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Orhan Lepara

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Amira Jagodić Ejubović, M. Ejubović, Rijad Jahić, Amer Brkovic, Emina Letic, Milorad Vujnic, O. Lepara, Avdo Kurtović, Minela Bećirović et al.

Background Acute pancreatitis (AP) is a condition with various etiological factors, marked by the sudden onset of inflammation in the pancreatic tissue. Predicting the severity and potential mortality of AP involves analyzing clinical data alongside laboratory tests and imaging. Among several grading methods with strong predictive capabilities for illness severity and mortality, the Bedside Index for Severity in Acute Pancreatitis (BISAP) score is notable. This study aims to explore the potential role of laboratory markers, specifically red cell distribution width (RDW), RDW/platelet (PLT) ratio, and mean platelet volume (MPV), in predicting disease severity, with patients being stratified according to the BISAP scoring system. Materials and methods This research included 161 patients hospitalized at Cantonal Hospital Zenica in Zenica, Bosnia and Herzegovina, with a diagnosis of AP. The BISAP score was determined based on laboratory and radiological analyses. This score was used to evaluate potential correlations between laboratory findings such as RDW, RDW/PLT ratio, and MPV. Results The age range was significantly higher in patients with BISAP scores ≥3 (68 years, 64-76) compared to those with BISAP scores <3 (59.5 years, 42.75-69) (p = 0.000). RDW values were also significantly higher in patients with BISAP scores ≥3 (15.6%, 14-16.9) compared to those with BISAP scores <3 (13.5%, 13-14.1) (p = 0.000). Hospital stay duration was significantly longer for patients with BISAP scores ≥3 (9 days, 6-11) compared to those with BISAP scores <3 (5 days, 5-7) (p = 0.000). Additionally, the RDW/PLT ratio was significantly lower in patients with BISAP scores <3 (0.063 ± 0.02) compared to those with BISAP scores ≥3 (0.09 ± 0.059) (p = 0.012). Conclusion Our results indicate a significant difference in RDW/PLT ratios between patient severity groups based on BISAP scores (scores <3 vs. ≥3). This suggests that the RDW/PLT ratio may serve as a useful predictor for assessing the severity of AP. However, further research is needed to explore the full potential of the RDW/PLT ratio in evaluating AP patients.

Introduction: Despite ongoing findings on the relationship between liver fibrosis in nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS), this association in diabetic patients remains unclear. Early diagnosis of liver fibrosis is important due to the easily available diagnostic tools, such as noninvasive indices that combine clinical and laboratory variables, and the possibility of preventing its complications in type 2 diabetes mellitus (T2DM) patients with MetS. Objective: This study examines the potential predictive values of non-invasive liver fibrosis indices for MetS in T2DM patients. Patients and methods: Over the course of a two-year prospective, observational, clinical study, 80 individuals with T2DM randomly selected from the Diabetes Counseling Centers of the Public Institution Health Center of Sarajevo Canton were divided into two groups: T2DM-MetS and T2DM-non-MetS, based on the development of MetS. The study included individuals with T2DM aged 30 to 60 who were clinically diagnosed without MetS, voluntarily agreed to participate, and provided complete data in the collection forms. Serum samples from the patients were assessed for levels of liver enzymes, platelet counts, total cholesterol, high-density lipoprotein cholesterol, fasting glucose, and triglycerides. Various equations were utilized to calculate liver fibrosis indices, including the Aspartate Aminotransferase to Platelet Ratio Index (APRI), Aspartate Aminotransferase to Gamma-Glutamyl Transferase to Platelet Ratio (AGPR), Aspartate Aminotransferase to Alanine Aminotransferase Ratio to Platelet Ratio Index (AARPRI), Fibrosis-4 (FIB-4) Index, Forns Index, and Gamma-Glutamyl Transpeptidase to Platelet Ratio (GPR). Receiver operating characteristic (ROC) analysis was utilized to determine the usefulness of noninvasive liver fibrosis indices for diagnosing MetS in individuals with T2DM. Logistic regression analysis was used to predict the onset of MetS in T2DM patients. Results: Significant differences in the values of APRI (p<0.001), AGPR (p<0.05), AARPRI (p<0.001), and the FIB-4 index (p=0.001) were observed in T2DM-MetS individuals compared to T2DM-non-MetS. According to ROC analysis, the area under the curve (AUC) was found to be highest for APRI (0.84), followed by FIB-4 (0.783) and AARPRI (0.747). Logistic regression analysis identified APRI as an independent positive predictor of MetS (OR 18.179, 95% CI 6.035-24.58, p=0.015). Conclusion: This research highlights the effectiveness of the APRI index as a reliable predictor of MetS development in individuals with T2DM.

