Understanding the Significance of Hypoxia-Inducible Factors (HIFs) in Glioblastoma: A Systematic Review.

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.

Low-Cost 3D Models for Cervical Spine Tumor Removal Training for Neurosurgery Residents.

BACKGROUND AND OBJECTIVES: Spinal surgery, particularly for cervical pathologies such as myelopathy and radiculopathy, requires a blend of theoretical knowledge and practical skill. The complexity of these conditions, often necessitating surgical intervention, underscores the need for intricate understanding and precision in execution. Advancements in neurosurgical training, especially with the use of low-cost 3D models for simulating cervical spine tumor removal, are revolutionizing this field. These models provide the realistic and hands-on experience crucial for mastering complex neurosurgical techniques, filling gaps left by traditional educational methods. MATERIALS AND METHODS: This study aimed to assess the effectiveness of 3D-printed cervical vertebrae models in enhancing surgical skills, focusing on tumor removal, and involving 20 young neurosurgery residents. These models, featuring silicone materials to simulate the spinal cord and tumor tissues, provided a realistic training experience. The training protocol included a laminectomy, dural incision, and tumor resection, using a range of microsurgical tools, focusing on steps usually performed by senior surgeons. RESULTS: The training program received high satisfaction rates, with 85% of participants extremely satisfied and 15% satisfied. The 3D models were deemed very realistic by 85% of participants, effectively replicating real-life scenarios. A total of 80% found that the simulated pathologies were varied and accurate, and 90% appreciated the models' accurate tactile feedback. The training was extremely useful for 85% of the participants in developing surgical skills, with significant post-training confidence boosts and a strong willingness to recommend the program to peers. CONCLUSIONS: Continuing laboratory training for residents is crucial. Our model offers essential, accessible training for all hospitals, regardless of their resources, promising improved surgical quality and patient outcomes across various pathologies.

Association between paediatric eye injuries, later academic success and social performance.

Aim: To investigate an association between eye injury and later academic and social performance. Materials: A retrospective longitudinal study of taking measurements multiple times was conducted including all severe eye injuries admitted during 2011-2017 at the main regional clinic to investigate changes in academic success and social inclusion before and after an injury. Parents/caregivers were surveyed asking questions on academic performance, and community/social involvement. In 2023 data on employment status were obtained. Kappa (ĸ) and non-parametric Wilcox-on signed-rank test for multiple comparisons were used. For association of employment status and post-injury visual acuity Fisher score was tested. Results: The total sample for assessing social inclusion and academic success was 36 and 25 children, respectively. In the following academic year ĸ agreements decreased from 0.88 (p<0.001) comparing pre-injury with a one-year post to 0.5106 (p<.0001) in the second year and 0.4750 (p=0.003) in the third, suggesting a deteriorating trend. A comparison of academic success before injury to two and three years after injury showed the trend significantly worsening with time (p=0.005, and 0.003, respectively). No association between an eye injury and social inclusion, as well as between employment and final visual acuity was noticed. Conclusion: Our findings suggest no association between social inclusion, employment, and eye trauma, while in later years academic success may be more impacted by the eye injury. Due to eye injury unpredictability in childhood age, both an informed and supportive climate environment at home and school is essential to minimize deleterious responses to eye trauma.

Four-level ACDF surgical series 2000-2022: a systematic review of clinical and radiological outcomes and complications.

OBJECTIVE: The primary objective of this investigation is to systematically scrutinize extant surgical studies delineating Four-Level Anterior Cervical Discectomy and Fusion (4L ACDF), with a specific emphasis on elucidating reported surgical indications, clinical and radiological outcomes, fusion rates, lordosis correction, and the spectrum of complication rates. METHODS: The literature review was conducted in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, employing the MEDLINE (PubMed), Embase, and Scopus databases. This analysis encompasses studies implementing the 4L ACDF procedure, with detailed extraction of pertinent data pertaining to surgical methodologies, types of employed interbody cages, clinical and radiological endpoints, rates of fusion, and the incidence of complications. RESULTS: Among the 15 studies satisfying inclusion criteria, a marginal increment in the year 2022 (21.4%) was discerned, with a preponderance of study representation emanating from China (35.7%) and the United States (28.6%). 50% of the studies were single-surgeon studies. Concerning follow-up, studies exhibited variability, with 42.9% concentrating on periods of five years or less, and an equivalent proportion extending beyond this timeframe. Across the amalgamated cohort of 2457 patients, males constituted 51.6%, manifesting a mean age range of 52.2-61.3 years. Indications for surgery included radiculopathy (26.9%) and myelopathy (46.9%), with a predilection for involvement at C3-7 (24.9%). Meta-analysis yielded an overall complication rate of 16.258% (CI 95%: 14.823%-17.772%). Dysphagia (4.563%), haematoma (1.525%), hoarseness (0.205%), C5 palsy (0.176%) were the most prevalent complications of 4L ACDF. Fusion rates ranging from 41.3% to 94% were documented. CONCLUSION: The 4L ACDF is commonly performed to address mylopathy and radiculopathy. While the surgery carries a complication rate of around 16%, its effectiveness in achieving bone fusion can vary considerably.

