure. In this study, the relative risk ratios were found to be higher compared with similar studies. This may be due to our smaller sample size. In addition, our study power may be insufficient to investigate the cause of death during the follow- up period due to its retrospective design. However, its results are consistent with the findings reported by other prospective studies.
Conclusion
High RDW level is a significant risk factor for early mortality and morbidity in ACS. The RDW level is a simple, fast, and reliable parameter in making decisions for and determining the prognosis of patients with ACS who are admitted to the emergency department.
Acknowledgment
The author appreciate kind support of Ministry of Health Mardin Province Nusaybin State Hospital
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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5. Celik A, Karayakali M, Altunkas F, Karaman K, Arisoy A, Ceyhan K, et al. Red cell distribution width is correlated with extensive coronary artery disease in patients with diabetes mellitus. Cardiovasc J Afr. 2017;28(5):319–23.
6. Dabbah S, Hammerman H, Markiewicz W, Aronson D. Relation Between Red Cell Distribution Width and Clinical Outcomes After Acute Myocardial Infarction. Am J Cardiol. 2010;105(3):312–7. DOI:10.1016/j.amjcard.2009.09.027
7. Bujak K, Wasilewski J, Osadnik T, Jonczyk S, Kołodziejska A, Gierlotka M, et al. The Prognostic Role of Red Blood Cell Distribution Width in Coronary Artery Disease: A Review of the Pathophysiology. Dis Markers. 2015;2015. DOI: 10.1155/2015/824624.
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9. Poludasu S, Marmur JD, Weedon J, Khan W, Cavusoglu E. Red cell distribution width (RDW) as a predictor of long-term mortality in patients undergoing percutaneous coronary intervention. Thromb Haemost. 2009;102(3):581–7.
10. Aslan D, Gumruk F, Gurgey A, Altay Ç. Importance of RDW value in differential diagnosis of hypochrome anemias. Am J Hematol. 2002;69(1):31–3.
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A glance at COVID-19 in Turkey with the concepts of health and poverty since Edwin Chadwick until today: Diyarbakir example
Mehmet Emin Kurt 1, Hıdır Sarı 2
1 Department of Healthcare Management, Dicle University Faculty of Economics and Administrative Sciences, 2 Department of Public Health, Dicle University, Faculty of Medicine, Diyarbakir, Turkey
DOI: 10.4328/ACAM.20555 Received: 2021-02-26 Accepted: 2021-04-16 Published Online: 2021-04-26 Printed: 2021-05-01 Ann Clin Anal Med 2021;12(5):522-526
Corresponding Author: Mehmet Emin Kurt, Department of Healthcare Management, Dicle University Faculty of Economics and Administrative Sciences, 21280, Diyarbakir, Turkey. E-mail: mekurt1@hotmail.com P: +90 5072273609 Corresponding Author ORCID ID: https://orcid.org/0000-0002-7181-8681
Aim: The aim of this study was to evaluate the direction of the pandemic spread on monthly COVID-19 case density maps in 4 districts of Diyarbakir city in the application software of the Republic of Turkey Ministry of Health “Hayat Eve Sığar (Life Fits Into Home)”, in terms of socio-economic development indices based on Edwin Chadwick’s relationship between health and poverty concepts.
Material and Methods: COVID-19 cases density maps in the same central districts over the last 5 months, and the amount of propagation and density of the pandemic in those districts were determined.
Results: When comparing areas of Diyarbakir with low and high socio-economic status, a parallelism was found between the density of the pandemic and the direction of spread.
Discussion: The vicious circle of poverty constantly creates negative health consequences in the presence of an unhealthy environment and low socioeconomic status.
Keywords: COVID-19; Poverty; Socioeconomic; Development index; Pandemic
Introduction
A pandemic is the spread of a disease, an infectious agent, or a health-related problem in various countries or a continent, and even in a very wide area such as the whole world (available at: https://hsgm.saglik.gov.tr/depo/mevzuat/genelge/Bulasici_ Hastaliklar_ile_Mucadele_Rehberi_Ustyazi.pdf). In December 2019, it was announced that an outbreak of an unknown cause with symptoms of severe pneumonia had started in Wuhan, the capital of China’s Hubei province. Right after, on January 7, 2020, Chinese scientists determined that these patients with pneumonia were actually infected with a new type of coronavirus. Later, in February 2020, this table was named COVID-19 by the World Health Organization (WHO) and declared a pandemic [1].
Due to the destruction they cause, pandemics are forcing governments to revise their health policies and plans. While pandemics significantly threaten the human life cycle and social life, they occur more and more frequently. The history of mankind has lived through pandemics for centuries. Historically, some of the outbreaks that occurred are plague pandemics and smallpox epidemics in the 14th century; cholera pandemics in 1879-81, the Spanish flu in 1918-20, the Asian flu in 1957- 58, the Hong Kong flu in 1968-69, the bird flu (H5N1) in 2005 and the swine flu (H1N1) in 2009. The last the coronavirus (Covid-19) pandemic that has started at the end of 2019, continues today.
As the outbreak started at the beginning of 2020 and spread all over the world in a short period of 3 months, governments, including those of developed countries, have been inadequate due to economic, social, psychological and health infrastructure reasonsö and have been inconsistent/indecisive in terms of pandemic management and transparency in sharing information. The attitudes of governments such as Brazil and America, which argue that even the newly defined measures to be taken against the transmission of the disease and its symptoms are unnecessary, have led to very serious problems in the control of the pandemic (an increase in the number of cases and deaths).
From a public health perspective, two important concepts affected the existing health policies and plans of the countries at the end of the 19th century. The first of these is the concept “health and poverty (inadequacy of the working class with a low socioeconomic status in the matter of their health)” in the 1840s; and the other “health promotion and maintenance”, which was defined by WHO in the 1980s.
According to the World Bank, poverty is the case of “hunger, the onset of illness, not being able to go to school or not knowing how to read, not having a job, not being able to sustain daily life, having fear of the future, high child mortality, lack of security, weakness and limited freedoms” [2]. The United Nations Development Programme (UNDP) describes the “Multidimensional Poverty Index” as recognition that poverty deprives families of health, education, and living standards and the ability to live in dignity (available at: https://feature.undp. org/covid-and-poverty/).
The fact that the income of individuals during the treatment of diseases is not enough to gain their health due to poverty, and that they physically push themselves too much to get out of this unhealthy situation (due to earnings, healthy housing, access to health services), will end in a vicious cycle of poverty and disease.
While the presence of diseases and poverty trigger each other in a vicious circle, this vicious circle had to be broken in the matter of income so that people could reach the concept of being a healthy individual, which is difficult to reach.
When different factors, such as the fact that the concept of promotion and maintenance of health and the concepts of poverty and diseases could not be presented or were not presented adequately and at the same time in a society in terms of both socio-economically and health services, and the life struggle of those who live in regional settlements as a result of the economic problems, come together conceptually, the common occurrence of possible infectious and non-infectious diseases in individuals according to the literature information happens to be an expected situation. It is known that global outbreaks like the COVID-19 manifest themselves at the highest levels in terms of influence in economically inadequate neighborhoods, districts, and provinces of countries and cities. This study aims to evaluate the direction of spread of the pandemic on monthly maps of COVID-19 cases density in 4 districts in the city of Diyarbakir (data for 1 day of each month) in the application software “Hayat Eve Sığar (Life Fits Into Home)”, which was developed by the Republic of Turkey Ministry of Health in March 2020 and can be installed on mobile phones; in terms of socio-economic development indices, based on Edwin Chadwick’s relationship between health and poverty concepts.
Health and poverty
In the “Report on the Sanitary Conditions of the Labouring Population of Great Britain” published by Edwin Chadwick in 1842, he stated that the bad conditions in which poor people live constantly cause unhealthiness, and as a result, premature deaths occur in the low-income areas of the cities. Chadwick suggested that there is a positive connection between poor living conditions and the development and spread of diseases; and that the government must intervene by providing clean water, improving the drainage systems, and making sure that the local councils get the garbage from homes and streets cleaned. Chadwick stated that the poor conditions that the impoverished and sick workers have to endure, prevent them from working efficiently, and since they cannot participate in the production, their poverty rate increases, and their state of illness continues (available at:https://navigator.health.org.uk/ theme/report-sanitary-conditions-labouring-population-great- britain; Çilingiroğlu N. Demography and Health. Ed. Güler Ç., Akın L. From the Book of Basic Information on Public Health Volume I. Ankara: Hacettepe University Publications, 2012). The main idea of the report, published in the 1840s, around the time the Queen of England was given the task of examining the living conditions of the workers who live in poor neighborhoods in the industrial areas, was actually describing a single cycle to the leaders of the past and present.
Poor countries tend to have worse health outcomes than better- off countries. Within countries, poor people have worse health outcomes than better-off people. The association between poverty and ill-health reflects a two-way causal relationship [3].
Patel et al. (2020) stated in their study that many factors increase the exposure of people with low socioeconomic status (SES) to COVID-19 [4]. These factors can be listed as follows:
1. First, economically disadvantaged people are more likely to live in overcrowded accommodation.
2. Financially poorer people are often employed in occupations that do not provide opportunities to work from home.
3. Those in low SES groups are more likely to have unstable work conditions and incomes, conditions exacerbated by the responses to COVID-19 and its aftermath. Such financial uncertainty disproportionately harms the mental health of those in low SES groups and exacerbates their stress. Heightened stress is known to weaken the immune system, increasing susceptibility to a range of diseases and the likelihood of health risk behaviors. Therefore, poverty may not only increase one’s exposure to the virus but also reduce the immune system’s ability to combat it.
4. People with low SES present to healthcare services at a more advanced stage of illness, resulting in poorer health outcomes. This will likely lead to poorer health outcomes from COVID-19 for economically disadvantaged people [4].
On behalf of the United Nations, in the United Nations Development Programme’s report that offers information and analysis of evaluations on the socioeconomic impacts of COVID-19 around the world, what are the main socio-economic problems caused by the pandemic, and the socio-economic impacts of COVID-19 on economies and societies, it was observed that according to many results obtained in the study conducted between March-May 2020 “Survey on Impact of COVID-19 on Enterprises in Turkey”, almost half of the enterprises in the country have stopped operating, 54% have lost more than half of their workload, half of them are having difficulties with the procurement, half of them are having problems with the payments, only 41% of them are capable of working remotely and the COVID-19 crisis has affected the female workers more negatively (available at:https://www.undp.org/content/undp/en/ home/coronavirus/socio-economic-impact-of-covid-19. html.). These results will show a negative reflection of the pandemic on citizens with low-income socioeconomic status.
Health promotion and maintenance
According to the 1948 constitution of WHO, health is a state of complete physical, mental and social well-being, and not merely the absence of disease or infirmity (available at:https://www. who.int/healthpromotion/about/HPR%20Glossary%201998. pdf). The concept of health promotion and maintenance has been emphasized since the Ottawa Charter for Health Promotion was signed at the first International Conference on Health Promotion in Ottawa, Canada in 1986; and studies in the field of public policy have been conducted by the states (available at:https://www.who.int/healthpromotion/conferences/6gchp/ hpr_conference_background.pdf, available at:https://www. who.int/healthpromotion/conferences/hpr_special%20issue. pdf?ua=1).
According to the charter, “Health promotion is the process of enabling people to increase control over, and to improve, their health” (available at: https://www.who.int/teams/health- promotion/enhanced-wellbeing/first-global-conference). Health promotion and maintenance also include actions to change social, environmental, and economic conditions [5].
The processes included in the concept itself have the potential to control outbreaks, reduce the disease burden of non- infectious diseases and social injustice. Health promotion and maintenance are essential to effectively address global public health issues and successfully reduce the burden of disease-related inequalities (available at: https://www.who.int/ mediacentre/events/ meetings /7gchp / en/).
The concept of health promotion reaffirms a positive view, describing not only disease prevention but also how to expand and advance one’s life potential [6]. Health promotion includes measures to continually improve physical health.
Health protection offers equal opportunities for people to enjoy the highest attainable level of health and is achieved through the development and implementation of legislation, policies, and programs in the areas of environmental health protection and community care facilities. Protection of public health focuses mainly on situations such as controlling infectious diseases, protecting the public against environmental hazards. Health protection aims at reducing the likelihood that people will encounter environmental hazards or behave in unsafe or unhealthy ways. The interventions are aimed at preventing people from falling into sickness or illness by building protective mechanisms [7, 8]. Preventive actions are defined as interventions directed to averting the emergence of specific diseases and reducing their incidence and prevalence in populations [7].
In this study, we will try to determine the direction of propagation and density of the COVID-19 pandemic in districts that are insufficient and sufficient in terms of socio-economic development index.
Material and Methods
In this study, the direction of propagation and density of the COVID-19 in 4 districts in the city of Diyarbakir in Turkey were tried to be determined using monthly images (case density map data for 1 day of each month) in the application software “Life Fits Into Home”, developed by the Ministry of Health in March 2020, which is open to the public, free and can be downloaded from Google Play and installed on mobile phones without permission.
The socio-economic development indices of the 4 central districts in Diyarbakir were ranked based on the 2017 socio- economic development ranking of the Ministry of Industry and Technology concerning the cities. The socioeconomic development levels of the districts and the covid-19 prevalence densities in the districts are shown.
Results
There are 4 districts in Diyarbakir: Sur, Yenishehir, Baglar and Kayapinar (Figure 1). The rankings of these districts by population and socioeconomic development are shown in Table 1. (available at: https://www.sanayi.gov.tr/bolgesel-kalkinma- faaliyetleri/analitik-cal%C4%B1smalar/01122b, http://www. diyarbakir.bel.tr/diyarbakir/genel-bilgiler/ilce-nufus.html). According to Table 1, Sur and Baglar districts are the two central districts with the lowest scores in terms of socioeconomic indicators. Development rankings were generated with 32 different variables used to create socioeconomic indicators for provinces in Turkey. These variables consist of 7 main headings: demographic, employment, education, health, competitiveness, financial, and quality of life. These main headings have 32 subheadings in total. The data generated in the table as a result of all these classifications and advanced analyses create the clearest indicators of the direction in which the conditions of a district in terms of health and work have evolved. In other words, the ranking goes from the districts with the highest number of unemployed and unhealthy individuals up to to the districts with the least.
The majority of the first rank developed districts are located in the most developed provinces of Turkey. In terms of geographical regions, it is seen that 32 districts are included in the Marmara region, 11 in the Aegean, 6 in the Central Anatolia, 5 in the Mediterranean, one district in the Black Sea, and one in the Southeastern Anatolia. From the Southeastern Anatolia region, Shehitkâmil district of the province Gaziantep is included. On the other hand, the reason why only 1 (Yenishehir) district from Diyarbakir is among the second-rank districts is that there are existing structures such as industrial areas, state offices, etc. and the public employees and retired people are high in number in the district (available at: https://www.sanayi.gov.tr/bolgesel- kalkinma-faaliyetleri/analitik-cal%C4%B1smalar/01122b).
The COVID-19 case density maps of the central districts in Diyarbakir and their proximity to each other by location are shown in Figure 2 (available at: https://webdosya.csb.gov.tr/db / diyarbakir/webmenu/webmenu3229.jpg).
When the 5 maps in Figure 2 are ranked according to the locations of the central districts: located in the lower end as shown in the case density maps is the Sur district, which is the historical part and center of the city. Next to it are its neighboring districts Baglar and Yenishehir, and in the last section, there is Kayapınar district, where the socioeconomic status and residential areas are more developed compared to the other 3 districts.
Based upon the COVID-19 case density map, it was determined that the spread of the disease in the 4 central districts of Diyarbakır increased dramatically in districts where poverty and unemployment are intense according to socioeconomic development indices. In other words, it shows that where the socioeconomic and health indicators are low, the density of the disease is higher than in the other districts.
Discussion
The Human Development Index, which is measured by taking into account the per capita income, life expectancy at birth, literacy, and schooling rates, has been published by UNDP each year for countries since 1990. Human development is also measured with education and health data as well as income. It was stated that in the 2017 report, Turkey’s human development index score was 0.767ö and the country was ranked 71st. According to this score, Turkey was found to be in the “High Human Development” group among other countries. In the study “Human Development Index-Districts (HDI-D) 2017 Transition from Consumer to Human” of the Human Development Foundation, it was stated that as well as education, indicators in the field of health are among the unchanging indicators of human development, and based on the study conducted in this context, the Health Index status of the districts, which is a subdimension of the HDI-D, was determined.
According to these results, indices of the districts are defined as follows: the highest group as green, the high group as blue, the middle group as yellow, and the low group as red. Baglar, Kayapinar, Yenishehir and Ergani districts from the city of Diyarbakır were included in the study sample, but Yenishehir was not included in the study because the district data could not be obtained. In the results of this report, Baglar district was found to be in the red group (low) with a health index score of 0,281 and Kayapinar in the yellow group (middle), with a health index score of 0,406 (available at: http://ingev.org/ raporlar/ IGE RAPOR 2017.pdf.). This result show parallelism with the COVID-19 case density maps of the central districts in Diyarbakır.
In the study conducted by Finch and H. Finch in 2020 regarding the potentially high degree of vulnerability to the effects of the COVID-19 pandemic for people living in poverty using data collected over 71 days were used, the relationship between poverty and the number of confirmed COVID-19 cases and deaths early in the pandemic in the United States was examined. According to the study, early in the pandemic, poorer counties had a higher rate of confirmed cases than did relatively fewer poor areas, and the death rate was higher for relatively poorer counties [9]. In our study, according to the socio-economic development ranking, it is seen that the case density increases in the central districts with low socioeconomic status as the duration of the pandemic extends. These findings are similar. One of the main problems of cities since E. Chadwick until today beyond any doubt is the unhealthy environments in which poor families live and the fact that low socio-economic status creating negative health consequences in the presence of a disease. This outcome has not changed even in the last 140 years and has once again manifested itself with the COVID-19 pandemic. It showed that this situation should be reviewed by the decision-makers who determine the country’s health and socio-economic policies.
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.20555
Mehmet Emin Kurt, Hıdır Sarı. A glance at COVID-19 in Turkey with the concepts of health and poverty since Edwin Chadwick until today: Diyarbakir example. Ann Clin Anal Med 2021;12(5):522-526
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This work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of the license, visit https://creativecommons.org/licenses/by-nc/4.0/
Effects of methylprednisolone alone and combined with erythropoietin on the antioxidant system in rats with induced acute spinal cord injury
Osman Ersegun Batcik 1, Turgay Bilge 2, Yasemin Erdogan Doventas 3
1 Department of Neurosurgery, Recep Tayyip Erdogan University Medical Faculty, Rize, 2 Self-employed Neurosurgeon, Istanbul, 3 Department of Biochemistry, Health Sciences University, Haseki Training and Research Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.20580 Received: 2021-03-11 Accepted: 2021-03-29 Published Online: 2021-04-04 Printed: 2021-05-01 Ann Clin Anal Med 2021;12(5):527-531
Corresponding Author: Osman Ersegun Batcik, Recep Tayyip Erdogan University Medical Faculty, Department of Neurosurgery, 53200, Rize, Turkey. E-mail: osmanersegun@gmail.com P: +90 464 212 30 09 F: +90 464 212 30 15 Corresponding Author ORCID ID: https://orcid.org/0000-0002-6095-3642
Aim: This experimental study was carried out to biochemically compare the effects of methylprednisolone (MP) alone and in combination with human recom- binant erythropoietin (EPO) on malondialdehyde (MDA), superoxide dismutase (SOD) and catalase.
Material and Methods: Twenty-four adult male Sprague-Dawley rats were randomly divided into three groups. Spinal cord injury (SCI) was created after laminectomy in all three groups. No treatment was given to the trauma group. In the MP group, 30mg/kg fast (within 15 minutes), and after 45 minutes, intraperitoneal MP was administered in 4 equal doses of 5.4 mg/kg continuously within 23 hours. In the EPO + MP group, 1000IU/kg intraperitoneal EPO was given in addition to the MP given in the same way. MDA, SOD and catalase levels were compared between the groups in the spinal cord samples taken from all rats at the 24th hour after the operation.
Results: Catalase level was higher in both the MP group and the EPO + MP group compared with the trauma group (p = 0.006, p = 0.001; respectively). Com- pared to the trauma group, the SOD level was higher only in the EPO + MP group (p = 0.006). Both catalase and SOD levels were higher in the EPO + MP group compared to the MP group (p = 0.006, p = 0.005; respectively). There was no difference between the groups in terms of MDA (p = 0.183).
Discussion: These results show that EPO given in addition to MP in SCI can be used effectively against oxidative damage.
Keywords: Spinal cord; Methylprednisolone; Erythropoietin; Malondialdehyde; Superoxide dismutase; Catalase
Introduction
Spinal cord trauma is a condition, which results in mortality as well as causes severe disability. Motor vehicle accidents, falls, violence, sports and occupational accidents are among the main causes of spine and spinal cord injuries [1]. In Turkey, between 1600-2000 cases of serious spinal injuries are reported annually [2]. Primary damage occurs as a result of mechanical impact in spinal cord injury. The damage to the spinal cord tissue secondary to mechanical injury increases over time, causing clinical worsening. The primary goal of clinical treatment is to stop or slow down this secondary damage cascade. Necrosis and apoptosis were initially identified as two main mechanisms of cellular death following SCI [1].
Normally, harmful effects of free radicals that form in the mitochondria are eliminated by antioxidant systems. If the amount of free radicals excessively increases, the antioxidant systems become insufficient, leading to cellular death. The superoxide radical (O2-), which forms in the mitochondria, converts superoxide dismutase (SOD) into hydrogen peroxide (H2O2), and the catalase enzyme converts hydrogen peroxide into H2O and O2. Thus, the tissue is protected from damage, preventing the formation and spreading of reactive O2 radicals [3]. However, these antioxidant mechanisms rapidly decrease following a trauma [4]. This causes more free radicals to appear. Following spinal cord injury, hemoglobin catalyzes the peroxidation of iron membrane phospholipids that are released by ferritin or transferrin. Eventually, the membrane breaks down and the cell dies. In addition, free oxygen radicals disrupt the blood–spinal cord barrier through endothelial damage, causing the accumulation of harmful substances in the injury site. The central nervous system is prone to free radical damage due to low activity of SOD and catalase [3,4]
These free radicals cause the oxidation of proteins and lipids in the cell membrane, impairing the membrane fluidity and ionic gradient. Malondialdehyde (MDA), the most prominent product of lipid peroxidation, is also used to determine lipid peroxidation. MDA diffuses easily, cross-binds to lipids and proteins in the membrane structure, and disrupts permeability by changing the specific properties of the membrane [5].
Numerous chemical agents have been used in order to protect tissues against the damage occurring after spinal cord trauma. Some agents have decreased tissue damage, while others have increased functional improvement. Although corticosteroids are one of the drugs used for this purpose, it is thought that their antioxidant features are more prominent rather than glucocorticoids-receptor association in the inhibition of lipid peroxidation. In a study, improvement in sensory and motor function was demonstrated with methylprednisolone (MP) used after spinal cord injury [6]. Another agent used in spinal cord injury is recombinant human erythropoietin (EPO), which is a hematopoietic growth factor that stimulates proliferation and differentiation in erythrocyte precursor cells. Studies have shown that erythropoietin and erythropoietin receptors are present in the central nervous system. In vivo and in vitro neural damage model studies searched antiapoptotic effect of erythropoietin, and it was reported to inhibit apoptosis, decrease inflammation, regulate excitotoxicity and increase neural proliferation [7]. In the light of this information, in a study comparing EPO and interleukin-6 in rats with induced acute SCI, EPO was shown to be effective [8].
In our study, we aimed to search studies in the literature and biochemically compare the effects of MP alone and combined with EPO on SOD, catalase, and MDA in rats with induced SCI.
Material and Methods
A total of 24 adult Sprague-Dawley rats produced in the Production and Purification Laboratory of the Istanbul Universitesi, Department of Experimental Animals Biology and Biomedical Application Techniques were used in this study. The rats weighed between 280-300 g. The animals were randomly divided into three groups of eight rats each. After the rats were anesthetized with 60 mg/Kg intraperitoneal ketamine hydrochloride and 10 mg/Kg intraperitoneal xylazine, the posterior part of the 8-10th spinal bones was removed and a non-dural trauma was created for 60 seconds using the Yasargil aneurysm clip at a pressure of 0.7 N. Hereafter, the groups were created as follows: i) Trauma group: did not receive any treatment ii) MP group: following 30 mg/Kg rapid MP administration (within 15 minutes), after 45 minutes, intraperitoneal MP was constantly given at 4 equal doses of 5.4 mg/Kg within 23 hours iii) EPO+MP group: following 30 mg/Kg rapid MP administration (within 15 minutes), after 45 minutes, a combination of MP + 1000 IU/Kg EPO was constantly administered intraperitoneally at 4 equal doses of 5.4 mg/Kg within 23 hours.
Following the operation, the rats were anesthetized with 60 mg/Kg intraperitoneal ketamine hydrochloride and 10 mg/Kg intraperitoneal xylazine, and the animals were then sacrificed with the perfusion of 100 mg/Kg sodium-pentothal. Spinal cord samples were collected and the levels of MDA, SOD and catalase were measured in these samples.
This study was carried out in accordance with the “Universal Declaration of Animal Rights”, the “European Convention on the Protection of Vertebrates for Experimental and Other Scientific Purposes (Council of Europe ETS 123)”, the “Handbook for the Care and Use of Laboratory Animals (National Research Council, USA)”, “Animal Protection Law (No. 5199)” and the “Regulation on the Working Procedures and Principles of Animal Experiments Ethics Committees” prepared by the Ministry of Environment and Forestry published in the Official Gazette (dated February 15, 2014 and No. 28914).
Preparation of Tissue Homogenate
Medulla spinalis was weighed and mixed with a 0.1 M phosphate buffer at a ratio of 1:9. The mixture was homogenized on the ice at 10.000 rpm for 1 second with a homogenizer (MICCRA GmbH Grißheimer Weg 5 79423 Heitersheim/Germany). The homogenized samples were centrifuged at 5000 g and +4oC in a refrigerated centrifuge. Protein determination was made in the supernatants of the homogenized samples in the Siemens Advia device (Block Scientific, 22 Sawgrass Drive Bellport, NY 11713 USA). Tissue protein levels were determined using the BOS protein measurement kit.
Measurement of Catalase Level:
Catalase level was spectrophotometrically evaluated, and its absorbance was read at 520 nm (Bioxytech catalase-520, catalog no: 21042 Oxis Research Product kits, USA). All
processes were carried out at room temperature. The results were expressed as Unite/g protein.
Measurement of Malondialdehyde (MDA) Level:
MDA levels were studied with the spectrophotometric methods (Bioxytech MDA-5861 catalog no: 21044-Oxis Research Product kits, USA). We aimed to measure free MDA levels following hydrolysis with the MDA-586 method. The results obtained in the spectrophotometry at 586 nm were expressed as μmol/g tissue.
Measurement of Superoxide Dismutase (SOD) Activity:
SOD (EC 1.15.1.1.) activity was measured on the basis of the reduction of nitroblue tetrazolium (NBT) by superoxide produced through the xanthine-xanthine oxidase system. The colorimetric plate where the reactions occurred was measured at 560 nm with the BioTek ELISA reader (BioTek Instruments, Kocherwaldstr. 34 D-74177 Bad Friedrichshall, Germany). The results were expressed as U/mg wet tissue.
Statistical Analysis
The data obtained in the study were evaluated using SPSS 20 (Statistical Package for Social Sciences) for Mac OS software. Descriptive statistics were expressed as median, 25th and 75th percentiles. When evaluating the study data, since the parameters were non-normally distributed, the Kruskal-Wallis test was used in the comparison of the variables between the groups, and the Mann-Whitney test was used to determine the group, which caused the difference. The level of statistical significance was set at p<0.05 for the Kruskal-Wallis test, and p<0.016 for the Mann-Whitney U test with Bonferroni correction.
Results
MDA parameter:
According to the results of the Kruskal-Wallis one-way variance analysis performed for multiple comparisons between the groups, no significant difference was found between the groups in terms of MDA parameter at 95% confidence interval and p<0.05 significance level (p=0.183).