Almira Hadžović-Džuvo, A. Valjevac, Asija Začiragić, Alen Kekić, O. Lepara

Aim This study aimed to assess the impact of forced repeated swimming stress on serum adiponectin and endothelin-1 levels in Wistar rats, comparing the effects between those fed a standard diet and those on a high-fat diet. Methods Twenty adult male Wistar rats were divided into two dietary groups: a standard food diet group (NFD, n=10) and a high-fat diet group (HFD, n=10). Both groups underwent daily forced swimming stress for six days, with durations increasing from 5 to 30 minutes. The protocol finished in an acute bout of swimming exercise on the seventh day with a duration of 40 minutes. Adherence to ethical guidelines was strictly maintained, and serum adiponectin and endothelin-1 levels were measured pre- and post-exercise using the ELISA method. Results Before swimming, the mean adiponectin levels were 4.30±1.50 ng/mL in the NFD group and 3.53±0.70 ng/mL in the HFD group. Post-exercise, these levels significantly decreased to 2.4±0.84 ng/mL (p=0.003) and 1.58±0.23 ng/mL (p=0.001), respectively. Endothelin-1 levels also showed significant decreases from 0.86 pg/mL (0.74-0.87) to 0.49 pg/mL (0.43-0.62) (p=0.003) in the NFD group, and from 0.89 pg/mL (0.86-0.93) to 0.69 pg/mL (0.60-0.75) (p=0.027) in the HFD group after swimming. Conclusion The study highlighted the significant effects of forced swimming stress on lowering serum adiponectin and endothelin-1 levels in Wistar rats, with more pronounced decreases observed in rats on a high-fat diet. The results of the study suggest the potential of exercise as a crucial component of strategies aimed at managing obesity and improving cardiovascular health, emphasizing the interaction between physical stress and dietary factors on metabolic and cardiovascular biomarkers.

Asija Začiragić, Marija Mikić, A. Dervišević, O. Lepara, N. Avdagić, N. Babic, Almir Fajkić, A. Valjevac

Objectives: The purpose of the present study was to assess neck-to-height ratio (NtHR) and its possible association with other anthropometric measures of obesity and blood pressure (BP) values in Bosnian university students stratified by new 2017 American College of Cardiology/American Heart Association Task Force hypertension (HT) guidelines.Methods: The present study included 417 subjects with median age 20 (19-21) years that were divided into normal BP, elevated BP, stage 1 HT, and stage 2 HT groups based on BP measurements using auscultatory methods. Standard anthropometric indices including neck circumference (NC) were measured. NtHR (cm/m) was calculated in each participant based on the NC and height. Differences between groups were assessed by Kruskal-Wallis followed by Man-Whitney test and correlations were determined by Spearman test.Results: The prevalence of elevated BP was 19.2%, stage 1 HT 21.6%, and stage 2 HT 11.0 %. NtHR was highest in the stage 2 HT group. NtHR correlated significantly with all anthropometric measures in all groups. No correlation between NtHR, systolic BP, and diastolic BP was found, except in the stage 1 HT group, where a significant correlation between NtHR and systolic BP was uncovered.Conclusions: Based on the observed correlations between NtHR and standard measures of obesity, NtHR could be included in clinical practice, since it is simple and does not induce discomfort. The high prevalence of elevated BP found in the present study suggests HT prevention requires the implementation of programs aimed at promoting healthy dietary habits, physical activity, as well as effective stress management and coping mechanisms.

