Glioblastoma (GBM) remains a major clinical challenge due to limited therapeutic success despite standard treatments including surgery, radiotherapy, and temozolomide (TMZ). Recent evidence links hyperglycemia to cancer progression, and altered glucose metabolism has emerged as a key factor in GBM development. Metformin, an antidiabetic drug, has shown promise in improving survival in GBM patients, possibly due to its ability to cross the blood-brain barrier and target metabolic pathways involved in tumor growth. Preclinical studies suggest metformin may enhance TMZ efficacy by acting on glioma stem cells and overcoming resistance mechanisms. Its activation of AMPK and modulation of Wnt signaling further support its therapeutic potential. However, while early studies and clinical trials have explored metformin’s safety and efficacy, its direct impact on GBM survival remains unclear. Ongoing research aims to clarify its mechanisms and identify responsive patient subgroups. Novel strategies, including PPARγ agonists and nanoerythrosome-based drug delivery systems, are also under investigation to improve metformin’s therapeutic profile. Rigorous clinical trials and mechanistic studies are essential to determine the role of metformin as adjunct therapy in GBM treatment.

<p class="Standard" style="line-height: 200%;"><strong><span lang="EN-GB" style="font-family: 'Times New Roman',serif; color: #202124;">ABSTRACT</span></strong></p> <p class="Standard" style="line-height: 200%;"><strong><span lang="EN-GB" style="font-family: 'Times New Roman',serif;">Aim</span></strong><span lang="EN-GB" style="font-family: 'Times New Roman',serif;"> This study compared the extent of coronary artery calcification in patients <span style="color: #202124;">with and without type 2 diabetes mellitus (T2DM) using Coronary Computed Tomography Angiography (CCTA).</span></span></p> <p class="Standard" style="line-height: 200%;"><strong><span lang="EN-GB" style="font-family: 'Times New Roman',serif; color: #202124;">Methods </span></strong><span lang="EN-GB" style="font-family: 'Times New Roman',serif; color: #202124;">This retrospective, observational cohort study included 107 patients who underwent CCTA at the Clinical Centre of the University of Sarajevo between July and December 2024. Patients were divided into two groups: those with T2DM (n=51) and those without T2DM (n=56). Laboratory parameters, demographic data, and calcium scores were analysed. The calcium score was categorised into six groups based on cardiovascular </span><span lang="EN-GB" style="font-family: 'Times New Roman',serif;">risk and the comparison was made using appropriate statistical analysis. </span></p> <p class="Standard" style="line-height: 200%;"><strong><span lang="EN-GB" style="font-family: 'Times New Roman',serif; color: #202124;">Results</span></strong><span lang="EN-GB" style="font-family: 'Times New Roman',serif; color: #202124;"> Patients with T2DM had significantly higher calcium </span><span lang="EN-GB" style="font-family: 'Times New Roman',serif;">scores than <span style="color: #202124;">non-diabetic patients (p=0.0001). In the T2DM group, 35.3% of patients had a calcium score &gt;400, indicating high cardiovascular risk. Patients without diabetes were more frequently classified into lower-risk categories (p=0.0001). A significant correlation was found between calcium score and age (r=0.442, p=0.001) and gender (r=-0.218, p=0.024), with men having higher calcium scores. Additionally, total cholesterol, LDL, and uric acid levels were significantly higher in diabetic patients (p=0.005; p=0.025; p=0.03, respectively).</span></span></p> <p class="Standard" style="line-height: 200%;"><strong><span lang="EN-GB" style="font-family: 'Times New Roman',serif; color: #202124;">Conclusion</span></strong><span lang="EN-GB" style="font-family: 'Times New Roman',serif; color: #202124;"> This study confirms a strong association between T2DM and increased coronary artery calcification. Age and male gender are significant predictors of higher calcium scores. Further research is needed to explore these relationships, particularly within the Bosnian population.</span></p> <p class="Standard" style="line-height: 200%;"><strong><span lang="EN-GB" style="font-family: 'Times New Roman',serif; color: #202124;">Keywords </span></strong><span lang="EN-GB" style="font-family: 'Times New Roman',serif; color: #202124;">Coronary angiography, coronary artery calcification, coronary disease, diabetes mellitus type 2</span></p>