On the other hand, there were statistically significant differences between the groups in terms of catalase and SOD (p<0.001 and p=0.004; respectively) (Table1). The comparison was made between paired groups to determine the groups, which caused the difference. Since there were three groups subjected to paired comparisons, (Group 1: Trauma-MP, Group 2: Trauma-EPO+MP and Group 3: MP-EPO+MP), the statistical significance level was taken as 0.05/3=0.016 with Bonferroni correction (Table 2).
Catalase parameter:
There was a statistically significant difference between the Trauma and MP groups (Z=-2,731; p= 0.006). The median catalase level was higher in the MP group. There was a statistically significant difference between the Trauma and EPO+MP groups (Z=-3,361; p= 0.001). The median catalase level was higher in the EPO + MP group. There was a statistically significant difference between the MP and EPO+MP groups (Z=-2,731; p= 0.006). The mean catalase level was higher in the EPO+ MP group. The differences between the groups in terms of catalase level are shown in Figure 1.
For SOD parameter:
No statistically significant difference was found between the Trauma and MP groups in terms of SOD parameter (Z=-1.155; p= 0.248). There was a statistically significant difference between the Trauma and EPO+MP groups (Z=-2,731; p= 0.006). The median SOD level was higher in the EPO+MP group. There was a statistically significant difference between the MP and EPO+MP groups (Z=-2,836; p= 0.005). The median SOD level was higher in the EPO+MP group. Differences between the groups in SOD levels are shown in Figure 2. An overall comparison of enzyme levels between the groups is given in Figure 3.
Discussion
Studies that have attempted to explain the etiology and pathogenesis of SCI have found that increased formation of reactive oxygen species (ROS) and resultant oxidative stress are crucial events related to SCI. Neurons and glia in the central nervous system, including the spinal cord tend to be subjected to oxidative and electrophilic stress because of numerous factors such as high polyunsaturated fatty acids content, high rate of oxidative metabolic activity, intense production of reactive oxygen metabolites, and relatively low antioxidant capacity. In fact, oxidative stress is considered a distinctive feature of the secondary phase of SCI. Therefore, alleviating oxidative stress is seen as an important step in the treatment of SCI [9].
Since each market has its own limitation in predicting oxidation in biological systems, it is recommended to use at least two biological markers [9]. In the present study, we biochemically investigated the effects of using MP alone or combined with EPO on MDA, SOD and catalase in rats with induced spinal cord trauma. As the most important and remarkable finding of our study, adding EPO to MP was more effective compared to administration of MP alone.
In the present study, catalase level was higher in the MP group compared to the Trauma group. Similarly, in a study on rabbits with induced SCI, catalase level was found to be higher in the animals given MP than the control group [10]. The role of MP in the antioxidant system has also been investigated in injuries other than SCI [11,12]. In one of these studies, the effect of MP on the glomerular the antioxidant system was examined in rats with glomerular damage, and catalase activity was found to increase with MP application [12]. It has been shown in other studies that administration of high-dose MP immediately after SCI exerts neuroprotective effects [13]. Although the underlying mechanisms have not yet been clarified, preventing lipid peroxidation, free radical formation and edema at the injury site are among the prominent mechanisms [14]. Thus, treatment with MP considerably decreases tissue necrosis and paralysis following injury [14]. In our study, the higher levels of catalase in the MP group are consistent with the studies in the literature.
In our study, no statistically significant difference was found between the Trauma and MP groups in terms of the SOD parameter. This result does not seem compatible with the studies in the literature. In a study comparing curcumin and MP, SOD levels were found to be higher in the curcumin group. However, in that study, SOD levels were higher in both curcumin and MP groups compared to the control group, which was not given any drug [15]. In addition, MP, which was given following damage in the glomerular cells of rabbits, was shown to decrease SOD level [12].
Various combinations with MP have been tried for the treatment of SCI. Studies using melatonin [11] and placenta-derived mesenchymal stem cells [10] in addition to MP are examples of combination therapies. As specified, in our study, EPO was used in addition to MP.
Although EPO’s mechanism of action on the central nervous system is unclear, according to current knowledge, its hematopoietic and neuroprotective properties act through different signaling systems. The receptor that produces the neuroprotective effect and the receptor that creates the hematopoietic effect are different from each other [16]. In a study by Grosso et al. [16], it was shown that erythropoietin and erythropoietin receptors increased in the neurons, glial cells and vascular epithelium of rats subjected to trauma, this increase started at the post-traumatic 8th hour and peaked on the 8th day, gradually decreased, and fell considerably 2 weeks after the trauma. In vivo experimental studies have demonstrated that decreased neuronal damage in focal ischemia, traumatic brain injury, inflammation, spinal cord injury and subarachnoid hemorrhage [17]. For this purpose, EPO was used in the treatment of 13 patients with acute paralysis, and very good results were obtained in the one- month follow-up of these patients [18].
Studies have shown that EPO provides efficient protection against ischemia-reperfusion damage in several tissues and organs including the brain [19] and heart [20]. It has been reported that the activity of enzymes such as SOD and catalase that directly or indirectly protect the erythrocyte membrane from peroxidative threat in hungry animals with low blood levels of EPO decreased due to hunger and returned to normal levels following EPO [21]. Similarly, in another study investigating the effectiveness of EPO, it was observed that EPO administered with melatonin following renal ischemia in rats, increased the levels of SOD and catalase [22]. Yazihan et al. [23] stated that treatment with EPO increased catalase level and EPO significantly decreased oxidative damage following SCI induced in rats. In our study, catalase and SOD levels were higher in the EPO+MP group compared to the Trauma group, in parallel with the findings reported in the literature.
Polyunsaturated fatty acids of membrane phospholipids in the damaged cells in the case of injury can be oxidized by themselves or by binding of oxidation products and turn into peroxide derivatives. MDA, one of these products, is used to determine the level of lipid peroxidation [8]. In our study, no difference was found among the three groups in terms of MDA. However, unlike our study, previous studies showed that MP decreased lipid peroxidation by decreasing MDA level [10,15]. This difference might result from the dose of MP administered per Kg, the duration and regimen of treatment. Differences between the studies might also be caused by other factors. Protection against secondary injury in acute spinal cord injury is called neuroprotection. For this purpose, many medical and surgical approaches such as drug treatments, correction of tissue oxygenation, removal of spinal cord compression and stabilization of the spine are tried. Numerous studies on pharmacological protection in spinal cord injury have been conducted in the last two decades, but none of these have been standard treatments for use in humans. Secondary injury is a process that begins within minutes to hours and continues for weeks, following the primary injury. Primary injury can be prevented only by preventive measures. The aim of research on secondary injury is to find and use pharmacological agents and precautions to protect the neurons in the lesion site, to increase their durability or to stop the pathological processes that would harm them. Modern pharmacological treatment protocols that are aimed to decrease progressive neuronal damage and minimize the neurological sequel that occurs. With our current information, dose and duration management should be studied with larger series in order to routinely use erythropoietin in neural trauma management.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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Osman Ersegun Batcik, Turgay Bilge, Yasemin Erdogan Doventas. Effects of methylprednisolone alone and combined with erythropoietin on the antioxidant system in rats with induced acute spinal cord injury. Ann Clin Anal Med 2021;12(5):527-531
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Knowledge and awareness level of mental health literacy among pediatricians
Şenay Kılınçel 1, Gürkan Muratdağı 2
1 Department of Child Development, Istanbul Gelişim University, Istanbul, 2 Department of Family Medicine, Sakarya University Medical Faculty, Sakarya, Turkey
DOI: 10.4328/ACAM.20590 Received: 2021-03-14 Accepted: 2021-04-01 Published Online: 2021-04-04 Printed: 2021-05-01 Ann Clin Anal Med 2021;12(5):532-536
Corresponding Author: Şenay Kılınçel, Istanbul Gelişim University, Department of Child Development, Istanbul, Turkey. E-mail: senaykilincel@gmail.com P: +90 505 825 74 05 Corresponding Author ORCID ID: https://orcid.org/0000-0001-5298-0264
Aim: This study aimed to assess pediatricians’ knowledge and awareness levels on mental health literacy (MHL) and investigate the factors affecting this level.
Material and Methods: This study was designed as a cross-sectional self-report questionnaire-based internet study conducted on 01 February–25 February 2021. The population of the study consisted of pediatricians. The data were collected using questionnaires sent to volunteer physicians’ smartphones. Partici- pants filled in the sociodemographic data and the MHL Scale.
Results: The data of 140 participants were analyzed in the study. The participants’ mean age was 37.7 years, and 62.1% were females, 73.6% were married, and 75.0% were working as specialists. Considering index scores, 15% of the participants were observed to have insufficient MHL. Participation in training on child psychiatry (OR:7.5) predicted excellent MHL, while increased years of professional experience were observed to the predictor of insufficient MHL (OR:0.9 per year).
Discussion: This study has investigated the knowledge levels and beliefs of pediatricians about mental health disorders and the important part of pediatricians have been observed to have insufficient MHL. The results have shown that organizing training and meetings in specialty training and intermittently afterward to improve MHL will be beneficial for pediatricians in recognizing and managing groups with mental illness.
Keywords: Child psychiatry; Mental health literacy; Stigma
Introduction
Mental health disorders are recognized as a global public health problem with a more significant impact on young adults than other age groups [1]. These disorders are typical of early-onset and are associated with psychological and physical impairments later in life [2]. According to the World Health Organization (WHO) World Mental Health Survey report, the prevalence of mental health disorders varies from 18% to 36% worldwide [3]. Recent studies have reported that the prevalence of mental health disorders among adolescents is 13–21%, and adolescents experience at least one mental illness until the age of 16 [4]. It has been reported that the rate of adolescents with severe mental disorders is 10–25%, and mental disorders occurring in adulthood start in adolescence [5]. Effective evidence-based interventions are available for many of these disorders and have lasting effects in the future [6]; however, many children with mental health disorders do not get professional help. When they get help, treatment is often delayed duration, or the frequency of treatment received is insufficient. In general, treatments are only received by individuals with severe disorders [7]. Untreated mental health problems and disorders in adolescents and young adults are strong predictors of poor professional achievements, problematic interpersonal relationships, and family functioning, as well as medical conditions associated with the reduced life expectancy, such as diabetes, heart and lung diseases, stroke, and suicide [8]. There are many reasons for the high prevalence rates and insufficient or delayed treatment intake. The low level of knowledge of childhood mental health disorders is one of the important ones. Evidence suggests that improved knowledge of mental health and mental health disorders, better awareness of how to seek help and treatment, and reducing stigma against mental illnesses can enable early diagnosis of mental disorders, improve mental health outcomes, and increase the use of health services [9].
Mental health literacy (MHL) was first defined by Jorm AF as “knowledge and beliefs about the recognition, management, and prevention of mental health disorders” [10]. The ability to support individuals with mental health problems and knowing where to seek help was added to this concept in 2012 [11]. Mental health literacy is a crucial component that ensures the mental health and well-being of individuals and populations in general. Significant barriers identified in providing mental health services to individuals include a lack of knowledge, presence of stigma, and limited access to mental health care [12]. In recent years, numerous scientists have highlighted the evidence of a positive association between low MHL and adverse health outcomes [13].
The literature review shows stigmatizing attitudes, lack of awareness, and false beliefs regarding mental health issues and patients with mental disorders among healthcare professionals (HCPs) throughout the world [14]. Furthermore, many HCPs are shown to have joint problems in feeling inadequate and discouraged in managing and treating individuals with mental illness [15]. It is further indicated that stigmatization culture continues to exist even in the field of health. For these reasons, HCPs with mental health problems avoid seeking help and talking to other colleagues about their problems [16].
There is a general perception that HCPs are better equipped for mental illnesses. They empathize with patients with such problems; however, besides the public, HCPs are known not to have sufficient knowledge about mental illnesses. Given their academic background and professional training, they are expected to deal with physical and psychological consequences that accompany mental disorders. Unfortunately, some studies reveal that HCPs are unaware of common mental disorders and have limited knowledge in this regard [17]. Moreover, most HCPs hold false beliefs about mental illness, which pose a major obstacle to the successful management of mental illness at the community level [18].
Despite research on MHL initiatives for adolescents and adults, literacy for mental health problems in childhood has been overlooked to a great extent. As no psychometric measurement has been developed to assess adults’ knowledge and beliefs about child mental health disorders, it has not been systematically evaluated in the interventions. There is a need for various interventions to improve the MHL level of the population regarding mental health disorders, which is higher among children and adolescents. It is believed that such interventions have the potential to improve appropriate help- seeking in the early period and treatment intake and thus, may reduce the prevalence of childhood mental health disorders. Interventions regarding child MHL should generally target all adults, even though they do not have children, parents, teachers, HCPs, and children. Nonetheless, studies involving these target groups are insufficient. All groups are essential targets in enhancing child MHL. However, the general adult population should be the primary target group to improve knowledge and beliefs about child mental health disorders and their treatment at the community level. Considering the field of health, pediatricians are often the first individuals with whom parents talk about their concerns regarding their children. Similarly, they are mostly the first to report the problems experienced by children and adolescents. Children and adolescents with chronic physical illnesses are more vulnerable to mental problems such as anxiety and depression. Mental illnesses that cannot be identified in children and adolescents, further impair the achievement of developmental tasks necessary for optimal health and life in adulthood. It becomes more valuable, particularly in regions where there is no child psychiatrist. Therefore, pediatricians’ MHL level is of great importance in the early diagnosis of mental problems that may have a lifelong impact and in directing patients to child psychiatry clinics for the appropriate treatment.
This study aimed to assess the knowledge and awareness levels of pediatricians on MHL.
Material and Methods
This study was designed as a cross-sectional self-report questionnaire-based internet study conducted from 01 February to 25 February 2021. The population of the study consisted of pediatricians. The data were collected using Google Forms questionnaires (Google, California, USA) sent to volunteer physicians’ smartphones, who were reached from hospital databases and research groups. Two hundred ten physicians answered the questionnaire, and 140 of them (66.6 %) completed the questionnaire.
Sociodemographic Data Form
Sociodemographic Data Form was created by the researchers. It includes questions about pediatricians’ age, sex, marital status, professional experience, and possible sources of information about child mental health.
Mental Health Literacy Scale (MHLS)
It ensures identification of the MHL levels of individuals and missing areas of knowledge. It is a Likert-type self-assessment tool consisting of 35 items and is evaluated over the total score. For items with four statements (items 1–15), assessment is made on a four-point scale: “strongly disagree” (1), “disagree” (2), “agree” (3), and “strongly agree” (4). For items with five statements (items 16–35), assessment is made on a five-point scale: “strongly disagree” (1), “disagree” (2), “neither agree nor disagree” (3), “agree” (4) and “strongly agree” (5). Although the original scale was one-dimensional, this research revealed six dimensions, as previously revealed in the study by Gorczynki et al. (2017). The scale has six sub-dimensions, namely F1: Ability to recognize disorders (items 1–8), F2: Knowledge of where to seek information (items 16–19); F3: Knowledge of risk factors and causes (items 9 and 10); F4: Knowledge of self-help/self- treatment interventions (items 11 and 12); F5: Knowledge of professional help available (items 13–15); and F6: Attitudes that promote recognition or appropriate help-seeking behavior for mental illnesses and attitudes towards mental disorders (items 20–35) (stigmatization). Some items are reverse coded (items 10,12,15 and 20–28). The scale score is calculated by adding all the scores in the answers given to the scale items. The total score to be obtained from the scale ranges from 35 (lowest) to 160 (highest). Cronbach’s alpha coefficient has been reported to be 0.87 in the validity and reliability study of the original language scale and to be 0.89 in the validity and reliability study of the Turkish version of the scale, which was conducted by Tokur-Kesgin et al [19].
Statistical Analysis
Statistical analysis was performed using SPSS version 22.0 software. Results were expressed as mean±standard deviation, median (minimum-maximum), and number (%) for ease of understanding. Visual (histogram and probability graphs) and analytical (Kolmogorov-Smirnov, Shapiro-Wilk tests) were used to determine whether the variables followed a normal distribution. To allow appropriate calculations and facilitate comparisons, health literacy index scores are obtained by being standardized on a metric between 0 and 50, using the formula: Index score = (Mean – a) * (50/b)
Index score refers to the index score calculated individually; mean refers to the mean of the relevant items for each participant; “a” refers to the smallest possible value of the mean (or the mean that causes the index score to be zero); “b” refers to the mean range; “50” refers to the maximum score (score) selected for the new metric. Participant’s MHL levels can be determined according to their MHL index scores. The 0–25 are considered insufficient MHL, and the values of 25–33 as limited MHL, 33–42 as sufficient MHL, and 42–50 as excellent MHL. A p-value of <0.05 was considered statistically significant. Ethical Considerations
The study was approved by the Non-Invasive Studies Ethics Committee of Sakarya University with the number E-71522473- 050.01.04-5954/08 on 29.01.2021.
Results
In the study, the data of 140 participants were analyzed. The participants’ mean age was 37.7 years, and 62.1% were females, 73.6% were married, and 75% were working as specialists. The mean professional experience was 12.5 years. Table 1 shows the sociodemographic variables.
When MHLS was evaluated, the median score was 113 out of 150 (min: 89, max: 134). The characteristics of total scores and sub-scores obtained from MHLS are summarized in Table 2. The level of MHL according to the index is accepted as insufficient MHL (0-25), limited MHL (25-33), sufficient MHL (33-42), and excellent (42-60). Considering index scores, 15% (n:21) of the participants were observed to have insufficient MHL. Other classes percentages were 37.1% (n:52) limited MHL, %19.3 (n:27) sufficient MHL and %28.6% (n:40) excellent MHL.
Logistic regression analysis was performed using sociodemographic variables to distinguish participants with excellent MHL from insufficient MHL. The variables given in Table 1 were analyzed by the retrospective elimination method. In the sixth step, the model correctly classified participants with excellent MHL by 85.1% and those with insufficient MHL by 61.2% (Nagelkerke R2: 0.27, p: 0.01). Participation in training on child psychiatry (odds ratio [OR]: 7.5) predicted excellent MHL, while increased years of professional experience were observed to predict insufficient MHL (OR: 0.9 per year). Logistic regression analysis performed to predict insufficient MHL is shown in Table 3.
Discussion
The present study included a total of 140 pediatricians. Half of the participants have been observed to have insufficient and limited MHL. Studies conducted in various countries, albeit rare, draw attention to the fact that childhood mental disorders are not sufficiently recognized and understood in the general population [20]. In a study conducted in a pediatric hospital in Arabia in 2017, low MHL levels have been reported among HCPs [21]. The literature review shows that studies involving HCPs have primarily included primary health care providers rather than specialized groups. This may be attributed to the fact that HCPs working in this field have a critical role in promoting positive mental health in the community and providing better access to primary care mental health services. Unfortunately, studies have revealed that even among primary care physicians and general practitioners, there is a stigmatization and shame culture that can be a significant barrier to mental illness’s efforts to receive and access better mental health services. A study from Zambia showed that primary HCPs were uncomfortable in dealing with mentally ill patients and recommended handcuffs [22]. In another study conducted in China, the authors found that stigmatizing attitudes were prevalent among primary HCPs. Their pessimistic beliefs toward the mentally ill led to a decrease in their capabilities in providing adequate mental health services to such individuals [23].
Training for mental illnesses plays a vital role in altering stigmatizing beliefs and attitudes of HCPs towards mental illnesses. We observed that attending training courses or meetings on child mental health predicted excellent MHL in the present study. A project implemented in the United States of America aimed to evaluate the two-stage training program to enhance family physicians’ skills and confidence in the diagnosis and treatment of patients with mental health problems. Within the program’s scope, family physicians were provided with adult mental health and mental health first aid training. At the end of the project, it was reported that the training had a positive effect on the clinical practice of the participants, and behavior change tools were effective [24].
The results have demonstrated that increased years of professional experience predict insufficient MHL levels. Medicine is a field that constantly improves and renews itself. Studies, particularly in areas such as human psychology, reveal new findings. Pediatricians attend many training courses and meetings during and after their specialty training. However, in the following years, they may not find the time and energy required to participate in training courses outside their specialty. Therefore, they may have difficulties in keeping up with the developing and changing literature. Literature data and our findings show a need for specialty training and subsequent training and meetings on mental health.
Conclusion
This study has investigated pediatricians’ knowledge levels and beliefs about mental health disorders, which may cause serious health, social, and family problems in children and adolescents when overlooked, and treatment is delayed. The present study shows that organizing training and meetings in specialty training and intermittently afterward to improve MHL will be beneficial among pediatricians in recognizing groups with mental illness or at risk, referring them to child psychiatry clinics and preventing potential future diseases. The effect of such interventions may initially be uncertain at the beginning. Therefore, there is a need for further research before appropriate planning.
Acknowledgment
The authors would like to thank Dr. Miraç Barış Usta for Statistical Analysis.
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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Hematotoxicity, hepatotoxicity and nephrotoxicity in rabbits (Oryctolagus Cuniculus) after short term exposure to solvent (EGME)
Djabali Nacira 1, Matallah Saida 2
1 Department of Biology, 2 Department of Agronomy, Faculty of Natural and Life Sciences, Chadli Bendjedid University, El-Tarf, Algeria
DOI: 10.4328/ACAM.20599 Received: 2021-03-17 Accepted: 2021-04-06 Published Online: 2021-04-13 Printed: 2021-05-01 Ann Clin Anal Med 2021;12(5):537-541
Corresponding Author: Djabali Nacira, Laboratory for Research on Biodiversity and Ecosystem Pollution, Department Of Biology, Faculty Of Natural And Life Sciences, Chadli Bendjedid University, El-Tarf, Algeria. E-mail: naciradjabali7@gmail.com P: 00213671590135 Corresponding Author ORCID ID: https://orcid.org/0000-0001-7441-2516
Aim: Exposure to chemicals spilled into different ecosystems represents a danger that threatens the survival of animal and plant populations. Currently, people need to use these products for industrial and / or domestic reasons without taking into account their effects on health and the environment. This work aims to study the effect of a solvent: Ethylene glycol monomethyl ether (EGME) which belongs to the family of ethylene glycol ethers, on the proper functioning of the liver, blood and kidney.
Material and Methods: For this, two groups of animals were treated with EGME by gavage. The solvent EGME was applied in two doses: 50 ppm and 150 ppm for four successive weeks. Biochemical and Hematological parameters were studied.
Results: The results showed significant changes in biochemical parameters, characterized by a disruption of metabolism product (glucose, lipid, protein) as- sociated with an increase in lipids (triglycerides and cholesterol), as well as disruption of alkaline phosphate levels in groups treated with EGME, increased levels of transaminases (GOT and TGP) and gamma GT in Group 2 (150 ppm) with a highly significant decrease in bilirubin in both groups. Markers of renal function (urea and creatine) were altered during the administration of EGME. Also, we found a significant increase in uric acid levels in both treated groups. Hematologically, there was a significant decrease in hemoglobin, red blood cell, white blood cell, and lymphocyte number, accompanied by an increase in platelet number in the EGME-treated groups. In the treated groups, there were decreased liver and testicular oxidative stress parameters (reduced glutathione) with lipid peroxidation MDA.
Discussion: According to the results, the administration of ethylene glycol monomethyl ether (EGME) to male rabbits Oryctolagus Cuniculus digestive at a concentration of 50 and 150 ppm causes functional disorders of many organs (liver, testis, kidney).
Keywords: Rabbit; Toxicity; Solvent; Ethylene glycol; Risk
Introduction
Organic solvents present a double risk, on the one hand, due to their flammability and explosiveness, and on the other hand, obvious or insidious health risks, during accidental or prolonged exposure, whether deliberate or accidental. There is hardly any human activity that escapes them. They have become more and more necessary in several industrial processes, for example we quote: the manufacture of glues, paints, varnishes, inks, plastic [1].
Solvent toxicity has become a public health problem. Indeed, the Institute of Health and Safety at Work (ISST) has just launched a study on the impact of the use of solvents in the workplace. The toxicity of solvents is very divers and affects different organs and systems (ISST. Institute for Occupational Health and Safety. Occupational risk assessment, 2016).
– The central nervous system (toluene, xylene, trichlorethylene, tetrachlorethylene …). Action on the CNS can cause addiction.
– The peripheral nervous system (hexane, petroleum ether, …).
– The liver (Trichlorethylene, Tetrachlorethylene, …)
– The kidneys (Styrene …).
– The hematopoietic system (benzene, ethylene glycol, …)
The toxicity of solvents may also interest other organs such as the respiratory tract, cardiovascular system, skin and the reproductive function, not to mention the carcinogenic action of some of them (benzene). For lighting and other measurable physical nuisances, solvents are the most commonly encountered, unknown, and underhanded abusers (Khayati N. Risk assessment of exposure to solvents in the leather processing sector (about 84 cases). University of Tunis El Manar, 2004).
Known since the 1930s, glycol ethers are a family of more than eighty representatives. Following early toxicological studies conducted in the 1970s, the safety of glycol ethers has been questioned. Since then, their toxicological profile has been studied in more detail. Work on animals has certainly identified target organs and potentially disturbed functions. However, transposition in humans remains difficult.
However, understanding the mechanisms of cellular and molecular actions can facilitate the assessment of the impact of long-term exposure to these products on human health. Nevertheless, in the current state of knowledge, the real risk of chronic toxicity in humans is limited to a set of presumptions derived from epidemiological studies in the workplace [2]. Glycol ethers are oxygenated solvents that have been widely used over the last thirty years. They constitute a diverse family of more than 30 different substances divided between those derived from ethylene glycol and those derived from propylene glycol [3].
Ethylene glycol is a colorless, odorless and relatively non- volatile liquid. It has a low vapor pressure and is completely miscible with water. According to short- and long- term oral studies on laboratory animals, the kidneys are the main target of ethylene glycol exposure [4].
Non-neoplastic degenerative changes have been consistently observed in the kidneys of several species at the lowest doses. According to a very large database, ethylene glycol has slight reproductive and developmental effects, including teratogenicity, in orally exposed rodents, although at doses greater than those associated with effects on the kidneys [5]. Since the first publication of Nagano in 1979, numerous studies on laboratory animals have shown that glycol ethylene glycol ethers (mainly methyl ether or EGME) have adverse effects on reproduction and reproduction development [6].
The objective of this work is to evaluate the deleterious effects of a solvent: ethylene glycol monomethyl ether (EGME) on some indicators of good health in the male rabbit Oryctolagus Cuniculus.
Material and Methods
The experimental work was approved by the Ethics Committee of the Health Department of the Wilaya El-Tarf, and validated by the Scientific Committee of the Biology Department at the El-Tarf University.
This study aims to illustrate the effects of a solvent that belongs to the family of glycol ethers on hematologic, hepatic and nephrotic profiles.
1. Biological material
The animals used in this study were male rabbits Oryctolagus cuniculus, widely used in various fields of research. Classification of the animal:
– Animal Kingdom
– Branching of vertebrates – Class of mammals
– Order of the Lagomorphs – Leporidae family
– Genus Oryctolagus
– Species Oryctolaguscuniculus
Breeding conditions
Our study was conducted on 12 mature male rabbits of a local breed, these rabbits were aged between 5 and 9 months and weighed between 1400 and 1900g at the beginning of the experiment.
These animals have been subjected to a period of adaptation to the conditions of the pet shop, 10 days approximately at room temperature (25 °), and a photoperiod of 12 h/12h.
The rabbits were grouped into three metal cages (50x60x53 cm), screened, provided with water troughs, each containing four rabbits and lined with a thick layer of wood chips renewed three times per week. The cages were cleaned daily until the end of the experiment.
Rabbits were fed 3 times a day, the diet consisted of vegetables (carrot, salad, cucumber) and dry food consisting of maize, barley and vitamin supplement. They had free access to water and food.
2. Chemical equipment
The solvent used in this experiment is ethylene glycol monomethyl ether (EGME) which belongs to the category “E” of glycol ethers or the category of derivatives of ethylene glycol. EGME (ethylene glycol monomethyl ether) is mainly used as a solvent for the manufacture of paints, varnishes, inks, dyes. It is also used as antifreeze for aviation fuels and as a cleaning and degreasing agent.
