BMScope: A scoping review to chart the evolving clinical study landscape in brain and leptomeningeal metastasis.

BACKGROUND: Recent studies have challenged the notion that patients with brain metastasis (BM) or leptomeningeal metastasis (LM) should be excluded from systemic therapy clinical trials. This scoping study summarises the BM/LM clinical studies published between 2010 and 2023. METHODS: MEDLINE, CINAHL, CAB Abstracts, PsycINFO, Cochrane Library, HINARI, International Pharmaceutical Abstracts, PubMed, Scopus, Web of Science, and EMBASE electronic databases were searched on 21 June 2021. An updated search was performed on 21 February 2023. Eligible studies should involve investigation of a therapeutic intervention in solid tumour patients with BM and/or LM and a reported patient outcome. Extracted study-level data, included study type, publication date, geographical location, number of BM/LM patients in study, primary tumour type and type of therapeutic intervention. RESULTS: 4921 unique studies were eligible for analysis. The key finding is that BM/LM clinical research is expanding globally, both observational studies and clinical trials. Despite the shift over time towards a higher proportion of systemic therapy trials, the majority still do not include patients with symptomatic disease and lack reporting of BM/LM specific endpoints. Globally, there has been a trend to more international collaboration in BM/LM clinical studies. CONCLUSIONS: This analysis of the BM/LM literature charts the evolving landscape of studies involving this previously excluded population. Given the increasing clinical research activity, particularly involving late-stage systemic therapy trials, it is imperative that due consideration is given to the intracranial activity of new investigational agents. Wider adoption of standardised reporting of intracranial-specific endpoints will facilitate evaluation of relative intracranial efficacy.

Diagnostic utility of Brain Injury Guidelines (BIG): systematic review and meta-analysis for prediction of neurosurgical intervention in traumatic brain injury.

BACKGROUND: The Brain Injury Guidelines (BIG) categorize the severity of Traumatic Brain Injury (TBI). The efficacy of BIG in predicting radiological deterioration and the necessity for neurosurgical intervention remains uncertain, as there is a lack of examination of pooled data from current literature despite validation in numerous single and multi-institutional studies. The aim of this study was to analyze existing studies to determine the diagnostic accuracy of BIG scoring criteria. METHODS: A systematic review and meta-analysis was conducted in accordance with PRISMA guidelines (PROSPEROID CRD42021277542). Three databases were searched, and articles published from 2000 to October 2022 were included (last search date: 25 November 2022). Pooled sensitivity and specificity were calculated using random effects meta-analysis. RESULTS: Of the 1130 articles identified, 13 were included in the analysis (9032 patients - 1433 BIG1, 2136 BIG2 & 3189 BIG3). A total of 2274 patients were not classified under either group. Pooled sensitivity for predicting neurosurgical intervention was 1.00 (95%CI:1.00-1.00), and 0.98 for radiological deterioration (95% CI: 0.927-0.996). The specificity in predicting radiological deterioration was 0.18 (95% CI: 0.16-0.21) and 0.05 for neurosurgical intervention (95% CI 0.05-0.05). CONCLUSIONS: The BIG score is highly sensitive at excluding TBI cases that do not require neurosurgical intervention; however, BIG-2 and BIG-3 might not be useful for ruling in TBI patients who require neurosurgical intervention.

Integrating Augmented Reality in Spine Surgery: Redefining Precision with New Technologies.

INTRODUCTION: The integration of augmented reality (AR) in spine surgery marks a significant advancement, enhancing surgical precision and patient outcomes. AR provides immersive, three-dimensional visualizations of anatomical structures, facilitating meticulous planning and execution of spine surgeries. This technology not only improves spatial understanding and real-time navigation during procedures but also aims to reduce surgical invasiveness and operative times. Despite its potential, challenges such as model accuracy, user interface design, and the learning curve for new technology must be addressed. AR's application extends beyond the operating room, offering valuable tools for medical education and improving patient communication and satisfaction. MATERIAL AND METHODS: A literature review was conducted by searching PubMed and Scopus databases using keywords related to augmented reality in spine surgery, covering publications from January 2020 to January 2024. RESULTS: In total, 319 articles were identified through the initial search of the databases. After screening titles and abstracts, 11 articles in total were included in the qualitative synthesis. CONCLUSION: Augmented reality (AR) is becoming a transformative force in spine surgery, enhancing precision, education, and outcomes despite hurdles like technical limitations and integration challenges. AR's immersive visualizations and educational innovations, coupled with its potential synergy with AI and machine learning, indicate a bright future for surgical care. Despite the existing obstacles, AR's impact on improving surgical accuracy and safety marks a significant leap forward in patient treatment and care.

Challenging assumptions: "unveiling meritocracy's reality in neurosurgery".