Sensitivity and specificity of machine learning and deep learning algorithms in the diagnosis of thoracolumbar injuries resulting in vertebral fractures: A systematic review and meta-analysis.

Introduction: Clinicians encounter challenges in promptly diagnosing thoracolumbar injuries (TLIs) and fractures (VFs), motivating the exploration of Artificial Intelligence (AI) and Machine Learning (ML) and Deep Learning (DL) technologies to enhance diagnostic capabilities. Despite varying evidence, the noteworthy transformative potential of AI in healthcare, leveraging insights from daily healthcare data, persists. Research question: This review investigates the utilization of ML and DL in TLIs causing VFs. Materials and methods: Employing Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) methodology, a systematic review was conducted in PubMed and Scopus databases, identifying 793 studies. Seventeen were included in the systematic review, and 11 in the meta-analysis. Variables considered encompassed publication years, geographical location, study design, total participants (14,524), gender distribution, ML or DL methods, specific pathology, diagnostic modality, test analysis variables, validation details, and key study conclusions. Meta-analysis assessed specificity, sensitivity, and conducted hierarchical summary receiver operating characteristic curve (HSROC) analysis. Results: Predominantly conducted in China (29.41%), the studies involved 14,524 participants. In the analysis, 11.76% (N = 2) focused on ML, while 88.24% (N = 15) were dedicated to deep DL. Meta-analysis revealed a sensitivity of 0.91 (95% CI = 0.86-0.95), consistent specificity of 0.90 (95% CI = 0.86-0.93), with a false positive rate of 0.097 (95% CI = 0.068-0.137). Conclusion: The study underscores consistent specificity and sensitivity estimates, affirming the diagnostic test's robustness. However, the broader context of ML applications in TLIs emphasizes the critical need for standardization in methodologies to enhance clinical utility.

Augmented Reality Integration in Skull Base Neurosurgery: A Systematic Review.

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.

Histopathological spectrum of lumbar disc changes in obesity: analysis of intervertebral discs in lumbar hernia patients in Zenica-Doboj Canton, Bosnia and Herzegovina.

Aim To investigate the correlation of body mass index (BMI) with severity of intervertebral disc degeneration. Methods The study enrolled patients who had undergone surgical intervention for a herniated disc at the Department of Neurosurgery of the Cantonal Hospital Zenica. Patients underwent thorough preoperative evaluation, including medical history, neurological and physical assessments, and radiological analysis. The surgical intervention consisted of a posterior lumbar discectomy, and the excised disc material was preserved and subjected to histopathological analysis based on Histopathologic Degeneration Score (HDS). Patients were divided in two groups according to Body Mass Index (BMI): study group with BMI≥25 and control group with BMI<25. Results Among 69 patients with herniated IVD, 26 (37.7%) were with BMI≥25 (study group), and 43 (62.3%) were with BMI<25 (controls). The study group displayed substantial increase in height, 1.80±0.06 m compared to controls, 1.74±0.06 m (p=0.001). Weight and BMI were significantly higher in the study group of patients (weight: 91.60±10.22 vs. 67.37±9.20 kg, BMI: 28±2 vs. 22±2; p<0.001). Differences were confirmed in HDS values in the study group comparing to the control group (p<0.001). The study group exhibited significant differences in chondrocyte proliferation, tears and clefts, granular changes, and mucous degeneration (p<0.05), and positive correlations were found between BMI and these alterations found in the herniated discs (p<0.05). Therefore, HDS showed positive correlations with BMI (R=0.599; p<0.001) and weight (R=0.696; p<0.001). Conclusion The study's findings confirmed that BMI has a significant impact on intervertebral disc degeneration, emphasizing the importance of weight management in preventing disc degeneration.