The substance is classified according to the data of the National Institute for Research and Security, Database (Ethylene glycol. Toxicological sheet. 2016; 25:3) as follows:
T: Toxic
R60: May impair fertility.
R61: Risks of adverse effects in children during pregnancy. R20 / 21/22: Harmful by inhalation, in contact with skin and if swallowed.
3. Experimental protocol
After the adaptation period, the 12 rabbits were divided into three batches, each batch comprising four rabbits (n = 4) kept under the same conditions.
The experiment consisted of administering 2 increasing doses of ethylene glycol monomethyl ether (EGME) to rabbits: 50 ppm and 150 ppm as follows:
Control group: control rabbits (T) which receive only water.
Lot 1 (D1): Rabbits treated with EGME at 50 ppm.
Lot 2 (D2): Rabbits treated with EGME at 150 ppm.
The product was administered by gavage once a day (1ml), 5 days a week, for 4 successive weeks.
Sacrifice and blood collection and organs
After 30 days of treatment rabbits from 3 lots were fasted for 15 hours and then sacrificed (by decapitation), the blood was immediately collected in two tubes. The first contained EDTA anticoagulant and the second contained heparin, the latter was centrifuged at 3000 revolutions for 15 minutes for the determination of biochemical parameters (glycemia, urea, creatinine, Transaminases (TGO: transaminase glutamooxaloacetic, TGP: pyruvic glutamic transaminase), uric acid, albumin, BT: total bilirubin, GGT: gamma-glutamyl transferase, alkaline phosphatase, cholesterol, triglycerides). The plasma obtained was stored at a temperature of -20 ° C. The blood was put in the other tube containing EDTA for the determination of hematological parameters.
After dissection, the liver and testes were carefully removed, stripped of adipose tissue, rinsed in 0.9% NaCl sodium chloride solution. These organs were stored in the freezer for the determination of oxidative stress parameters: tissue protein, reduced glutathione (GSH), malondialdehyde (MDA).
Results
1. Variation in renal, hepatic and metabolic parameters
The urea level increased in the 50 ppm EGME group and decreased in the 150 ppm group compared to the control group. These variations were statistically significant (p<0.05). Our results also showed that there was a non-significant decrease (p>0.05) in creatinine levels in both treatment groups compared to controls. Thus, there was a decrease in the albumin level in the batch treated at a dose of 50 ppm and an increase in the batch treated at the dose of 150 ppm compared to controls. These variations were also non-significant (p>0.05). We recorded a non-significant increase (p>0.05) in uric acid level in the EGME-treated groups compared to controls.
There was a significant increase (p<0.05) in the activity of transaminases TGO, TGP and alkaline phosphatase in the groups receiving a dose of 150 ppm compared with the batch treated with dose 1 and the control, a significant decrease (p<0.05) in the total bilirubin level in 2 groups treated with EGME compared to controls. GGT levels were higher in the 2 treated groups compared to controls.
We found a non-significant (p>0.05) increase in glucose, cholesterol and triglyceride levels in two EGME-treated groups compared to controls (Table 1).
2. Variation in hematological parameters
The results show a non-significant decrease (p>0.05) in the number of white blood cells and lymphocytes with a non- significant increase (p>0.05) in platelets number in the two groups treated with EGME. The number of red blood cells showed a non-significant decrease (p>0.05) in the treated groups and a significant decrease (p<0.05) in hemoglobin levels in EGME-treated groups compared to controls (Table 2).
3. Effect of EGME on oxidative stress biomarkers (glutathione
GSH level) and lipid peroxidation (Variation in malonaldehyde MDA) in the liver and testis
We noted a significant decrease (p<0.05) in glutathione levels, and a highly significant increase (p<0.01) in malonaldehyde MDA (the potential of lipid peroxidation) in the liver and testis in EGME-treated groups compared to the control (Table 3).
Discussion
Most chemicals for industrial use have toxic effects on the indicators of good health in humans and animals. Ethylene glycol monomethyl ether, as an example of a study, exerts its toxicity via acid metabolites and even more aldehydes. These are able to penetrate the cell’s nucleus and alter the structure and function of the genome governing growth and cell development.
Through our results, ethylene glycol monomethyl ether (EGME) affects certain biological functions in male rabbits, by ingestion, altering the liver, testes and kidneys following the action of oxidative stress.
The effect of this solvent on liver function manifests itself at two levels: metabolic and structural. All products of physiological metabolism (glucose, lipid, protein) are disrupted in the treated groups. This effect is well documented in several studies at the national level (Djabali N. Effects of a solvent: Ethylene Glycol Monomethyl Ether (EGME) on male fertility and some biochemical and cellular parameters of the blood in the rabbit Oryctolagus cuniculus, Badji Mokhtar Annaba University; 2011) and international [7].
We noticed a disruption of glucose and protein (albumin) associated with an increase in lipids (triglycerides and cholesterol). All these disturbances are due to alteration in liver functions by EGME metabolites (aldehyde function) that can inhibit oxidative phosphorylation, glucose metabolism (glycolysis and Krebs cycle, main producers of ATP), protein synthesis, DNA replication and ribosomal ARNa. In the same context, EGME mainly causes metabolic acidosis (accumulation of acidic products e.g glycolic acid, oxalic acid and lactic acid). In addition, there is an increase in the blood concentration of lactic acid contributing to lactic acidosis. The formation of acidic metabolites also causes inhibition of other metabolic pathways such as oxidative phosphorylation [8]. With respect to other biochemical metabolites, triglycerides and cholesterol appear to be affected by EGME. The administration of the solvent in both the 50 and 150 ppm groups induces an alteration of the lipid profile, which is manifested by an increase in the level of cholesterol and plasma triglycerides [9].
This result is consistent with Benjedou’s study of rabbits treated with dermal EGME. All these disturbances are due to the alteration of liver functions by EGME metabolites [7].
A significant increase in cholesterol concentration in the treated groups compared to the control is associated with liver tissue damage, which may be due to an imbalance in the enzymes responsible for the conversion of cholesterol to male sex hormones, which causes a decrease in testosterone concentration [10,11].
The results obtained show that there is an increase in the alkaline phosphatase level in the treated groups (150 ppm), this increase is due to the excess of iron in the body, this effect is dose-dependent (significant increase in group II). Our results are consistent with Adams’ (1991) investigations, which indicate that excess iron induces an increase in alkaline phosphatase activity. These enzymes are normally contained in the cells of the liver. If the liver is injured, liver cells reverse enzymes in the blood; the level is increased in cases of liver cell death [11-13]. As well as an increase in alkaline phosphatase activity results from liver and bone dysfunction (Ait Hamadouche. Effects of chronic lead exposure on the reproductive system and the hypothalamic-pituitary axis in male Wistar rats: Histological and biochemical study. University of Es-Senia Oran, 2009;171). In our study, we found a significant increase in transaminase levels (TGO and TGP). This effect is dose-dependent. Transaminases are essential enzymes in cytolysis [13]. They pass into the serum in case of hepatic or muscular cytolysis, a significant increase is observed in the cytolysis of toxic hepatitis [14].
The results show that there is a significant decrease in bilirubin in both groups treated with EGME. This decrease may be due to liver and gall bladder dysfunction, probably a problem in the stage that allows the excretion of bilirubin in the bile [15].
Our results also revealed an increase in the gamma GT level in the 150 ppm-treated group. An increase in serum gamma GT concentration is a good indicator of the involvement of bile duct epithelial cells (Dridi N, Segueni N. Study of the antitoxic effect of the methanolic extract of the Cotulacinarea species with respect to the pesticide Chlorpyriphos in albino wistar rats. Echahid Hamma Lakhdar University of El-Oued) 2015) Conclusion
According to the results, the administration of ethylene glycol monomethyl ether (EGME) to male rabbits Oryctolagus Cuniculus digestive at a concentration of 50 and 150 ppm causes functional disorders of many organs (liver, testis, kidney). Our results seem very useful to confirm the harmful effects of this solvent:
• Hematotoxicity is expressed by an effect on the bone marrow • Hepatotoxicity is manifested by the effect on enzymes and metabolism products.
• Alteration of the detoxifying potential (glutathione reduced GSH).
• Altered markers of renal function.
• Hepatic and testicular oxidative stress; Lipid peroxidation in the liver and testis.
Acknowledgment
We would like to thank all the people who contributed to the accomplishment of this work, we quote: the workers and staff of the laboratory of biochemistry and hematology and workers of pet store of the El-Oued University. The direction of health and occupational medicine services in Wilaya of El-Tarf. The collaboration of the students of Master and license, in particular was very important, during the application of the experimental work, as well as the discussion of the results and preparation of this manuscript.
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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Retrospective analysis of sequential bilateral hip fractures in elderly patients: A nested case-control study
Fevzi Birişik, Yücel Bilgin
Department of Orthopedics and Traumatology University of Health Sciences, Istanbul Education and Research Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.20613 Received: 2021-03-26 Accepted: 2021-04-11 Published Online: 2021-04-16 Printed: 2021-05-01 Ann Clin Anal Med 2021;12(5):542-546
Corresponding Author: Fevzi Birişik, University of Health Sciences, Istanbul Education and Research Hospital, Department of Orthopedics and Traumatology, Org. Abdurahman Nafiz Gürman Street, 34098, Fatih, Istanbul, Turkey. E-mail: dr.fevzibirisik@gmail.com P: +90 555 625 35 64 F: +90 212 459 62 30 Corresponding Author ORCID ID: https://orcid.org/0000-0003-3274-6096
Aim: The aim of the present nested case- control study was to compare the results and mortality rates of patients with consecutive bilateral hip fractures with those of patients with unilateral hip fractures selected from patients with similar characteristics.
Material and Methods: Patients diagnosed with acute hip fracture, age >65 years, with a minimum of 1-year follow-up (for surviving patients), low-energy fractures, and available demographics and medical records were included in this study. A total of 46 patients with consecutive hip fractures who met the evaluation criteria for the study were included (Group 1). A control group of 138 patients was selected based on their age, sex and type of fractures (Group 2). Demographic data, comorbidities and mortality rates were compared between the two groups.
Results: When comparing 2 groups in terms of age, gender distribution, ASA score, time to surgery, length of hospitalization stay, and time from fracture to surgery, no statistically significant difference was noted (p>0.05). No significant differences were noted between the groups in terms of fracture type and treat- ment modality (p>0.05). There was an obvious relationship between the bilateral hip fracture and a lower Singh Index (SI) (grade ≤3) (p<0.001). Neurological diseases rate was 30.4% (n=14) in Group 1 and 15.2% (n=21) in Group 2. There was a significant difference between the 2 groups (p=0.023). No difference was noted in the 1-year death rates between the groups (p=0.059).
Discussion: In our nested case- control study, an increased risk of secondary hip fracture was associated with lower SI and neurological diseases.
Keywords: Hip fracture; Mortality; Comorbidity
Introduction
Hip fracture is an important health concern, especially in terms of its increasing rate among the elderly population. Hip fractures are an important healthcare issue throughout the world due to the high incidence, associated mortality, and health care expenditure [1]. Non-simultaneous bilateral hip fractures have been reported with increasing frequency in elderly patients [2]. The cumulative incidence of contralateral hip fracture after the first hip fracture is 9% after one year and 20% after 5 years [3]. A history of hip fracture has been well-established as a risk factor for subsequent contralateral hip fracture [4,5]. Several factors, such as female gender, older age, dementia, Parkinson’s disease, a history of falls, low vision, osteoporosis, cardio- respiratory disease, and institutionalization have been found to increase the risk of a second hip fracture [6–8]. These second hip fractures have been associated with poorer postoperative outcomes, including complications and mortality [9,10]. Although there are several studies on the frequency and causes of the development of a second hip fracture after the first hip fracture in elderly patients, it seems insufficient. The aim of the present nested case-control study was to compare the results and mortality rates of patients with consecutive bilateral hip fractures with those of patients with unilateral hip fractures selected from patients with similar characteristics.
Material and Methods
The design and protocol of this study were approved by the Institutional Review Board (IRB) of Istanbul Education and Research Hospital (IRB number; 2693/01.2021). This retrospective nested case-control study was conducted by evaluating the records of 724 patients operated for hip fractures at the mentioned hospital between January 2014 and December 2019.
Patients diagnosed with an acute hip fracture (e.g., femoral neck and perthrochanteric fractures), aged over 65 years, with a minimum of 1-year follow-up (for surviving patients), low- energy fractures, and available demographics and medical records were included in this study. Patients with a fracture due to high-energy trauma or with a pathological fracture, isolated fractures of the greater or lesser trochanter, and fractures of the sub-trochanteric region were excluded.
A total of 46 patients with consecutive hip fractures who met the inclusion criteria for the study were included (Group 1). A nested case-control design was used to compare the outcomes of patients with contralateral hip fractures to those without them. A control group of 138 patients was selected from the remaining 724 patients, based on their age, sex, and type of fractures (1:3 ratio of cases to control; Group 2).
The overall information and complete health history were obtained from the medical history. Data on comorbid medical conditions were based on the presence of the following conditions: hypertension, diabetes mellitus, neurological diseases (such as dementia, Parkinson’s disease), heart diseases (such as heart failure), renal diseases, and respiratory diseases (such as chronic obstructive pulmonary disease).
The demographic data comprised of age, gender distribution, fracture type, ASA score (11), treatment modality type (e.g., proximal femoral nailing, hemi-arthroplasty, and dynamic hip screw), time to surgery, length of hospitalization stay, and time between death and last hip fracture. The structure of the bony trabeculae in the proximal femur changes with the effect of osteoporosis. Osteoporosis is classified in 6 different degrees according to the trabecular structure in proximal femur radiographs in the index defined by Singh et al [12]. Finally, radiographs (anteroposterior-lateral hip and pelvis) at the first fracture occurrence were assessed for the degree of osteoporosis with Singh-Index (SI).
The Social Security Administration Death Master File (Social Security Death Index) was used to determine the mortality and expiration date of the patients. The 1-month, 1-year, and overall survival of the patients were also assessed. Patient characteristics included in the analysis of risk factors for contralateral hip fracture were as follows: age, sex, medical comorbidities, fracture type, and SI. The data obtained were compared between the two groups.
Statistical Analysis
All analyses were performed using the Statistical Package of the Social Sciences version 26.0 (SPSS Inc., Chicago, IL, USA). Mean, standard deviation, median, minimum value, maximum value, frequency and percentage were used for descriptive statistics. The distribution of variables was checked with the Kolmogorov-Smirnov test. The Mann-Whitney U test was used for the comparison of quantitative data. The Kaplan-Meier method was used for survival analysis. A p- value of less than 0.05 was considered statistically significant.
Results
Contralateral hip fractures were observed in 46 out of 724 patients (6.3%). The demographic and clinical features of these 2 groups are summarized in Table 1.
The mean age at admission for the first hip fracture was 82.3 ± 7.0 years. The median interval between both hip fractures in 46 patients who suffered from a contralateral hip fracture during the follow-up was 28.8 ± 16.2 months. The mean age of the patients at the time of the contralateral hip fracture was 84.2 ± 7.2 years, which was greater than the mean age of 80.1 ± 8.1 years in the group of 138 patients unilateral hip fracture, although the difference was not statistically significant (p > 0.05).
When 2 groups unilateral hip fracture in terms of age, gender distribution, ASA score, time to surgery, length of hospitalization stay, and time from fracture to surgery, no statistically significant difference was noted (p > 0.05; Table 1).
The fracture type and treatment modality type in the two groups are cited in Table 2. No significant differences were noted between the groups in terms of fracture type and treatment modality (p > 0.05).
The SI was categorized into 2 degrees: grade 1-3 and grade 4-6. While the rate of patients with grade 1-3 in Group 1 was 69.6 (n = 32), and the rate of patients with grade 4-6 was 30.4% (n = 14); in Group 2, the corresponding numbers were 37.7 (n = 52) and 62.3 (n = 86), respectively. There was an obvious relationship between the bilateral hip fracture and a lower SI (grade ≤3) (p < 0.001; Table 1).
Comparison of comorbid medical conditions between the two groups is given in Table 3. The comorbidities observed in the two groups were not significantly different for hypertension, diabetes mellitus, heart disease, renal disease, and respiratory disease (p > 0.05). Among the comorbid medical conditions, neurological diseases (such as dementia or Alzheimer) rate was 30.4% (n = 14) in Group 1 and 15.2% (n = 21) in Group 2. There was a significant difference between the two groups (p = 0.023; Table 3).
The mean survival durations after surgery were 26.5 months (range: 1–58 months) in Group 1 and 27.9 months (range: 1–49 months) in Group 2 (p > 0.05). Among the 184 patients, 106 (57.6%) eventually died, while 78 (42.4%) survived. The overall death rates in the respective groups were 71.7% (n = 33) and 52.9% (n = 73) in Groups 1 and 2, respectively. The overall survival rates were significantly different between the groups (p = 0.025) (Figure 1).
The death rates at 1-month were 8.7% (n = 4) and 8.0% (n = 11) in the Groups 1 and 2, respectively. No difference was noted in the 1-month death rates between the groups (p = 0.87). The death rates at 1-year were 39.1% (n = 18) in Group 1 and 24.6% (n = 34) in Group 2. No difference was noted in the 1-year death rates between the groups (p = 0.059; Table 1).
Discussion
In this retrospective nested case-control study, the rate of contralateral hip fracture development in patients after the first hip fracture was 6.3%. When compared with the control group with unilateral hip fracture, it was found that the SI value, which indicates the degree of osteoporosis in the hip roentgenogram, was statistically significantly lower in patients with consecutive bilateral hip fractures. We believe that it should be considered a risk factor for contralateral hip fracture in patients with low SI. When the two groups were compared in terms of comorbid medical conditions, the presence of neurological diseases was found to be statistically significantly higher in Group 1.
There appears to be an increased risk for contralateral hip fracture in patients with neurological diseases. Although there was no statistically significant difference in the 1-month and 1-year mortality rates between the groups, it was found to be nearly significant for the 1-year mortality rate comparison (p = 0.059). However, the overall survival rates were significantly different between the groups (p = 0.025).
For patients who suffered from a hip fracture, the contralateral hip fracture development rates have been reported to be 3.4–10% [2,13-15]. In the present study, 46 patients had a contralateral hip fracture among 724 hip fracture patients (approximate rate 6.3%), which is consistent with the reports of other studies.
Egan et al. [16] stated that older age is one of the risk factors for a second contralateral hip fracture after the first one, while Yamanashi et al. [18] demonstrated no significant difference in the incidence of second hip fracture in relation to age in the elderly. In our study, no statistically significant difference was noted in the comparison of mean age between the groups (p > 0.05).
Female gender is considered a risk factor for a second hip fracture [6]. In our study, no statistically significant difference was found in terms of gender distribution during the comparison between the two groups (p > 0.05).
Some studies have focused on factors affecting the development of contralateral hip fractures. Several risk factors including neurological diseases, falls, poor perceived health, low weight gain, absence of walking for exercise, dizziness, and osteomalacia have been reported to be associated with an increased risk for a second hip fracture [4,17]. Senile dementia and Parkinson’s disease are also major risk factors for second hip fractures [18]. In this study, in the comparison of comorbidities between the groups, it was found that the presence of neurological diseases was significantly higher in patients with contralateral hip fracture. No significant difference was noted in the comparison of other common comorbidities studied (such as hypertension and diabetes mellitus). Neurological diseases can thus be considered a risk factor for contralateral hip fracture.
Singh et al. [12] described that there is a break in the continuity of the principal tensile group of trabeculae that can be clearly seen in grade ≤3. According to some studies, lower SI grades are not clearly related to osteoporosis [18,19].
Yamanashi et al. [18] reported no significant difference between the first and second hip fractures with regard to the SI, which was divided into 6 grades. On the other hand, in their prospective study, Gluer [20] reported that low SI was a risk factor for hip fracture. According to our study, when compared with the control group with unilateral hip fracture, it was found that the SI value, which indicates the degree of osteoporosis in the hip roentgenogram, was statistically significantly lower in patients with consecutive bilateral hip fractures.
Ryg et al. [3] performed a nationwide population-based cohort study on 169 patients, 145 of whom had their first hip fracture. The authors reported that patients with a second hip fracture had substantial mortality rates of 27% and 64% in men and 21% and 58% in women after 1-year and 5-years, respectively. In our study, the death rates at 1-month were 8.7% and 8.0% in Groups 1 and 2, respectively. No difference was noted in the 1-month death rates between the groups (p = 0.87). The death rates after 1 year were 39.1% and 24.6% in Groups 1 and 2, respectively. No difference was noted in the 1-year death rates between the groups. However, it was found to be close to statistically significant difference (p = 0.059).
The limitation of our nested case control study is that it is a retrospective cohort review that only included patients with surgically treated hip fracture. The nonsurgically treated hip fracture patients were excluded, as they were usually medically unfit for surgery, which potentially underestimated the overall incident and mortality. The exclusion criteria from the study were the presence of osteoporosis and whether the patients took antiosteoporosis medications. Another limitation was that the mobility status of the patients was not assessed before hip fracture. In addition, complications such as infection and implant failure can be seen after hip fracture surgery [21]. In our study, no evaluation was made in this respect.
Conclusion
The incidence of contralateral hip fractures in this nested case- control study was 6.3%. There was no significant difference between the groups in terms of 1-month and 1-year mortality rates. However, overall survival rates varied significantly between the groups. There was no significant difference between the groups in terms of fracture type and treatment modalities. The comorbidities observed in the two groups were not significantly different for hypertension, diabetes mellitus, heart disease, renal disease, and respiratory disease. There appears to be an increased risk for contralateral hip fracture in patients with neurological diseases (such as dementia or Alzheimer’s). We thus recommend that these risk factors be identified and corrected properly in patients who sustain their first hip fracture.
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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The fungicide thiram induced hepatic and renal injuries in domestic pigeons (Columba livia domestica)
Souheila Slımanı 1, Sarra Sılını 2, Cherif Abednnour 2, Meryem Nassar 3
1 Departement of Biology, University of 20 Auguest 1955, Skikda, 2 Departement of Biology, Laboratoty of Animal Ecophysiology, University of Annaba, 3 Laboratory of Research in Biodiversity Interaction, Ecosystem and Biotechnology ‘LRIBEB’, University of 20 Auguest 1955, Skikda, Algeria
DOI: 10.4328/ACAM.20620 Received: 2021-03-30 Accepted: 2021-04-24 Published Online: 2021-04-27 Printed: 2021-05-01 Ann Clin Anal Med 2021;12(5):547-552
Corresponding Author: Souheila Slimani, Department of Biology, University of 20 Auguest 1955, El hadaiek, 21000, Skikda, Algeria. E-mail: shsouheila@yahoo.fr P: 213 558783045 F: 213 38714568 Corresponding Author ORCID ID: https://orcid.org/0000-0002-9991-7905
Aim: Prolonged occupational exposure and the extensive agricultural use of thiram may affect animal and human health. The aim of this study is to investigate the effects of the dithiocarbamate fungicide thiram on hepatic and renal functions of domestic pigeons.
Material and Methods: Twenty-four (24) pigeons (Columba livia domestica) weighing 200 250g were divided into three (3) equal groups as follows: (CT) served as control, T, t groups were administrated orally 5 and 10 mg/Kg/day of thiram, respectively, for ten weeks. Each group was subdivided into four males and four females. In addition to the histopathological study of liver and kidney, levels of alkaline phosphatase (ALP), alanine aminotransferase (ALT), Gamma-glutamyl transferase (GGT), total bilirubin, total proteins, total cholesterol, triglycerides, glucose, uric acid and creatinine were evaluated.
Results: The obtained results indicated a significant increase in ALT, ALP and GGT activities with a slight increase in bilirubin, total proteins and glucose con- centrations. However, total cholesterol and triglycerides were significantly elevated. The augmentations of uric acid and creatinine levels were dose-dependent. The liver and kidney somatic indexes were remarkably higher in the thiram-treated pigeons. Histological examination revealed hepatic architectural disorga- nization, lymphocyte infiltrations, accompanied by structural degradations of the renal parenchyma, glomeruli wall and tubules.
Discussion: In the present study, exposure of domestic pigeons (Columba livia) to thiram at 5 and 10 mg/Kg/day resulted in certain biochemical disorders. Hence, the determination of liver and kidney markers in pigeons exposed to thiram can give some indication of the general health status of birds. Oral exposure to thiram at 5 and 10 mg/Kg/day induced liver and renal perturbations.
Keywords: Thiram; Columba Livia Domestica; Liver; Kidney; Histology
Introduction
Dithiocarbamate fungicides constitute a large group of used pesticides; due to low cost, good efficacy and a broad spectrum of antifungal activity. They are already used in agriculture and medicine. Thiram (tetramethyl thiuram disulfide: TMTD) is a protective dithiocarbamate fungicide used as a foliar treatment of fruits, vegetables, and ornamentals; it is applied to protect seeds before planting. Also, it is used as a rodent repellent to protect crops [1]. Thiram can disperse in the environment as an oxidation product of the fungicides, ziram, and ferbam. In spite of the extensive use, thiram has poor solubility in water (30 ppm at 25 °C); this makes it immobile in soils rich in clay and organic matter content. Thiram incorporation into the food chain could harm animal and human beings [2]. It exhibits low to moderate acute toxicity via the oral and dermal ways [3]. Chronic exposure has been found to cause adverse reproductive and developmental effects [4].TMTD is known as an inducer of allergic contact dermatitis and as an inhibitor of angiogenesis [5].Thiram residues in combination with nitrite could lead to carcinogenic nitrosamines. The neurotoxic, cytotoxic, genotoxic and mutagenic effects of thiram have already been reported [6]. Mainly metabolized in the liver, thiram cause some toxic effects on this organ, as indicated by hepatic enlargement, dysfunction, hepatitis, degenerative changes, and focal necrosis are reported[7].It can be metabolized to dimethyl dithiocarbamate (DMDC), carbon disulfide (CS2) and other products that had incriminated to inhibit microsomal enzymes [6].It has been reported that the disulfide groups present in thiram caused cells oxidation of proteins, peptides, and cofactors which provokes cytotoxicity [6]. Disulfide groups also can affect mitochondria and membrane lipid peroxidation, resulting in enhanced release of lactate dehydrogenases within the cells, increased serum aminotransferases activities and liver MDA contents, while it decreases serum alkaline phosphatase and hepatic antioxidant enzymes SOD, GSH-PX [8]. Samreen et al. [9] reported inhibition of all major antioxidant enzymes activities, elevated lipid and proteins’ oxidation and hydrogen peroxide level in thiram treated erythrocytes. However, the same survey has shown a decrease in total sulfhydryl group content, glutathione hemoglobin oxidation levels and the release of free iron. Moreover, thiram may also cause damage to kidneys, in addition to disturbing glucocorticoid homeostasis [10].
Birds in the field may be exposed to thiram by ingesting treated seeds or by incidental ingestion of contaminated soil. Ecologically, high LC50 is not toxic to birds, but it could affect their reproductive mechanism [11,12]. Defined tibiae dyschondroplasia as a disease found in fast-growing strains of chickens, turkeys, and ducks.
Due to the lack of information on thiram toxic effects on birds, the present study aims to investigate the outcome of thiram on certain biochemical markers and histological profiles related to liver and renal functions of (Columba livia domestica) pigeon.
Material and Methods
Chemicals
Thiram (tetramethylthiuram disulfide, CAS 13726- 8), chemical purity 80%, 5.5% surface additives, and about 14.5% kaolin, was supplied by Sigma-Aldrich.
Animals
Twenty-four domestics pigeons (Columba livia domesica), (weighing 200250g) were captured locally in early February and were placed in metal cages (Animal house, Department of Biology, University of Skikda), with a free food (chick crumbs) and water intake. During ten weeks of experimental trial (from the last week of February to the first week of May), the pigeons were under a natural photoperiod, ambient temperature, and humidity. The birds were divided into three groups of 8 individuals (4 males and 4 females); the first group was the control (c), the second (d1) and the third (d2) orally received 5mg/Kg/day and 10mg/Kg/day of thiram, respectively. The doses administered in this experiment were chosen according to the LD50 of thiram to birds (670-2800 mg/Kg).