Background Non-ST-elevation myocardial infarction (NSTEMI) is frequently associated with systemic inflammation and metabolic dysregulation. Indices derived from routine laboratory tests that reflect systemic inflammatory and lipid-inflammatory status may offer better prognostic insight. This study aimed to evaluate the association between selected indices and short-term major adverse cardiovascular events (MACE) and all-cause mortality in patients with NSTEMI treated with dual antiplatelet therapy (DAPT) and statin. The selected indices reflect key mechanisms involved in NSTEMI pathophysiology, including insulin resistance, atherogenic dyslipidemia, and inflammation. Materials and methods This prospective observational study included 171 patients with NSTEMI admitted to the Intensive Care Unit of the Clinic for Internal Medicine at the University Clinical Centre Tuzla between February 1, 2022, and January 31, 2023. Blood samples were collected upon admission and 24 hours subsequently. The following indices were calculated: triglyceride-glucose index (TyG), triglyceride-to-high-density lipoprotein ratio (TG/HDL), atherogenic index of plasma (AIP), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and pan-immune-inflammation value (PIV). Outcomes were tracked during hospitalization and up to three months post-discharge. MACE was defined as cardiovascular death, reinfarction, stroke, or unplanned revascularization. All patients underwent coronary angiography; revascularization was performed when clinically indicated. Exclusion criteria included active malignancy, infection, or inflammatory disease. Logistic regression was adjusted for age, diabetes, and other clinical variables. Missing data were handled using the pairwise deletion method. Results High levels of TyG at admission were independently associated with MACE (odds ratio (OR) 1.7; 95% confidence interval (CI) 1.0-2.8; p = 0.037). All-cause mortality occurred in 14.6% of patients (n = 25), while MACE occurred in 60 patients. Independent predictors of mortality included elevated TyG at admission (OR 2.2; 95% CI 1.1-4.4; p = 0.034), TG/HDL at 24 hours (OR 1.4; 95% CI 1.1-1.7; p = 0.007), AIP at 24 hours (OR 5.7; 95% CI 1.1-28.9; p = 0.035), and NLR at 24 hours (OR 1.1; 95% CI 1.0-1.2; p = 0.002). PLR and PIV at 24 hours were also significantly associated with mortality. Optimal cut-off values were TyG ≥ 8.9, AIP ≥ 0.35, and NLR ≥ 4.5. NLR had the highest estimated area under the curve (AUC ≈ 0.78). Conclusion In NSTEMI patients treated with DAPT and statin, several inflammatory and lipid-inflammatory indices were independently associated with short-term mortality. Indices measured at 24 hours had a stronger prognostic value than baseline values. Serial monitoring may aid early risk stratification. Outcomes were assessed during hospitalization and via structured follow-up up to three months post-discharge.

Background Acute cholecystitis (AC) is a frequent surgical emergency associated with significant variability in clinical outcomes and hospital length of stay (LOS). Early identification of patients at risk for prolonged hospitalization can improve triage and resource planning. Inflammatory markers such as C-reactive protein (CRP), white blood cell count (WBC), and total bilirubin (TBil), along with biliary complications like choledocholithiasis and Mirizzi syndrome, may have prognostic value. Materials and methods This retrospective study included 150 patients who underwent cholecystectomy for AC at the Department of General and Abdominal Surgery, University Clinical Centre Tuzla, Tuzla, Bosnia and Herzegovina, between January 1, 2024, and January 31, 2025. Demographic, laboratory, and intraoperative data were collected. Receiver operating characteristic (ROC) analysis identified optimal cut-offs for inflammatory markers predicting prolonged LOS (≥7 days). Multivariate linear regression was used to assess independent predictors, including CRP, WBC, TBil, and intraoperative findings. Results We found that CRP was significantly higher in patients with prolonged LOS and demonstrated the highest predictive accuracy, with an area under the curve (AUC) of 0.733 (95% CI: 0.630-0.835), followed by TBil and WBC. In multivariate analysis, only CRP ≥110.5 mg/L (p<0.001), the presence of choledocholithiasis in 26 patients (17.3%; p=0.010), and Mirizzi syndrome in seven patients (4.7%; p=0.017) remained significant predictors. WBC and TBil lost significance after adjustment. Conclusion CRP is the most reliable independent laboratory predictor of prolonged LOS in AC. The presence of choledocholithiasis and Mirizzi syndrome further contributes to extended hospitalization. These factors should be considered in early clinical risk assessment.

