Despite recent advances in endovascular therapy, up to half of acute ischemic stroke patients experience incomplete reperfusion (expanded Thrombolysis in Cerebral Infarction, eTICI<3) after intervention. However, many of these patients will achieve complete delayed reperfusion at the 24h follow‐up, which is linked to good clinical outcome and minimal new infarct development. We aimed to systematically review literature and perform a meta‐analysis on the natural evolution of incomplete reperfusion after endovascular therapy. We conducted a systematic review of MEDLINE, Embase and PubMed up until March 1, 2024 using a predefined search strategy. Only full‐text English written articles reporting rates of either favorable (i.e. delayed reperfusion) or unfavorable progression (i.e. persistent perfusion deficit) of incompletely reperfused tissue were included. Primary outcome was the rates of delayed reperfusion 24h post‐intervention and its association with functional independence (modified Rankin Scale, mRS 0‐2) at 90 days post‐intervention. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using a random‐effects model. Publication bias was assessed using funnel plots and the Luis Furuya‐Kanamori (LFK) index. Six studies involving 950 patients (50.7% female; median age 71, IQR 60 ‐ 79) were included. Four studies assessed the evolution of incomplete reperfusion on MRI perfusion imaging, while two studies used DWI and NCCT imaging, where new infarct was used to denote unfavorable progression. Complete delayed reperfusion, or absence of new infarct, occurred in 41% (inter‐quartile range, IQR 33% ‐ 51%) of cases 24h post‐intervention. Achieving delayed reperfusion was associated with higher likelihood of functional independence at 90 days (OR 2.53, 95%CI 1.88 ‐ 3.42). No evidence of publication bias was found (LFK=0.2). Nearly half of patients with incomplete reperfusion achieve complete delayed reperfusion, leading to favorable clinical outcomes. This subgroup of eTICI<3 patients may derive limited or potentially harmful effects from pursuing additional reperfusion strategies (e.g. intra‐arterial lytics or secondary distal thrombectomy). Accurately predicting the progression of incomplete reperfusion could optimize patient selection for adjunctive reperfusion attempts at the end of an intervention.

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.

Red fox, Vulpes vulpes, is a globally distributed species characterized by its high adaptability to diverse habitats and a broad range of food resources. This remarkable adaptability has allowed the red fox to thrive in various environments, from urban areas to remote wilderness. In this study, we used a set of microsatellite markers for the comparative genetic analysis of red fox populations from two countries. We included populations from the Eastern Alps and the northern Dinaric Mountains in Slovenia, as well as the Central Dinaric Mountains in Bosnia and Herzegovina. We successfully isolated DNA and genotyped 118 red fox samples. Our analyses, which included Bayesian clustering techniques, revealed a weak genetic differentiation among the studied populations. However, it is noteworthy that statistically significant differences in estimates of genetic differentiation were only apparent when comparing the populations between the two countries. Further spatial genetic clustering analyses provided additional insights, unveiling a differentiation into four genetic clusters. These clusters comprised two distinct groups in Bosnia and Herzegovina and two in Slovenia. This pattern of differentiation suggests that isolation by distance is a key factor influencing the genetic structure of the red fox in this studied region. Additionally, our findings highlighted that populations from the Alps and northern Dinaric Mountains exhibit higher genetic diversity and observed heterozygosity compared to their counterparts in the Central Dinaric Mountains. The genetic diversity is also notable when compared to other European red fox populations. Studying genetic diversity is crucial for the resilience and adaptability of populations, ensuring their survival amid environmental changes and human-induced pressures.

Background/Objectives: The study of microbiome composition shows positive indications for application in the diagnosis and treatment of many conditions and diseases. One such condition is autism spectrum disorder (ASD). We aimed to analyze gut microbiome samples from children in Bosnia and Herzegovina to identify microbial differences between neurotypical children and those with ASD. Additionally, we developed machine learning classifiers to differentiate between the two groups using microbial abundance and predicted functional pathways. Methods: A total of 60 gut microbiome samples (16S rRNA sequences) were analyzed, with 44 from children with ASD and 16 from neurotypical children. Four machine learning algorithms (Random Forest, Support Vector Classification, Gradient Boosting, and Extremely Randomized Tree Classifier) were applied to create eight classification models based on bacterial abundance at the genus level and KEGG pathways. Model accuracy was evaluated, and an external dataset was introduced to test model generalizability. Results: The highest classification accuracy (80%) was achieved with Random Forest and Extremely Randomized Tree Classifier using genus-level taxa. The Random Forest model also performed well (78%) with KEGG pathways. When tested on an independent dataset, the model maintained high accuracy (79%), confirming its generalizability. Conclusions: This study identified significant microbial differences between neurotypical children and children with ASD. Machine learning classifiers, particularly Random Forest and Extremely Randomized Tree Classifier, achieved strong accuracy. Validation with external data demonstrated that the models could generalize across different datasets, highlighting their potential use.

Bariatric surgery has emerged as the most effective treatment for morbid obesity, offering substantial and sustained weight loss and improvement in comorbid conditions. This paper reviews the development, implementation, and outcomes of bariatric surgery at the University and Clinical Centre Tuzla based on a retrospective analysis of patients who underwent bariatric surgery over a three-year period. A significant weight loss was observed, postoperative complications were minimal, with no in-hospital mortality. The bariatric surgery program demonstrates a significant progress in treating morbid obesity in Bosnia and Herzegovina.