Sample preparation
At the end of the tenth week, the pigeons were sacrificed; then3 ml of blood was collected into heparinized tubes and centrifuged (3000 rpm. for 20 min) at 4°C. The livers and kidneys were immediately removed, weighed, and fixed in 10% formol solution for 24 hours, then passed in increasing alcohol grades for dehydration. After they cleared in toluene, the specimens were embedded in paraffin wax. Finally, sections (5μm thick) were mounted on diesterase phthalate xylene after they were stained with haematoxylin and Eosin.
Analytical procedures
The collected plasma was used for the measurement of alanine aminotransferase (ALT), glutamyl transferase (GGT), alkaline phosphatase (ALP), total bilirubin (TB), total proteins (TP), uric acid (UC) and creatinine using commercially available diagnostic kits supplied by Randox Laboratories (Ardmore, Northern Ireland, UK) using an automate CX9 (BECKMAN, Brea, CA, USA). Plasma glucose was estimated using assay kits supplied by Diamond Diagnostics. Total cholesterol (TC) and triglycerides (TG) were estimated by colorimetric methods using Randox reagents.
Statistical analysis
Data were expressed as mean ± SEM. Statistical analysis was obtained using two-way analysis of variance (ANOVA) with multiple comparisons using Tukey’s test at p≤0.05 using the Minitab version 19.
Ethical Approval:
Experiments on pigeons were carried out according to the national animal welfare and to the EU Directive N° 2010/63/ EU on the protection of animals used for scientific purposes.
Results
None of the pigeons treated with thiram 80, at doses of 5 and 10 mg/ Kg/day have shown signs of morbidity or mortality during the study, but diarrhea and the decrease in food intake were observed along the experimental period.
Effects of treatment on body, liver and kidney weights
The results indicated that relative weights of livers and kidneys were increased (insignificantly) in the two sexes of pigeons treated with the two thiram doses compared to the control (Table 1), with no remarkable variations in total body weight between all groups
Effect of treatment on plasma biochemical parameters
Table 2 reports the mean values of various biochemical
parameters of domestic pigeons Columba livia domestica treated with thiram at doses of 5 and 10 mg/ Kg/ day for 10 weeks.
Thiram induced a significant increase in hepatic enzyme activities (ALT, GGT, and ALP) in both male and female pigeons. However, plasma glucose and total proteins significantly increased with the increasing dose in both males and females. In term of lipid profile, the level of total cholesterol and triglycerides were higher in the treated groups increased significantly. Total triglycerides were higher in treated females. Concerning the renal function, Table 2 shows statistically more significant increases in acid uric and creatinine levels in the treated groups. It is interesting to note that the higher levels of acid uric and creatinine were among the treated females. Effect of treatment on hepatic histology
The histological examination of the liver section of the control group showed normal healthy parenchyma. However, liver section of treated pigeons demonstrated necrotic and degenerative changes with congestions of the hepato-portal blood vessel, and inflammatory infiltrations (Figure 1).
Effect of treatment on kidney histology
Sections of the treated pigeons showed that the proximal and distal convoluted tubules were less condensed than those in the control group. A change in the structure of the renal glomerulus compared to the control with important changes in the renal parenchyma (decreased branching), depletion of the glomeruli wall and the presence of eutrophication in the parenchyma and in the glomeruli. Thiram at different concentrations showed a dilating effect on the renal tubules and disorganization of the capillary pellets of the glomeruli (Figure 2).
Discussion
In the present study, exposure of domestic pigeons (Columba livia) to thiram at doses of 5 and 10 mg/Kg/day resulted in certain biochemical disorders. Hence, the determination of liver and kidney markers in pigeons exposed to thiram can give some indication of the general health status of the birds. Alanine aminotransferase and alkaline phosphatase have already been used to evaluate hepatic damage in clinical investigations [13]. The present study showed a significant increase in plasma ALT, GGT and ALP activities of pigeons after thiram exposure. These results are consistent with that recorded by Samreen [9], where thiram raised plasma ALT and AST and liver MDA, while they decreased in male broiler chicks. Moreover, an increase in serum ALP activity and liver antioxidant enzymes (SOD, G-Px) was observed in maneb and paraquat-treated rats [14], and as well as after treatment with carbofuran Clarias gariepinus[15]. Abd-Alrahman et al [16] have reported a higher ALT activity in the albino rats treated with difenoconazole, or diclofop-methyl alone, or in combination. All of these perturbations are related to liver damages, which is compatible with histopathological lesions that clearly showed degeneration and necrosis of the hepatic cells, accompanied by an increase in AST and ALT activities and confirm the pesticide induced liver injury. A slight increase in plasma total bilirubin may be associated with primary periportal necrosis as a result of liver malfunction. In this study, a slight increase in the concentrations of total proteins plasma confirms the thiram toxicity. It is known that proteins could preserve the organism from xenobiotics, parasites and infections [17].
Glucose is one of the important sources of energy for cell functions and it is believed that glucose level might be used as an indicator of stress from pollution and from other physical factors. Actually, thiramtreatment at the dose of 5 and 10 mg/ Kg/day increased serum glucose in a dose-dependent manner in Columba livia. Mekkawyet al. [18] indicated that the elevation of corticosteroid hormones and plasma catecholamines caused liver glycogenolysis, which lead to hyper-glycemia. Gluconeogenesis from amino acids also may be incremented in glucose elevation. Accordingly, an increase in glucose levels was recorded after exposure to thiram on freshwater fish (Cyprinus carpio) [19] and exposure to propineb on pigeons (Columba livia) [20]. In this study, serum creatinine levels were increased with increasing dose of thiram; this elevation may be associated with the impairment of the glomerular function and to damage to the renal tubules, which is in-line with the tubular histopathological studies. Serum cholesterol and triglycerides were significantly elevated, that may indicate certain changes in the hepatic cell permeability [21]. In fact, the increase in total cholesterol assessed in this study may be related to the blocking of hepatic bile ducts, causing, however, a decrease in cholesterol secretion into the duodenum [22].
The data from the histopathological study indicated alterations of thiram in the liver and kidney of pigeons of both sexes, as that of the biochemical markers’ impairments. Destruction of the liver architecture, necrotic and degenerative changes with congestions of the hepatic portal blood vessel, and inflammatory infiltrations were observed in thiram-treated pigeons. Dithiocarbamates fungicides (DTCs) like thiram were toxic to the liver, kidney and testis [23]. Earlier, O ̈zbay et al. [24] showed that maneb and zineb caused some pathological changes in the liver of mice indicated by vein congestion and mononuclear inflammatory cell infiltrations. Accordingly, the current histopathological investigation confirmed that thiram at different concentration induces harmful effects on renal architecture, where the proximal and distal convoluted tubules are less condensed, decreased branching of renal parenchyma, depletion of the glomeruli wall and the presence of eutrophication in both parenchyma and the glomeruli. Thus, thiram had dilated the renal tubules and disorganized the capillary pellets of the glomeruli. Guven et al. [25] reported that the kidneys of the propineb-treated rats showed oedema, cell degeneration, and irregularities in tubular structure. Furthermore, kidneys section of maneb-treated rats shows clearly dense hemorrhage, disappearance of epithelium cells around tubules, infiltration of inflammatory cells towards tubules’ lumen and clear edema between tubules.
In conclusion, thiram modified liver and the kidney markers in domestic pigeons (Columba livia domestica).
Acknowledgment
The authors are grateful to the PNR projects, Algiers for the financial support. Thanks are given to the university of 20 august 1955- Skikda, where this work was carried out.
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 Ph D project (Award number 05/2016) was supported by the General Directorate of Scientific Research and Technological Development (DGRSDT) for Laboratory of Animal Ecophysiology.
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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Souheila Slımanı, Sarra Sılını, Cherif Abednnour, Meryem Nassar. The fungicide thiram induced hepatic and renal injuries in domestic pigeons (Columba livia domestica). Ann Clin Anal Med 2021;12(5):547-552
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Does polycystic ovarian syndrome increase the risk of congenital anomalies in intracytoplasmic sperm injection cycles?
Arzu Yurci 1, Nur Dokuzeylul Gungor 2, Tugba Gurbuz 3
1 Gynecology Obstetrics & Reproductive Medicine, Memorial Kayseri Hospital IVF Center, Kayseri, 2 Gynecology Obstetrics & Reproductive Medicine, Bahcesehir University Goztepe Medical Park Hospital, Istanbul, 3 Gynecology and Obstetric Clinic, Medistate Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.20628 Received: 2021-03-30 Accepted: 2021-04-18 Published Online: 2021-04-26 Printed: 2021-05-01 Ann Clin Anal Med 2021;12(5):553-557
Corresponding Author: Arzu Yurci, Memorial Kayseri Hospital IVF Center, Gevher Nesibe Mahallesi Çiçek Sokak No: 10, Kayseri / TURKEY. E-mail: arzuyurci@yahoo.com / arzu.yurci@memorial.com.tr P: +90 5334247890 F: +90 3522221050 Corresponding Author ORCID ID: https://orcid.org/0000-0003-4808-9019
Aim: In this study, we aimed to investigate the effects of polycystic ovary syndrome (PCOS) on the increased risk of congenital anomaly (CA) in intracytoplasmic sperm injection (ICSI) cycles.
Material and Methods: This cross-sectional retrospective study was done on 437 participants who attended our hospital’s infertility clinic from January 2019 to January 2020. The participants were divided into two groups: PCOS and normoresponder group (NR). The number of patients was 178 (40.7%) in the PCOS group and 259 (59.3%) in the NR group, respectively. Demographic characteristics and baseline clinical characteristics included maternal age, body mass index (BMI), anti-Mullerian hormone (AMH) level, total gonadotropin dose used, number of retrieved oocytes, metaphase II oocytes.
Results: The mean age of mothers was 30.46 years (±3.99), and the mean BMI was 24.3(±3.2). There is a statistically significant relationship between maternal age and increased CA risk (p-value=0.03). There was also a statistically significant relationship between high AMH levels and increased CA risk (p-value=0.03). AMH levels were significantly higher in the mothers of babies with CA than in mothers of babies without CA. There was a statistically significant relationship between the number of pronuclear oocyte and CA (p-value=0.02). A significant relationship was also found between CA and PCOS (p-value=0.005). The risk of congenital cardiac anomaly (CCA) was significantly higher in the PCOS group than in the NR group (p-value=0.02).
Discussion: We found that the incidence of CA, especially CCA, was higher in PCOS patients. Therefore, women should be informed in ICSI cycles about the increased risk of CA if they had PCOS.
Keywords: Congenital anomalies; Intracytoplasmic sperm injection; Normoresponder; Polycystic ovary syndrome
Introduction
Congenital anomalies (CA) are defined as any anatomic malformations at birth, which can be diagnosed in approximately 3 to 5% of newborns [1]. The World Health Organization (WHO) reports approximately 3 million infants and fetuses with major CA born every year. They are found in approximately 3% of newborns [2]. CA have risk factors, including 20 to 25% for the interplay of environmental and genetic factors, 10% for environmental exposures, and 15% for chromosomal and genetic factors [3]. Although diagnostic advancements, major CA still cause neonatal deaths in approximately 22% of cases. Individuals may suffer from such malformations as cardiovascular, renal, and pulmonary anomalies later in life, rather than at birth [4]. One of the serious congenital disorders is congenital heart defects (CHD) [5]. Ventricular septal defect (VSD) in the pediatric age group has the incidence of 1-2 out of 1000 live births as the most common CHD [6]. CHD occurs in almost 1% of live births [7]. CHD causes perinatal mortality as the most common form of congenital disorders [8]. Different studies have reported CHD in 0.6-1 for every 100 live births [9]. The etiology of CHD is complex and has not been yet understood well, but it may be caused by hereditary and multifactorial factors, environmental factors such as medicines, infection, maternal diseases [10], one of which may be polycystic ovary syndrome (PCOS). PCOS is the most common endocrine disorder affecting women of reproductive age, leading to infertility and anovulation; 4–12% of women are affected by it [11,12]. Generally,women with PCOS are more obese than those without PCOS. Pregnant women with PCOS may confront a growing risk of pregnancy complications such as hypertensive disorders, gestational diabetes, increased cesarean section rates, and premature delivery. PCOS women’s offspring may be at increased risk of congenital abnormalities and may be hospitalized during childhood [13]. In other words, the main pathologies of PCOS contributing to the outcomes include endocrine and metabolic factors related to gestational diabetes mellitus (GDM), leading to CA and premature rupture of membranes (PPROM) [14]. There are limited data to understand the pathophysiological associations between PCOS and pregnancy and delivery outcomes [15]. Therefore, the present study aims to investigate the risk factors of congenital anomaly in PCOS and cardiac abnormalities to see if some variables, i.e., age of mothers, body mass index (BMI), Anti Mullerian hormone (AMH), total oocyte, metaphase II oocyte (MII), pronuclear oocyte (PN), smoking, etc. were associated with general anomaly and cardiac anomaly, and if there is a difference between PCOS and normoresponder (NR) group in terms of these variables and congenital anomalies.
Material and Methods
This cross-sectional retrospective study was conducted with 437 participants who attended our hospital’s infertility clinic from January 2019 to January 2020. This study was approved by the Ethics Committee of Beykoz University, Turkey (No: 2020/3). All procedures conducted in studies, including human participants, were in accordance with the national or institutional research committee’s ethical standards and the 1964 Helsinki Declaration and its later amendments or other ethical standards.
The participants were divided into two groups: PCOS and NR group. The total number of patients in the PCOS group was 178 (40.7%) and 259 (59.3%) in the NR group, respectively. Patients with severe male factor, azoospermia, low ovarian reserve, and chronic disease were excluded from the study. Demographic characteristics and baseline clinical characteristics, including the age of the mother, age of the father, BMI, AMH, the total dose of gonadotropin, number of retrieved oocytes, MII oocytes, PN were collected. Those with chronic illnesses and chromosomal abnormalities were excluded from the study. The inclusion criteria were age less than 40 years and 1 or 2 in vitro fertilization (IVF) treatment.
Statistical analysis
Statistical Package for Social Sciences (SPSS) version 26.0 (SPSS Inc., Chicago, IL, USA) was used to perform statistics. Logistic regression was used to assess the factors associated with Anomaly exposure. In this case that we have zero events in a subgroup, penalized maximum likelihood estimation was used. The variables with P < 0.05 in the univariate logistic regression analysis were included in the adjusted logistic regressions models.
Results
This study sample consisted of 437 participants (178 PCOS cases and 259 NR) with a mean age of 30.46 years (±3.99). Table 1 shows the descriptive statistics for the variables. As can be seen from Table 1, the mean age of the mothers was 30.46 years (±3.99), and the mean age of the fathers was 34.7 years (±3.8). The mean BMI of the participants was 24.3 (±3.2). The mean number of IVF trial is 0.93 (±1.1). The mean AMH is 3.4 (±3.5) ng/ml. The total mean gonadotropin used was 2249.3(±516.4) IU. The mean duration of treatment was 10.2 (±0.7) days. The mean number of retrieved oocytes was 9.9 (±5.7). The mean MII and PN were 7.7(4.5) and 7.0892(4.07), respectively. Three hundred forty-four (78.7%) of patients had primary infertility and 93 (21.3%) had secondary infertility. Four hundred twenty subjects (96.1%) did not smoke. Four hundred thirty subjects (98.4%) had no heart anomaly, while 7 subjects (1.6%) had heart anomalies. Four hundred and ten subjects (93.8%) had no congenital anomalies, while 1 subject (0.2%) had congenital hip displacement. Seven subjects (1.6%) had a heart anomaly and 3 subjects (0.7%) had hydrocephalus.
Table 2 shows that the mean age of mothers with anomalous babies was 31.9 (±3.4) years. The mean BMI of the participants with anomalous babies was 25.3 (±4.7). The mean number of IVF trial is 0.7 (±1.2). The mean AMH level was 3.9 (±2.1) ng/ml. The total mean gonadotropin dosage used was 2075 (±433.9) IU. The mean duration of treatment was 10.3 (±0.6) days. The mean number of retrieved oocytes was 11.7 (±6.4). ThemeannumberofMIIandPNwere9.4(±5.3)and8.8(±4.4), respectively. The number of patients in the PCOS group was 160 (39%), and in the normoresponder group was 250 (61%), respectively. Three hundred and twenty subjects (78%) had primary infertility; 90 subjects (22%) had secondary infertility. Three hundred ninety-three subjects (95.9%) did not smoke. There is a statistically significant relationship between maternal age and the risk of congenital anomaly (p-value=0.03).
Those women who had a baby with CA were older than those who did not have a baby with CA. There is also a statistically significant relationship between AMH and congenital anomaly (p-value=0.03). The subjects with CA had higher AMH than those without CA. There is a statistically significant relationship between PN number and the risk of congenital anomaly (p-value=0.02). The subjects with anomalies had a higher PN than those without anomaly.
The results of the Kolmogorov test show that not all quantitative variables had a normal distribution. Table 3 examines the relationship between the studied variables and the anomaly variable using the Mann-Whitney. Table 3 shows that there is a statistically significant difference between the PCOS and NR groups in terms of CA (p-value=0.005). In the PCOS group, 18 (66.7%) participants had CA, while 9 (33.3%) participants in the NR group had CA, indicating a significant relationship between CA and PCOS.
Anomaly Yes and No means whether there is a congenital anomaly or not.
The relationship between qualitative variables and Cardiac Anomaly was determined using Fisher’s exact test. There was a statistically significant relationship between maternal age and CCA (p-value=0.03). There was no statistically significant relationship between other studied variables and CCA (p>0.05). There was a statistically significant relationship between cardiac anomaly and the PCOS group (p-value=0.02). Six subjects in the PCOS group had an anomaly, and one subject in the NR group had CCA. The results show that CCA was more common in the PCOS group. Two subjects in the PCOS group had VSD, while one subject in the NR group had VSD. Three subjects in the PCOS group had tetralogy of Fallot (TOF), while no subjects in the NR group had TOF. One subject in the PCOS group had atrial septal defect (ASD)-VSD, while no subject in the NR group had ASD-VSD. TOF was the most common heart anomaly in the PCOS group.
Discussion
The aim of the present study was to investigate the risk factors for congenital anomaly and the cardiac anomaly in the PCOS to see if some variables, i.e., maternal age, BMI, AMH, total oocyte, MII, PN, smoking were associated with CA and CCA and if there was a difference between PCOS and normoresponder group in terms of these variables and CA and CAA. The findings show that those who had the CA and CCA were older than those who did not have anomalies. The subjects with anomalies had higher AMH levels than those without anomaly. The subjects with anomalies had higher PN number than those without anomaly. The number of subjects in the PCOS group with CA was higher than that of the NR group. In other words, PCOS is associated with an increased risk of CA. Increased maternal age was also associated with an increased cardiac anomaly risk. Two subjects in the PCOS group had VSD, while one subject in the NR group had VSD. Three subjects in the PCOS group had TOF, while none of the subjects in the NR group had TOF. One subject in the PCOS group had ASD-VSD, while none of the subjects in the NR group had ASD-VSD. TOF was the most common heart anomaly in the PCOS group.
Maternal age significantly affects the congenital malformation of the fetus [16]. Studies in Turkey show that 5.2% of the mothers are over 35 years old [17], while older mothers had 8.7% of anomalous births, but this was not statistically significant [16]. Their result is in line with the results of our study, but not in line with the results of the study by Francine et al. Francine et al. also found that congenital cardiovascular anomalies (16.6%) and limb anomalies were the most common ones in their study [18]. The studies on singleton pregnancies showed that PCOS women are older, have early pregnancy, need ART to conceive, and have a higher BMI than those without PCOS [19]. In older women, CCA has more risk factors, such as poor oocyte quality, infections, autoimmune diseases, pre-gestational diabetes, uterine aging drug exposure, or other causes of infertility [8]. Most women with PCOS are overweight or obese, and a higher risk of preterm delivery was observed in overweight and obese women during pregnancy, as reported by a recent study [20], and obesity is metabolically associated with PCOS [11]. Liu et al. found an association between pregravid obesity and an increased risk of adverse pregnancy outcomes after adjusting the variations of parity, PCOS, maternal age, etc. There was an association between obesity and congenital anomalies, and that PCOS had endocrine and metabolic effects on the GDM, contributing to congenital anomalies [14]. Our study found that BMI in the women with anomaly was higher than that in those without anomaly, but this association was not significant, but found that PCOS could significantly contribute to the congenital anomalies. Our study found that VSD and TOF were the most common cardiac anomaly in the groups. TOF was common in only the subjects with PCOS, while VSD was common in both groups, which is in line with the results of the study by Kirklin et al. [6], who found that VSD is the most common congenital anomaly. Francine et al. found that limb anomalies (16.6 %), including abnormal palmar crease (4.16%) and polydactyly (12.2%) and congenital cardiovascular anomalies (16.6%), were observed in most malformed stillbirths [18]. Mills et al. [21] found that those with PCOS more likely to have infants with congenital anomalies than those without PCOS, which is in line with our study results. Doherty et al. [22] also found that cardiovascular and urogenital malformations were more common in children of women with PCOS, supporting our study findings. Hart [12] found impairment of the glucostasis for some women with PCOS, leading to intergenerational influence that is not immediately detected during pregnancy, resulting in a higher risk of cardiometabolic and congenital malformations for the offspring.
Conclusion
It is concluded that PCOS was significantly associated with an increased risk of CA and CCA. The subjects with anomalies had higher age, AMH level and PN numbers than those without anomaly. Therefore, women should be informed about the increased risk of CA if they had PCOS.
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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Carotid intima-media thickness and related factors in chronic kidney disease
Can Sevinc 1, Recep Demirci 2
1 Department of Nephrology, Ataturk University Faculty of Medicine, Erzurum, 2 Department of Nephrology, Kanuni Sultan Süleyman Research and Training Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.20629 Received: 2021-03-31 Accepted: 2021-04-20 Published Online: 2021-04-30 Printed: 2021-05-01 Ann Clin Anal Med 2021;12(5):558-562
Corresponding Author: Can Sevinc, Ataturk University Faculty of Medicine, Department of Nephrology, Erzurum, Turkey. E-mail: can.sevinc@atauni.edu.tr P: +90 534 6157812 Corresponding Author ORCID ID: https://orcid.org/0000-0002-4069-9181
Aim: Cardiovascular diseases are the most important cause of mortality. Evaluation of atherosclerosis is important to prevent the development and progres- sion of cardiovascular disease. Carotid intima-media thickness (CIMT) is an indicator of generalized atherosclerosis. In this study, we aimed to examine CIMT and related factors in CKD.
Material and Methods: The study was conducted with the patients who applied to the Nephrology outpatient clinic. The control group consisted of healthy volunteers. Patients over 18 years of age with a diagnosis of CKD, without active infection, without malignancy, without obesity, without lipid and uric acid- lowering medication, without thyroid hormone replacement, and without uncontrolled hypertension were included in the study. The CIMT of the patients and their laboratory and demographic data were compared statistically.
Results: Proteinuria in patients increased with increasing stages, and no significant difference was found between the CIMT values. The risk of atherosclerosis increased approximately 4 times over the age of 60, and the risk increased approximately 2.5 times in the presence of proteinuria above 500 mg/day.
Discussion: Our study has shown that the presence of proteinuria, independent of GFR in CKD increases CIMT and thus cardiovascular mortality. We think that evaluation of patients with CIMT may be important for early diagnosis of cardiovascular events, especially in elderly patients with proteinuria.
Keywords: Atherosclerosis; CIMT; CKD; Proteinuria
Introduction
Chronic Kidney Disease (CKD) is a serious public health problem with high mortality and morbidity all over the world [1]. Cardiovascular diseases are the most important cause of mortality. Despite advances in the management of cardiovascular diseases in the last 40–50 years, the risk is still high in patients with end-stage renal disease (ESRD) [2–5]. The risk occurs from the early stages of CKD [6,7]. Traditional atherosclerosis risk factors such as age, increased blood pressure, diabetes mellitus (DM), lipid disorders, obesity and tobacco use habits revealed in epidemiological studies such as the Framingham study cannot fully explain early-rapidly developing atherosclerosis and its associated high morbidity and mortality rate in CKD. In addition to traditional risk factors for atherosclerosis, novel risk factors associated with uremia are thought to play an important role in the development of early-onset and rapidly progressing atherosclerosis in the CKD process. Therefore, the evaluation of atherosclerosis is important to prevent the development and progression of cardiovascular disease [8,9]. Carotid intima-media thickness (CIMT) is an indicator of generalized atherosclerosis. It is an easy, non-invasive, inexpensive and reproducible method to measure CIMT using ultrasonography. In recent years, there have been studies showing the relationship between CIMT, atherosclerosis and cardiovascular events in CKD, but no consensus has been reached yet [10–13]. In our study, we aimed to examine CIMT and related factors in CKD.
Material and Methods
The study was conducted with patients who applied to the Nephrology outpatient clinic. The study was conducted with the necessary permissions from the Istanbul Health Sciences University Kanuni Sultan Suleyman Training and Research Hospital Ethics Committee (Dated 14.01.201 and numbered 2021.01.235). The study was conducted according to the recommendations of the Human Subjects Biomedical Research Helsinki Declaration. Patients who wished to participate in the study voluntarily were included. Demographic characteristics such as age, gender, drug use were questioned. Blood pressures were measured with the same sphygmomanometer in a sitting position in a quiet room, and the results were recorded as systolic blood pressure (SBP) and diastolic blood pressure (DBP) (in mm/Hg). Pulse rate, Body Mass Index (BMI) of the patients were recorded. The study included patients over 18 years of age with a diagnosis of CKD, with no active infection, with no malignancy, no obesity, no lipid and uric acid-lowering medication, no thyroid hormone replacement, and with no uncontrolled hypertension. The control group consisted of healthy volunteers.
Biochemical Analysis:
Complete blood count (hemogram), blood urea nitrogen (BUN, mg/dl), creatinine (mg/dl), sodium (Na, mmol/l), potassium (K, mmol/l), calcium (Ca, mg/l). dl), phosphorus (P, mg/dl), magnesium (Mg, mg/dl), uric acid (mg/dl), albumin (g/dl), total protein (gr/dl), total cholesterol (mg/dl), triglyceride (TG, mg/ dl), low density lipoprotein (LDL, mg/dl), high density lipoprotein (HDL, mg/dl), c-reactive protein (CRP, mg/l), ferritin (ng/ml), free triiodothyronine (FT3, pg/ml), free thyroxine (FT4, ng/dl) and thyroid stimulating hormone (TSH, μIU/ml), 25 OH vitamin D (ng/ml) and parathyroid hormone (PTH, pg/ml) values were measured. Protein excretion in patients was calculated by dividing the spot urine total protein amount by the spot urine amount of creatinine. The glomerular filtration rate (GFR) was calculated using the MDRD formula. (MDRD formula = 170 x (serum Cr) – 0.999 x (age) – 0.176 x (0.762 if the patient is female) x (1.180 if the patient is black) x (serum BUN) -0.170 x [(Albumin) + 0.318]). Complete blood count was studied in 3700 CELL DYN device with an autoanalyzer method. BUN, creatinine, Ca, P, Mg, uric acid, albumin, total protein, total cholesterol, TG, LDL, HDL, total protein in spot urine, and creatinine were studied using photometric Beckman Coulter preanalytical and modular system (UniCel Dxc 800) device. With the sodium and potassium ISE method, Beckman Coulter preanalytical and modular system (UniCel Dxc 800) was studied. CRP was studied using the nephelometric method on the Beckman Coulter preanalytical and modular system (IMMAGE 800). FT3, FT4, TSH and PTH were studied on the Abbott Architect i2000 device using the imunokemiluminasan assay method. Hemogram analysis was done automatically on Beckman-Coulter device, ferritin analysis was performed in Hitachi E170 device, 25 OH vitamin D analysis was performed with Trinity Biotech Captia Reader device.
