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.

Background/Objectives: This study aimed to evaluate the diagnostic and prognostic utility of B7-H3 expression in differentiating low-grade gliomas (LGGs) from high-grade gliomas (HGGs) and to examine its association with clinical outcomes. Methods: This retrospective study included 99 patients with histopathologically confirmed gliomas (42 LGGs and 57 HGGs). B7-H3 expression was assessed using immunohistochemistry and scored by immunoreactive score (IRS). Results: B7-H3 expression was significantly higher in HGG compared to LGG (p < 0.001). The total IRS (B7-H3 A × B) demonstrated strong discriminative power (AUC = 0.816). High B7-H3 expression independently predicted disease progression (OR = 4.9, 95% CI: 2.4–10.1; p < 0.001) and was associated with IDH wild-type status and elevated Ki-67 index. Patients with high B7-H3 had significantly shorter overall survival (median 6 months vs. 42 months) and progression-free survival (median 3 months vs. 25 months) (both p < 0.001). Cox regression confirmed high B7-H3 as an independent predictor of mortality (HR = 2.9, 95% CI: 1.7–4.7; p < 0.001) and progression (HR = 2.6, 95% CI: 1.6–4.2; p < 0.001). Conclusions: B7-H3 expression is a reliable biomarker for distinguishing HGG from LGG and is independently associated with worse survival outcomes. Its assessment may aid in glioma classification and prognostication.

Background and Objectives: Idiopathic normal-pressure hydrocephalus (NPH) is a treatable, but diagnostically challenging condition in the elderly marked by gait disturbance, cognitive decline, and urinary incontinence. Ventriculoperitoneal (VP) shunting is effective, but the prognostic significance of symptom duration before surgery remains unclear. This systematic review evaluates symptom duration in NPH patients with postoperative outcomes. Methods: A systematic search of PubMed, Scopus, and Embase was conducted per PRISMA guidelines. Studies were included if they assessed clinical or radiological outcomes of VP shunting in adult NPH patients, reported symptom duration, and had a follow-up of at least one month. Clinical outcomes (MMSE, TUG, NPH score) were qualitatively analyzed due to study heterogeneity. Results: Twenty-four studies comprising 1169 patients were included (mean age: 72.45 years; mean symptom duration: 33.04 months). Most studies reported clinical improvement after VP shunting. However, few directly evaluated the effect of symptom duration, yielding inconsistent findings: some suggested better outcomes with shorter symptom duration, while others found no clear correlation. Larger studies often lacked conclusive data, and no randomized controlled trials were identified. Conclusions: VP shunting remains an effective intervention for NPH; however, evidence supporting the predictive value of preoperative symptom length is inconclusive. This review highlights the need for standardized diagnostic protocols and larger prospective studies to clarify this association and optimize surgical timing.

OBJECTIVES Brain tumor-related epilepsy management poses significant challenge in clinical practice. Healthcare providers must tailor treatment based on each patient's unique circumstances. Different antiepileptic drugs can be used, including oxcarbazepine. Several studies show this drug's efficacy and safety in brain tumor-related epilepsy. METHODS Observational, prospective study, monitoring the efficacy and safety of the drug oxcarbazepine in the prevention of epileptic seizures, included adult patients of both sexes with a supratentorial tumor and a risk of epileptic seizures after neurosurgery. RESULTS The study included 153 hospitalized patients. The percentages of amplified waves, sharp waves, and spike waves decreased in the second and third compared with the first visit. Significantly lower percentages of sharp waves (P = 0.028) on the second compared with the first measurement and spike waves (P = 0.002) on the third compared with the first measurement were determined. Deterioration from normal to low hemoglobin concentration was observed in 40 (26%) patients at the second visit and 17 (12%) at the third visit, compared with the first visit. However, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration values did not change significantly during the 6 months of follow-up. A transient drop in the number of thrombocytes was observed on the second visit. Adverse reactions to the drug were mild. Therapeutic adherence was low, as measured by the Morisky Medication Adherence Scale (MMAS-4). CONCLUSIONS The drug oxcarbazepine has shown good efficacy and safety in the prevention of epileptic attacks after neurosurgery in patients with supratentorial tumors. Additional education of patients on the importance of taking regular therapy is crucial.

