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Rijad Jahić, A. Selimovic, Nabil Naser, M. Čampara, Almir Fajkić

Background: Endocrine-disrupting chemicals (EDCs) represent a group of chemicals which are related to the disturbances in the human hormonal system. Due to the newest research, it was discovered that their actions did not exclusively point to the hormonal system but rather to all organs of the human body. EDCs are metabolized and may excrete the influence on human metabolism. That influence can be related to the activity of different enzymes included in human metabolism. Those effects can be classified as epigenetic effects. Objective: The aim of the study was to make analysis, evaluation, examination and determination of the possible mechanisms through which EDCs may interact with different metabolically-driven diseases. Methods: This paper represents a review article that includes original and review articles that were used being published in the following databases: Medline/PubMed, ScienceDirect, Oxford Academic, and Google Scholar. Results: EDCs interact through nuclear or steroid receptors excreting their influence onto diseases such as obesity, metabolic syndrome (MetS) and non-alcoholic fatty liver disease (NAFLD). Those mechanisms are mediated through metabolic or immunological pathways. It encompasses different types of hormones, such as vistafin or inflammatory cytokines. Conclusion: It has been noticed that EDCs may influence the appearance of specifically related diseases in offspring excreting epigenetic effects. Further research must be oriented towards potential consequences and ideal pathways for prevention and treatment options.

Introduction: Diabetes mellitus type 2 (T2DM) significantly increase the risk of cardiovascular (CV) disease morbidity and mortality. This study aimed to evaluate the potential of some novel anthropometric indices and adipocytokines to evaluate CV risk among T2DM patients. Methods: A total of 112 patients (men, 57; women, 55) with T2DM visiting Family Medicine and Endocrine counseling in the area of Health centers of Sarajevo Canton were included in this study. The sera samples were analyzed for fasting blood glucose (FBG), HbA1c, lipid profile parameters, adiponectin, and resistin levels. The Adiponectin/Resistin Index (A/R Index) was estimated using the formula. The novel anthropometric measurements, including the Conicity index (CI), Lipid Accumulation Product (LAP), visceral adiposity index (VAI), abdominal volume index (AVI), and Body adiposity index (BAI) were estimated. The 10-year risk for coronary heart disease (CHD) and fatal coronary heart disease (fCHD) is calculated by using UKPDS Risk software. Results: The adiponectin was shown as a statistically significant negative association with CHD in female subjects, and the A/R index as a statistically significant association with CHD and fCHD in male subjects. The AVI is superior to the CI, LAP, VAI, and BAI in assessing cardiometabolic risk in T2DM patients. Conclusions: Our study indicated that measuring adiponectin and A/R index, together with measuring AVI as a measure of general volume, can be used as surrogates in the evaluation of high cardiovascular risk among T2DM patients.

Introduction: Diabetes mellitus type 2 (T2DM) significantly increase the risk of cardiovascular (CV) disease morbidity and mortality. This study aimed to evaluate the potential of some novel anthropometric indices and adipocytokines to evaluate CV risk among T2DM patients. Methods: A total of 112 patients (men, 57; women, 55) with T2DM visiting Family Medicine and Endocrine counseling in the area of Health centers of Sarajevo Canton were included in this study. The sera samples were analyzed for fasting blood glucose (FBG), HbA1c, lipid profile parameters, adiponectin, and resistin levels. The Adiponectin/Resistin Index (A/R Index) was estimated using the formula. The novel anthropometric measurements, including the Conicity index (CI), Lipid Accumulation Product (LAP), visceral adiposity index (VAI), abdominal volume index (AVI), and Body adiposity index (BAI) were estimated. The 10-year risk for coronary heart disease (CHD) and fatal coronary heart disease (fCHD) is calculated by using UKPDS Risk software. Results: The adiponectin was shown as a statistically significant negative association with CHD in female subjects, and the A/R index as a statistically significant association with CHD and fCHD in male subjects. The AVI is superior to the CI, LAP, VAI, and BAI in assessing cardiometabolic risk in T2DM patients. Conclusions: Our study indicated that measuring adiponectin and A/R index, together with measuring AVI as a measure of general volume, can be used as surrogates in the evaluation of high cardiovascular risk among T2DM patients.