Morphometric and Ki-67 proliferative index-related characteristics of meningiomas and their correlation with demographic, clinical, histopathological, and postoperative features.

Aim To investigate the correlations between tumour characteristics, symptoms, intraoperative findings, and outcomes in patient with meningioma. Methods A retrospective study was conducted on 86 surgically treated patients at Department of Neurosurgery of Cantonal Hospital Zenica from 2010 to 2020. Patients with intracranial meningiomas underwent neurological evaluation and MRI scans to analyse tumour characteristics, including volume (TV), peritumoral brain oedema (PTBE) and oedema index (EI). Surgical treatment was performed, followed by postoperative MRI and outcome assessment. Intraoperatively, the tumour's relationship with cortex, pial membrane, skull bones, and sinuses was evaluated, and the extent of tumour resection was graded. Meningioma samples underwent histopathological analysis to assess the grade and regularity of borders, and Ki-67 labelling index was determined using immunohistochemistry. Results Significant correlations were found between PTBE and Ki67 expression (p<0.001), PTBE and vomiting/nausea (p=0.002), cognitive impairment (p=0.047), venous compression (p=0.001), cortical, pial and dural invasion (p<0.05), and the postoperative presence of oedema (p=0.002). Venous compression, cortical, pial, dural and bone invasion positively correlated with Ki-67 expression (p<0.001). Grade and tumour border positively correlated with Ki-67 expression (p<0.001). Oedema persistence postoperatively showed a positive correlation with Ki-67 expression (p<0.001). Conclusion The study revealed significant correlations between Ki-67 expression and PTBE, with notable associations with clinical symptoms, tumour characteristics, and postoperative oedema presence.

CRISPR/Cas9-Mediated Gene Therapy for Glioblastoma: A Scoping Review.

This scoping review examines the use of CRISPR/Cas9 gene editing in glioblastoma (GBM), a predominant and aggressive brain tumor. Categorizing gene targets into distinct groups, this review explores their roles in cell cycle regulation, microenvironmental dynamics, interphase processes, and therapy resistance reduction. The complexity of CRISPR-Cas9 applications in GBM research is highlighted, providing unique insights into apoptosis, cell proliferation, and immune responses within the tumor microenvironment. The studies challenge conventional perspectives on specific genes, emphasizing the potential therapeutic implications of manipulating key molecular players in cell cycle dynamics. Exploring CRISPR/Cas9 gene therapy in GBMs yields significant insights into the regulation of cellular processes, spanning cell interphase, renewal, and migration. Researchers, by precisely targeting specific genes, uncover the molecular orchestration governing cell proliferation, growth, and differentiation during critical phases of the cell cycle. The findings underscore the potential of CRISPR/Cas9 technology in unraveling the complex dynamics of the GBM microenvironment, offering promising avenues for targeted therapies to curb GBM growth. This review also outlines studies addressing therapy resistance in GBM, employing CRISPR/Cas9 to target genes associated with chemotherapy resistance, showcasing its transformative potential in effective GBM treatments.

The New Era of Spinal Surgery: Exploring the Use of Exoscopes as a Viable Alternative to Operative Microscopes-A Systematic Review and Meta-Analysis.

BACKGROUND: The growing interest in exoscopic (EX) technology has prompted a comprehensive evaluation of its clinical, functional, and financial outcomes in neurosurgery. This systematic review and meta-analysis aimed to explore the utilization of EX in spine surgery and assess their safety, efficacy, and impact on surgical outcomes. METHODS: A thorough literature review was conducted using PubMed, Scopus, and Embase databases in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The study focused on articles concerning the application of EXs in spinal surgical procedures. The inclusion criteria encompassed various study designs presenting clinical data and intraoperative experiences related to EX utilization in spine surgery. RESULTS: The meta-analysis included studies examining various aspects of EX utilization, such as intraoperative complications, video/image quality, surgical field visualization, ease of manipulation, ergonomic characteristics, educational utility, surgical duration, and team involvement. Findings indicated that EXs offered superior video quality and favorable ergonomic features. Comparable outcomes were observed in surgical duration, intraoperative blood loss, time to discharge, and postoperative pain levels between EX and conventional microscope approaches. CONCLUSIONS: This study provides valuable insights into the utilization of EXs in spine surgery, demonstrating their potential advantages and comparable outcomes with conventional microscopes.