Introduction: Despite the presence of various constraints, Bosnia and Herzegovina has managed to establish healthcare services in the field of spinal surgery. Limiting factors associated with resource scarcity and a shortage of neurosurgeons may pose challenges, but they are not insurmountable in the context of spinal tumor surgery. This study aims to provide a comprehensive 10-year analysis of intradural spinal tumors in resource-constrained healthcare settings and assess surgical outcomes in these challenging environments. Methods: A retrospective study was conducted involving 39 patients with intradural spinal tumors in Zenica-Doboj Canton, Bosnia and Herzegovina, from 2011 to 2021. Patients underwent neurological examinations and spinal magnetic resonance imaging scans, followed by post-surgery assessments at 3 and 6 months using the McCormick scale. Results: Among the 39 patients, tumor distribution was as follows: meningioma (15, 38.5%), ependymoma (3, 7.7%), schwannoma (11, 28.2%), neurenteric cyst (1, 2.6%), primary melanoma (2, 5.1%), lipoma (1, 2.6%), and metastasis (6, 15.4%) (p < 0.001). A majority of patients reported localized and radicular pain (37, 94.9%, p < 0.001) and paresthesia (33, 84.6%, p < 0.001). Motor weakness was noted in 20 (51.3%) patients, while sphincteric dysfunction was reported by 17 (43.6%) patients. The average symptom duration was 397.9 ± 380.9 days, ranging from 14 to 1460 days (p < 0.001). Pneumonia and liquorrhea were reported by 1 (2.6%) patient each. Regarding mortality, 1 (2.6%) patient passed away within a 6-month follow-up period (p < 0.001), and 2 (5.1%) patients were diagnosed with primary malignant melanoma. Significant improvements in McCormick scores were observed between postoperative and 3-month assessments (p < 0.001) and between 3-month and 6-month assessments (p = 0.024). Conclusions: This study offers valuable insights into the management of intradural spinal tumors in resource-constrained healthcare settings. Timely diagnosis and surgical intervention are essential for achieving positive patient outcomes in these challenging environments.

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.

AIM To investigate clinical and morphometric characteristics of patients with lower urinary tract symptoms (LUTS) due to lumbar spinal stenosis (LSS). METHODS This study evaluated LSS patients using clinical assessments of motor, sensory, bladder, and bowel functions, and functional disability scores from the Oswestry Disability Index (ODI) and Swiss Spinal Stenosis Questionnaire (SSSQ). Morphometric analysis included MRI measurements of the anteroposterior diameter of the intervertebral disc and dural sac, and the modified Torg-Pavlov ratio (mTPR), with follow-up re-evaluations at 6 months. RESULTS Of 159 patients, 49 (30.8%) had LUTS and 110 (69.2%) were in the control group. LUTS patients had a significantly higher prevalence of neurogenic claudication (100% vs. 47.3%; p<0.001), lower back pain (93.9% vs. 77.3%; p=0.011), and lower extremity pain (57.1% vs. 34.5%; p=0.008). The LUTS group also had higher ODI (54.0 vs. 50.0; p=0.019) and SSSQ score (44.0 vs. 34.0; p<0.001). Morphometric analysis showed significantly lower mTPR in LUTS patients (median 0.31 vs. 0.45; p<0.001), with an AUC of 0.704 (95%CI 0.627-0.774). mTPR ≤0.31 predicted surgical revision within 6 months (OR:3.4, CI: 1.2-9.8), motor deficiency (OR:2.1, 95%CI: 1.4-5.2), and persistent LUTS post-surgery (OR:4.5, 95%CI: 1.1-18.9). mTPR ≤0.34 was associated with worse follow-up outcome, including increased ODI (β:3.2; 95%CI: 1.1-5.3; p=0.004) and SSSQ score (β:4.8; 95%CI:2.1-7.5). CONCLUSION LUTS patients with LSS exhibit more severe symptoms and poorer outcome, with mTPR ≤0.34 being a predictor of adverse clinical outcome and the need for surgical revision within 6 months.

Introduction: Aim of this study is to analyze gender-related epidemiological characteristics of cauda equina syndrome (CES) in Zenica-Doboj Canton in 10 years period. Methods: The study was conducted in the Zenica-Doboj Canton, and data were obtained from the time period between 2012 to 2022. The study included a total sample of 1709 patients diagnosed with disc herniation who underwent surgical decompression. In total, 48 patients developed cauda equine syndrome (CES). Results: The analysis unveiled noteworthy gender disparities, with male predominance (79.2% vs. 20.8%, p<0.001) and varying employment distributions (males: 23.7% unemployed, 63.2% employed, 13.1% retired; females: 40.0% unemployed, 20.0% employed, 40.0% retired, p<0.001). The calculated OR for 2012-2022 was 2.969 (95% CI: 1.576-5.593, p=xxx), signifying a substantial gender-incidence relationship for CES. CES-I incidence ranged 0.80-1.60/100,000 and CES-R ranged 0.25-0.83/100,000. Highest CES incidence was 4.17/100,000 (2015); the lowest was in 2019 with no CES-R cases reported. Male incidence peaked at 2.64/100,000 (2018), and the lowest was 1.06/100,000 (2013, 2017). For females, the highest was 1.17/100,000 (2018, 2021), with no cases reported in certain years. The affected level demonstrated gender differences, with L4/L5 prevalence in males (47.4%) and L3/L4 in females (50%, p=0.165). Conclusion: This study revealed a higher incidence of CES in males compared to females in the Zenica-Doboj Canton. The heterogenicity of data regarding CES occurring due to the lumbar disc herniation is significant. This indicates a clear need for additional research and epidemiological studies that would highlight the population of patients that have higher risk of CES onset.