Abstract Background: Low-grade chronic inflammation is an important feature of chronic kidney disease (CKD). Aim: To determine the values of C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in patients with different stages of CKD and to examine how they change depending on the progression of renal damage. Materials and methods: A cross-sectional descriptive comparative study included 157 subjects at different stages of CKD which was assessed based on glomerular filtration rate (GFR) calculated according to the MDRD equation. CRP was analyzed by an immunoturbidimetric method. NLR and PLR were calculated by a mathematical calculation after a blood count was performed. Results: The present study showed an increase in serum creatinine, CRP, and NLR values with progression of renal failure. There was a statistically significant difference in the creatinine and CRP concentrations between groups with different stages of CKD (p <0.001 for all comparisons). A significant positive correlation was found between NLR and CRP, while negative, significant correlations were observed between NLR and eGFR as well as between PLR and eGFR. There was a slight increase in PLR value with the progression of renal impairment, but the correlation between PLR and CRP was not significant. Conclusion: These results suggest that NLR, together with CRP, may serve as an indicator of systemic low-grade inflammation progression in patients with CKD. Larger prospective studies are required to observe the possibility of using NLR as a surrogate marker for CRP in patients with CKD.

F. Nišić, Aida Pidro, O. Lepara, Almir Fajkić, Ajla Pidro Mioković, E. Suljic, Aida Nišić, I. Kovačević

Objective: This study aimed to determine the intravitreal concentration of VEGF in eyes with PDR and to evaluate the effects of previous PRP on its level. Methods: It was a cross-sectional study performed at the Clinical Centre University. It included 90 eyes surgically treated with PPV, divided into three groups, group A - patients with PDR with previous PRP, group B - patients with PDR without previous PRP, and group C - PPV performed due to the indication unrelated to diabetes. A vitreous sample was obtained during PPV, and the VEGF concentration was determined using an Enzyme-linked immunosorbent assay test (ELISA). Shapiro-Wilk, nonparametric tests Kruskal-Wallis, Mann-Whithney U test, ANOVA and Spearman’s correlation test were used. Results: The highest vitreous VEGF concentration was in group B - 972.96 (743.33-1149.13) and was higher than in group A - 69.22 (37.33-225.15) and in group C - 19.93 (1.15-32.17) (p<0.001). There was a positive correlation between VEGF vitreous concentration and glucose level in group A patients (Rho=0.410; p=0.027). Conclusion: As a treatment before PPV surgery, PRP showed to be effective in the reduction of VEGF levels, which also highlighted a decrease in complications during and postoperatively. Abbreviations: DRS = Diabetic Retinopathy Study, PDR = proliferative diabetic retinopathy, VEGF = vascular endothelial growth factor, PRP = pan-retinal photocoagulation, PPV = pars plana vitrectomy, HbA1c = glycosylated hemoglobin, ETDRS = Early treatment diabetic retinopathy study, ESR = erythrocyte sedimentation rate, BCVA = best corrected visual acuity, OCT = optical coherent tomography, ILM = internal limiting membrane, PHACO = phacoemulsification, IOL = intraocular lens, ELISA = Enzyme-linked immunosorbent assay test, AUC = area under the curve, DME = diabetic macular oedema, TDR = tractional retinal detachment, VMT = vitreomacular traction

