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Hakija Bečulić

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Emir Begagić, Amina Džidić-Krivić, Hakija Bečulić, Ragib Pugonja, Adnana Ljevaković, Binasa Bašić, Adem Nuhović, Elma Milanović, Semir Hadžić et al.

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.

Emir Begagić, Amina Džidić-Krivić, Hakija Bečulić, Ragib Pugonja, Adnana Ljevaković, Binasa Bašić, Adem Nuhović, Elma Milanović, Semir Hadžić et al.

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.

Fatima Juković-Bihorac, S. Đuričić, Emir Begagić, Hakija Bečulić, A. Efendic, S. Vranić, Mirza Pojskić

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.

I. Omerhodžić, B. Rovčanin, A. Džurlić, Mirsad Hodžić, Rasim Skomorac, Hakija Bečulić, S. Zahirović, Fahrudin Alić, E. Suljic et al.

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.

H. Sefo, Hakija Bečulić, Rasim Skomorac, Fahrudin Alić, Emir Begagić, Ermin Hadžić, Mirza Pojskić

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.

Amina Džidić Krivić, Emir Begagić, Semir Hadžić, Amir Bećirović, E. Bećirović, Harisa Hibić, Lejla Tandir Lihić, Samra Kadić Vukas, Hakija Bečulić et al.

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.

Harun Hodzic, Hakija Bečulić, Emir Begagić, Nejla Huseinspahić, Igor Sladojević, Andrej Popov, Rasim Iriškić, Tarik Zulović, E. Bećirović et al.

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.

H. Sefo, Emir Begagić, Hakija Bečulić, Amina Krivić-Džidić, Rasim Skomorac, Fahrduin Alić, Ragib Pugonja, Ermin Hadžić, Igor Sladojević

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.

Hakija Bečulić, Emir Begagić, S. Šegalo, Fatima Juković-Bihorac, Emsel Papić, Ragib Pugonja, Amina Džidić-Krivić, Adem Nuhović, Goran Lakičević et al.

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.

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