Measurement of Carotid Intima-Media Thickness (CIMT):
All subjects were in supine position, and the anterior neck was fully exposed, with the head back. Two separate measurements were made on the left common carotid artery and the right common carotid artery (1 cm proximal to the bulbus), and the average of these two measurements was taken. No measurements were taken in places where atheroma plaques were visible. Carotid artery intima-media thickness was evaluated between two echogenic lines seen between the intima-lumen interface and the media-adventitia interface. The mean carotid artery intima-media thickness was calculated by dividing the sum of the right and left carotid artery intima- media thickness into two. CIMT was measured in the Radiology Outpatient Clinic of Istanbul Health Sciences University Kanuni Sultan Süleyman Training and Research Hospital using the B mode of Mindray DC-7 device. The cut-off value for CIMT was 0.75 mm [14].
Statistical analysis:
The data were recorded and analyzed using IBM SPSS Statistics version 22.0 package program. Conformity of the variables to the normal distribution was examined by visual (histogram and probability charts) and analytical methods (Kolmogorov- Smirnov/Shapiro-Wilk tests). Descriptive analyzes were performed using means and standard deviations for normally distributed variables. While analyzing the data, independent groups t- test (Student’s t-test) was used to compare the two groups, and the Mann-Whitney U test was used if the conditions were not met. With one-way analysis of variance and the Tukey HSD test, one of the multiple comparison tests, for comparin three or more groups; when the conditions were not met, the Kruskal Wallis and Bonferroni-Dunn test from multiple comparison tests were used. The Chi-square and Fisher Exact’s tests were used in the analysis of categorical data. The statistical significance level was accepted as p<0.05.
Results
A total of 95 patients (51 females (53.7%), 44 males (46.3%) and (41%) total 22 healthy volunteers (13 females (59%), 9 males) were included in the study. The mean age of the patients was 59.5 ± 13.9, while the mean age of the control group was 34.8 ± 9.7. In comparison of control group and patient group, age, BUN, creatinine, phosphorus, uric acid, triglyceride, CRP, PTH, ferritin, right CIMT, left CIMT and mean CIMT values were found to be statistically significantly higher in the patient group, and the levels of calcium, albumin, FT3 values were statistically significantly lower.
In the evaluation of the patients according to the CKD stages, 40 patients were Stage-3 (42.1%), 33 patients were Stage-4 (34.7%), and 22 patients were Stage-5 (23.2%). When the patients were compared according by their stages, no significant difference was found in terms of age, disease duration and comorbid diseases. As the stage progresses, the levels of Calcium, phosphorus, CaXP of the patients were found to be high, albumin and hemoglobin levels were low. While the proteinuria of the patients increased with increasing stages, no significant difference was found between the CIMT values. Patients with and without DM and coronary artery disease (CAD) were compared. While there is no significant difference between CIMTs of patients with and without DM regardless of the stage, when the patients with CAD were evaluated, CIMTs were found to be significantly higher (Table 1).
Patients were divided into two groups according to CIMT. Those with CIMT greater than 0.75 mm and those below were compared. In the group with CIMT above 0.75 mm, age, female gender and proteinuria were found to be significantly higher (Table 2).
Diagnostic decision-making features in predicting subclinical atherosclerosis for proteinuria and age were examined with the ROC curve. The cut-off value for age was found to be 60 with 72.2% sensitivity and 64.4% specificity. This value for proteinuria was found as 500 mg/day with 64.4% sensitivity and 68.2% specificity (Figure 1, Table 3). As a result of the logistic regression analysis, it was shown that the risk of atherosclerosis increased approximately 4 times over the age of 60, and the risk increased approximately 2.5 times in the presence of proteinuria above 500 mg/day (Table-3).
Discussion
Carotid intima-media thickness (CIMT) is an indicator of atherosclerotic vascular disease. It is considered a comprehensive picture of all changes in the arterial wall that occur over time and are caused by cardiovascular risk factors. In some studies, it has been found that CIMT is high in CKD at any age. It has been suggested that CIMT may be an indicator of cardiovascular and all-cause mortality in CKD cases. It has been shown that CIMT is significantly higher, especially in those with CKD over 50 years of age [15,16]. In our study, CIMT thickness was found to be significantly higher in CKD group. Of course, in this case, it should not be forgotten that age may also affect. It is known that atherosclerosis and an increased risk of cardiovascular events occur from the early stages of CKD. As the CKD stage increases, this risk increases and CIMT increases significantly [17]. In our study, a significant difference was found between stage-3 patients and the control group, while no significant difference was found between stage-3, stage-4, and stage-5 patients. Systemic inflammation in CKD plays an important role in the development of atherosclerosis [18]. In addition, renal dysfunction changes the quality of the blood lipid profile, causing a more atherogenic lipid profile. Dyslipidemia in CKD is largely due to increased triglyceride levels, decreased HDL and altered LDL levels [19]. In our study, a significant difference in CRP levels was found between the patient and control group, which is an indicator of inflammation. While triglyceride levels were significantly higher in the patient group, HDL levels were significantly lower, and no difference was found in LDL and total cholesterol levels.
The presence of proteinuria is a powerful marker for the progression of chronic kidney disease, as well as an indicator of increased cardiovascular morbidity [20]. In a study by Momeni et al., a significant relationship was shown between proteinuria and CIMT in Type 2 DM patients [21]. In another study by Ito et al., a relationship was found between CIMT and GFR in patients with type 2 DM, but there was no relationship between proteinuria levels [22]. In our study, when comparing patients with and without type 2 DM, no significant difference was found between CIMT values in terms of both total and stages, but there was a significant difference between proteinuria levels. CIMT values were higher in CAD patients, as expected. In a study by Modi et al., in patients who were prepared for transplant, they observed that CIMT above 0.75 mm was a strong predictor for
CAD in patients with ESRD and that it could be used as a non- invasive screening test for pretransplant cardiac evaluation with its high sensitivity, specificity, and positive predictive value for these patients [14]. According to this value, we divided our patients into two groups. In the group with CIMT > 0.75 mm, age, female gender, and proteinuria levels were found to be significantly higher. However, no significant difference was found in the patients in terms of other parameters. It is an interesting result that there is no difference in terms of GFR and stages. The relationship between age and proteinuria with CIMT was evaluated with subsequent examinations. In our study, it was shown that the risk of atherosclerosis increased approximately 4 times in patients above 60 years of age, and the risk increased approximately 2.5 times in the presence of proteinuria above 500 mg/day. Our study has shown that the presence of proteinuria, independent of GFR in CKD, increases CIMT and thus cardiovascular mortality. We think that evaluation of patients with CIMT may be important in the early diagnosis of cardiovascular events, especially in elderly patients with proteinuria.
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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The relationship between vitamin D deficiency and the frequency of Helicobacter Pylori and peptic ulcer in childhood
Mehmet Agin 1, Serap Tas 2
1 Department of Pediatric Gastroenterology, Hepatology and Nutrition, Van Education and Research Hospital, 2 Department of Pathology, Van Education and Research Hospital, Van, Turkey
DOI: 10.4328/ACAM.20630 Received: 2021-03-31 Accepted: 2021-04-21 Published Online: 2021-04-28 Printed: 2021-05-01 Ann Clin Anal Med 2021;12(5):563-566
Corresponding Author: Mehmet Agin, Department of Pediatric Gastroenterology, Hepatology and Nutrition, Van Education and Research Hospital, Van, Turkey. E-mail: drmehmet47@yahoo.com P: +90 506 8011083 F: +90 4322175600 Corresponding Author ORCID ID: https://orcid.org/0000-0001-6177-2635
Aim: In the present study, the purpose was to examine the relation between Vitamin D deficiency, and the presence of Helicobacter Pylori (HP) and peptic ulcer.
Material and Methods: A total of 291 patients who presented to our Pediatric Gastroenterology Clinic with dyspeptic complaints were included in the study. The age, gender, and Vitamin D levels, endoscopic and histopathological findings of patients with and without Vitamin D deficiency were compared. Patients with peptic ulcers were compared in terms of Vitamin D levels and HP prevalence.
Results: Vitamin D deficiency was found to be higher in men. Although 70% of patients who had Vitamin D deficiency tested positive for HP, it was detected in 33% of patients without Vitamin D deficiency. In 19% of patients who had Vitamin D deficiency, there were peptic ulcers, and 9% of patients without Vitamin D deficiency had peptic ulcers, and the difference was statistically significant. Although the mean Vitamin D level in patients who had peptic ulcer was 15.8 ng/ ml, it was 23 ng/ml in patients without peptic ulcers, and the difference was statistically significant (P=0.003). A total of 61% of patients with peptic ulcer had Vitamin D deficiency, 39% of patients without peptic ulcer had Vitamin D deficiency, and the difference was statistically significant.
Discussion: No effect of Vitamin D level on HP prevalence was detected. Since Vitamin D levels may be lower in patients who have peptic ulcer, Vitamin D levels must be examined in such patients.
Keywords: Endoscopy; Helicobacter Pylori; Vitamin D
Introduction
Helicobacter Pylori (HP) is a gram-negative bacterium in spiral form colonizing in the gastric mucosa, and is the most common cause of resistant bacterial infection in the world [1]. HP localizes in the gastric mucosa, causing diseases such as peptic ulcer, B-Cell Lymphoma and gastric cancer as well as gastritis [2].
Vitamin D is a fat-soluble vitamin, and robust small intestines, sufficient amount of bile, and pancreatic secretion are required for its absorption. For this reason, many diseases of the gastrointestinal tract in children affect Vitamin D levels [3]. Vitamin D is a powerful immunomodulator other than calcium hemostasis. Different forms of Vitamin D have immunomodulatory effects on T and B-lymphocytes. Vitamin D also inhibits cellular differentiation, proliferation, and apoptosis [4], and is important in controlling the inflammation in HP infection. Some conflicting results have been reported that vitamin D deficiency may negatively affect the immune system and cause allergic diseases. Recently, a study conducted by Dogan et al.claimed that vitamin D deficiency may not play a role in the etiology and physiopathology of allergic gastrointestinal diseases like cow’s milk protein allergy [5]. Previous studies have shown that active Vitamin D use reduces HP infection by more than 50% [6]. It has been reported with the recent discovery of Vitamin D receptors in different tissues that Vitamin D plays roles in diabetes, cardiovascular diseases, as well as in allergic, immunological and inflammatory diseases [7]. Peptic ulcer is generally seen in HP infection, nonsteroidal anti- inflammatory drugs, systemic diseases, and stress [8-10]. No studies investigating the relations between peptic ulcer and Vitamin D deficiency in the child age group were found in the literature. Many factors that affect immunity also have effects on HP infection. One of these factors is Vitamin D. The purpose of the present study was to determine the relations between Vitamin D deficiency and HP presence and peptic ulcer.
Material and Methods
A total of 291 patients who admitted to the University of Health Sciences, Van Education and Research Hospital, Children’s Gastroenterology Clinic with recurrent abdominal pain and dyspeptic complaints, and who underwent gastric tissue biopsy with endoscopy of the upper gastrointestinal tract between April 2017 and April 2019 were included in the study.
The inclusion criteria for the study were age 1-18 years, the ability to undergo endoscopy of the upper gastrointestinal tract, no previous eradication therapy for HP, and volunteering to participate in the study.
Exclusion criteria for the study were as follows: 1) the use of drugs that might affect the metabolism of Calcium and Vitamin D (Calcium, Vitamin D, bisphosphonates, calcitonin, selective estrogen receptor modulators, anti-epileptic drugs, thyroid hormone drugs, steroids and colchicine); 2) the presence of liver and kidney disease, Cushing Syndrome, Diabetes Mellitus, thyroid diseases, bone diseases, rheumatological and autoimmune diseases that affect Vitamin D metabolism, 3) the use of proton pump inhibitors, H2 receptor blockers, bismuth compounds, and antibiotics in the last month; 4) previous gastric and intestinal surgeries; 5) being over the age of eighteen.
The demographic data (age, gender), and Vitamin D levels of all patients were documented, and 25(OH) Vitamin D levels in the blood were measured with Vitamin D Kit Electrochemiluminescence Method. Those whose laboratory data did not comply with the hospital standard values were not included in the study. Vitamin D values >20 ng/ml were evaluated as normal, and those under 20 ng/ml were evaluated as Vitamin D deficiency [11].
Endoscopy of the patients was performed in the Endoscopy Unit of Van Training and Research Hospital using a Fujinon EG530WR Endoscopy Device. All patients fasted for 6 hours before endoscopy. The patients were sedated with Midazolam 0.1 mg/kg and Ketamine 1 mg/kg after local pharyngeal xylocaine anesthesia, after which the endoscopic procedure was initiated. During endoscopy, the esophagus, cardia, fundus, corpus and antrum regions of the stomach were examined respectively in detail along with the duodenum. Endoscopic evaluations of the patients, the presence of esophagitis, the appearance of gastric mucosa, the appearance of bulbous and duodenum, the presence of peptic ulcer and endoscopic diagnosis were recorded.
The corpus, antrum, and duodenal biopsies that were taken endoscopically were sent to the pathology laboratory in 10% formaldehyde. After the routine tissue follow-up procedures, tissue samples were embedded in paraffin, cut into 5-micron sections, stained with routine Hematoxylin – Eosin (H-E), and were then evaluated under the light microscope. Then, the sections were stained with modified Giemsa to evaluate the presence of HP. Biopsies were reported according to the updated Sydney Classification (inflammation, activation, dysplasia, intestinal metaplasia, atrophy, and HP density).
The patients were divided into two groups as those with and without Vitamin D deficiency, and were compared in terms of age, gender, White Blood Cell (WBC), Hemoglobin (HBG), Platelet, Vitamin D levels, vitamin D deficiency, and the presence of HP. Also, Vitamin D levels, Vitamin D deficiency, and presence of HP were compared in patients with and without duodenal ulcer. Ethics statement
All participants provided written permission to participate in the study. The ethical approval was obtained from the Ethics Committee of our hospital for this study (Approval number 19/01, Van/Turkey). All procedures were in line with the ethical standards of the human testing committee of our institution and the Helsinki Declaration. Written informed consent forms were obtained from all participants, who were evaluated by a gastroenterologist and then included in the study.
Statistical Analysis
The normality of the distribution of continuous variables was tested by the Shapiro- Wilk test. The Mann-Whitney U test was used to compare 2 independent groups for non-normal data and the Chi-square test was applied to investigate the relationship between 2 categorical variables. Multivariate logistic regression analysis was performed to adjust the effect of gender from results. ROC curve analysis was performed to determine the diagnostic value of Vitamin D levels. Statistical analysis was performed with SPSS for Windows version 24.0 and a P -value < 0.05 was accepted as statistically significant.
Results
Among the 291 patients who were included in the present study, 197 (68%) were boys and 94 (32%) were girls. The mean age of the patients was 12.7±3.9 years. HP was detected in 199 (68%) patients. Vitamin D deficiency was detected in 121 (42%) patients. The mean Vitamin D level was 20.7±9 ng/ml in all patients.
The mean age of patients with Vitamin D deficiency was 15 years, and the mean age of patients with normal Vitamin D levels was 14 years; and 31/121 (26%) of patients with vitamin D deficiency were girls, and 90/121 (74%) were boys; 63/170 (37%) of patients without vitamin D deficiency were girls, and 107/170 (63%) were boys. Vitamin D deficiency was significantly higher in boys (P=0.040). HP positivity was detected in 85/121 (70%) of patients with vitamin D deficiency, and in 56/170 (33%) of patients without vitamin D deficiency. A total of 23/121 (19%) of patients with vitamin D deficiency had peptic ulcer, 15/170 (9%) of patients without vitamin D deficiency had peptic ulcers, and the difference was statistically significant (P=0.011) (Table 1).
Peptic ulcers were detected in 38/291 (13%) of the patients who were included in the study. When the patients with and without peptic ulcers were compared, the mean age in both groups was 14 years. The mean vitamin D level was 15.8 ng/ml in patients with peptic ulcer, and 23 ng/ml in patients without peptic ulcer; and the difference was statistically significant (P=0.003). In total, 23/38 (61%) of patients with peptic ulcer had vitamin D deficiency, vitamin D deficiency was detected in 98/253 (39%) of patients without peptic ulcer, and the difference was statistically significant (P=0.723). HP positivity was detected in 27/38 (71%) of patients with peptic ulcer, and in 172/253 (68%) in the group without peptic ulcer, and no statistically significant differences were detected in this respect (P=0.723) (Table 2).
ROC Curve Analysis was performed to evaluate the diagnostic value of vitamin D levels for peptic ulcer. Classification success according to the AUC (Area Under the Curve) value (0.651±0.04) was found to be low. As a result of the Roc Curve Analysis, the best cut-off value was determined when vitamin D was less than and equal to 21 ng/ml for peptic ulcer. The sensitivity of this value was 68.42% (95% CI=51.3-82.5), and specificity was 58.50% (52.2-64.6). When the effects of other variables were eliminated with Regression Analysis, the significant effect of vitamin D continued (P=0.001).
Discussion
Vitamin D is a powerful immunomodulator playing roles in both natural and acquired immunity. Vitamin D increases antimicrobial peptide production. It was reported that people with low vitamin D levels have higher rates of tuberculosis infection with more severe progression [12]. It was reported in previous studies that people with vitamin D receptor polymorphism were more prone to tuberculosis infections [13]. It was reported in another study that people who received vitamin D had a lower HP prevalence than the group that did not receive vitamin D [14]. It was reported in another study conducted in Italy patients with autoimmune gastritis had lower vitamin D levels and higher HP levels [6]. In a study that was conducted by Surmeli et al. in Turkey, it was reported that vitamin D levels were lower in HP (+) group than in HP (-) group [15].
Hamid Nasri et al. reported in their study that vitamin D serum levels had positive effects on chronic inflammatory status in chronic hemodialysis patients, strengthening the immune response [16]. In another study, Kouichi Hosoda et al. reported that vitamin D could eradicate HP infection [17]. Yildirim et al. reported that patients with vitamin D deficiency had lower HP eradication rates [18]. A study that was conducted by Guo et al. in China showed that vitamin D receptors were involved in gastric mucosa homeostasis with effects protecting from HP infection [19]. In our study, it was found that HP prevalence was at similar rates in the group with and without vitamin D deficiency. Contrary to the results of previous studies, we did not find any association between HP and vitamin D deficiency. It was reported in a previous study that vitamin D increases the tight connections between cells in cell cultures at significant levels, and maintains structural integrity. However, intestinal mucosal integrity is impaired in vitamin D receptor -/- mice. In the study in question, it was also reported that it can stimulate epithelium migration, playing critical roles in mucosal barrier homeostasis and maintaining the healing capacity of the colon epithelium [20]. Vitamin D stimulates cell differentiation, which is essential for cell growth and wound healing, reducing cell reproduction. Peptic ulcers are pathological lesions detected in the upper gastrointestinal tract and mucosa, and can go as deep as to the submucosa. HP also plays roles in many factors, such as increased stomach acidity, non-steroidal anti-inflammatory drugs, stress, and ‘O’ blood type.
In the study by Zubair et al., it was reported that diabetic foot ulcers were more frequent in patients with diabetes and patients with low plasma vitamin D levels [21]. In a study conducted by Burkiewicz et al. to compare patients with and without leg ulcers, it was found that patients with leg ulcers had lower vitamin D levels [22]. A study that investigated relations between vitamin D levels and pressure ulcers found significant relations between vitamin D deficiency and pressure ulcers [23]. It was reported in the study by Joachim et al. that vitamin D support accelerates wound healing in patients with diabetic foot ulcers, and patients with diabetic foot ulcers are at risk for vitamin D deficiency [24]. In the present study, the average vitamin D levels were found to be lower, and the prevalence of vitamin D deficiency was higher in the group with vitamin D deficiency compared to the group without vitamin D deficiency. However, in the ROC analysis, the specificity and sensitivity of vitamin D deficiency were found to be low for peptic ulcer. The prevalence of vitamin D deficiency increases since nutritional problems and absorption disorders are also common in gastrointestinal tract diseases. For this reason, we believe that vitamin D deficiency may occur due to nutritional problems and absorption disorder in patients with peptic ulcers.
Many factors, such as geographical location, seasons, air pollution, exposure to the Sun, and dressing affect vitamin D synthesis through the skin [25]. Since the season in which a study is conducted will also affect the results, our study was designed to cover all seasons. The strong side of our study was that it is the first study examining the relations between the prevalence of peptic ulcer and HP, and vitamin D that affect the gastrointestinal tract in childhood. The limitation of our study was that conditions, such as diet and exposure to the Sun, which might affect vitamin D levels, were not known since it had a retrospective design.
Conclusion
No relations were detected between vitamin D levels and HP prevalence. Since vitamin D levels may be lower in patients who have peptic ulcer, vitamin D levels must be examined in such patients.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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4. Mansournia N, Mansournia MA, Saeedi S, Dehghan J. The association between serum 25OHD levels and hypothyroid Hashimoto’s thyroiditis. J Endocrinol Invest 2014; 37:473-6.
5. Dogan E, Sevinc E. The vitamin D status and serum eosinophilic cationic protein levels in infants with cow’s milk protein allergy. Am J Transl Res. 2020; 12(12): 8208–15x.
6. Antico A, Tozzoli R, Giavarina D, Tonutti E, Bizzaro N. Hypovitaminosis D as predisposing factor for atrophic type A gastritis: a case-control study and review of the literature on the interaction of vitamin D with the immune system. Clin Rev Allergy Immunol. 2012;42(3):355-64.
7. Yin K, Agrawal DK. Vitamin D and inflammatory diseases. J Inflamm Res. 2014; 7:69-87.
8. Egbaria R, Levine A, Tamir A, Shaoul R. Peptic ulcers and erosions are common in Israeli children undergoing upper endoscopy. Helicobacter. 2008;13:62-8.
9. Tam YH, Lee KH, To KF, Chan KW, Cheung ST. Helicobacter pylori-positive versus Helicobacter pylori negative idiopathic peptic ulcers in children with their long-term outcomes. J Pediatr Gastroenterol Nutr. 2009;48(3):299-305.
10. Moll Harboe K, Midtgaard H, Wewer V, Cortes D. Development of a perforated peptic ulcer in a child during high dose prednisolone treatment. Ugeskr Laeger. 2012;174:2308-10.
11. Munns CF, Shaw N, Kiely M, Specker BL, Thacher TD, Ozono K, et al. Global consensus recommendations on prevention and management of nutritional Rickets. J Clin Endocrinol Metab. 2016; 101(2):394-415.
12. Nnoaham KE, Clarke A. Low serum vitamin D levels and tuberculosis: a systematic review and meta-analysis. Int J Epidemiol. 2008;37(1):113-19.
13. Jafari M, Nasiri MR, Sanaei R, Anoosheh S , Farnia P, Sepanjnia A, et al. The NRAMP1, VDR, TNF-α, ICAM1, TLR2 and TLR4 gene polymorphisms in Iranian patients with pulmonary tuberculosis: A case-control study. Infect Genet Evol. 2016;39:92-8.
14. Kawaura A, Takeda E, Tanida N, Nakagawa K, Yamamoto H, Sawada K, et al. Inhibitory effect of long term 1α-hydroxyvitamin D3 administration on Helicobacter pylori infection. J Clin Biochem Nutr. 2006;38(2):103- 6.
15. Surmeli DM, Surmeli ZG, Bahsi R, Turgut T, Oztorun HS, Atmis V, et al. Vitamin D deficiency and risk of Helicobacter pylori infection in older adults: a cross-sectional study. Aging Clin Exp Res. 2019;31(7):985-91.
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Endovascular treatment experiences on complex aorto-iliac aneurysms
Tanıl Özer, Mustafa Akbulut, Mustafa Mert Ozgur, Mehmet Aksut, Mesut Şişmanoğlu, Kaan Kırali
Department of Cardiovascular Surgery, Health Sciences University, Kartal Kosuyolu High Specialization Training and Research Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.20635 Received: 2021-04-05 Accepted: 2021-04-25 Published Online: 2021-04-30 Printed: 2021-05-01 Ann Clin Anal Med 2021;12(5):567-572
Corresponding Author: Tanıl Özer, Cardiovascular Surgery Department, Health Sciences University, Kartal Kosuyolu High Specialization Training and Research Hospital, Denizer Cad. Cevizli Kavşağı No: 2 Kartal, 34865 Istanbul, Turkey. E-mail: drtanilozer@gmail.com P: +90 2165001500 F: +902164596321 Corresponding Author ORCID ID: https://orcid.org/0000-0002-2701-2058
Aim: Nowadays, endovascular approach in abdominal aortic aneurysms has almost replaced open surgery. The strategy is common and relatively easy when it can be terminated in both common iliac arteries. Conversely, in cases where it has to be extended to the external iliac artery, the decision for additional intervention in the internal iliac artery is controversial. This study aimed to share our experiences on endovascular approaches to aorto-iliac aneurysms.
Material and Methods: This study included 28 patients who underwent EVAR, which was extended to the EIA. Anatomical shape of IIA, interventional success, presence of leakage, presence of complication related to IIA occlusion, and any time results were recorded and evaluated.
Results: The mean age was 68 + 9,3 (42–81) years with a higher male population (n: 24, 85,7%). Follow-up durations varied between 2 days and 26 months. In four patients, interventions were performed under emergency conditions. Iliac branched grafts were used for six patients. In three patients, IIA was occluded with occlusion devices. There was no transition to open surgical repair. Buttock claudication was seen in 8 patients (28,5%), and there was no new onset erectile dysfunction after occlusion of IIAs.
Discussion: AIAs may be treated with favorable results through endovascular approaches. Since decision- making will depend on the available devices in the clinic, treatment options can occasionally be changed. Therefore, learning different approaches might be helpful for practitioners.
Keywords: Abdominal aorta; Aortic aneurysm; Aorto-iliac aneurysm; Endovascular repair; Iliac artery
Introduction
Abdominal aortic aneurysms have a higher mortality risk with follow-up without any intervention when diameters exceed threshold [1]. In recent years, endovascular methods for aortic disorders have become more common than open surgeries [2]. Although open surgical repair (OSR) remains as a back- up technique for inappropriate anatomical situations, with increasing experiences, the rate of switching to open surgery has considerably decreased. Moreover, these experiences showed that some branches of major arteries also can be occluded without creating significant symptoms. Besides, some opinions were formed on how and when the occlusions can be performed. In some cases, particularly for the distal landing zone, extension to the external iliac artery (EIA) becomes inevitable. Thus, additional interventions may be necessitated to occlude or preserve the patency of the internal iliac artery (IIA), which has collateral branches to the pelvis and upper part of the lower extremities [3]. Consequently, the preferred intervention is related to the anatomical appropriateness of IIA, the content of the center, and the practice of performers. In this study, we would like to share our experiences on endovascular approaches to aorto-iliac aneurysms.
Material and Methods
From November 2015 to January 2020, 223 patients who underwent endovascular aortic repair (EVAR) for AAAs were retrospectively analyzed. Of these, 28 patients whose EVAR application needed extension to the EIA due to the absence of an appropriate distal landing zone at the common iliac artery (CIA) were included in the study. Those with aortic pathologies above iliac bifurcation were excluded. Approaches to the IIA while extending were evaluated. The anatomical shape of IIA, interventional success, the presence of leakage, the presence of complication related to IIA occlusion, and any time results were assessed. Two classifications which were mentioned in European Society for Vascular Surgery (ESVS) 2019 clinical practice guidelines on the management of abdominal aorto-iliac artery aneurysms were just used to simplify the visualization of the readers: Reber’s classification was used for the definition of the anatomical structure of CIA, while Fahrni’s classification was used in considering the options for intervention to IIA (4,5). The success of the intervention was mentioned for the usage of any iliac branched graft (IBG) and defined as the ability to completely place the IBG. Any type of endoleak was included if it was present. Complications related to IIA occlusion were identified as follows: new onset erectile dysfunction, buttock claudication, and ischemia of the colon, which was proved with radiologic imaging.
Informed consent forms to share their data, excluding personal identification information, were obtained from all patients who participated in this study. The study protocol was approved by the Institutional Clinical Trial Review Board of Health Science University Kartal Kosuyolu High Specialization Training and Research Hospital (2020.4/27-332). The study was conducted in accordance with the principles of the Declaration of Helsinki. Statistical Analyses:
Statistical analyses were performed using the SPSS version23 software (IBM Inc, Armonk, NY). The Kolmogorov–Smirnov and
Shapiro–Wilk tests were used to assess the normality of the variables. Continuous variables were expressed as mean± 1 standard deviation, and categorical variables as percentages.