Almir Fajkić, Rijad Jahić, Almira Hadžović-Džuvo, O. Lepara

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common chronic liver condition. Due to pathophysiological processes, MASLD's relation to type 2 diabetes mellitus (T2DM) is still unclear, especially when the role of adipocytokines is taken into consideration. Objective: This study aims to examine the potential predictive value of adiponectin and resistin for MASLD in T2DM. Patients and methods: In a two-year study, 71 T2DM patients were categorized into MASLD-T2DM and non-MASLD-T2DM groups according to MASLD development. Serum samples were tested for resistin, adiponectin, high-density lipoprotein cholesterol, fasting glucose, and triglycerides. An appropriate equation is used to calculate the adiponectin/resistin (A/R) index. The optimal cut-off values for differentiating MASLD patients from non-MASLD patients were determined using receiver operating characteristic (ROC) curves and the corresponding areas under the curve (AUC). To predict the onset of MASLD in patients with T2DM, a logistic regression analysis was performed. Results: There were significant differences in adiponectin (p<0.001), resistin (p<0.001), and A/R index (p<0.001) between T2DM individuals with and without MASLD. The ROC curve for resistin produced an AUC of 0.997 (p<0.001) with a sensitivity of 96.1% and a specificity of 100% for the cut-off point of 253.15. Adiponectin (OR, 0.054; 95% CI, 0.011-0.268; p<0.001) and resistin (OR, 1.745; 95% CI, 1.195-2,548; p=0.004) were found to be independent predictors for MASLD by logistic regression analysis. Conclusion: This study confirms the potential of adiponectin and resistin as predictors of MASLD development in T2DM.

BACKGROUND Metabolic syndrome (MetS) is a group of comorbidities related to regulating hyperglycemia and acute cardiovascular incidents and complications. With the increasing prevalence in individuals with type 2 diabetes mellitus (T2DM), MetS represents an increasing public health problem and clinical challenge, and early diagnosis is necessary to avoid the accelerated development of diabetic complications. OBJECTIVE To investigate the role of Complete Blood Count-derived Inflammation Indexes (CBCIIs) in predicting MetS in T2DM individuals. METHODS The study was designed as a two-year prospective study and included 80 T2DM individuals divided into MetS and non-MetS groups based on MetS development over two years. The sera samples were analyzed for complete blood count parameters and C-reactive protein (CRP). Based on the laboratory test results, 13 CBCIIs were calculated and analyzed. The receiver operating characteristic (ROC) curve and their corresponding areas under the curve (AUC) were used to determine prognostic accuracy. RESULTS There were significant differences between T2DM participants with Mets and those without MetS concerning Neutrophil to Platelet Ratio (NPR) values (p< 0.001), Neutrophil to Lymphocyte and Platelet Ratio (NLPR) (p< 0.001), Platelet to Lymphocyte Ratio (PLR) (p< 0.001), Lymphocyte to C-reactive protein Ratio (LCR) (p< 0.001), C-reactive protein to Lymphocyte Ratio (CRP/Ly) (p< 0.001), Systemic immune inflammation index (SII) (< 0.001), and Aggregate Index of Systemic Inflammation (AISI) (p= 0.005). The results of ROC curve analysis have shown that the LCR (AUC of 0.907), CRP/Ly (AUC of 0.907) can serve as excellent predictors, but NPR (AUC of 0.734), NLRP (AUC of 0.755), PLR (AUC of 0.823), SII (AUC of 0.745), and AISI (AUC of 0.688) as good predictors of MetS in T2 DM individuals. CONCLUSION This study confirms the reliability of the CBCIIs as novel, simple, low cost and valuable predictors of MetS developing in T2DM.

