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Rijad Jahić

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Introduction: Diabetes mellitus is associated with systemic complications, including the development of pulmonary injury, characterized mainly by excessive accumulation of extracellular matrix components and inflammatory cell infiltration in lung tissue. This process is driven by oxidative stress and chronic inflammation, both caused and exacerbated by hyperglycemia. N-acetylcysteine (NAC) and glycine, known for their antioxidant and anti-inflammatory effects, offer potential therapeutic benefits in mitigating diabetes-induced lung injury. Objective: The study aimed to investigate the effects of supplementation by either NAC or glycine or their combination on reducing lung injury in rats with type 1 diabetes Materials and methods: The study used 30 adult Wistar albino rats (10 weeks old, weighing between 180 g and 380 g). Six of them were used as controls, while 24 adult rats (10 weeks old, 180-380 g) with type 1 diabetes, induced through a single intraperitoneal injection of streptozotocin (STZ) at a dose of 55 mg/kg, were randomly assigned to four experimental groups: control (CTL), diabetic (Db), NAC treatment (diabetic+NAC), glycine treatment (diabetic+glycine), and combined NAC and glycine treatment (diabetic+NAC+glycine). NAC (100 mg/kg) and glycine (250 mg/kg) were administered orally for 12 weeks. At the end of the study, lung tissues were collected for histopathological examination. Qualitative, semi-quantitative, and stereological histological analysis was used to analyze structural changes in the lung tissue. Semi-quantitative scoring was carried out to evaluate the extent of inflammation, while stereological analysis was performed to determine the volume density of alveolar spaces and septal connective tissue. The semi-quantitative scoring included scores ranging from 0 (absent), 1 (minimal), 2 (mild), 3 (moderate), to 4 (severe). Results: Qualitative histological analysis revealed pronounced inflammation and fibrosis in the lungs of untreated diabetic rats, characterized by thickened alveolar septa and immune cell infiltration. Both treatments with NAC and glycine individually reduced inflammation and fibrosis compared to untreated diabetic rats. The greatest improvement was observed in the NAC+glycine group, where the alveolar structure appeared almost normal, with minimal inflammation. Semiquantitative analysis showed statistically significant differences in peribronchial and peribrochiolar infiltrates between the diabetic group (2.16±0.47) and the control group (0.33±0.21, p=0.026). The combination of NAC and glycine significantly reduced peribronchial and peribronchiolar infiltrates (0.33±0.33, p=0.026) compared to the diabetic group. Similarly, septal inflammatory infiltrates were significantly lower in the NAC+glycine group (1±0.36) compared to diabetic rats (3.33±0.33, p=0.004). Total airway inflammatory infiltration was also significantly reduced in the NAC+glycine group (1.33±0.33, p=0.002) compared to the diabetic group (5.5±0.5). Conclusion: As the combination of NAC and glycine demonstrated protective effects against lung inflammation and fibrosis in diabetic rats, a synergistic effect of NAC and glycine in mitigating pulmonary complications associated with type 1 diabetes may be suggested. These findings warrant further exploration of the combination for managing diabetic lung disease and potentially other fibrotic conditions.

Background and Objectives: This study aimed to investigate the novel adiponectin–resistin (AR) index as a predictor of the development of metabolic syndrome (MetS) in individuals with type 2 diabetes mellitus (T2DM). MetS is common in T2DM and increases cardiovascular risk. Adiponectin and resistin, adipokines with opposing effects on insulin sensitivity and inflammation, make the AR index a potential marker for metabolic risk. Materials and Methods: This prospective observational study included 80 T2DM participants (ages 30–60) from Sarajevo, Bosnia and Herzegovina, over 24 months. The participants were divided into two groups: T2DM with MetS (n = 48) and T2DM without MetS (n = 32). Anthropometric data, biochemical analyses, and serum levels of adiponectin and resistin were measured at baseline and every six months. The AR index was calculated using the formula AR = 1 + log10(R) − 1 + log10(A), where R and A represent resistin and adiponectin concentrations. Logistic regression identified predictors of MetS. Results: T2DM patients who developed MetS showed a significant decline in adiponectin levels (40.19 to 32.49 ng/mL, p = 0.02) and a rise in resistin levels (284.50 to 315.21 pg/mL, p = 0.001). The AR index increased from 2.85 to 2.98 (p = 0.001). The AR index and resistin were independent predictors of MetS after 18 months, with the AR index showing a stronger predictive value (p = 0.007; EXP(B) = 1.265). Conclusions: The AR index is a practical marker for predicting MetS development in T2DM participants, improving metabolic risk stratification. Incorporating it into clinical assessments may enhance early detection and treatment strategies.

