Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS), characterized by neurodegeneration, axonal damage, demyelination, and inflammation. Recently, gut dysbiosis has been linked to MS and other autoimmune conditions. Namely, gut microbiota has a vital role in regulating immune function by influencing immune cell development, cytokine production, and intestinal barrier integrity. While balanced microbiota fosters immune tolerance, dysbiosis disrupts immune regulation, damages intestinal permeability, and heightens the risk of autoimmune diseases. The critical factor in shaping the gut microbiota and modulating immune response is diet. Research shows that high-fat diets rich in saturated fats are associated with disease progression. Conversely, diets rich in fruits, yogurt, and legumes may lower the risk of MS onset and progression. Specific dietary interventions, such as the Mediterranean diet (MD) and ketogenic diet, have shown potential to reduce inflammation, support neuroprotection, and promote CNS repair. Probiotics, by restoring microbial balance, may also help mitigate immune dysfunction noted in MS. Personalized dietary strategies targeting the gut microbiota hold promise for managing MS by modulating immune responses and slowing disease progression. Optimizing nutrient intake and adopting anti-inflammatory diets could improve disease control and quality of life. Understanding gut-immune interactions is essential for developing tailored nutritional therapies for MS patients.

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.

<p><strong>Aim</strong> 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.<br /><strong>Methods</strong> 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.<br /><strong>Results</strong> 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.<br /><strong>Conclusion</strong> 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.</p>

<p><strong>Aim</strong> To investigate the predictors of biochemical relapse (BCR) among patients with non-metastatic prostate cancer treated with radiotherapy as the first-line therapy.&nbsp;<br /><strong>Methods</strong> The study included 91 patients diagnosed with prostate cancer at the University Clinical Centre in Tuzla, Bosnia and Herzegovina. After the radiation treatment as the first line of treatment, the patients were monitored for the next 36 months. If patients were classified in medium and high-risk groups, hormone therapy was administered. The occurrence of BCR was determined based on prostate-specific antigen (PSA) values. Potential prognostic parameters, including Gleason score (GS), PSA, tumour size (TNM), and standardised risk classification (RC), were monitored.<br /><strong>Results</strong> A total of 46 (50.5%) patients were aged 66-75, with a median PSA of 14.50 ng/mL. A Gleason score &lt;6 was found in 72 (79.1%) of patients, and 31 (34.1%) had T2c tumours. The BCR occurred in 32 (35.2%) patients, with a median relapse time of 18 months. Significant predictors of BCR were Gleason score &ge;6 (OR:4.46; p=0.006) and tumour stage &gt;T2b (OR:3.59; p=0.021). The RC showed an Area Under Curve (AUC) of 0.634 (p=0.050), indicating its potential diagnostic accuracy.<br /><strong>Conclusion</strong> Gleason score &ge;6 and TNM&gt;T2b are significant predictors of biochemical relapse in prostate cancer patients treated with radiotherapy. These results emphasize the need for additional monitoring and timely treatment of clinical disease progression in patients with Gleason score &ge;6 and tumour stage &gt;T2b.</p>

<p><strong>Aim</strong> To compare the impact of electrical cardioversion (ECV) and pharmacological cardioversion (PCV) on left atrial size (LA) and left ventricular ejection fraction (LVEF), as well as to identify predictors of rhythm disorder recurrence in patients with atrial fibrillation (AF) or atrial flutter (AFL).<br /><strong>Methods</strong> A prospective observational cohort study was conducted on 105 patients with persistent AF or AFL at the University Clinical Centre Tuzla. The patients were divided into two groups: 53 underwent ECV and 52 received PCV. Demographic and clinical data, including ECG and transthoracic echocardiography, were collected. Follow-up assessments were conducted at 7 days, 1 month, and subsequently every 3 months for a year.<br /><strong>Results</strong> Baseline characteristics were similar between the groups. Recurrence of rhythm disorder within one year was observed in 52.4% of cases, with ECV showing a slightly lower, though not significantly different, primary failure rate at 7 days compared to PCV (13.2% vs. 23.1%). Significant predictors of recurrence included longer duration of disorder (p&lt;0.001), hypertension (p=0.016), lack of pre-cardioversion amiodarone (p=0.027), and larger LA (p&lt;0.001). Both ECV and PCV significantly reduced LA over time, with no significant differences in LVEF between groups.<br /><strong>Conclusion</strong> Both ECV and PCV are effective in restoring sinus rhythm, with a trend towards lower recurrence in the ECV group. Predictors such as disorder duration, hypertension, lack of pre-cardioversion amiodarone, and LA should be considered when planning cardioversion to optimize patient outcomes.</p>