Results
The mean age of the patients was 68 + 9,3 (min: 42 – max: 81) with the male population generally higher than that of females (n:24, 85,7%; n:4, 14,3%). The most frequent features of patients were smoking (n:14, 50%) and hypertension (n:10, 35,7%) and coronary artery disease (CAD) (n:9, 32,1%) (Table 1). Three of the patients were treated for primarily iliac artery aneurysm (IAA) as the AAAs have not reached the interventional threshold yet. The IAA was mostly seen bilateral (n:018 (64,2%), and the mean CIA diameter was approximately the same for both right and left sides (31,9+15,2 mm; 29,9+17,5 mm) (Table 2). While the iliac arteries were assessed separately, the anatomical structures of the CIA were mostly similar with type 1 according to Reber’s classification (n: 24, 42,8%). The structural assessment of IIAs for any intervention was mostly appropriate with type 1b of Fahrni’s classification (n: 36, 62,2%) (Table 2). In four patients, interventions were performed under emergency conditions. IBGs were used in six patients [1 x Gore Excluder IBE (W. L. Gore and Associates, Flagstaff, Ariz), 5 x E-liac (JOTEC, Hechingen, Germany)]. While introduction of IBG to one patient was not successful due to anatomical difficulties, bilateral introduction was performed successfully to another patient (Figure 1). Bilateral IIA occlusions were performed in 6 patients, and the most used method for occlusion was the extension of stent graft to EIA without any occlusion devices. The vascular plug was used in only three patients, while the coil was not used in any patient. Switching to OSR was not needed, and concomitant interventions were required for three patients. These additional interventions were embolectomy (n:2) and stent implantation to EIA due to kinking of the extended stent graft caused by massive angling of EIA. Only four patients’ interventions were completed with the presence of endoleak, which could be seen in an angiographic view. Three patients had type 2 endoleak, and one patient whose IBG implication was considered unsuccessful had type 3 endoleak (Table3).
All patients were discharged from the hospital. The mean length of ICU stay was 1,17 + 0,49 days (min: 1 – max: 3), and the mean length of hospital stay 3,69 + 1,55 days (min: 2 – max: 7). During follow-up, 3 patients had an endoleak: one type 1b (Figure 2), one type 2, and one type 3. The new onset erectile dysfunction occurred in only one patient. This patient was the one whose bilateral IIAs were protected with IBGs. Buttock claudication was seen in 8 patients, and only one of them lasted more than 2 months.
Six patients underwent re-intervention at any time during the follow-up. Procedures performed were as follows: embolectomy and stent implication to extended stent graft at postoperative day 2 (n:2), extension with a stent graft after 14 months due to enlargement of CIA (n:1), stent implication to extended stent graft due to kinking at the stent graft (n:1), cross femoral bypass (n:1), and coil embolization to the collateral branch, which caused type 2 endoleak (n:1) (Figure 3).
The duration from performing the case to last CTA control ranged from 2 days to 26 months.
Discussion
With the increase in the technological infrastructure and experiences of physicians, the use of endovascular methods in AAAs has become more frequent than OSR [2].
According to the ESVS guideline, which was published last year, EVAR had a lower mortality rate compared with both the OSR and no-intervention groups among patients with reasonable life expectancy and suitable anatomy [6].
Performing EVAR applications may be relatively easier if the patient’s anatomy is in accordance with the manufacturer’s instruction for use (IFU). This appropriateness means that the presence of proper sealing zones for both the distal and proximal parts without significant angulations. However, it is known that approximately 10% of AAAs are present with IAAs and are called aorto-iliac aneurysms (AIA) [7]. In our clinic, we met a little more frequently with 12,5% (28/223).
Aorto-iliac aneurysms mainly have to overcome two issues when placing the distal legs of the stent grafts: first is about the landing zones, and the second one is about IIA. Despite these debates, endovascular repairs, whose advantages have been commonly mentioned in publications, became more preferable than OSR due to the higher risk for pelvic structure injury during challenging exploration of IIAs [8,9].
Several techniques have been described to ensure IIA openness during EVAR [10]. The bell-bottom technique (also called flared limb technique) is preferred when the maximum CIA diameter does not exceed 26 mm. Although it is an easy technique compared to others, it is applied assuming that the main iliac artery is healthy. However, the risk of the requirement to re- intervention or rupture due to continuing enlargement of the CIA limits the preference for this technique. This technique may be preferable to reduce the operation time and radiation exposure, especially for elderly patients [11]. In this study, the bell-bottom technique has been used for two patients. Both patients had bilateral IAAs, while only one side was appropriate for the bell- bottom technique (Reber’s type 1, Fahrni’s 1b). We preferred this technique to both patients, not only to preserve openness of the IIA, but also to avoid possible kinking due to a very narrow angulation. One of these patients underwent iliac extension with a stent graft as a re-intervention due to enlargement of the CIA after 14 months, while the comparatively young one (58 years) had no re-intervention. Consequently, in our opinion, the bell-bottom technique may be considered when the existence of massive tortuosity or angulations restricts extension to EIAs. Other methods, which require additional tools and accesses, are thought that all segments of AIA can be excluded while preserving the IIA’s patency [12-14]. Among these techniques, IBG has been gaining popularity in recent years owing to be the most appropriate with natural anatomy and can be applied via the same femoral accesses [15]. On the other hand, their restriction includes the requirement to comply with the IFU of manufacturers such as all endovascular devices. A study by Muzepper et al. evaluated the anatomical suitability of two different brands of IBGs with Chinese [16]. According to their study, only 20.6% of Chinese patients were eligible for IBGs. It is obvious that this study had significant limitations due to not including all brands in the market. However, in many clinics, the provision of treatment strategies can be limited, since product supply is provided through periodic contracts. Thus, similar limitations might implicate practitioners while decision- making. IBG was performed to 6 patients, and the E-liac stent grafts were used 5 times. While the application techniques of both devices were very similar, diameter ranges were wider at Gore Excluder IBE, which turned out to be an unsuccessful case. This patient has been surviving for more than 2 years with a type 3 endoleak, which was tried to be resolved with extension with another stent graft as a re-intervention one month after the first case. We also experienced the application of IBGs bilaterally to a patient This patient was a very active 64-year- old male, and we considered to try to preserve both sides of the IIA to minimize the erectile dysfunction (ED) and buttock claudication (BC) risks, which were the most frequently seen uncomfortable complications after IIA occlusion [17]. Although bilateral placement of IBGs has been successfully performed and patency of bilateral IIAs was secured, interestingly the patient suffered with new-onset ED. ED, which is associated with many causes, may develop after EVAR, which is not related to IIA occlusion.
Endovascular treatment strategies of AIAs originally involved occlusion of IIA and extension to EIA with a stent graft. The occlusion of IIA has collateral branches that supply the pelvic viscera, and also some muscle groups in the buttocks and thighs may cause disruption of the circulation. Thankfully, although these possible ischemic complications seemed serious, these are seen very rarely owing to pelvic collateral circulation [18,19]. In our experience, eight patients encountered BC, while only one of them complained that it lasted for more than two months. Serious ischemic complications related to occlusion of the IIA were not observed.
The occlusion of the IIAs was another issue during extension to EIAs for endovascular treatment of AIAs. These can be achieved with plug, coil, or coverage alone. Fahrni et al. suggested a classification with a study in 2003 about occlusion options for IIA when the extension to EIA was needed [4]. In this study, although we did not meet treatment options, we used this classification to give an idea in terms of anatomical suitability. Additionally, we have never used any coil to occlude any segment of IIA during EVAR procedures. Tefera et al. in their publication in 2004 showed that the coverage alone without a coil effectively created embolization with even lesser complication rates [20]. The vascular plug was used in only three patients whose IIA orifice seemed wide. On the other hand, with increasing experience, performing occlusion with coverage alone is encouraged for most situations. Additionally, only 2 patients had a type 2 endoleak related to IIA, with spontaneous resolutions, which occurred in 2 months without causing sac expansion.
Since the resolution of type 2 endoleaks mostly occurs spontaneously, following minimal type 2 endoleaks with a conservative approach is recommended until the expansion of sac diameter reaches 1cm threshold [21]. While type 2 endoleaks in 2 patients spontaneously thrombosed, the other type 2 endoleak lasted 20 months in a patient whose bilateral IIAs were preserved with IBGs. This patient also was under warfarin treatment due to mechanical aortic valve replacement history. Consequently, this endoleak, which originated from the collateral artery between the IIA and lumbar artery, was followed through so that the enlargement did not reach 1cm, until a deterioration at graft configuration occurred. This endoleak was occluded with a coil through the left IIA percutaneously. Hereby, it might be considered that the preservation of IIA enabled us to perform this intervention through trans-arterial approach. Accordingly, this situation may be counted as another advantage of preserving IIA during EVAR.
Although experts have recommended that type 1 and 3 endoleaks should be resolved promptly [6], 2 patients in this study had endoleaks type 1b and type 3 as far as we know. The patient who was already mentioned above with an unsuccessful implantation of IBG had a type 3 endoleak. This patient was under close follow-up, and the endoleak did not cause expansion at AAA or IAA.
Another patient with type 1b endoleak underwent emergency surgery. Although the last control with digital subtraction angiography (DSA) showed successful deployment of the stent graft with extensions to both EIAs, migration proximally from the distal sealing zone, causing type 1b endoleak, was observed with CTA two days later. Thus, although additional contrast usage was needed at a very close time intervals, CTA control might be considered promptly after the intervention, if it cannot be determined accurately prior to the intervention due to emergency conditions. On the other hand, since this patient did not give consent, no further attempts could be made to resolve the problem. To the best of our knowledge, this patient still lives with a current endoleak outside our follow-up.
Additional interventions, which include switching to OSR, may be needed during primary case or follow-up periods. Among patients whose vascular structures were affected by several comorbidities like age, atherosclerosis, etc., the risk for additional or re-interventions may increase with a strong relationship with anatomic disruptions [22]. In this study, switching to OSR was not necessary, while two patients underwent additional femoral embolectomy. Additionally, except for the re-interventions mentioned above, our re-intervention experiences included iliac occlusions due to stenosis and kinking of iliac extensions. Particularly, kinking might be predicted using 3D-converted images when planning treatment strategies. Otherwise, the stiff wires may mislead performers to flatten its tortuosity, which assumed that favorable results were obtained during DSA imaging. In addition, adjunctive stenting to narrow angled part as prophylaxis might be a good idea particularly for high- risk patients [23].
In conclusion, AIAs could be treated with favorable results via endovascular approaches.
To preserve the patency of IIA with any technique may be the first target for the patients with suitable anatomy. However, occlusion of IIAs, even with just extended stent graft, does not has significantly worse outcomes than preserving clinical results. Additionally, evaluation with multi-planar reconstruction and 3D imaging before interventions should be considered to predict possible issues and develop strategies to overcome such issues. Since decision- making will depend on the available devices in the clinic, treatment options can occasionally be changed. Therefore, learning different approaches might be helpful for practitioners.
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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Does infertility trigger fibromyalgia in women?
Nur Dokuzeylül Güngör 1, Arzu Yurci 2
1 Department of Obstetrics Gynecology and Reproductive Medicine, Medical Park Göztepe Hospital, Istanbul, 2 Department of Obstetrics Gynecology and Reproductive Medicine, Memorial Hospital, IVF Center, Kayseri, Turkey
DOI: 10.4328/ACAM.20638 Received: 2021-04-03 Accepted: 2021-04-18 Published Online: 2021-04-28 Printed: 2021-05-01 Ann Clin Anal Med 2021;12(5):573-576
Corresponding Author: Arzu Yurci, Department of Obstetrics Gynecology and Reproductive Medicine, Memorial Hospital, IVF Center, Gevher Nesibe Mahallesi Çiçek Sokak No 10, 38010, Kocasinan, Kayseri, Turkey. E-mail: arzuyurci@yahoo.com P: +90 5334247890 Corresponding Author ORCID ID: https://orcid.org/0000-0003-4808-9019
Aim: Fibromyalgia syndrome (FS) is a syndrome identified by dispersed body pain, with a prevalence of 0.5% in men and 3.4% in women. This study aims to assess the association between infertility in women and fibromyalgia.
Material and Methods: To participate in this study, 476 patients referred to our hospital were selected. The study group consisted of 230 infertile participants, and the control group consisted of 246 fertile participants. The participants were examined and 43 of them were diagnosed with FS according to the 2010 ACR criteria. General information about the participants was received, and their BMI was measured. Participants responded to the Common pain scale (YGAS), Symptom Severity Scale (SSS), and Fibromyalgia Impact Questionnaire (FIQ).
Results: The age of the participants ranged from 20 to 45, with a mean of 29.5 (±5.05) years. The participant’s BMI range was 20 to 29.8, with a mean of 24.7 (±2.4). The common pain scale in the study and control groups was 4.24 (±2.3) and 3.3 (±1.7), respectively. The difference in this variable between the two groups was significant (P-value= 0.000). The symptom severity scale in the study and control groups was 2.4 (±1.3) and 1.6 (±1.06), respectively. The difference in this variable between the two groups was significant (P-value= 0.000). The Fibromyalgia Impact Questionnaire score for fertile participants ranged from 30 to 70, with an average of 53 (±14.8). There was no significant difference between the groups.
Discussion: Our results showed that infertile women have more fibromyalgia symptoms than fertile women. This result may indicate an association between fibromyalgia and infertility.
Keywords: Infertility; Fibromyalgia; In vitro fertilisation
Introduction
Fibromyalgia syndrome (FS) is a syndrome identified by dispersed body pain, with a prevalence of 0.5% in men and 3.4% in women [1]. Like most chronic diseases, the etiology of this condition is unclear, but recent studies on the existence of disorders of the central nervous system confirm the existence of this disorder as a specific and chronic disease [2]. Usually, the first and most common symptom of this condition is body pain, and fatigue, sleep, and cognitive disorders are other symptoms of this condition [3]. Fibromyalgia is a complex and multifaceted disease with an unpredictable course [3]. Since the response to treatment and tolerance varies from patient to patient, treatment is a clinical problem for physicians and patients [1,2].
In 1990, the American College of Rheumatology (ACR) defined fibromyalgia syndrome based on an analysis of approximately 300 variables, such as physical signs and examinations and radiographic and laboratory findings, and proposed diagnostic criteria [4]. Fibromyalgia is essentially based on chronic pain that cannot be explained by an inflammatory or degenerative musculoskeletal disorder [5]. The ACR also found that many disorders are associated with fibromyalgia, including sleep disorders, fatigue, paresthesia, anxiety, headaches, and defecation [4].
Pregnancy is associated with weight gain and increased hormonal fluctuations, which puts pressure on various body systems and worsens fibromyalgia [6]. Many women often experience pain and discomfort, memory problems, and other signs and symptoms during this period that are very similar to fibromyalgia during pregnancy [6]. A pregnant woman with fibromyalgia may find that physical and emotional stress can worsen the signs and symptoms of the disorder [7]. Pregnant women with fibromyalgia experience pain, fatigue, and stress, which are common during the first and third trimesters [8]. Despite all these complications, the number of pregnant women with fibromyalgia who give birth to healthy babies is considerable [9], and the risk of infertility is a debatable issue in women with fibromyalgia.
However, studies, which shown a link between fibromyalgia and infertility are limited, and most studies in this area have focused on the relationship between fibromyalgia and female sexual function. This study aims to assess the association between infertility in women and fibromyalgia.
Material and Methods
From January 2020 to December 2020, 476 patients referred to our hospital were selected to participate in the study. The exclusion criteria were patient reluctance to participate in the study, systemic diseases, severe infections, and comorbidities associated with pregnancy. The participants were examined, and 43 were diagnosed with FS according to the 2010 ACR criteria. General information about participants was received, and their BMI was measured. Participants responded to the Common pain scale (YGAS) and Symptom Severity Scale (SSS) questionnaires. The SSS evaluates the symptoms by severity, frequency, time, and type, consisting of 11 questions with multiple-choice responses, scored from 1 point (mildest) to 5 points (most severe). We also considered a Total variable, which was the sum of two questionnaires, YGAS and SSS. Participants diagnosed with FS also answered the Fibromyalgia Impact Questionnaire (FIQ). FIQ was introduced by Burckhardt et al. in 1991 to assess the effect of the disease on patients’ pain, quality of life, fatigue, and well-being [10].
The study group consisted of 230 infertile participants, and the control group consisted of 246 fertile participants. The information of infertility duration, infertility cause, and ovarian reserve of infertile participants was obtained. Ethics approval was obtained from the institutional review board (approval number: 4, date: 16/01/2021). The entire study procedure was conducted in accordance with the Helsinki Declaration, and the necessary approvals were obtained from the Ethics Committee. The Kolmogrov test was used to show that quantitative variables were normally distributed. The Mann-Whitney test was used to examine the differences between the fertile and infertile groups. An independent samples t-test was used to compare Fibromyalgia Impact Questionnaire scores for fertile and infertile groups. For all tests, a significance level of 0.05 was considered. Data were analyzed using SPSS for Windows, Version 23.0 (Armonk, NY: IBM Corp).
Results
Out of 476 participants in this study, 230 were included in the study group (infertile), and 246 were included in the control group (fertile). The age of the participants ranged from 20 to 45, with a mean of 29.5 (±5.05) years. The participant’s BMI range was 20 to 29.8, with a mean of 24.7 (±2.4). The common pain scale range was 2 to 13, with a mean of 3.7 (±2.09). The symptom severity scale range was 1 to 7, with a mean of 2.02 to 1.2. Among the participants, 43 were diagnosed with FS for these participants, the Fibromyalgia Impact Questionnaire scores ranged from 30 to 75, with a mean of 53.6 (±12.05). In the study group, infertility time was assessed based on the number of infertility years, ranging from 1 to 13, with a mean of 4.1 (±2). Also, for the infertile group, the cause of infertility frequency for endometriosis, inexplicable, male factor, ovulatory dysfunction, and tubal was 23 (±4.8), 51 (±10.7), 78 (±16.4), 42 (±8.8), and 36 (±7.60, respectively. Descriptive Statistics of the patients are given in Table 1.
The results of the Klomogrov test show that not all quantitative variables were normally distribution. The Mann-Whitney test was used to examine the differences between the Fertile and Infertile groups. The comparison of the study and control groups according to fibromyalgia status is given in Table 2.
As shown in Table 2, the mean age for the study group was 29.5 (±5.5) and 29.6 (±4.5) for the control group. The measured BMI for the study and control groups was 24.6 (±2.4) and 24.8 (±2.4), respectively. There was no significant difference between the age and BMI of fertile and infertile groups (P-values = 0.2 and 0.5, respectively). The common pain scale in the study and control groups was 4.24 (±2.3) and 3.3 (±1.7), respectively. The difference in this variable between the two groups was significant (P-value= 0.000). Also, the Symptom severity scale in the study and control groups was 2.4 (±1.3) and 1.6 (±1.06), respectively. The difference in this variable between the two groups was significant (P-value= 0.000). The total variable, which was the sum of two YGAS and SSS variables, was also significantly different in the two groups (P-value= 0.000). Three variables associated with fibromyalgia had higher values in the infertile group. This result shows that the infertile group had more symptoms of fibromyalgia than the fertile group.
As shown in Table 3, the infertile participants’ scores on the Fibromyalgia Impact Questionnaire ranged from 30 to 68, with a mean of 52.4 (±10). The score for fertile participants ranged from 30 to 70, with an average of 53 (±14.8). There was no significant difference between the fertile and infertile groups in the effect of FS on the quality of life of the participants (P-value = 0.893).
Discussion
FS is a chronic disease in which the patient experiences somatic symptoms and diffuse sensitivities. Following the introduction of the disease by the ACR in 1990 and the introduction of new criteria in 2010, researchers became interested in the disorder. In this study, the 2010 ACR criteria were used to diagnose FS. FS is more common in females in general, especially during childbearing years, and can have a negative impact on patients’ quality of life [11]. Studies in this area have focused on the effects of FS on pregnant women, but in this study, we examined the relationship between FS and infertility. Our results show that infertile women have significantly higher FS- related scores, which means that people with FS are more likely to be infertile. The findings of our study were consistent with the findings of Schochat and Beckmann [12]. In this study, the authors found a correlation between FS, reduced fertility, and late menarche.
In a similar study, Shakir, Badr [13] examined FS in infertile Iraqi women. The study included 202 infertile Iraqi women, and the results showed that the prevalence of FS was significantly higher in infertile Iraqi women than in the general population. These results are consistent with the results obtained in our study. Our results showed that FS symptoms are more common in infertile women compared to the fertile populations. Another study found that women who reported FS had higher infertility rates [14]. This study concludes that the presence of FS may be an influential factor in female infertility. Our results also showed that FS symptoms are more common in infertile women, and this result can be interpreted as a correlation between FS and infertility.
Since FS is not directly related to the reproductive system, and infertility is a complex issue and is influenced by various factors, many factors affect this relationship. For example, many studies have examined the relationship between FS and endometriosis [15-17]. Endometriosis is a condition in which cells similar to the uterus’ lining cells grow outside the uterus [16]. This condition can cause infertility [17]. Studies have shown that women with endometriosis are significantly more exposed to FS [15-17].
Studies have shown that psychological factors such as stress and anxiety can also play a role in infertility [18,19]. Since research has shown that fibromyalgia increases stress levels in patients [18-20], FS can also indirectly affect infertility. Environmental stress in women is one of the important factors in reducing ovulation and infertility [20]. It is important to consider that the mother’s body must be emotionally, mentally, and physically ready to accept the child’s stress and responsibilities. The mother should try to reduce her stress during and after pregnancy to reduce the severity of signs and symptoms of depression [19].
Studies have shown that there is a possible link between fibromyalgia and the following disorders: 1) intrauterine growth restriction (IUGR), in which fetal growth is restricted in the mother’s uterus and causes the fetus to be small; 2) Recurrent miscarriage 3) Polyhydramnios where the level of amniotic fluid is very high. FS is also associated with preterm birth, congenital disabilities, fetal overgrowth, and stillbirth [6,7].
Hormonal disorders can also have a great impact on infertility in women. Female hormones play a very important role in the menstrual cycle [5]. Deficiency in the production of these hormones, production rate, the balance between hormones, and defects in the organs producing these hormones can cause infertility in women. In patients with fibromyalgia, several disorders regulating the hormones such as the hypothalamus, pituitary, and adrenal glands have been observed [21-24]. These factors can also cause indirect effects of FS on infertility. Many other factors can also affect this relationship. Unfortunately, the research done to identify the relationship between fibromyalgia and infertility is very limited. To investigate this relationship, more studies should are needed taking into account psychological factors, hormonal levels, and various reproductive disorders. The results of this study indicate the association between fibromyalgia and infertility, which can be used as a basis for future studies in this field. Conclusion
In this study, the association between fibromyalgia and infertility was investigated. Our results showed that infertile women have more fibromyalgia symptoms than fertile women. This result may indicate an association between fibromyalgia and infertility. Further studies are needed to evaluate the influencing factors and how they affect this relationship.
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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Nur Dokuzeylül Güngör, Arzu Yurci. Does infertility trigger fibromyalgia in women? Ann Clin Anal Med 2021;12(5):573-576
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The relationship between inflammation and hematological parameters in chronic kidney disease
Recep Demirci 1, Kamuran Sanli 2, Can Sevinc 3
1 Department of Nephrology, Kanuni Sultan Süleyman Research and Training Hospital, Istanbul, 2 Department of Microbiology and Clinical Microbiology, Kanuni Sultan Süleyman Research and Training Hospital, Istanbul, 3 Department of Nephrology, Ataturk University Faculty of Medicine, Erzurum, Turkey
DOI: 10.4328/ACAM.20642 Received: 2021-04-06 Accepted: 2021-04-28 Published Online: 2021-04-30 Printed: 2021-05-01 Ann Clin Anal Med 2021;12(5):592-596
Corresponding Author: Can Sevinc, Ataturk University Faculty of Medicine, Department of Nephrology, Erzurum, Turkey. E-mail: can.sevinc@atauni.edu.tr P: +90 5346157812 Corresponding Author ORCID ID: https://orcid.org/0000-0002-4069-9181
Aim: The progression of Chronic Kidney Disease (CKD) is closely related to systemic inflammation and oxidative stress. This situation causes malnutrition, atherosclerosis, coronary artery calcification, heart failure, anemia, mineral and bone disorders, increasing mortality and morbidity. An increased number of leukocytes and their subtypes is a feature of the inflammatory process. The neutrophil- lymphocyte ratio (NLR), derived from leukocyte counts has been shown to be a strong indicator of acute and chronic inflammation, associated with cardiovascular risk. In our study, it was aimed to investigate the relationship between hematological parameters and Glomerular Filtration Rate (GFR) and proteinuria, which is an indicator of inflammation, in patients with CKD stage 3-5 without dialysis treatment.
Material and Methods: In the study, patient files were analyzed retrospectively. Patients with diabetes mellitus, active infection, malignancy, obesity, taking lipid and uric acid-lowering drugs, taking thyroid hormone replacement, and uncontrolled hypertension were not included in the study. A total of 178 patients (96 (53.9%) females, 82 (46.1%) males) and 20 healthy controls (12 (60%) females and 8 (40%) males) were included in the study. Patients were compared with the control group in terms of CKD stages, median values of hematological parameters and proteinuria status.
Results: A significant difference was found between the patient group and the control group in the neutrophil-lymphocyte ratio (NLR) and lymphocyte- mono- cyte ratio (LMO). While the GFR and albumin values were significantly lower in patients with proteinuria, the NLR values were found to be significantly higher. Correlation analysis revealed a positive correlation between the NLR value and proteinuria and ferritin, and a negative correlation with GFR and albumin.
Discussion: NLR, which is an easily applicable and inexpensive method, can be used as an indicator of proteinuria and inflammation in predialysis CKD. Although it seems to be usable in other hematological parameters, comprehensive studies are needed.
Keywords: Hemogram; Inflammation; CKD; Proteinuria
Introduction
Chronic Kidney Disease (CKD) is a global public health problem with significant mortality and morbidity. The progression of CKD is closely related to systemic inflammation and oxidative stress. This condition causes malnutrition, atherosclerosis, coronary artery calcification, heart failure, anemia, mineral and bone impairment, increasing mortality and morbidity [1]. Inflammation is a complex biological response of vascular tissue to injury, infection, ischemia, and autoimmune diseases. In physiological conditions, the inflammatory response provides removal of the cause and initiates the healing process. Various cytokines and acute phase proteins are released to increase or decrease the inflammatory response. As a result, levels of positive acute phase reactants such as C-reactive protein (CRP) increase, while levels of negative acute phase reactants such as albumin decrease [2]. While this continuous inflammation seen in CKD is inversely proportional to kidney function, it is positively proportional to the amount of proteinuria. Studies have shown that inflammation is more common in cases of lower kidney function and higher proteinuria with an increased cardiovascular risk [3,4]. An increased number of leukocytes and their subtypes is a feature of an inflammatory process. The neutrophil- lymphocyte ratio (NLR), derived from the leukocyte count, has been shown to be a strong indicator of acute and chronic inflammation and is associated with cardiovascular risk [5]. Likewise, the platelet lymphocyte ratio (PLR) has been shown to be associated with significant cardiovascular outcomes [6]. Again, in a meta-analysis, it was stated that high NLR in patients with CKD was associated with all-cause and cardiovascular mortality [7]. In our study, in the light of all these data, it was aimed to investigate the relationship between hematological parameters and Glomerular Filtration Rate (GFR) and proteinuria, which is an indicator of inflammation, in patients with stage 3-5 CKD who did not receive dialysis treatment.
Material and Methods
The files of patients who applied to the Nephrology Policlinic were retrospectively analyzed. Patients over 18 years of age with a diagnosis of CKD were included in the study. Patients with diabetes mellitus, active infection, malignancy, obesity, taking lipid and uric acid-lowering drugs, taking thyroid hormone replacement, and uncontrolled hypertension were not included in the study. As a control group, healthy volunteers who do not have any known illnesses, and who do not use regular medication and do not use alcohol or smoking were included. Patients’ demographic data such as age, gender, chronic diseases, medications used, body mass indexes (BMI) were scanned from the follow-up files of the patients.