Introduction: Neovascular glaucoma (NVG) is a severe type characterized by forming new blood vessels on the iris and the anterior chamber angle, often resulting from ischemic retinal diseases. Pars plana vitrectomy (PPV) is a standard surgical procedure for treating various retinal and vitreous conditions. Understanding the risk factors associated with NVG development following PPV is crucial for improving patient outcomes. Objective: To identify and evaluate demographic, clinical, and surgical risk factors associated with developing NVG following PPV. Patients and methods: A prospective cohort study was conducted over two years, involving 60 type 2 diabetes mellitus (T2DM) patients (31 males and 29 females; mean age 60.48±9.63 years) who underwent PPV at the Eye Clinic and Department of Clinical Immunology, University Clinical Center Sarajevo, Sarajevo, Bosnia and Herzegovina. Patients were thoroughly informed about the study, and written informed consent was obtained. Comprehensive data collection included demographic information, medical history, preoperative and postoperative eye examinations, and intraoperative details. Statistical analyses were performed using IBM SPSS Statistics for Windows, Version 21 (Released 2012; IBM Corp., Armonk, New York, United States). Results: Within 12 months postoperatively, 17 patients (28.3%) developed NVG. Significant preoperative risk factors for NVG included prolonged duration of T2DM (p=0.037), elevated preoperative intraocular pressure (IOP) (p=0.024), and higher levels of vascular endothelial growth factor (VEGF) (p=0.011). Intraoperative factors, such as sharp dissection (p=0.000) and operative complications (p=0.004), were also significantly associated with NVG development. Multivariate logistic regression analysis identified prolonged T2DM duration (OR 1.132, p=0.023), increased preoperative IOP (OR 1.192, p=0.029), elevated VEGF levels (OR 1.002, p=0.016), and intraoperative sharp dissection (OR 0.114, p=0.006) as independent risk factors. Conclusions: Multiple preoperative and intraoperative factors influence the development of NVG post-PPV. Prolonged T2DM duration, elevated preoperative IOP, high VEGF levels, and specific intraoperative techniques significantly increase the risk of NVG. These findings underscore the importance of careful preoperative assessment and tailored intraoperative strategies to mitigate NVG risk in PPV patients.

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.

Aim: To assess Red blood cell Distribution Width (RDW) and platelet indices values in patients with type 2 diabetes mellitus (T2DM) and to verify its association with kidney dysfunction (KD). Patients and Methods: A cross-sectional study included 149 T2DM subjects divided into two groups with (T2DM – KD; n=52) and without (T2DM-nKD; n=97) presence of kidney dysfunction and 30 healthy subjects. White Blood Cells (WBC) count, C-reactive protein (CRP), fibrinogen, RDW, platelet indices, urea, and creatinine, were measured in all participants. Kidney function was evaluated by the estimated glomerular filtration rate (eGFR) calculated using the simplified Modification of Diet in Renal Disease (MDRD) formula. Results: T2DM-KD subjects showed statistically significantly higher values of the parameters RDW (p<0.01), Mean Platelet Volume - MPV (p<0.01), Platelet Distribution Width-PDW (p<0.01), Platelecrit-PCT (p<0.01), and Platelet Mass Index-PMI (p<0.01) compared to T2DM-nKD subjects, and statistically significantly lower values of the WBC count in T2DM-KD subjects compared to subjects suffering from T2DM without kidney dysfunction (p<0.01). ROC curve analysis revealed that RDW (sensitivity of 80.8%, specificity of 78.3%), MPV (sensitivity of 75%, specificity of 78.4 %), and PDW (sensitivity of 80.8%, specificity of 83.5%) could be used as markers in distinguishing between T2DM subjects with and without kidney dysfunction. Conclusion: This study confirms the reliability of the RDW,MPV, and PDW as simple, low cost and useful markers in distinguishing between T2DM subjects with and without kidney dysfunction.

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.

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.

Background: Deep Acute pancreatitis (AP) is an urging cause of hospitalization in the gastroenterology due to different causes and an unpredictable outcome. Known causes are grouped into four main groups: metabolic, mechanical, vascular and infectious. Objective: To determine the role of certain biochemical or radiological parameters as predictors of an involvement of other organs in AP different pathological staging and the surgical outcome in the treatment of AP. Methods: Ninety-seven AP patients hospitalized in General Hospital “Prim.dr Abdulah Nakaš” Sarajevo, in a period between 2016 and 2021 for both sexes, were divided according to the etiological factors of AP into four groups: nutritional factors, biliary concernments, alcohol and morphological changes of the pancreas. Beside laboratory tests, the imaging methods of abdomen (transabdominal ultrasound, abdominal computed tomography) used in determining morphological changes in the pancreas and other organs were analyzed in relation to parameters that predict the need for surgical outcomes. Results: AP etiological factors of patients differ significantly by gender and showed the dominance of dietary factors in female subjects (51%), followed by the presence of concernments in the biliary tract in 36% of cases, and alcohol consumption in male subjects in 28% of cases. The only variable correlated with the indicator of necessity for surgery is the existence of pleural effusion (coefficient of correlation was 0.38; risk ratio was 5.5) resulting that patients with pleural effusion have a 5.5 times higher chance of surgery indication than other patients. Conclusion: The application of simple parameters such as creatinine value with the values of amylases in serum and urine and the presence of pleural effusion confirmed by radiological imaging of the lungs opens the possibility of a simple and effective selection of patients for surgical treatment with a more severe form of AP.

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.

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