F. Nišić, Aida Pidro Gadzo, Almir Fajkić, Aida Nišić, Ajla Pidro Mioković, Goran Damjanovic, E. Begić, N. Bešlić, O. Lepara

Objective: Advanced proliferative diabetic retinopathy can lead to serious ophthalmological complications, including blindness. This research aimed to determine visual outcomes after pars plana vitrectomy secondary to proliferative diabetic retinopathy, as well as to identify its predictors. Methods: This prospective clinical study was performed in the Ophthalmology Clinic of the Clinical Centre University of Sarajevo. 60 subjects (eyes) with performed pars plana vitrectomy secondary to proliferative diabetic retinopathy were included in the study. Results: After univariate linear regression analysis, glucose, HbA1c, vascular endothelial growth factor, previous pan-retinal laser photocoagulation, baseline best corrected visual acuity, gas injection, vitreous haemorrhage, iris rubeosis, and glaucoma were found to be statistically significant parameters associated with postoperative visual outcome (p<0.05). Multivariate linear regression analysis was performed to evaluate the association between factors and postoperative best corrected visual acuity. Only intravitreal vascular endothelial growth factor concentration, previous pan-retinal photocoagulation, and gas injection remained statistically significant associated with postoperative best corrected visual acuity (p<0.05). Conclusion: Vitrectomy is an effective treatment for advanced proliferative diabetic retinopathy. Factors correlated with the better visual outcome are good systemic control, previous pan-retinal photocoagulation, low intravitreal vascular endothelial growth factor concentration, younger age, intraoperative internal gas tamponade, combined phacoemulsification and pars plana vitrectomy surgery, and the absence of postoperative complications. Abbreviations: PDR = proliferative diabetic retinopathy, VEGF = vascular endothelial growth factor, TDR = tractional retinal detachment, BCVA = best corrected visual acuity, DR = diabetic retinopathy, RDD = rhegmatogenous retinal detachment, NVG = neovascular glaucoma, BRVO = branch retinal vein occlusion, CBC = complete blood count, DBT = differential blood count, ESR = erythrocyte sedimentation rate, HbA1c = glycosylated hemoglobin, PHACO = phacoemulsification, ILM = internal limiting membrane, PPV = pars plana vitrectomy, IOP = intraocular pressure, PRP = pan-retinal photocoagulation, ETDRS = Early treatment diabetic retinopathy study

G. Bakalović, Tarik Jarkoč, N. Begić, O. Lepara, D. Bokonjić, Dušan Mihajlović, A. Pašić, Almir Fajkić

Aim Compare the efficacy of nebulized hypertonic saline and normal saline in the treatment of infants hospitalized for bronchiolitis. Methods This retrospective study was conducted at the Department of Pulmonology, Paediatric Clinic, Clinical Centre University of Sarajevo, covering the period from January 2015 to December 2019 and comprising 380 children aged between 1 and 12 months having bronchiolitis. One group received nebulized hypertonic saline (NHS, 3% NaCl)), and another group received nebulized normal saline (NNS, 0.9% NaCl). The control group did not receive any of these treatment options. Results There was no statistically significant difference between the treatment groups regarding length of hospital stay (LOS) and Clinical Severity Score (CSS) at admission and discharge as well as in oxygen therapy duration and antibiotic use, the duration of symptoms before hospital admission, frequency of nasal discharge, elevated temperature, dyspnoea, cough and dehydration. Conclusion The results of this study are consistent with several recent studies or meta-analyses and support the evidence against the use of NHS in hospitalized infants with mild or moderate bronchiolitis.

A. Durak-Nalbantić, E. Begić, A. Begić, A. Džubur, O. Lepara, R. Baljic, A. Hamzić-Mehmedbašić, D. Rebić, E. Hodžić et al.