A. Mujaković, T. Kovačević, E. Begić, Almir Fajkić, Goran Barić, Anida Jamakosmanović, N. Ismic, P. Kovačević

Objective. To identify the type of the non-invasive ventilatory treatment for patients diagnosed with chronic obstructive pulmonary disease (COPD), with respiratory status deteriorated by COVID-19 pneumonia, and in need of treatment in the Intensive Care Unit (ICU). Materials and Methods. This cross-sectional study was conducted over a one-year period in the medical intensive care units of two hospitals. As the patients’ clinical condition deteriorated and the parameters of the arterial blood gas (ABG) analysis worsened, oxygen support was applied via a high flow nasal cannula (HFNC) or by non-invasive positive pressure ventilation (NPPV). According to the control values of the arterial oxygen saturation (SaO2) and the parameters of ABG, the patients were enabled to be transferred between the two types of non-invasive ventilatory support. The primary outcome was the length of hospital stay, while secondary outcomes were the rate of intubation, the mortality rate, and respiratory support-free days. Results. Out of 21 critical patients with COPD and COVID-19, 11 (52.4%) were initially treated with NPPV and 10 (47.6%) with HFNC. The ages (67±9.79 in NPPV group vs. 70.10±10.25 in HFNC group) and severity of illness (SOFA score 5 (3.5) in NPPV group vs. 5 (2.8) in HFNC group) were similar between the two groups. Switching the mode of respiratory support was more common in NPPV (58.3% in survivor group vs. 41.7% in non-survivor group). Patients treated with NPPV compared to HFNC had a nominally longer length of stay (15 (11) vs. 11.5 (4.25)), and higher risk of intubation (66.7% vs. 33.3%) and mortality (66.7% vs. 33.3%), but the comparisons did not reach statistical significance. Survivors had significantly longer Medical Intensive Care Unit and hospital stays, but significantly lower FiO2 (0.60 vs.1) and higher values of PaO2/FiO2 (78(32.4) vs. 56.3(17.8)) than non-survivors. All patients were treated with corticosteroids, and the duration of treatment was similar between groups. Conclusion. In critically ill patients with COPD and COVID-19, both HFNC and NPPV were commonly used as the initial mode of ventilation. Switching to a different mode and adverse patient outcomes were more frequent in patients initially treated with NPPV. Survivors had higher values of PaO2/FiO2 than non-survivors.

Aim To investigate infl uence of neutrophil-to-lymphocyte ratio (NLR) and proatherogenic risk factors to improve the accuracy of pneumonia severity index (PSI) in the prediction of community acquired pneumonia (CAP) outcome in healthy individuals. Methods A retrospective observational cross-sectional study conducted at the Clinic for Pulmonary Diseases and Tuberculosis "Podhrastovi", University Clinical Centre Sarajevo, included 83 patients with the diagnosis of CAP during the period March 2019-March 2021. Once diagnosed with CAP, PSI score was calculated and according to its value the need for hospital treatment was identifi ed. Patients were divided in two groups: low risk of CAP (PSI <90), and high risk of CAP (PSI> 90). Results The overall average hospital stay was 22.76±10.154 days. In the patients diagnosed with CAP, a positive correlation was established between the following parameters PSI score and age (r=0.670; p<0.01), C-reactive protein-CRP (rho=0.287; p<0.01), leukocytes (rho=0.406; p<0.01), NLR (rho=0.313; p<0.01) and platelet to lymphocyte ratio (PLR) (0.296; p<0.05). CRP, leukocytes, NLR and PLR were statistically signifi cantly higher in patients with high risk of CAP compared to patients with low risk of CAP. Diastolic blood pressure, lymphocytes, eosinophils were signifi cantly lower in patients with high risk of CAP (p<0.05;) compared to patients with low risk of CAP (p<0.01). The optimal cut-off value of NLR for CAP patients was 3.089 with an estimated area under curve (AUC) of 0.664. Conclusion Proatherogenic parameters such as age, systolic blood pressure and leukocytes in combination with neutrophil-lymphocyte count ratio could improve accuracy of the pneumonia severity index in community acquired pneumonia outcome.