Molecular Targeted Therapies in Glioblastoma Multiforme: A Systematic Overview of Global Trends and Findings.

This systematic review assesses current molecular targeted therapies for glioblastoma multiforme (GBM), a challenging condition with limited treatment options. Using PRISMA methodology, 166 eligible studies, involving 2526 patients (61.49% male, 38.51% female, with a male-to-female ratio of 1.59/1), were analyzed. In laboratory studies, 52.52% primarily used human glioblastoma cell cultures (HCC), and 43.17% employed animal samples (mainly mice). Clinical participants ranged from 18 to 100 years, with 60.2% using combined therapies and 39.8% monotherapies. Mechanistic categories included Protein Kinase Phosphorylation (41.6%), Cell Cycle-Related Mechanisms (18.1%), Microenvironmental Targets (19.9%), Immunological Targets (4.2%), and Other Mechanisms (16.3%). Key molecular targets included Epidermal Growth Factor Receptor (EGFR) (10.8%), Mammalian Target of Rapamycin (mTOR) (7.2%), Vascular Endothelial Growth Factor (VEGF) (6.6%), and Mitogen-Activated Protein Kinase (MEK) (5.4%). This review provides a comprehensive assessment of molecular therapies for GBM, highlighting their varied efficacy in clinical and laboratory settings, ultimately impacting overall and progression-free survival in GBM management.

Accessible Spinal Surgery: Transformation Through the Implementation of Exoscopes As Substitutes for Conventional Microsurgery in Low- and Middle-Income Settings.

Advancements in neurosurgical visualization have been made possible by the introduction of the operating microscope (OM) and the emergence of exoscopic technology (EX). Both OMs and EXs provide enhanced magnification and illumination, but they come with their own set of advantages and disadvantages. OMs provide high-quality magnification and illumination and have been used successfully in a variety of surgical procedures. They can be customized to fit the specific needs of the surgeon and are a well-established technology. However, they can be bulky, expensive, and cause discomfort during extended procedures. EXs provide high-definition magnification and illumination, improved depth perception and ergonomics, and can be cost-effective. They can be customized to fit the specific needs of the surgeon and can be made using locally available materials, reducing the need for expensive imports. However, they may require adjustment and have a learning curve for surgeons who are used to operating with OMs. Additionally, they may have limited availability in some healthcare settings. The choice between OMs and EXs will depend on the specific needs of the surgeon and the healthcare setting. The integration of 3D EX systems has revolutionized neurosurgery, offering improved depth perception and ergonomics. EX's cost-effectiveness addresses accessibility concerns, making it an attractive alternative, particularly for low and middle-income healthcare settings. The exoscope seems to be a safe alternative compared to an operative microscope for the most common brain and spinal procedures. The exoscope may help expand access to neurosurgical care and training worldwide. In conclusion, both technologies have their own set of advantages and disadvantages, and the choice between them will depend on the specific needs of the surgeon and the healthcare setting.

Breaking Barriers in Cranioplasty: 3D Printing in Low and Middle-Income Settings-Insights from Zenica, Bosnia and Herzegovina.

Background and Objectives: Cranial defects pose significant challenges in low and middle-income countries (LIMCs), necessitating innovative and cost-effective craniofacial reconstruction strategies. The purpose of this study was to present the Bosnia and Herzegovina model, showcasing the potential of a multidisciplinary team and 3D-based technologies, particularly PMMA implants, to address cranial defects in a resource-limited setting. Materials and Methods: An observational, non-experimental prospective investigation involved three cases of cranioplasty at the Department of Neurosurgery, Cantonal Hospital Zenica, Bosnia and Herzegovina, between 2019 and 2023. The technical process included 3D imaging and modeling with MIMICS software (version 10.01), 3D printing of the prototype, mold construction and intraoperative modification for precise implant fitting. Results: The Bosnia and Herzegovina model demonstrated successful outcomes in cranioplasty, with PMMA implants proving cost-effective and efficient in addressing cranial defects. Intraoperative modification contributed to reduced costs and potential complications, while the multidisciplinary approach and 3D-based technologies facilitated accurate reconstruction. Conclusions: The Bosnia and Herzegovina model showcases a cost-effective and efficient approach for craniofacial reconstruction in LIMICs. Collaborative efforts, 3D-based technologies, and PMMA implants contribute to successful outcomes. Further research is needed to validate sustained benefits and enhance craniofacial reconstruction strategies in resource-constrained settings.