(1) Background: This study investigates the effects of curing light intensity, exposure time, and distance on the Vickers microhardness (VMH), hardness bottom-to-top ratio (HR), and temperature rise (TR) of conventional dental resin-based composite (RBC). (2) Materials and Methods: Specimens of one conventional RBC (Tetric EvoCeram, Ivoclar Vivadent) were cured with 12 different curing protocols (CPs), created with three different light intensities (Quartz Tungsten Halogen 300 mW/cm2, LED 650 mW/cm2, LED 1100 mW/cm2), two exposure times (20 and 40 s), and two distances of curing tip (0 and 8 mm). The VMH of top (VMH-T) and bottom (VMH-B) surfaces was measured. The hardness bottom-to-top ratio (HR) was calculated from VMH-B and VMH-T. The HR below 80% was rated as inadequate polymerization. The TR at the depth of 2 mm within the RBC was measured using a K-type thermocouple. Data were analyzed using Levene’s test and the multivariate analysis of variance (MANOVA). The level of significance was set at p < 0.05. (3) Results: Exposure time and distance significantly influenced VMH-B and HR. Increased distance significantly reduced VMH-B, HR, and TR. CPs 300 mW/cm2/8 mm/20 s and 650 mW/cm2/8 mm/20 s produced inadequate polymerization (HR < 80%). Prolonged exposure time produced higher values of VMH-B and HR. The TR was significantly influenced by light intensity and distance. (4) Conclusions: Suboptimal light intensity (<800 mW/cm2) can produce inadequate polymerization at the lower side of the composite layer when used from a distance. Prolonged irradiation can improve the polymerization to a certain extent. Clinicians are advised to monitor the intensity of the LCUs in order to optimize the photopolymerization process. Caution is required when polymerizing with high-intensity curing light in direct contact with the RBC with longer exposure times than recommended.

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.

Precision medicine is a developing trend in oncology, and it includes the prognosis and treatment of advanced-stage ccRCC. New predictive factors and therapeutic targets for this disease are steadily needed. The aim of this study was to explore the tumor expression of inversin as a potential prognostic factor and/or therapeutic target in ccRCC. We compared the expression of inversin between primary ccRCC and normal renal tissues by using immunohistochemistry and rtPCR in our cohort, and we also analyzed publicly available data from the TCGA-KIRC cohort. We found that the expression of inversin was significantly lower in primary tumor tissue, in comparison to solid normal tissue. Data from the KIRC study confirmed that a lower INVS expression level in ccRCC was significantly related with the overall and disease-specific survival, as well as with a shorter progression-free interval (p < 0.05). Four out of ten inversin interactome partners were significantly related with the overall and disease-specific survival in ccRCC. A lower expression of ANKS6 was a negative survival predictor, while a higher expression of NPHP3, DVL1, or DVL3 was related with a lower survival. The expression of INVS and its interactome partners in ccRCC was correlated with the differentiation of the tumor and metastasis. The expression of INVS and its partners was also correlated with tumor leukocyte infiltration and the expression of immune checkpoint genes. The results of this study point to inversin and a distinguished group of its interactome partners as potential prognostic factors in ccRCC, with their predominant involvement in the modulation of the inflammatory infiltration of the tumor microenvironment and a strong relationship with the metastatic potential of the tumor.

AIM To investigate the predictors of biochemical relapse (BCR) among patients with non-metastatic prostate cancer treated with radiotherapy as the first-line therapy. METHODS 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. RESULTS A total of 46 (50.5%) patients were aged 66-75, with a median PSA of 14.50 ng/mL. A Gleason score <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 ≥6 (OR:4.46; p=0.006) and tumour stage >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. CONCLUSION Gleason score ≥6 and TNM>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 ≥6 and tumour stage >T2b.

AIM Care for the inflammatory bowel disease (IBD) patients presents unique challenges as decisions regarding therapy must consider numerous distinct characteristics of each patient. The aim of the study was to recognize patients' characteristics as predictors of success in vedolizumab treatment. METHODS In a retrospective observational study, data regarding age, gender, body mass index (BMI), length of disease, previous exposure to anti-tumour necrosis factor (TNF), drugs, and smoking status were extracted from the routine clinical practice. Patients were assessed for clinical remission and steroid-free remission after the 26-week treatment with vedolizumab. RESULTS The study included 76 patients with UC and 63 with CD. A total of 63 (out of 76; 82.9%) (Cl: 72.5-90.6% ) of UC and 54 (out of 63; 85.7%) (Cl: 74.6-93.3%) CD patients achieved clinical remission in the 26-week vedolizumab treatment. Over five years, illness was noticed in 32 (53.1%) CD patients. Clinical remission was not achieved in six (out of 13; 46.1%) UC patients aged 40-49 years and six (out of nine; 66.6%) CD patients aged 30-49 years. Among CD patients, remission was achieved in 22 (85.7%) females and 23 (63.6%) males. Remission rates were generally higher in patients with a BMI of 18.6-25 and 25.1-30. Previous exposure to anti TNF drugs and smoking status did not influence treatment outcomes. CONCLUSION The efficacy of vedolizumab is a viable treatment option for both ulcerative colitis and Crohn's disease. The exploration of individual patient characteristics holds promise in predicting a treatment outcome.

AIM 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). METHODS 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. RESULTS 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< 0.001), hypertension (p=0.016), lack of pre-cardioversion amiodarone (p=0.027), and larger LA (p< 0.001). Both ECV and PCV significantly reduced LA over time, with no significant differences in LVEF between groups. CONCLUSION 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.