Background Non-ST-elevation myocardial infarction (NSTEMI) represents a prevalent form of acute coronary syndrome associated with substantial early risk of adverse outcomes. Inflammatory and metabolic disturbances are increasingly recognized as key contributors to the disease. Hematologic indices such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and pan-immune-inflammation value (PIV), along with the triglyceride-glucose index adjusted for BMI (TyG-BMI), have emerged as promising prognostic markers. However, their dynamic behavior in early NSTEMI remains insufficiently explored. Materials and methods This prospective study included 170 patients hospitalized for NSTEMI at the University Clinical Centre Tuzla between February 2022 and January 2023. Hematologic and metabolic indices were calculated at admission and repeated 24 hours later. Patients were followed for three months to document major adverse cardiovascular events (MACE), including cardiovascular death, reinfarction, and urgent revascularization. The median age was 67 years, and 60.6% of patients were male. Hypertension, hyperlipidemia, and diabetes mellitus were the most common comorbidities. Results Significant 24-hour reductions were observed in NLR, PLR, SII, SIRI, and PIV (all p < 0.01), while C-reactive protein (CRP) levels more than doubled (p < 0.001). Patients who developed MACE showed persistently elevated inflammatory indices and smaller declines in PIV and SIRI. Change in SIRI (ΔSIRI) demonstrated the strongest predictive value (AUC = 0.63), followed by SII and TyG-BMI. Notably, reduced resolution of PIV and persistently elevated TyG-BMI were significantly associated with adverse outcomes. Overall, MACE occurred in 51.2% of patients, including a 14.7% mortality rate. Conclusion Early changes in systemic inflammation and metabolic stress, particularly SIRI and TyG-BMI dynamics, offer valuable prognostic insight and may enhance early risk stratification in NSTEMI patients.

Background Heart failure (HF) is characterized by impaired cardiac function. Based on left ventricular ejection fraction (LVEF), it is classified into HF with reduced ejection fraction (HFrEF), mildly reduced ejection fraction (HFmrEF), and preserved ejection fraction (HFpEF). Each phenotype has distinct pathophysiological mechanisms and clinical features. Recent findings indicate that systemic inflammation is a significant factor in the progression of heart failure. Inflammatory biomarkers, including neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and lymphocyte-to-monocyte ratio (LMR), may serve as valuable tools for evaluating the inflammatory response in heart failure. Materials and methods This prospective observational study, which included 171 HF patients, was conducted from February 2022 to January 2023 at the Intensive Care Unit, University Clinical Centre Tuzla. Based on LVEF, patients were categorized into HFrEF, HFmrEF, and a control group (HFpEF). The study aimed to assess the prognostic value of NLR, MLR, and LMR in predicting major adverse cardiovascular events (MACE) and mortality over a 12-month follow-up period. Results NLR and MLR were significantly higher, while LMR was lower in both HFrEF and HFmrEF compared to controls, indicating a strong inflammatory response, particularly in HFrEF. NLR demonstrated a strong ability to distinguish between HF phenotypes. HFmrEF's markedly higher high-sensitivity troponin I (hsTroponin I) level suggested higher cardiac stress. MACE rates were similar across groups; mortality was significantly higher in HFrEF. Conclusion Inflammatory biomarkers NLR, MLR, LMR, and hsTroponin I could be crucial in assessing heart failure, particularly in patients with HFrEF and HFmrEF.

BACKGROUND Non-ST segment elevation myocardial infarction (NSTEMI) poses significant challenges in clinical management due to its diverse outcomes. Understanding the prognostic role of hematological parameters and derived ratios in NSTEMI patients could aid in risk stratification and improve patient care. AIM To evaluate the predictive value of hemogram-derived ratios for major adverse cardiovascular events (MACE) in NSTEMI patients, potentially improving clinical outcomes. METHODS A prospective, observational cohort study was conducted in 2021 at the Internal Medicine Clinic of the University Hospital in Tuzla, Bosnia and Herzegovina. The study included 170 patients with NSTEMI, who were divided into a group with MACE and a control group without MACE. Furthermore, the MACE group was subdivided into lethal and non-lethal groups for prognostic analysis. Alongside hematological parameters, an additional 13 hematological-derived ratios (HDRs) were monitored, and their prognostic role was investigated. RESULTS Hematological parameters did not significantly differ between non-ST segment elevation myocardial infarction (NSTEMI) patients with MACE and a control group at T1 and T2. However, significant disparities emerged in HDRs among NSTEMI patients with lethal and non-lethal outcomes post-MACE. Notably, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were elevated in lethal outcomes. Furthermore, C-reactive protein-to-lymphocyte ratio (CRP/Ly) at T1 (> 4.737) demonstrated predictive value [odds ratio (OR): 3.690, P = 0.024]. Both NLR at T1 (> 4.076) and T2 (> 4.667) emerged as significant predictors, with NLR at T2 exhibiting the highest diagnostic performance, as indicated by an area under the curve of 0.811 (95%CI: 0.727-0.859) and OR of 4.915 (95%CI: 1.917-12.602, P = 0.001), emphasizing its important role as a prognostic marker. CONCLUSION This study highlights the significant prognostic value of hemogram-derived indexes in predicting MACE among NSTEMI patients. During follow-up, NLR, PLR, and CRP/Ly offer important insights into the inflammatory processes underlying cardiovascular events.