Introduction: Heart failure (HF) still remains as one of the most common causes of hospital admission with a high mortality rate. Aim: To investigate the possible prognostic role of brain natriuretic peptide (BNP), high-sensitivity (hs) cardiac troponin (cTn) I, cystatin C, and cancer antigen 125 (CA125) in the prediction of decompensation after an index hospitalization and to investigate their possible additive prognostic value. Patients and Methods: Two hundred twenty-two patients hospitalized with acute HF were monitored and followed for 18 months. Results: BNP at discharge has the highest sensitivity and specificity in the prediction of decompensation. For a cutoff value of 423.3 pg/ml, sensitivity was 64.3% and specificity was 64.5%, with a positive predictive value of 71.6% and an area under the curve (AUC) of 0.69 (P < 0.001). The hazard risk (HR) for decompensation when the discharge BNP was above the cutoff value was 2.18. Cystatin C, at a cutoff value of 1.46 mg/L, had a sensitivity of 57% and specificity of 57.8%, with a positive predictive value of 65.8% and an AUC of 0.59 (P = 0.028). CA125, in the prediction of decompensation in patients with acute heart failure (AHF) and at a cutoff value of 80.5 IU/L, had a sensitivity of 60.5% and specificity of 53.3%, with a positive predictive value of 64.5% and an AUC of 0.59 (P = 0.022). The time till onset of decompensation was significantly shorter in patients with four versus three elevated biomarkers (P = 0.047), with five versus three elevated biomarkers (P = 0.026), and in patients with four versus two elevated biomarkers (P = 0.026). The HR for decompensation in patients with five positive biomarkers was 3.7 (P = 0.001) and in patients with four positive biomarkers was 2.5 (P = 0.014), compared to patients who had fewer positive biomarkers. Conclusion: BNP, cystatin C, and CA125 are predictors of decompensation, and their combined usage leads to better prediction of new decompensation.

S. Šegalo, E. Kiseljaković, Emsel Papić, A. Jogunčić, Aleksandra Pašić, Mubera Sahinagic, O. Lepara, L. Sporišević

Background: Coronavirus disease 2019 (COVID-19) can cause a wide clinical spectrum, ranging from asymptomatic to severe disease with a high mortality rate. In view of the current pandemic and the increasing influx of patients into healthcare facilities, there is a need to identify simple and reliable tools for stratifying patients. Objective: Study aimed to analyze whether hemogram-derived ratios (HDRs) can be used to identify patients with a risk of developing a severe clinical form and admission to hospital. Methods: This cross-sectional and observational study included 500 patients with a confirmed diagnosis of COVID-19. Data on clinical features and laboratory parameters were collected from medical records and 13 HDRs were calculated and analyzed. Descriptive and inferential statistics were included in the analysis. Results: Of the 500 patients, 43.8% had a severe form of the disease. Lymphocytopenia, monocytopenia, higher C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were found in severe patients (p < 0.05). Significantly higher neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), neutrophil-to-platelet ratio (NPR), neutrophil-to-lymphocyte-to-platelet ratio (NLPR) and CRP-to-lymphocyte ratio (CRP/Ly) values were found in severe patients (p < 0.001). In addition, they have statistically significant prognostic potential (p < 0.001). The area under the curve (AUC) for CRP/Ly, dNLR, NLPR, NLR, and NPR were 0.693, 0.619, 0.619, 0.616, and 0.603, respectively. The sensitivity and specificity were 65.7% and 65.6% for CRP/Ly, 51.6% and 70.8 for dNLR, 61.6% and 57.3% for NLPR, 40.6% and 80.4% for NLR, and 48.8% and 69.1% for NPR. Conclusion: The results of the study suggest that NLR, dNLR, CRP/Ly, NPR, and NLPR can be considered as potentially useful markers for stratifying patients with a severe form of the disease. HDRs derived from routine blood tests results should be included in common laboratory practice since they are readily available, easy to calculate, and inexpensive.

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