Lumbar disc herniation (LDH) often results in significant pain and disability, and histopathologic (HP) evaluation of intervertebral discs (IVDs) offers critical insights into treatment outcomes. This prospective observational study explores HP changes in IVDs and their association with clinical outcomes following surgical treatment for LDH. A cohort of 141 patients undergoing MRI-confirmed LDH surgery underwent HP evaluation using a semi-quantitative HP degeneration score (HDS). Preoperatively and at a six-month follow-up, the comprehensive clinical assessment included the Oswestry disability index (ODI) and visual analog scale (VAS), with a minimal clinically important difference (MCID) calculated from ODI and VAS. Results indicated significant associations between higher HDS and adverse clinical outcomes, including persistent pain and greater disability post-surgery. Specifically, an HDS ≥ 7 was predictive (OR ═ 6.25, 95% CI: 2.56–15.23) of disability outcomes measured with MCID-ODI (AUC: 0.692, 95% CI: 0.609–0.767, P < 0.001), and HDS ≥ 8 was predictive (OR ═ 1.72, 95% CI: 1.04–2.77) of persistent pain measured with MCID-VAS (AUC ═ 0.628, 95% CI: 0.598–0.737, P ═ 0.008), highlighting the diagnostic potential of HDS in assessing postoperative recovery. This study underscores the potential of HP evaluation using HDS to provide valuable insights into disease progression and outcomes in LDH patients, complementing conventional radiologic methods. The findings support the application of personalized treatment strategies based on HP findings while acknowledging challenges in interpretation and clinical implementation.

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.

This study aimed to assess the impact of the war in Ukraine on the mental health of individuals who had previously experienced the war in Bosnia and Herzegovina. A total of 649 respondents aged 35 and above, who were either directly recruited or indirectly affected as civilians during the war in Bosnia and Herzegovina, participated in this cross-sectional survey. The World Health Organization's Impact Event Scale (IES) and Self-Reporting Questionnaire (SRQ) were used to measure the impact of war events in Bosnia and Herzegovina and Ukraine on the respondents and to assess their mental health, respectively. The findings demonstrate a significant association between war events in Ukraine and the reactivation of post-traumatic stress disorder (PTSD) symptoms in individuals previously exposed to the war in Bosnia and Herzegovina. The results highlight the significant influence of the war in Ukraine on the reactivation of PTSD symptoms in individuals with prior exposure to the war in Bosnia and Herzegovina. Additionally, considering the various risk factors associated with PTSD reactivation, this study provides insights into the broader impact of war activities, including factors beyond the specific conflict in Ukraine.

Aim: To examine whether there is a correlation between blood pressure, heart rate, and pain with the level of preoperative and postoperative anxiety in surgery of impacted third molars under local anesthesia. Subjects and Methods: In the study, which included adult patients of both sexes with an indication for surgical extraction of impacted third molars, research parameters were measured as follows: 1st measurement (day of examination) - blood pressure, heart rate, preoperative anxiety with Spielberger’s State-Trait Anxiety Inventory (STAI); 2nd measurement (immediately before the intervention) - blood pressure, heart rate, preoperative anxiety with STAI; 3rd measurement (day after intervention) - blood pressure, heart rate, postoperative anxiety with STAI, postoperative pain with visual analog scale. Results: The values of preoperative and postoperative anxiety and the measured parameters of blood pressure, heart rate, and postoperative pain were statistically significantly positively correlated with each other during all measurements. Conclusion: In order to increase the satisfaction of both the patient and the ordinarius, and to prevent possible complications in this type of oral surgical intervention, it would be useful to consider adequate therapy in order to prevent the development of anxiety, considering the confirmed correlation with the measured parameters.

The topic of this research, chronic subdural hematoma (CSH), is one of the most common pathologies in neurosurgery, and it is more frequent in the elderly. Surgical evacuation has been widely considered the gold standard treatment. Despite the excellent outcomes, sometimes some cases require a different approach. The treatment choice depends on the general condition of the patients, as well as the clinical presentation and hematoma volume. Also, preexisting comorbidities in elderly patients, postoperative complications, and the ability to recover must be considered. Consequently, conservative treatment can be effective in carefully selected cases, and can be considered if the patient's neurological and physical conditions allow. Some drugs contribute to CSH resolution by changing the capsule membrane permeability and inhibiting the fibrinolytic and inflammatory systems. Our work is based on the efficacy of dexamethasone as a method of conservative therapy, and it was demonstrated in the case of a 91-year-old patient.

This study explores the anatomical relationship between iliac blood vessels and the lower lumbar spine during supine and prone patient positions. The average height of participants was 174.02 cm ± 9.01, while the average weight was 80.38 kg ± 13.48. Body mass index (BMI) analyses showed differences (p = 0.002), with 34.7% classified as normal weight, 53.1% as overweight, and 12.2% as moderately obese. The study examined the distances between iliac arteries and veins in relation to intervertebral anterior and posterior disc contours. Patient positioning significantly affected these measurements at both L4/L5 and L5/S1 levels. The findings highlight the critical influence of body position on anatomical relationships in the context of lower lumbar spine surgery. The study underscores the importance of preoperative awareness of vascular anatomy to prevent iatrogenic lesions during spine surgery, contributing valuable insights for optimizing surgical approaches and minimizing complications in spine surgery, particularly microdiscectomy.