Background: Conflicting data exist on traditional lipid profiles in patients with Alzheimer’s disease (AD) and vascular dementia (VD), whereas scarce number of studies evaluated non-traditional lipid profiles in patients with AD and VD. Studies have shown that ethnic background may affect lipid profile. Objective: The aim of the present study was to conduct comparative assessment of traditional and non-traditional lipid profiles in Bosnian patients with AD and VD. Methods: A controlled, cross-sectional study was performed with 66 patients with AD, 50 patients with VD, and 60 control subjects. The Montreal Cognitive Assessment (MoCA) test was used for an evaluation of the global cognitive function. The Hachinski ischemic score was used to distinguish patients with VD from those with AD. Plasma total cholesterol (TC), high-density lipoprotein -cholesterol (HDL-C), and triglycerides (TG) levels were determined using standard enzymatic colorimetric techniques, whereas the Friedewald formula was used to calculate low-density lipoprotein-cholesterol (LDL-C) levels. The non-traditional lipid indices such as TG/HDL-C, TC/HDL-C, and LDL-C/HDL-C ratio were separately calculated. The differences between the groups were analyzed with ANOVA followed by the Tuckey posthoc test or with the Kruskal Wallis test followed by the Mann-Whitney test. Results: Results of the present study have shown that patients in AD group had significantly lower level of TC, TG, LDL-C, VLDL-C, Non-HDL-C and significantly lower atherogenic index compared to the control group (CG) and compared to the VD patients. Significant difference in values of TG and VLDL-C was observed between VD and the CG, whereas no significant difference in values of TC, LDL-C, atherogenic index and Non-HDL-C was observed between these two groups. Our results have also shown that TG/HDL-C, TC/HDL-C, and LDL-C/HDL-C ratios were significantly lower in AD patients compared to the VD and CG. Moreover, TG/HDL-C ratio was significantly lower in VD compared to the CG. However, a significant difference in TC/HDL-C and LDL-C/HDL-C was not observed between VD and the CG. Conclusion: Based on the results of the present study it can be deduced that there is a difference in traditional and non-traditional lipid profiles between AD and VD patients of Bosnian descent. Obtained results suggest that lipids are decreased in AD and in VD to a certain extent. However, since there is an inconsistence in literature whether there is an association between cholesterol and cognition, large prospective studies are required to elucidate this controversy.

Background: Lipids and lipoproteins are significantly involved in maintaining structural and functional components of the human brain and neurons, but their role in the development of Alzheimer’s disease (AD) and vascular dementia (VD) remains unclear. Objective: The aim of the present study was to explore the differences in the standard and novel lipid profile parameters in patients with AD and VD, stratified by the degree of cognitive impairment (CI). Methods: Present study included 66 patients with AD, 50 patients with VD, and 60 control subjects. For an evaluation of the global cognitive function the Montreal Cognitive Assessment (MoCA) test was used. In order to distinguish patients with VD from those with AD the Hachinski ischemic score was used. Plasma total cholesterol (TC), high-density lipoprotein -cholesterol (HDL-C), and triglycerides (TG) levels were determined using standard enzymatic colorimetric techniques, whereas the Friedewald formula was used to calculate low-density lipoprotein-cholesterol (LDL-C) levels. The non-traditional lipid indices such as TG/HDL-C, TC/HDL-C, and LDL-C/HDL-C ratio were separately calculated. The differences between the groups were analyzed with the Kruskal Wallis test followed by the Mann-Whitney test or with ANOVA followed by the Tuckey posthoc test. Results: Results of the conducted study have found that the patients in AD group with moderate CI and patients in AD group with severe CI exhibited significantly lower levels of serum TC, TG, LDL-C, VLDL-C, Non- HDL-C, atherogenic index, TG/HDL-C, TC/HDL-C and LDL-C/HDL-C compared to cognitively normal control subjects. Moreover, patients in VD group with severe and moderate CI had significantly lower level of TG compared to control group of subjects. Our results have also shown that patients in AD group with moderate CI had significantly lower level of TC, TG, LDL-C, Non-HDL-C, atherogenic index, TG/HDL-C, TC/HDL-C compared to VD patients with moderate CI. In addition, patients in AD group with severe CI had significantly lower level of TC, LDL-C, Non-HDL-C and TC/HDL-C compared to VD patients with severe CI. Conclusion: The results of this study have shown dysregulation of lipid metabolism in AD and VD patients with different degree of CI. In both moderate and in severe CI, patients with AD had lower levels of majority of standard and novel lipid parameters compared to patients with VD. Further larger prospective studies are required to elucidate the accuracy of standard and novel lipid parameters in the assessment of different degree of CI in AD and VD.

