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 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.

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.

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.

Background and Objectives: To investigate the role of augmented reality (AR) in skull base (SB) neurosurgery. Materials and Methods: Utilizing PRISMA methodology, PubMed and Scopus databases were explored to extract data related to AR integration in SB surgery. Results: The majority of 19 included studies (42.1%) were conducted in the United States, with a focus on the last five years (77.8%). Categorization included phantom skull models (31.2%, n = 6), human cadavers (15.8%, n = 3), or human patients (52.6%, n = 10). Microscopic surgery was the predominant modality in 10 studies (52.6%). Of the 19 studies, surgical modality was specified in 18, with microscopic surgery being predominant (52.6%). Most studies used only CT as the data source (n = 9; 47.4%), and optical tracking was the prevalent tracking modality (n = 9; 47.3%). The Target Registration Error (TRE) spanned from 0.55 to 10.62 mm. Conclusion: Despite variations in Target Registration Error (TRE) values, the studies highlighted successful outcomes and minimal complications. Challenges, such as device practicality and data security, were acknowledged, but the application of low-cost AR devices suggests broader feasibility.