Simple Summary This study explores hypoxia-inducible factors (HIFs) in glioblastoma development, progression, and treatment. Reviewing 104 relevant studies, it highlights diverse global contributions, with China leading at 23.1%. The most productive year was 2019, contributing 11.5% of the studies. Key factors studied included HIF1α, HIF2α, osteopontin, and cavolin-1, involving pathways such as GLUT1, GLUT3, VEGF, PI3K-Akt-mTOR, and ROS. HIF expression correlates with glioblastoma progression, survival, neovascularization, glucose metabolism, migration, and invasion. Overcoming treatment resistance and the lack of biomarkers is crucial for integrating HIF-related therapies into glioblastoma treatment to improve patient outcomes. Abstract Background: The study aims to investigate the role of hypoxia-inducible factors (HIFs) in the development, progression, and therapeutic potential of glioblastomas. Methodology: The study, following PRISMA guidelines, systematically examined hypoxia and HIFs in glioblastoma using MEDLINE (PubMed), Web of Science, and Scopus. A total of 104 relevant studies underwent data extraction. Results: Among the 104 studies, global contributions were diverse, with China leading at 23.1%. The most productive year was 2019, accounting for 11.5%. Hypoxia-inducible factor 1 alpha (HIF1α) was frequently studied, followed by hypoxia-inducible factor 2 alpha (HIF2α), osteopontin, and cavolin-1. Commonly associated factors and pathways include glucose transporter 1 (GLUT1) and glucose transporter 3 (GLUT3) receptors, vascular endothelial growth factor (VEGF), phosphoinositide 3-kinase (PI3K)-Akt-mechanistic target of rapamycin (mTOR) pathway, and reactive oxygen species (ROS). HIF expression correlates with various glioblastoma hallmarks, including progression, survival, neovascularization, glucose metabolism, migration, and invasion. Conclusion: Overcoming challenges such as treatment resistance and the absence of biomarkers is critical for the effective integration of HIF-related therapies into the treatment of glioblastoma with the aim of optimizing patient outcomes.

2Univerzitet of Tuzla, School of Medicine, Tuzla, Bosnia and Herzegovina KeYWORdS: myocardial infarction, exercise training, cardiovascular rehabilitation. citAtiON: Cardiol Croat. 2018;13(11-12):416. | https://doi.org/10.15836/ccar2018.416 *AddReSS fOR cORReSpONdeNce: Emir Bećirović, JZU Univerzitetski klinički centar Tuzla, Klinika za interne bolesti, Prof. dr Ibre Pasica, 75 000 Tuzla, Bosnia i Herzegovina. / Phone: +387-61-876-152 / E-mail: becirovic.emir@live.com ORcid: Emir Becirovic, https://orcid.org/0000-0002-4134-987X • Ammar Brkic, https://orcid.org/0000-0002-5436-3670 Esad Brkic, https://orcid.org/0000-0002-7784-328X • Tarik Brkic, https://orcid.org/0000-0003-2054-2571 Ermina Mujanovic, https://orcid.org/0000-0001-8154-586X • Amir Becirovic, https://orcid.org/0000-0002-7012-8064 Semir Hadzic, https://orcid.org/0000-0002-3308-8331 • Amila Jasarevic, https://orcid.org/0000-0003-4861-6683 Majda Skokic, https://orcid.org/0000-0001-5913-1863 • Esref Becirovic, https://orcid.org/0000-0003-3759-7878