A. Džubur, Delila Lisica, Emir Hodžić, E. Begić, O. Lepara, Almir Fajkić, Ena Gogić, M. Ejubović

Aim To examine the prevalence of depression in patients after acute myocardial infarction (AMI), as well as the relationship between the depression and quality of life. Methods The survey was conducted via sociodemographic questionnaire, Beck Depression Inventory (BDI), and Short Form 36 Health Survey questionnaire (SF-36). The result of SF-36 is expressed in subscales that make up the health status profile, i.e. physical functioning, physical role, emotional role, social functioning, mental health, vitality, pain and general health. Results The study included 120 patients, of which 70 males and 50 females aged between 41 and 88 years (mean 64.73±11.218). All patients were hospitalized at the Clinical Centre of the University of Sarajevo, Clinic for Cardiovascular Disease and Rheumatism, due to complications caused by AMI. After AMI 59 (49.17%) patients had depression. Depression was negatively associated with physical functioning, physical role, emotional role, social functioning, mental health, vitality, pain and general health. Physical functioning (r= -0.701; p<0.01) and physical role (r = -0.538; p<0.01) had the highest correlation with depression. Conclusion The evaluation of depressive symptoms after AMI is imperative, because the appearance of symptoms could have an effect on the patient's quality of life.

Background/Aim. For the first time, we evaluated and presented the socio-demographic characteristics, clinical manifestations and laboratory findings of hospitalized coronavirus disease 2019 (COVID-19) patients from Canton Sarajevo, Bosnia and Herzegovina. Methods. This retrospective, single-centre study included 159 RT-PCR verified COVID-19 patients (92 mild/moderate; 67 severe/critical) consecutively hospitalized at the General Hospital "Prim. dr Abdulah Nakaš" in Sarajevo, Bosnia and Herzegovina. Socio-demographic, clinical, and laboratory data on admission were retrospectively obtained from each patient's electronic medical record and patient files by two experienced physicians. Results. 43.4% of the patients belonged to the age range of 46-65 years; 71.1% were men, and 68.6% had comorbidities; hypertension was the most prevalent comorbidity (100%), followed by diabetes (91.7%) and ischemic heart disease (35.8%). The leading clinical symptoms were fever (87.44%), tiredness (77.8%), and body/muscle aches (70.3%). There was significant reduction of blood oxygen saturation (p = 0.005), and significant elevation of D-dimer (p = 0.003), CRP (p = 0.044), and fasting plasma glucose (p = 0.047) in the severe/critical patients group compared to mild/moderate group. Conclusion. Older age, the male gender, confirmed comorbidities, decreased blood oxygen saturation, increased levels of CRP, D-dimer, and fasting plasma glucose, together with symptoms of chest pain/shortness of breath and/or diarrhea occurred more frequently in severe/critical than mild/moderate COVID-19 patients.