Biochemical Analysis:
Complete blood count (hemogram), blood urea nitrogen (BUN, mg / dL), creatinine (mg / dL), sodium (Na, mmol / L), potassium (K, mmol / L) taken during routine outpatient clinic controls, calcium (Ca, mg / dL), phosphorus (P, mg / dL), magnesium (Mg, mg / dL), uric acid (mg / dL), albumin (g / dL), total protein (gr / dL), total cholesterol (mg / dL), triglyceride (TG, mg / dL), low density lipoprotein (LDL, mg / dL), high density lipoprotein (HDL, mg / dL), CRP (mg / L), ferritin (ng / mL), free triiodothyronine (FT3, pg / mL), free thyroxine (FT4, ng / dL) and thyroid stimulating hormone (TSH, μIU / mL), 25 OH vitamin D (ng / mL) and parathyroid hormone (PTH, pg / mL) values were recorded. Protein excretion of the patients was calculated by dividing the total amount of protein in the spot urine by the amount of creatinine. GFR was calculated using the MDRD formula (MDRD formula = 170 x (serum Cr) -0.999 x (age) -0.176 x (0.762 if patients are female) x (1.180 if patients are black) x (serum BUN) -0.170 x [(Albumin) + 0.318]). NLR, absolute neutrophil count divided by lymphocyte count, PLR, platelet number divided by lymphocyte number, neutrophil to monocyte ratio (NMR), neutrophil count divided by monocyte and lymphocyte to monocyte ratio (LMR) was calculated by dividing the lymphocyte count by the monocyte count. The necessary ethics committee approval was obtained for the study (Erzurum BEAH KAEK Decision No: 2021 / 04-69). Statistical analysis:
The data were evaluated using the IBM SPSS Statistics 22 program. The compliance of the variables to normal distribution was examined by visual (histogram and probability graphs) and analytical methods (Kolmogorov-Smirnov/Shapiro-Wilk tests). Descriptive analyzes were performed using means and standard deviations for normally distributed variables. While analyzing the data, independent groups t- test (Student’s t-test) was used to compare two groups, and the Mann-Whitney U test was used if the conditions were not met. With one-way analysis of variance and Tukey HSD test, one of the multiple comparison tests, for comparing three or more groups, when the conditions were not met, the Kruskal-Wallis and Bonferroni-Dunn test from multiple comparison tests were used. Chi-square and Fisher Exact’s test methods were used in the analysis of categorical data. A p-value less than 0.05 was considered statistically significant. Receiver Operating System (ROC) curve analysis was performed for diagnostic decision-making features. The existence of significant limit values, sensitivity and specificity values of these values were calculated. Then, a logistic regression analysis of these cut-off values was performed.
Results
A total of 178 patients (96 (53.9%) females, 82 (46.1%) males) and 20 healthy controls (12 (60%) females, 8 (40%) males) were included in the study. The mean age of the patient group was 59.2 ± 14.3 years, and the mean age of the control group was 36 ± 9.4 (p <0.001) years. While the NLR value was found to be statistically significantly higher in the patient group, the LMR value was found to be significantly lower (p <0.001, p <0.001). There was no significant difference between PLR and NMR. The Stage-3 CKD group and control group were compared. The mean age of the patient group was 60 ± 14.9 years, which is significantly higher than the average age of the control group (p <0.001). Uric acid, CRP, triglyceride and NLR levels of the patient group were found to be significantly higher, and albumin, LMR and FT3 levels were found to be significantly lower (p <0.001).
The patients were then compared with each other according to their stages. There was no significant difference between the ages of the patients (p = 0.293). As the stage of the patients increased, albumin, hemoglobin, 25-OH vitamin D and
FT3 levels were found to be significantly lower. A significant difference was found between the NLR levels of Stage-3 and Stage-5 patients and Stage-4 and Stage-5 patients (p = 0.003, p = 0.019, respectively). However, no significant difference was found between the other parameters, PLR, NMR, LMR, MPV and CRP values. Comparison of patient data according to stages is given in Table1.
The median values of the hematological parameters of the patients were determined. The median value for NLR was 2.8, 129 for PLR, 9.1 for NMR, 3.1 for LMR and 10.5 for MPV. The patients were then compared according to these median values. While albumin and LMR values were significantly lower in patients with NLR values of 2.8 and above, proteinuria, ferritin, PLR and NMR values were found to be significantly higher. However, no significant difference was found in GFR and CRP values. NLR values were found to be significantly higher in patients with a PLR of 129 and above, while the albumin and MPV values were found to be significantly lower. NLR values and proteinuria levels were found to be significantly higher in patients with NMR value of 9.1 and above. The comparison of the patients according to the median values for hematological parameters is given in Table 2.
Patients were divided into two groups, with and without proteinuria and compared. While the GFR and albumin values of patients with proteinuria were found to be significantly lower, NLR values were found to be significantly higher. Comparative data are given in Table 3.
In correlation analysis with hematological parameters, positive correlation was found between NLR value and proteinuria (r= 0.242, p= 0.020) and ferritin, and negative correlation with GFR and albumin. There was a negative correlation between PLR value and albümin (r= -0.367, p < 0.001).
As a result of the ROC analysis performed for the diagnostic value of NLR in predicting proteinuria, this value was found to be 2.4 (AUC:0.906, 95% C.I. 0.838-0.974, Sensitivity 83%,
Specificity 79%). In the subsequent logistic regression analysis, it was determined that NLR being 2.4 and above increased the probability of proteinuria 18 times (95% C.I. 5.110-64.284, O.R: 18.125, Wald: 20.119).
Discussion
The relationship between CKD and cardiovascular disease has been known for a long time. Current guidelines recommend that patients with CKD be considered at high cardiovascular risk [8]. Studies have shown that inflammation seen in the course of CKD has an important role in the progression of both cardiovascular disease and kidney disease [9,10]. The presence of proteinuria or albuminuria in urine has obvious clinical significance as an early indicator of underlying renal pathology, before a concrete decline in renal filtration function. In addition to its role as a marker for CKD risk, it is now widely accepted that proteinuria is an independent predictor of cardiovascular morbidity and mortality in different populations [11, 12]. The white cell count in peripheral blood is a well-known marker of systemic immunoinflammatory activity. In recent studies, NLR has been shown to be a powerful indicator in determining inflammation in cardiac and non-cardiac diseases. These studies confirm a strong association of NLR with the progression of end-stage renal failure (ESRD), especially in CKD patients. Therefore, monitoring proteinuria has an important role in CKD patients. While there are studies on NLR and CKD to date, information on the relationship between different peripheral leukocyte counts and proteinuria is limited. Studies generally include patients with DM [13,14]. In a study by Binnetoğlu et al., NLR was associated with the presence and degree of proteinuria in patients with stage 3 and 4 CKD [15]. In another study by Tatar et al., it was shown that NLR is an important parameter in predicting mortality in elderly patients with stage 3-5 CKD [16]. In another study of patients with CKD stage 1-3, similar to albuminuria and uric acid, NLR was shown to be a specific marker for patients with CKD Stage 3 [9]. In our study, NLR was found to be significantly higher in patients compared to the healthy control group. In addition, it was found that NLR levels increased with proteinuria in the stage 5 CKD group, in other words, NLR levels increased with CKD progression. In addition, when the patients were evaluated according to the presence of proteinuria, the NLR was found to be significantly higher in patients with proteinuria, while a negative correlation was found between NLR and GFR and albumin, and a positive correlation between proteinuria. The cut-off value for predicting proteinuria for NLR was found to be 2.4 and above. When the NLR is 2.4 and above, the probability of proteinuria increases at least 18 times, which is an important result.
Platelets play an important role in the pathogenesis of atherosclerosis, thrombosis and inflammation. It has been shown that PLR obtained from platelet count is a prognostic factor in some diseases, such as cardiovascular diseases and malignancies, and is associated with mortality [16-18]. Various studies have been conducted in various patient groups on PLR in CKD. In a study by Chen et al. on 70 patients with peritoneal dialysis (PD), it was shown that PLR is associated with cardiovascular events and that high PLR levels can predict the risk of cardiovascular events in these patients [19]. In a study by Turkmen et al., they showed that PLR can predict inflammation better than NLR in 62 patients with ESRD [20]. In a meta-analysis published by Valga et al., it was stated that PLR is associated with erythropoietin resistance and may be a better marker of inflammation than NLR in Stage-5 CKD population [21]. However, in our study, no significant difference was found between the patients in terms of either GFR values or the presence of proteinuria in PLR. Only a negative correlation was found between PLR value and albumin. Our results are not compatible with the literature may be due to the low number of our patients, but also suggest that NLR may be a more sensitive inflammation marker than PLR.
There are some publications showing that LMR and NMR values can be used as a prognostic factor in various inflammatory conditions and malignancies [22, 23]. Our study examined the relationship of these values with GFR and proteinuria. In terms of NMR values, there was no significant difference between the patient and control groups and between patients according to the stages. LMR value was found to be significantly higher in the control group compared to both the patient group and the stage-3 CKD group. However, in the comparison of these values according to the median values, significant differences detected for both proteinuria and uric acid suggest that these parameters should be studied. The strength of our study is that it has been comprehensively examined not only for NLR but also for other hematological parameters, with GFR and proteinuria as well as other parameters. However, the fact that diabetic patients were not included, and the number of our patients was relatively small, restricts our study to some extent.
As a result, our study has shown that NLR, which is an easily available and inexpensive method, can be used as an indicator of proteinuria and inflammation in predialysis CKD patients. Although it seems to be usable in other hematological parameters, comprehensive studies are needed.
Scientific Responsibility Statement
The authors declare that they are responsible for the article’s scientific content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientific review of the contents and approval of the final version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Funding: None
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
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8. Sarnak MJ, Levey AS, Schoolwerth AC, Coresh J, Culleton B, Hamm LL, et al. Kidney Disease as a Risk Factor for Development of Cardiovascular Disease: A Statement From the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. Circulation. 2003;108(17):2154-69. DOI:10.1161/01.CIR.0000095676.90936.80
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11. Trimarchi H, Muryan A, Dicugno M, Young P, Forrester M, Lombi F, et al. Proteinuria: An ignored marker of inflammation and cardiovascular disease in chronic hemodialysis. Int J Nephrol Renovasc Dis. 2012; 5:1-7. DOI:10.2147/ijnrd. s27675
12. Currie G, Delles C. Proteinuria and its relation to cardiovascular disease. Int J Nephrol Renovasc Dis. 2013; 7:13-24. DOI:10.2147/IJNRD.S40522
13. Mühlhauser I, Verhasselt R, Sawicki PT, Berger M. Leucocyte count, proteinuria and smoking in type 1 diabetes mellitus. Acta Diabetol. 1993; 30(2):105-7. DOI:10.1007/BF00578223
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The evaluation of additional payments during COVID-19 in Turkey: A qualitative study
Mehmet Emin Kurt 1, Cuma Çakmak 1, İsmail Biçer 2
1 Department of Healthcare Management, Healthcare Management, Dicle University, Diyarbakır, 2 Healthcare Management Program, Çivril Atasay Kamer Vocational School, Pamukkale University, Denizli, Turkey
DOI: 10.4328/ACAM.20644 Received: 2021-04-06 Accepted: 2021-04-29 Published Online: 2021-04-30 Printed: 2021-05-01 Ann Clin Anal Med 2021;12(5):577-581
Corresponding Author: İsmail Biçer, Healthcare Management Program, Çivril Atasay Kamer Vocational School, Pamukkale University, Denizli, Turkey. E-mail: ismailbiceer@gmail.com P: +90 507 4165175 Corresponding Author ORCID ID: https://orcid.org/0000-0003-1878-0546
Aim: The study aimed to determine healthcare professionals’ perceptions and attitudes towards additional payments made from working capital due to the pandemic.
Material and Methods: In the study, focus group interviews were made via snowball sampling method in order to identify the views of the healthcare profes- sionals about the additional payment from the indicated ceiling and to find out what kind of perception developed as a result of this evaluation (injustice, burnout, etc.).
Results: When the answers given to these questions were examined, it was seen that the healthcare professionals stated that not enough additional payments were given to them. Additional payments are made to employees by hospitals, but delays have occurred at the point of making additional payments due to the pandemic, and such a perception has emerged as a result of late payment of these additional payments.
Discussion: The working capital is not fairly distributed among healthcare professional, and shifts are exceeding 24 hours, which causes unpaid labor, and also, the assignments of healthcare personnel in COVID-19 clinics and intensive care units are not made fairly. Also, a stable additional payment to the wages should be made instead of working capital payments. Finally, the lack of wage peace among healthcare personnel is also a nature that will weaken the fight against the pandemic.
Keywords: Working capital; COVID-19; Healthcare professional
Introduction
The Ministry of Health has been continuously fighting against pandemics since March 11, 2020, when the first patient was diagnosed with COVID-19. Unlike the increase in the number of deaths due to pandemic in many countries with developed healthcare systems worldwide, Turkey has proven itself internationally in the fight against the virus, and it is also supported with the statement of the European Region Director of the WHO, Kluge: “A reduction of more than in cases and deaths detected in Turkey is an extraordinary achievement.” (available at: https://www.hurriyet.com.tr/dunya/ dsoden-turkiyenin-COVID-mucadelesine-ovgu-olaganustu- bir-basari-41562210.). Due to the COVID-19 pandemic, the Ministry of Health announced in the official gazette on April 9, 2020, that in order to carry out the fight against COVID-19 effectively and comprehensively, it was decided to make additional payments according to the ceiling rates, which will be determined by the ministry, to the personnel working in the facilities affiliated to the Ministry of Health mentioned in the above-mentioned official gazette dated 04.03.2020 and numbered 31058, for the said personnel for three months, effective from 01.03.2020. (available at: https://dosyamerkez. saglik.gov.tr/Eklenti/37085,COVID-19-pandemisi-nedeniyle- ek-odeme-usul-ve esaslaripdf.pdf?0&_tag1=5B606BDBE7C 1C9B547350A7B2FF7340A5826118D.). The aim was both to increase patient satisfaction as a result of increased quality and effectiveness in the services, and to increase personnel satisfaction through the working capital payments made to the personnel [1].
Based on the updated regulation of the Official Gazette dated March 4, 2020, and numbered 31058 on “Additional Payments to Personnel Working in Health Facilities Affiliated to the Ministry of Health,” the rates, procedures, and principles of additional payments to be made based on working capital were determined according to many factors determined by the ministry such as the titles, duties, working terms and periods of the personnel, their contribution to the service, their performance, the examinations, education, and training, as well as research activities, examinations, surgeries, general medical (anesthesia and interventional procedures) procedures, special medical procedures, giving international healthcare services, and efforts, were made to provide quality services, improve them and encourage efficient service provision (available at: https://www.resmigazete.gov.tr/eskiler/2020/03/20200304-4. html.).
However, it was seen that the ministry’s decision regarding the increase in the working capital, along with some deficiencies, was mentioned by both the national press and national non- governmental organizations and by the healthcare professionals performing the services (available at: http://www.sagliksen. org.tr/haber/9036/sagliksen.org.tr-https://www.dw.com/tr/ yo%C4%9Fun-bak%C4%B1m-hem%C5%9Firesine-tavandan- ek-%C3%B6deme-20-tl/a-53463930.-https://www.ttb.org. tr/kollar/COVID19/haber_goster.php?Guid=d0aed23e-7bee- 11ea-a12d-7aee3f6e69c5.). The first from the mentioned complaints is that the additional payment ceiling for physicians is set at 100%, while subsidiary health personnel are paid from the bottom. Also, assistant healthcare professionals such as medical secretaries, cleaning staff, caretakers were not included in this decision. Moreover, there are also issues such as deprivation of healthcare professionals from the working capital income for the days that they are considered on leave due to getting sick when working in COVID-19 clinics and intensive care units. In addition to these complaints, the family physicians’ payments, who were the first units that many people referred to on the first days of the pandemic, were not even on the agenda. Increasing complaints and the separation of staff caused this issue to be reviewed by the ministry. Thus, it was decided to make an additional three month-payment due to the COVID-19 pandemic to the family physicians and family health personnel as of August 1, 2020, with the “Regulation Amending Family Medicine Payment and Contract Regulation.” With this change, it was decided to make an additional payment of 3000 TL to family physicians and to pay no more than 850 TL to family health personnel. It can be seen that, although the regulations aim to cover all healthcare professionals with additional payment, healthcare professionals do not get what they want exactly, and allegations of discrimination between personnel come up. Even though making additional payments to family physicians was decided with the said regulation, there is an additional payment response from family physicians’ associations for these practices (available at: https://www. sozcu.com.tr/2020/gundem/aile-hekimlerinden-ek-odeme- tepkisi-cezalandiriliyoruz-6024001/).
Material and Methods
In the study, participants selected from the same population were reached via snowball sampling method, and their perceptions of working capital were tried to be revealed via online interviews because of the pandemic. Focus group discussions with the participants were held via the Zoom program (https://zoom.us/ download). Online video calls were used as the interview method due to the pandemic. Also, the study’s data were collected via an online questionnaire method between 20-28 August 2020. Ethics approval was obtained from the Non-Interventional Clinical Research Ethics Committee of Istanbul Arel University. In the study, however, focus group interviews were made with 18 professionals. In qualitative research, the sample size is not determined before the study, and the sample size increases until similar answers are obtained from the interviewees [2]. In the study, the participants chosen from the same population were reached via snowball sampling method, and their perceptions of working capital were tried to be revealed via online interviews because of the pandemic. Since the answers were repeated, there were no more interviews with the participants.
Results
In the first part the study, 100 healthcare professionals were involved. The majority of the participants (61%) stated that they worked 24 hours or more and 61% of the participants answered the question “Do you believe the assignments made to the COVID-19 units are fair?” that the assignments were not fair. After this, interviews were done with 18 volunteer healthcare professionals from different duties. Interviews were done with 9 nurses, 2 doctors, 1 midwife, 3 medical secretaries, 2 cleaning staff, 1 security staff (Table 1). Since the answers were repeated, there were no more interviews with the participants. The answers were noted since the participants did not allow any voice or video recordings. The interviews of each participant lasted about 10-15 minutes. The answers to the following 5 fundamental questions were investigated in this study.
Could You Indicate Your Opinions about the Ministry of Health’s Decision on Additional Payment to the Healthcare Professionals during Pandemic?
When the answers given to these questions were examined, it was seen that the healthcare professionals stated that no additional payments were given to them. Additional payments are made to employees by hospitals, but delays have occurred at the point of making additional payments due to the pandemic, and such a perception has emerged as a result of late payment of these additional payments. Moreover, the participants also stated that the additional payments are not enough, and they are not distributed fairly; therefore, they also complain about these issues.
According to the participant,
I see this to be a positive but insufficient application. Also, determining the additional payments as 3 months is not right, since healthcare professionals are always at risk…
According to another participant;
Of course, it is a good thing to make an additional payment to the healthcare professionals who show great devotion and sacrifice, but the payments should be made without any distinction to all healthcare professionals (without title discrimination or any other kind of discrimination).
Do You Believe that the Working Capital Revenues are Fairly Distributed during the Pandemic?
Almost all of the participants gave the same answer to this question. The participants do not believe that working capital payments are distributed fairly.
According to the participant,
The working capital payment is absolutely and never fairly distributed. We, the nurses, who work at the forefront, do not deserve the least working capital coefficient.
To another participant,
I definitely do not think this is fair. The coefficient gap between the specialist doctor and the assistant healthcare personnel is a huge injustice. If they want to be fair, they should ensure that cleaning, security, automation personnel, and personnel working other additional units also benefit from the additional payment taking into account the laborers’ rights. Healthcare service is teamwork. Do only doctors give healthcare services?
Another participant states,
I don’t believe that it is distributed fairly. Everybody suffers from this extraordinary situation, so everybody needs to be paid equally, regardless of the unit. I can even say that the additional payment is given to only doctors.
What Are Your Opinions About Paying or Not Paying Additional Payments to the Healthcare Professionals Who Caught COVID-19 on Their Duty for the Days They Are on Sick Leave? Healthcare professionals who work with great devotion, can sometimes get epidemic diseases while helping individuals to regain their health. It is known that some healthcare professionals who actively take part in the treatment of COVID-19 have passed away or enter quarantine after being diagnosed with COVID-19. It is asked the participants if additional payments are given during this period, and they said they have no additional payments during these quarantine periods. In addition, some participants indicated that this should be regarded as a work accident, and the procedures should be applied accordingly.
According to the participant,
Healthcare workers caught with COVID-19 while working should receive additional payments on their days off. For an employee who is already putting his life at risk, this is nothing.
Another participant states,
Additional payment is given on days off, but as healthcare professionals, we don’t understand why it is not regarded as a work accident.
Could You Indicate Your Opinions about the Effects of Additional Working Capital Payment Made during Pandemic on Work Motivation?
Various factors can be listed among motivation factors. One of these factors is the effect of the increase in the workers’ revenue. Although the healthcare professionals indicate that the additional payments are not distributed fairly, it is clear that these additional payments are a source of motivation. As a matter of fact, healthcare professionals stated that additional payments increased their motivation to work.
The participant states:
Working capital payment can be beneficial for the motivation if it is distributed fairly, but provided that it is distributed fairly. According to another participant,
The benefit of the additional payments to the motivation is definitely a lot. If I didn’t get any payment, worked longer, and had the risk of getting an epidemic (COVID-19), why would I work? I wouldn’t want to go to work. Like everyone, I think like this. If there is no additional payment, productivity also decreases.
Would You Request a Permanent Wage Increase in Your Salary Instead of Working Capital?
Participants stated that a fixed payment to the salary would be better instead of additional payments since additional payments are made in 3-month periods and are temporary. According to the participant:
We should get our salary fixed in the same way as soldiers or police officers, and this should be reflected in our retirement because now there is a full salary debacle.
Another participant said:
Of course, I would, because the working capital is in no way distributed equally; instead, it would be fairer to raise all healthcare professionals’ salaries. The working capital should be abolished; instead, salaries should be raised, and working conditions should be improved. Everything will be better for us, healthcare professionals, if this happens.
Another participant states:
Additional payments are problematic as their current status. Also, the fact that they are not reflected in the retirement is complete nonsense because a tax reduction is made from the money paid. I want 3600 additional indicators to be implemented, our additional payments to be reflected on retirement, branching out in the profession, nepotism to be prevented, and giving importance to merit.
According to another participant:
I don’t think that any payment will be made on time since the working capital payments are not clear and the payment has not been made regularly and sufficiently in the last 3-4 years. Therefore, the combination of salary increases, salary, and fixed additional payment will make us feel more secure so that we can make plans more comfortably with the amount that we are paid. We won’t have to deal with the stress of whether we get additional payment this month or not.
Discussion
In their study, Kavas and Develi found that there were long shifts with the pandemic, only physicians working capital revenue increased in terms of working capital, there was no fair system for additional payments, and professionals with chronic diseases were made to work in COVID-19 clinics and intensive care units [3]. Yüncü and Yılan determined in their study that healthcare professionals did not receive any additional satisfying payment or reward [4]. These results are consistent with the results of the study. The nurses had problems such as having no additional payment, obligatory unpaid leaves, and not getting paid for overtime during the pandemic. The announcement by the Republic of Turkey Ministry of Health that additional payments will be made from the ceiling (100%) for the personnel working in the places where services are provided within the scope of the COVID-19 pandemic has caused expectations among nurses as well as other healthcare workers. However, there have been cases such as making no payments or incomplete payments at university hospitals, differences in payments between institutions and within the institutions, and the deduction of administrative leaves from working hours due to flexible working. These issues with the payments shook nurses’ belief in justice, caused frustration and anger, and affected the work peace and tranquility. Payments based on working capital, performance, etc., which the Turkish Nurses Association has been fighting against for years, stood out as a serious example of injustice during pandemic [5]. Çakır and Sakaroğlu investigated the perception that occurred when the waging peace among employees cannot be achieved due to additional payments from working capital [1].
In their study, Güvenç and Baltacı stated that healthcare workers do not receive a reward for their efforts despite the increase in occupational risks and working hours in this process; unfortunately, the working capital is paid from the ceiling for a period that does not include all the healthcare professionals, assistant healthcare professionals couldn’t benefit from the facilities such as free accommodation and transportation, additional payments during the pandemic, giving different rights to the personnel working in the same risky environment affects the peace in the working environment and the burnout of the assistant healthcare professionals (Güvenç R, Baltacı E. COVID-19 ve Sağlık Çalışanlarının Ruh Sağlığı; Türk Tabipleri Birliği COVID-19 Pandemisi Altıncı Ay Değerlendirme Raporu/ COVID-19 and Mental Health of Health Workers; Turkish Medical Association’s COVID-19 Pandemic Sixth Month Assessment Report. 2020;349-54). Also, they reached the results that making the additional payments to the healthcare professional, not through the salary system but working capital, causes inequality between colleagues and disruption in the perception of “getting what they deserve.”
The healthcare workers in our study think that the additional payment should not be limited to 3 months. Also, they stated that the additional working capital payments are insufficient, and a fair distribution should be made among all healthcare professionals with removing title differences. The healthcare professionals stated that the working capital payments are not distributed fairly, and in fact, the reason for this is that the distribution according to the title prevents fair distribution among other assistant healthcare professionals. Also, the fact that other technical workers in the hospital do not benefit from this payment creates a more problematic situation in terms of fair share. The healthcare professionals also stated that they did not receive any payment during this period, and this situation should be considered as a workplace accident (Healthcare professionals are in despair due to workload, low wages, increased number of patients, and unfavorable working conditions Işıkhan, V. Çalışanlarda tükenmişlik sendromu, akciğer kanserinde destek tedavisi. TÜSAD Eğitim Kitapları Serisi/ Burnout syndrome in employees, supportive treatment in lung cancer. TÜSAD Education Books Series. 2016; 366-91). As a result of the study, it is detected that while the additional payment made to the healthcare professionals affect their motivation positively, the unfair distribution of the payments among the professionals affects their motivation negatively. Additionally, the study concluded that a fixed payment to the salary would be better than additional payments because there has been a gradual decrease in the working capital revenues. Since there is no equal distribution, healthcare professionals want a fixed payment to their salaries so that they can feel more secure in terms of payment.
As a result, it was found that the working capital is insufficiently and unfairly distributed among the healthcare professionals or never given at all. It is also found that the assignments of the healthcare professionals to the COVID-19 clinics and intensive care units are not fair. In addition to these results, a fixed payment should be made to the salaries instead of working capital revenue, and the salary agreement between the healthcare professionals can be achieved.
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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The evaluation of colon polyps and factors affecting malignancy of polyps
Rıfat Peksöz 1, Serkan Borazan 2, Esra Dişçi 3, Enes Ağırman 3
1 Department of General Surgery, Muş State Hospital, Muş, 2 Department of Gastroenterology, Muş State Hospital, Muş, 3 Department of General Surgery, Atatürk University Faculty of Medicine, Erzurum, Turkey
DOI: 10.4328/ACAM.20651 Received: 2021-04-10 Accepted: 2021-04-28 Published Online: 2021-04-30 Printed: 2021-05-01 Ann Clin Anal Med 2021;12(5):582-586
Corresponding Author: Rıfat Peksöz, Department of General Surgery, Muş State Hospital, 49100, Muş, Turkey. E-mail: rifat-peksoz@hotmail.com P: +90 5349214382 Corresponding Author ORCID ID: https://orcid.org/0000-0003-4658-5254
Aim: The aim of the study is to examine the demographic and histopathological characteristics of colorectal polyps and to discuss the risk factors for polyps to become malignant.
Material and Methods: A total of 3285 patients who underwent colonoscopy between 2016-2020 were examined. The age and gender of patients, the histo- pathological type, size, and the number of the polyps, and the region where the polyp was located in the colon were recorded.