A correlation of demographic characteristics, preoperative conservative therapy and timing with postoperative outcome in herniated disc-associated cauda equina syndrome: Do they really matter?

Aim To examine a correlation of demographic characteristics of patients, preoperative modality of conservative therapy and timing on the postoperative outcome of patients six months after the operation. Methods A retrospective, non-randomized, clinical study involved 48 patients of different age and gender with a verified diagnosis of cauda equina syndrome (CES). The inclusion criteria were patients with CES caused by discus hernia. Observed research variables were age, gender, affected vertebral level, conservative modalities of perioperative therapy (nonsteroidal anti-inflammatory drugs - NSAIDs and physiotherapy), duration of symptoms, and outcome parameters (motor and sensory function, sphincter function of the urinary bladder and bowel). Results A statistically significant negative correlation was found between age and postoperative outcome (p<0.05). The affected vertebral level was positively correlated with the motor and sensory outcome (p<0.05). A positive correlation between the use of NSAIDs and the outcome was found (R=0.570; p<0.001), as well as a negative correlation with perioperative physiotherapy (R=-0.201; p= 0.001). Postponement of surgery was negatively correlated with outcome variables (p<0.001). Conclusion The results of the study bring new conclusions that were not previously observed. Possible new characteristics associated with the outcome of cauda equina syndrome were determined.

Magnetic resonance morphometry of the lumbar spinal canal in Zenica - Doboj Canton in Bosnia and Herzegovina.

Aim To investigate morphometric determinants of lumbar canal in patients treated in Cantonal Hospital Zenica, and their variation according to gender. Methods Morphometry of lumbar spinal canal was assessed in 52 patients treated at the Department of Neurosurgery of Cantonal Hospital Zenica in the period between September 2022 and November 2022. Data were collected retrospectively: anteroposterior and transverse diameter of lumbar vertebrae and intervertebral discs, as well as anteroposterior diameter of the spinal canal. Results Gender appeared to be an important morphometric determinant, since it significantly differed when it comes to lumbar vertebral anteroposterior and transverse diameter, being mostly larger in males. Conclusion This study increases anatomical knowledge of the vertebras and spinal canal of the lumbar region. Therefore, the measured dimensions of the lumbar vertebrae and spinal canal could be used as a baseline point for evaluation of patients presenting with low back pain and potential spinal canal stenosis.

Usage of students' potential in biomedical and health care research in Bosnia and Herzegovina.

OBJECTIVE: To provide relevant insight into the current degree of usage of the research potential of students of biomedical sciences in Bosnia and Herzegovina. METHOD: The chosen data collection method was online surveying via Google search engine. The target group were students of biomedical sciences in Bosnia and Herzegovina. The surveying was conducted in July 2019, and responses were subjected to descriptive statistics. RESULTS: Although the majority of participants claimed that they were familiar with the seminar and scientific papers writing methodology and that the related course is available in their faculty's curriculum, the quality of such courses may be questioned as the majority of study participants self-reported that they do not possess or did not posses necessary knowledge for writing and publishing a scientific paper. Also, the majority of respondents reported that they have never participated in any scientific research, which questions the involvement of students in scientific research in our country as well. More than half of respondents were actively reading scientific papers, but a third of them did not have that habit. Two-thirds of students reported that they have never attended any scientific event where they could learn more about the scientific research methods. Inadequate awareness of the importance of research, lack of students' interest in making a research, and lack of knowledge were characterized as main obstacles in conducting scientific research according to survey responses. CONCLUSION: Information obtained through research indicate that the student potential in scientific research in Bosnia and Herzegovina has not been used in its maximal capacity, requiring several steps to be taken towards its improvement.