Different qualitative and quantitative changes in platelets are involved in the pathophysiological processes in inflammatory bowel diseases (IBD): ulcerative colitis (UC) and Crohn's disease (CD). The aim of the study was to determine the diagnostic accuracy of Platelet mass Index (PMI) and other platelet parameters in assessment disease activity in patients with UC and CD. A cross-sectional, observational study consisted of 60 IBD patients (30 UC and 30 CD) and 30 healthy subjects (Control group). Patients were grouped according to disease activity into active and inactive (remission). Platelet count (PLC), Plateletcrit (PCT), Mean Platelet Volume (MPV), Platelet Distribution Width (PDW) and PMI were determined for all study participants. Receiver operating characteristic (ROC) curve and their corresponding areas under the curve (AUC) were used to determine diagnostic accuracy. Although PLC had the highest AUC (0.756) compared to PCT (AUC: 0.731), PDW (AUC: 0.722) and PMI (AUC: 0.724), they all had fair diagnostic accuracy in distinguishing active and inactive UC patients. Discriminatory accuracy of PLC was excellent (AUC: 0.909), PCT and PMI good to excellent (AUC: 0.809 and AUC: 0.893, respectively) and PDW fair (AUC: 0.789) in classifying CD patients as active and inactive. Platelet parameters are simple, routinely available biomarkers more useful for assessing disease activity for patients with CD than for patients with UC. Our results indicate, for the first time, that PMI may serve as a novel and simple marker in identifying whether IBD patients are in the active or inactive phase of the disease.

Different qualitative and quantitative changes in platelets are involved in the pathophysiological processes in inflammatory bowel diseases (IBD): ulcerative colitis (UC) and Crohn's disease (CD). The aim of the study was to determine the diagnostic accuracy of Platelet mass Index (PMI) and other platelet parameters in assessment disease activity in patients with UC and CD. A cross-sectional, observational study consisted of 60 IBD patients (30 UC and 30 CD) and 30 healthy subjects (Control group). Patients were grouped according to disease activity into active and inactive (remission). Platelet count (PLC), Plateletcrit (PCT), Mean Platelet Volume (MPV), Platelet Distribution Width (PDW) and PMI were determined for all study participants. Receiver operating characteristic (ROC) curve and their corresponding areas under the curve (AUC) were used to determine diagnostic accuracy. Although PLC had the highest AUC (0.756) compared to PCT (AUC: 0.731), PDW (AUC: 0.722) and PMI (AUC: 0.724), they all had fair diagnostic accuracy in distinguishing active and inactive UC patients. Discriminatory accuracy of PLC was excellent (AUC: 0.909), PCT and PMI good to excellent (AUC: 0.809 and AUC: 0.893, respectively) and PDW fair (AUC: 0.789) in classifying CD patients as active and inactive. Platelet parameters are simple, routinely available biomarkers more useful for assessing disease activity for patients with CD than for patients with UC. Our results indicate, for the first time, that PMI may serve as a novel and simple marker in identifying whether IBD patients are in the active or inactive phase of the disease.

Introduction Although extracorporeal shock wave lithotripsy (ESWL) is minimally invasive and highly efficient for the management of kidney stones, adverse effects have been described. Available indicators of renal function exhibit insufficient sensitivity in acute renal injury (AKI). We aimed to evaluate the severity of the kidney tissue response to ESWL injury by measuring the urinary neutrophil gelatinase-associated lipocalin (uNGAL), which can indicate AKI in its early phase. Material and methods The prospective, controlled study included 62 patients with nephrolithiasis undergoing single ESWL treatment. uNGAL level was measured before the procedure, and 6 h and 12 h after. Results The median uNGAL level increased by 126.0%, 6 h after ESWL (p <0.001). The growth rate continued and 12 h after was higher by 583.7%, compared to the pre-treatment level (p <0.001). The median value of estimated glomerular filtration rate (eGFR) dropped by 15.3% 12 h after the treatment (p <0.001). It increased by 5.0% in the period 7 days to 3 months after (p <0.001) and after 3 months it was lower by 10.1% compared to pre-ESWL values (p <0.001). uNGAL level after 12 h was significantly negatively associated with eGFR, 12 h, 7 days and 3 months after the ESWL. The sensitivity of uNGAL 12 h after ESWL was 60.6%; its specificity was 75.0%, with a positive predictive value of 74.0% and negative predictive value of 61.7%. Conclusions uNGAL appears to be a useful biomarker for the assessment and prediction of AKI. It was noticed that uNGAL had the highest predictive value 12 h after the ESWL treatment.

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