The aim of the current research was to investigate the association between plasma endocan levels and metabolic control parameters, as well as to evaluate its predictive value for clinical complications in patients with type 2 diabetes mellitus (DMT2). A total of 100 DMT2 patients participated in this prospective observational study. Plasma endocan levels were significantly elevated in DMT2 patients with HbA1c > 7% (1.38 ± 0.33 vs 0.68 ± 0.23 ng/mL; P < 0.0001), compared to patients with HbA1c ≤ 7%. Patients with plasma endocan concentrations >1.10 ng/mL (median value of 1.10 ng/mL) demonstrated significantly higher levels of metabolic parameters: body mass index (BMI), HbA1c (%), fasting glucose level, LDL cholesterol, total cholesterol, triglycerides, along with significantly lower HDL cholesterol levels. Furthermore, patients with plasma endocan levels >1.10 ng/mL were found to have an increased risk for the following complications: retinopathy (relative risk [RR]: 2.7500; 95% confidence interval [CI]: 1.2150–6.2244; P ═ 0.0152, nephropathy (RR: 2.0952; 95% CI: 1.2294–3.5710; P ═ 0.0065), neuropathy (RR: 1.9945; 95% CI: 1.2025–3.3081; P ═ 0.0075), angina pectoris (RR: 2.4881; 95% CI: 1.0865–5.6979; P = 0.0311, hypertension (RR: 1.1372; 95% CI: 1.0060–1.2856; P = 0.0398), cardiomyopathy (RR: 2.6190; 95% CI: 1.1507–5.9612; P = 0.0218), myocardial infarction (RR: 9.4286; 95% CI: 1.2742–69.7697; P = 0.0280) and stroke (RR: 4.4638; 95% CI: 1.3765–14.4758; P = 0.0127). Correlation analysis revealed that plasma endocan levels were positively correlated with HbA1c (%) (r ═ 0.856, P < 0.0001), fasting glucose level (r ═ 0.631, P < 0.0001), LDL (r ═ 0.347, P ═ 0.0004), cholesterol (r ═ 0.282, P ═ 0.0045), and triglycerides (r ═ 0.366, P ═ 0.0002). Conversely, plasma endocan levels were negatively correlated with HDL cholesterol (r ═ −0.429, P < 0.0001). In conclusion, higher plasma endocan levels were strongly associated with poor metabolic control in DMT2 patients and exhibited significant predictive value for both microvascular and macrovascular complications.

AIM Acute kidney injury (AKI) presents a high mortality complication in patients with acute myocardial infarction (AMI). Yet, its correlation with non-ST elevation myocardial infarction (NSTEMI) remains neglected in the literature. This study aims to investigate the prevalence, risk factors, clinical features, and short-term outcomes associated with AKI development in patients with acute NSTEMI. METHODS A one-year prospective observational cohort study involved 170 consecutive patients hospitalized in the Intensive Care Department of the Internal Medicine Clinic at the University Clinical Centre Tuzla diagnosed with acute NSTEMI. Patients were subsequently categorized into AKI and non-AKI groups based on AKI development within 48 hours. Demographic characteristics, laboratory findings, and short-term clinical outcomes were compared between the groups. RESULTS Of 170 patients, 31 (18.2%) developed AKI within 48 hours of acute NSTEMI. Significant age differences, blood urea nitrogen (BUN), creatinine, estimated glomerular filtration rate (eGFR), blood glucose level (BGL), C-reactive protein (CRP), and high sensitivity (hs) troponin were observed, making patients with lower baseline kidney function, more extensive myocardial infarction, and a heavier systemic inflammatory response following acute NSTEMI more susceptible to AKI development. In the follow-up period, mortality rates were significantly higher in the AKI group, amounting to 35.5% compared to 10.1% in the non-AKI group. Additionally, mortality increased with the severity of AKI, reaching 100% in AKI stage 2. CONCLUSION This study highlights demographic, clinical and laboratory findings in patients with acute NSTEMI, which contribute to AKI development. Early detection and tailored interventions are crucial in mitigating AKI-associated morbidity and mortality.