Results: Three hundred ninety-five patients were included, and 547 polyps were examined; 67% of the patients were male, 33% were female, and the mean age was 55.4 years. Adenomatous polyps accounted for 62.5% of all polyps, 30.71% were hyperplastic polyps, 6.8% were other polyps. Polyps were located with a rate of 33.45% in rectum, 26.87% in sigmoid colon, 6.2% in ascending colon, 15.9% in transverse colon, 13.71% in descending colon, and 3.83% in cecum. Patients were divided into 2 groups: Group 1: low- risk group 85.8% and Group 2: high -risk group 14.2%. The number of males was higher in both groups. The mean of polyps and polyp diameters were higher in Group 2, and a significant difference was detected between the groups (p <0.001).
Discussion: Colon polyps are more common in men, especially after the age of 50. The patient’s age, and the polyp’s number, size, and histopathological type are effective factors in the malignancy’s development. The majority of polyps are located in the rectosigmoid region, and sigmoidoscopy alone can detect the majority of colorectal polyps and contribute to the diagnosis and treatment of polyps.
Keywords: Colonic polyps; Histopathology; Localization; Size; Malignancy
Introduction
Gastrointestinal system polyps are lesions that can be proliferative and neoplastic, which protrude into the stomach and gut lumen and originate from the lumen and submucosal epithelium. Polyps are encountered more frequently in the colorectal region [1]. Although colon polyps are generally asymptomatic, they can cause rectal bleeding, tenesmus, and even intestinal obstruction should they reach very large sizes. The most important feature of polyps is that those with malignancy potential can turn into colorectal cancer [2,3]. Various features such as the size of the polyp, number of adenomas, histological type, and degree of dysplasia are the indicators that demonstrate the malignancy potential [4,5]. Polyps encountered during the colonoscopy need to be removed due to their potential cancer risk. Performing polypectomy and monitoring patients according to the histopathological type decrease the incidence and mortality of colorectal cancers [6- 7]. For advanced adenomatous polyps, colonoscopy should be performed within the next 3 years, and for low- risk adenomas, colonoscopy should be performed once every 5 years until a negative colonoscopy examination [8].
In this study, it was aimed to examine the demographic and histopathological features of colorectal polyps and to discuss the risk factors affecting the polyps to become malignant in the light of the literature.
Material and Methods
For this study, ethics committee approval was obtained from the Erzurum Hospital Ethics Committee with the decision number 2020/06-67. A total of 3285 patients who underwent lower gastrointestinal system endoscopy in the endoscopy unit of Muş state hospital between the dates of March 2016–March 2020 were retrospectively examined.
The consent form was obtained from the patients before the colonoscopic procedure. The patients were monitored after their 8 hours of fasting, and the colonoscopy procedure was carried out via the device of Fujinon EC-530WL3 with oxygen support. Only about half of the procedures were carried out under sedation due to the inadequacy of technical installation and equipment.
Lesions that were in the appearance of a polypoid structure but, were reported as a result of histopathology (normal mucosa, solitary rectal ulcer, increase of lymphoplasmacytic cells), patients who had 10 or more reported lesions and were referred to the advanced center without the polypectomy procedure, patients whose biopsy was taken for diagnostic reasons but were not reported as a polyp, and patients whose data could not be obtained were excluded from the research. The age and gender of the patients included in the study, the histopathological type, size, and the number of the polypoid lesions, and the region where the polyp was located in the colon were recorded. In patients who were found to have multiple polyps, the average size of polyps with the same histopathologic types was calculated.
Polypoid lesions were grouped as neoplastic mucosal polyps, non-neoplastic mucosal polyps, and submucosal lesions [7,9] (Table 1). In our study, patients were divided into two groups as low- risk group (Group 1) and high- risk group (Group 2), according to the risk classification in the literature {10]. Polyps whose size of adenoma was equal to or more than 1 cm, polyps whose number of adenomas was equal to or more than 3, polyps with villous components, high-grade dysplasia, or patients whose polyps had the feature of invasive cancer were considered as a high- risk group [9,10].
Statistical analysis
The software package SPSS 21.00 was utilized for statistical analysis. Results were presented as numbers for categorical variables, and as mean ± standard deviation for continuous percentage variables. For the comparison of the means of the groups, Student’s t-test was utilized for the variables that demonstrated a normal distribution, and the Mann-Whitney U test was used for the variables that did not demonstrate normal distribution, and a p- value <0.05 was considered significant, while p<0.001 was considered extremely significant.
Results
Biopsies were taken from 995 (30.3%) of 3285 patients who underwent colonoscopic procedures in the endoscopy unit. Four hundred fifty-eight (13.94%) of the patients had lesions in a polypoid structure. In accordance with the purpose of the study 63 patients in total were excluded from the study (25 patients were reported as a solitary rectal ulcer or lymphoplasmacytic cell, 25 patients with normal mucosa, 5 patients who had more than 10 polyps but have not undergone polypectomy, 3 patients were under the age of 18, and 5 patients whose data could not be obtained). The study included 395 patients and 547 polyps were examined.
Two hundred sixty-six of the patients (67.3%) were males and 129 (32.6%) of them were females, and the mean age was 55.4 ± 13.2 (20-89) years. The rate of patients who were over the age of 50 was 64.3%.
When examining the number of polyps, it was calculated that there are 168 (30.7%) hyperplastic polyps, 342 (62.5%) adenomatous polyps, 15 (2.7%) serrated polyps, 14 (2.55%) inflammatory polyps, and 8 (1.46%) polyps under the name of other polyps group, which constitutes a total of 547 polyps. When the colon localization, where the polyps are placed, was investigated, 183 (33.45%) of them were found in the rectum, 147 (26.87%) were found in the sigmoid colon, 34 (6.21%) were found in the ascending colon, 87 (15,9%) were found in the transverse colon, 75 (13,71%) were found in the descending colon, and 21 (3.83%) were found in the cecum (Table 2).
A single polyp in 283 patients (71.6%) and multiple polyps in 112 patients (28.4%) were detected. The mean number of polyps was 1.38 (1-6). 98.5% of the polyps were less than 1 cm in length and 78.7% of them were less than 5 mm. The average diameter of all polyps was 3.92 mm (2-25 mm).
The patients were divided into two groups according to the neoplasia risk group: Group 1: low-risk group including 339 patients (85.8%) and Group 2: high-risk group including 56 patients (14.2%). The mean age of the patients in Group 1 was 54.4±12.9 years, and the mean age of the patients in Group 2 was 61.2±13.6, and a statistically significant difference between the two groups was detected (p <0.001). Two hundred thirty of the patients (67.8%) in Group 1 were males and 109 of them (32.2%) were females, whereas 36 of the patients (64.3%) in Group 2 were males and 20 of them (35.7%) were females, and the number of males in both groups is clearly higher. However, no significant difference was detected between the groups in terms of gender difference (p> 0.05). The mean number of polyps was 1.28±0.5 in Group 1 and 2±1.3 in Group 2, and a significant difference was detected between the two groups (p <0.001). The polyp diameter was 3.6±0.9 mm in Group 1 and 5.9±3.7 mm in Group 2, and a significant difference was detected between the two groups (p <0.001). (Table 3).
Discussion
Colon polyps are among the lesions that are mostly asymptomatic and detected incidentally during the endoscopy. The rate of detecting polyps in colonoscopic procedures was found to be in the range of 10.4-14.4% [7,9,11]. In addition to the male gender, constituting the majority of the patients, the number of patients over the age of 50 is seen in the rate of 76.5-78.1% [9,11,12]. In the literature, the mean age of the patients has been reported to be 59-59.8 years [9,11,12,13]. The rate of polyp detection in patients that we performed endoscopy is 13.9%. Males were constituting a great majority, 67% of the patients and the mean age was 55.4 years. The rate of patients over the age of 50 was 64.3%. Although the rate of the patients over the age of 50 was relatively less than the literature findings, other findings show similarity with the literature.
In the studies conducted in our country, it has been demonstrated that most of the colon polyps were placed in the left colon. Colorectal polyps were detected with a rate of 23.4-37.7% in the rectum, 10.3-26.8% in the sigmoid colon, 13.3-20.3% in the descending colon, 15.3-16.9% in the transverse colon, 3.7- 13.2% in the ascending colon, and 2.5-6.2% in the cecum [7,14]. In our study, when examining polyps’ distribution in the colon, they are observed with a rate of 33.4% in the rectum, 26.8% in the sigmoid colon, 13.7% in the descending colon, 15.9% in the transverse colon, 6.2% in the ascending colon, and 3.8% in the cecum. The polyps’ distribution in the colon in our study shows parallelism with the literature.
Colon polyps are divided into 2 main groups as non-neoplastic polyps and neoplastic polyps [1,7]. Hyperplastic polyps are the most commonly encountered non-neoplastic polyps and are generally assumed not to turn into cancer. However, hyperplastic polyps and neoplastic polyps might get located in the same colon, and since the histopathological type of polyps is indistinguishable macroscopically, polypectomy or biopsy from the lesion is required [15,16].
Hyperplastic polyps are usually located in the rectum and sigmoid colon, and most are less than 5 mm in diameter [17]. In our study, 30.7% of polyps were hyperplastic polyps, and the mean of the polyps’ diameters was 3.7 mm; 72.6% of them were located in the rectum and sigmoid region.
Serrated polyps are endoscopically and pathologically unheeded, and their characteristics are still being argued. According to the 2010 WHO classification, serrated polyps are grouped into three as hyperplastic polyps, sessile serrated adenoma, and traditional serrated adenoma [18]. The rate of serrated adenoma was 2.7% in our study, 86.6% of which were located in the left colon. The mean age of the patients was 56.2 years, and 21.4% of the polyps were in the high-risk patient group. It is not yet known in which risk group serrated polyps will be deemed. Thus, it would be more accurate to consider serrated polyps as neoplastic polyps.
Inflammatory polyps are also non-neoplastic polyps. These are polyps that develop in response to chronic inflammation and occur in conditions such as inflammatory bowel diseases. Most polyps are found in the rectum, and their diameters range between 1-3 cm [7]. The incidence of inflammatory polyps in our study was 2.6%, and 78.6% of polyps were located in the rectosigmoid region. The mean of the inflammatory polyps’ diameters was 4 mm, which is lower than the literature data. Most colorectal polyps are adenomatous polyps that have neoplastic characteristics [19]. Adenomatous polyps are named tubular, tubulovillous, or villous adenoma, depending on the presence and volume of villous tissue [20]. In the conducted studies, adenomatous polyps constitute 81.7-82.5% of all polyps. Among these polyps, tubular adenoma has a portion of 86.8-90.6%, tubulovillous has a portion of 7.7-8.1%, and villous adenoma has a portion of 1.3-3.5% [7,10]. In our study, while adenomatous polyps constituted the 62.5% of all polyps, tubular adenoma constituted the 90.3%, tubulovillous adenoma constituted the 8.6%, and villous adenoma constituted a portion of 1.1%. These findings coincide with the rates in the literature. Polyps are considered as low and high-risk groups according to the cancer risk. The risk of colorectal cancer increases with the presence of villous/tubulovillous polyps (especially in large numbers) and the presence of adenomatous polyps larger than 1 cm. Adenomas that contain a high degree of dysplasia and/ or invasive cancer and that are 1 cm or larger and polyps with villous histology are named advanced adenoma [21]. As age advances, the incidence of encountering polyps in adenomas, the polyp size, and the growth rate of dysplasia increase. While low-grade dysplasia is higher in young patients, the rate of high-grade dysplasia increases with the advancement of age [22]. In the study by Solakoğlu et al., 37.6% of the polyps were considered in the high-risk group. The mean age of high-risk patients was significantly higher and no significant difference was detected between the genders [9]. The ratio of the patients in the higher risk group was 14.2%. The low rate is due to the fact that half of the endoscopic procedures could not be performed under sedation in our hospital, which is a secondary hospital, and the referral of polypoid lesions that were considered as complicated to advanced centers due to technical inadequacies. No significant difference was found between the groups in terms of gender, albeit the majority of the patients in the low and high-risk groups were males. The mean age of patients in the low-risk group was 54.4 years, the mean age of the patients in the high-risk group was 61.2 years, and a significant difference was detected between the two groups. Although there is a limited number of studies in the literature, the number and size of polyps are important and known factors in terms of malignancy development [5,8,23]. In our study, along with the literature, the mean number and diameter of polyps were found to be significantly greater in the high-risk group. When studying the literature, it was observed that the number of studies examining the localization area of polyps in the high- risk group was very limited. Neoplastic colorectal polyps are also mostly encountered in the rectosigmoid region, like the other polyps [24]. In our study, no significant difference was detected between the risk ratio of polyps and the colon segment where they were encountered. Correspondingly to the literature, the majority, 51% of high-risk polyps were detected in the rectosigmoid region. However, an important portion of high-risk polyps (24.1%) was found to be in the transverse colon region. This number is above the literature data.
Conclusion
Colorectal polyps are more common in males. While the majority of polyps occur in people over the age of 50, polyps are seen relatively more often between the decades of 4-5. The majority of polyps are encountered in the rectosigmoid region. Even the sigmoidoscopy procedure alone can detect the majority of colorectal polyps and contribute to the diagnosis and treatment of polyps. The age of the patient, the size, number, and the histopathological type of the polyp are the factors that influence the development of malignancy. There are few studies in the literature that discuss risk factors by classifying patients according to their cancer risk groups. There is a need for studies that would be conducted with a wide range of patients, especially in tertiary hospitals where technical equipment and equipment are adequate.
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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Rıfat Peksöz, Serkan Borazan, Esra Dişçi, Enes Ağırman. The evaluation of colon polyps and factors affecting malignancy of polyps. Ann Clin Anal Med 2021;12(5):582-586
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Sources used to obtain information and their impact on the mothers’ complementary feeding practices
Mehmet Semih Demirtas 1, Huseyin Erdal 2
1 Department of Pediatrics, Aksaray Education and Research Hospital, 2 Department of Medical Genetics, Aksaray University, Faculty of Medicine, Aksaray, Turkey
DOI: 10.4328/ACAM.20656 Received: 2021-04-13 Accepted: 2021-04-29 Published Online: 2021-04-30 Printed: 2021-05-01 Ann Clin Anal Med 2021;12(5):587-591
Corresponding Author: Mehmet Semih Demirtaş, Aksaray University Education and Research Hospital, Centre/ Aksaray. E-mail: md.semihdemirtas@gmail.com P: +90 382 520 10 20/8598 F: +90 382 520 10 20/8598 Corresponding Author ORCID ID: https://orcid.org/0000-0003-2965-1811
Aim: When, how and which nutrients complementary food is given, how the baby adapts to this situation is important for the growth, development, psychoso- cial, motor and cognitive development of the infant during childhood. The aim of this study was to learn the methods of obtaining information from mothers about the complementary feeding period.
Material and Methods: Mothers who had 6-36 months old children applied to the Pediatric outpatient clinics between May 2019 and May 2020 were included in the study on a voluntary basis. The socio-demographic information of the mothers, information about babies and complementary food were asked through a survey, which consisted of 3 parts.
Results: One hundred forty mothers (65.7%) stated that they exclusively breastfed before complementary feeding. The most preferred method was to obtain information by traditional methods (61.5%). Families get more information from pediatricians (54.1%) as professional support. When we look at 79 mothers who stated that they obtained information via websites, it was found that 9 out of 15 mothers (60%) had a master’s/doctorate degree, 28 out of 64 mothers (43.8%) were university graduates, 21 of 62 mothers (33%) were high school graduates (p = 0.001).
Discussion: Though getting information about complementary feeding period from websites and social media may appeal to families due to fast and easy access, the presence of inaccurate or incomplete information, inability to control the information and lack of scientific basis will lead to misinformation and confusion.
Keywords: Complementary feeding; Complementary food; Infant nutrition; Parents information sources
Introduction
The newborn baby is dependent on the mother for the continuity of life. In order to grow and develop in a healthy way, this continuity can only be achieved through successful nutrition based on mutual care and trust between mother and baby. The most important food for the healthy growth and development of babies is breast milk, which is special for each baby [1].
It is recommended to start complementary feeding from the 6-month period with the continuity of breastfeeding. Starting the complementary feeding period early, may decrease breast milk supply and cause breastfeeding to cease. With contributions of the World Health Organization (WHO) and the United Nations Children’s Fund (UNICEF), a program of baby-friendly hospitals has been initiated in 152 countries around the world to promote breast milk [2-3].
Starting complementary (solid) foods early or late may induce some problems such as diarrhea, food allergies, and obesity [4, 5]. It is known worldwide that over 40 million children under the age of 5 are considered overweight/obese. Studies on obesity in the literature have shown that starting complementary feeding before four months and high protein food intake in the early period increase obesity. Prolonged transition to complementary food intake can cause micronutrient deficiency and nutritional behavior problems [4, 6].
In this study, we aimed to investigate how and where mothers learned about complementary feeding.
Material and Methods
Sampling
This study included mothers of 216 children on a voluntary basis, who were admitted to the Aksaray University Education and Research Hospital pediatric outpatient clinics.
Data collection tools
In collecting data, questions about the sociodemographic characteristics of mothers, babies/children and complementary feeding period were asked through a survey, which consisted of 3 parts. Information about the mothers’ sociodemographic characteristics was obtained using 1-5 questions in the first part. In these questions, the mothers were asked about their age, education level, monthly income level of the family, employment status and the region where they live.
In the second part of the survey (questions 6-10), mothers were asked about their babies. The mother was asked whether the birth was by cesarean section or normal birth, where and in what environment the delivery took place, the gender of the baby and the birth weight of the baby. The birth weight of babies was <2500g. 2500-4000 g. and> 4000 g. Before the complementary food, the nutrition status of the babies was questioned, and the questions were asked with 3 answers: exclusively breastfed, only formula and breast milk + formula. In the third part, questions about the complementary feeding period were asked; complementary food start time as <4 months, 4-6 months, 6-8 months,> 8 months; The number of examinations performed by the pediatrician and whether she received information from the pediatrician or family physician during the examination were asked. The mothers were asked in which environment and under what conditions the additional food was given. In addition, whether there was a history of forced feeding in cases where the baby refused to eat was asked.
They were asked whether the mothers received support during the complementary food period, and if so, from whom. In addition, it was asked where and how the mothers obtained information on complementary food. In this context, an 8-answer multiple-choice question was asked (traditional ways of obtaining information, from a pediatrician, family physician, dietician, television programs, social media accounts, nutrition books and the internet).
Collection of data
Data were collected during the May 2019- 2020 period. Before the data was collected, detailed information was given to the families about the study and their written consent was obtained. Mothers who had a child aged between 6 and 36 months who applied to Pediatrics outpatient clinics between May 2019 and 2020 were included in the study on a voluntary basis.
Families of infants/children with refugee status, who do not have children under the age of 3, who cannot clearly remember the complementary food period, were not included in the study. Refugee babies/children were excluded from the study due to the lack of clear understanding with their families and the thought that reliable data could not be collected due to the traumatic events they experienced and their current conditions. Ethics
After the necessary explanations and procedures related to the research were explained to the participants, written informed consent was obtained from all participants after the study procedures had been fully explained. This study has been carried out in accordance with the Code of Ethics of the World Medical Association (Declaration of Helsinki). This survey was approved by ethical committee of Aksaray University (Number: 2020 / 01-12). The participants were assured that their participation was voluntary and that anonymity, privacy, and confidentiality of the data were guaranteed. Furthermore, they were informed about the purpose and the method of the study before signing a written informed consent.
Statistical analysis
In our study, mean, standard deviation, minimum and maximum values are given in descriptive statistics regarding continuous data, and percentages are given in discrete data. The Shapiro- Wilk test was used to examine the compatibility of continuous data with a normal distribution. Multiple response sets are used in multiple choice questions. Pearson’s correlation coefficient was used to examine the relationship between the data obtained by measurement. The Chi-square test was used in group comparisons (cross tables) of nominal variables. IBM SPSS Statistics (Statistical Package for the Social Sciences version 22, Chicago, IL, USA) program was used in the evaluations, and p <0.05 was accepted the statistical significance limit.
Results
Forty-eight (22.2%) of the 216 mothers participating in the study were <25 years old; 83 mothers were (38.4%) 25- 29 years old, 46 mothers (21.3%) were 30-34 years old, 36 mothers (16.7%) were 35-40 years old and 3 mothers (1.4%) were> 40 years old. While 61.6% (n = 133) of the mothers who participated in the study lived in cities, 38.4% (n = 83) lived in rural areas. When the babies were examined in terms of their gender, it was found that 127 babies (58.8%) were female and 89 (41.2%) were male.
When the participants were asked about the form of feeding before complementary feeding period, 142 mothers (65.7%) stated that they exclusively breastfed their child, 59 mothers (27.3%) breastfed along with formula and the rest of them (6.9%) gave just only formula. Thirteen mothers (6%) started complementary feeding period of their child before 4 months, 95 (44%) of them at 4-6 months, 102 (47.2%) of them at 6-8 months and 6 (2.8%) mothers after 8 months. Considering the birth weights of the babies who were examined, it was determined that there were 50 babies (23.1%) with <2500 g, 144 babies (66.7%) with 2500-4000 g, and 22 babies (10.2%) with> 4000 g.
One of 7 mothers (14.3%) who stated that they had no education, 10 of 17 mothers (58.8%) who were primary school graduates, 22 of 51 (43.1%) mothers who were secondary school graduates, 13 of 62 (21%) mothers who were high school graduates, 14 out of 64 (21.9%) mothers who were university graduates, and 4 out of (26.7%) 15 mothers who had master’s and doctorate degrees stated that they forced their babies to eat during the complementary feeding period (p=0.006). Comparing the educational status of mothers who exclusively breastfed before starting complementary food, we found that 10 mothers (66.7%) who had master’s and doctorate degrees, 47 mothers (73.4%) who were university graduates, 48 (77.4%) mothers who were high school graduates, and 25 (49%) mothers who graduated from secondary school, exclusively breastfed their babies before the complementary feeding period (p = 0.017).
When we compared the education level of the mothers and time of starting complementary feeding of the babieswere, we stated that 4 babies of mothers (71.4%) who did not have education started in the 4-6 month period, and 1 (14.3%) in the 6-8 month period; 8 babies of mothers (47.1%) who graduated from primary school were started complementary feeding in the 4-6 month period, 5 of them (29.4%) in the 6-8 month period; 64 babies of mothers who graduated from university, 25 (39.1%) of them started in the 4-6 month period, 38 (59.4%) of them started in the 6-8 month period, and 7 babies of mothers (46.7%) who received doctorate degree started in 4-6 months and rest of them (53.3%) started in 6-8 month period (p = 0.022) (Table 1).
One hundred thirty-three (61.5%) mothers obtained information about complementary feeding period using traditional methods, 117 (54.1%) received information from pediatricians, 49 (22.6%) from family physicians, 43 (19.9%) through social media/popular accounts, 68 (31.4%) through nutrition books, 79 of mothers (36.5%) stated that they got information via websites (Figure 1).
Among 133 mothers who obtained information through traditional methods, 6 (85.7%) mothers were not educated, 15 (88.2%) mothers were primary school graduates, 29 (61.7%) mothers were secondary school graduates, and 8 were master/ doctoral graduates (53%). Considering 68 mothers who obtained information from nutrition books, it was found that 16 mothers (25.8%) were high school graduates, 31 mothers (48.4%) were university graduates, and 10 mothers (66.7%) were master’s/doctoral graduates. When we look at 79 mothers who stated that they obtained information via websites, it was found that 9 mothers (60%) had master’s/doctorate degree, 28 of 64 mothers (43.8%) graduated from university, and 21 mothers (33%) graduated from high school (p = 0.001) (Table 2).
Discussion
It is observed that 1.3 million babies in the world return from death to life every year with supplemental nutrients after exclusively breastfeeding for the first 6 months [2, 7]. According to the Turkey Demographic and Health Surveys in 2013, it was stated that 12% of infants received complementary food before the 6th month and were not commencing at the correct time. This situation shows that the transition to complementary food is still an important problem [7].
In the study by Sivri [8], it was determined that the rate of transition to complementary food in the 4-6 month period was 57.4%. In our study, 16 (7.4%) infants began to receive complementary food before 4 months, 93 (43.1%) between 4-6 months, 101 (46.8%) between 6-8 months, and 6 infants over 8 months (2.8%). The time of starting complementary food in infants and the educational status of the mothers (p = 0.22) and the number of living children they have (p = 0.322) were compared, and in both cases, it was found that there was no effect on the early complementary period.
In infants <6 months, the rate of breastfeeding is 16% in Afghanistan, 51% in China, 32% in East Asia and 30% in South Africa; In Turkey, this rate was found as 30.1% [9]. One of the most important results of our study is that the rate of exclusive breastfeeding before complementary period was found to be 65.7% (n=142). On the other hand, we found that 46.8% (n = 101) started complementary food intake in <6 months period. This result shows us that mothers exclusively breastfed their babies prior to complementary feeding period, but did not comply with the recommended commercing time of complementary food of 6 months. In line with the existing literature, we found similar results, according to which the amount of mother’s breast milk was insufficient, and a child’s first relationship with food tasting might be a factor affecting the initiation of complementary food [10,11].
Studies have shown that the level of education positively affects the duration of breastfeeding. In a study on 384 mothers from India, it was observed that the increase in the education level of the mothers positively affected the duration of breastfeeding [12]. In another study conducted in the United States of America (USA), it was shown that the increase in education level positively affects the increase in breastfeeding time [13]. In our study, we found similar results with the literature (p = 0.017).
In the relationship between mother and baby, good communication should be established in order to acquire the appropriate nutritional habits. Therefore, the mother should be aware of the hunger and satiety symptoms of the baby, and should feed on time and in the appropriate amount. This should encourage the baby’s participation in the feeding activity. Since feeding time is also a time of love and learning, babies should be fed patiently and with pleasure, without verbal and physical pressure by making eye contact, encouraging them. In case of refusal of food, it is necessary to try again by spreading over time without being excessive [14-15]. While the rate of forced feeding was 58.8% in mothers who graduated from primary school, it was found to be significantly lower in university and doctorate groups which had higher education levels (21.9%, 26.7% respectively) (p= 0.006). From this result, we concluded that education is a prominent factor in forced feeding, which disrupts babies’ nutritional patterns.
It is predicted that it can be a stressful period for parents and caregivers when their babies are introduced to complementary feeding experience. Therefore, it is not surprising that parents usually look for accurate feeding information along with professional support from health professionals [16]. Choice of snacks, healthy diet, initiation time, and fruit and vegetable preferences were the most sought parameters of the complementary feeding period by mothers. The most important knowledge that mothers eager to learn about complementary feeding regarding their babies is starting time of complementary food period and tasting period with new foods such as soups, fruits and vegetables. Mothers who want to get information about complementary feeding depend on not only on living social environment and cultural attitudes, but also living time conditions [16, 17]. In a study conducted in England [18], it was found that 33% of traditional methods called friends/ family members in obtaining information about complementary feeding, 55% obtained information from websites, 55% from professional health professionals, 49% from books and other printed materials. Our results indicate that families get more information from Pediatricians (54.1%) as professional help. In addition, traditional methods were the most preferred method for obtaining informations (61.5%). The most important finding in our study was that the rate of obtaining information via the internet (36.5%) and social media (19.9%) was above our expectations. In the study by Garcia et al. [19], they indicated that the rate of obtaining information about complementary feeding from websites has increased from 29 percent to 55 percent from 2010 to 2016.
The main factors using website/social media methods for families are the low level of knowledge and awareness of pediatricians and family physicians on complementary feeding, access to information expeditiously without wasting time [19, 20]. We found that in mothers who obtained from the websites the education level was higher (p = 0.001).
Limitations
Since the study is cross-sectional, the findings require careful interpretation in terms of cause-effect relationships. Due to the fact that the study was conducted with mothers who presented to the outpatient clinic, its results can hardly be generalized to the general population. There is a need for multi-center, larger population cohort studies on complementary feeding. Conclusion
In conclusion, it is predicted that increasing internet usage will gain an important place in obtaining information on complementary nutrition in the future. Therefore, in order to reach accurate scientific information, it is necessary to present information on the internet at a professional level.
Acknowledgment
The authors are thankful to all our parents who voluntarily 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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Mehmet Semih Demirtas, Huseyin Erdal. Sources used to obtain information and their impact on the mothers’ complementary feeding practices. Ann Clin Anal Med 2021;12(5):587-591
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