Introduction: Meritocracy, a concept revered as the cornerstone of fairness and equal opportunity, is critically examined in the context of neurosurgery. This article challenges the notion that success in this demanding field is solely determined by individual abilities and effort. It reveals that factors such as background, gender, and socioeconomic status significantly influence one's career trajectory. By investigating how these systemic barriers impact admissions to neurosurgical training programs and professional advancement, the paper underscores the complexity of meritocracy in neurosurgery, suggesting that the meritocratic ideal is more nuanced and influenced by external variables than commonly believed. Results: Certain universities deemed elite offer a curriculum divergent from that of their counterparts in low and middle-income countries. Students at these "elite" institutions gain exposure to new technologies and research incentives, which brings us to the realm of research. Remarkably, 75% of articles originating from developed nations account for just 25% of traumatic brain injury cases. This disparity highlights a significant research imbalance, and the common refrain underscores the need to bolster research capabilities in low-income countries. For neurosurgeons in the developing world, engaging in research often becomes a luxury due to multifaceted challenges. Financial barriers, including publication costs and paywalls for accessing articles, pose significant hurdles. Comparing salaries between countries underscores the glaring divide according to "Neurosurgeon Salary" in 2024. Neurosurgeons in the United States receive a median salary of $412,000 dollars per year, compared to $13,200 dollars in Latin America, as of June 2023. Given such incongruities, the prospect of even attending conferences or workshops abroad remains difficult for neurosurgeons from developing nations. Research isn't cast aside due to a lack of interest but due to resource limitations. The present landscape demands reconsideration. Conclusion: We underscore the journey towards a more inclusive and equitable future in neurosurgery as not just a goal, but a dynamic process fuelled by resilience, collaboration, and a commitment to diversity. The narrative promotes a collective endeavour to dismantle barriers and embrace innovation, emphasizing the importance of mentorship, cross-institutional collaboration, and the amplification of underrepresented voices.

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.

The importance of social networks in neurosurgery training in low/middle income countries.

Introduction: Neurosurgery is evolving with new techniques and technologies, relies heavily on high-quality education and training. Social networks like Twitter, Facebook, Instagram and LinkedIn have become integral to this training. These platforms enable sharing of surgical experiences, fostering global knowledge-sharing and collaboration among neurosurgeons. Virtual conferences and courses are accessible, enhancing learning regardless of location. While these networks offer real-time communication and collaborative opportunities, they also pose challenges like the spread of misinformation and potential distractions. According to the PICO format, the target population (P) for the purpose of this paper are medical students, neurosurgical residents and consultants on the role of social media (I) in neurosurgery among Low-Middle income countries (C) with the main outcome to understand the collaborative domain of learning. Material and method: This cross-sectional survey, conducted in June-July 2023, involved 210 medical students, neurosurgery residents, fellows, and practicing neurosurgeons from low and middle-income countries. A structured questionnaire assessed social network usage for neurosurgery training, covering demographic details, usage frequency, and purposes like education, collaboration, and communication. Participants rated these platforms' effectiveness in training on a 1-5 scale. Data collection employed emails, social media groups, and direct messaging, assuring respondent anonymity. The survey aimed to understand and improve social networks' use in neurosurgery, focusing on professional development, challenges, and future potential in training. Results: In a survey of 210 participants from low and middle-income countries, 85.5% were male, 14.5% female, with diverse roles: 42.9% neurosurgery residents, 40% practicing neurosurgeons, 14.6% medical students, and 2.4% other healthcare professionals. Experience ranged from 0 to 35 years, with Mexico, Nigeria, and Kenya being the top participating countries. Most respondents rated neurosurgery training resources in their countries as poor or very poor. 88.7% used social media professionally, predominantly WhatsApp and YouTube. Content focused on surgical videos, research papers, and webinars. Concerns included information quality and data privacy. Interactive case discussions, webinars, and lectures were preferred resources, and most see a future role for social media in neurosurgery training. Conclusions: Our study underscores the crucial role of social media in neurosurgery training and practice in low and middle-income countries (LMICs). Key resources include surgical videos, research papers, and webinars. While social media offers a cost-effective, global knowledge-sharing platform, challenges like limited internet access, digital literacy, and misinformation risks remain significant in these regions.

Letter: Estimating the baseline local recurrence rate for a brain metastasis after neurosurgical resection.

Brain metastases represent a growing healthcare challenge with a rising incidence attributed to earlier detection and improved systemic cancer treatments. We conducted a systematic review and meta-analysis to investigate the local recurrence rate following surgical resection of a brain metastasis without adjuvant therapy. The analysis included four studies with a total of 235 cases. It was found that the rate of local recurrence by 12-months was 48.1% (95% CI 41.2-58.9). These findings underscore the high rate of patients who will experience local recurrence within 12-months of surgery, emphasising the need for vigilant surveillance when omitting adjuvant radiotherapy in favour of systemic treatments with potential but unproven CNS penetrance. The analysis highlights unmet needs in this patient population.

Outcomes of endoscopic third ventriculostomy (ETV) and ventriculoperitoneal shunt (VPS) in the treatment of paediatric hydrocephalus: Systematic review and meta-analysis.

PURPOSE: To evaluate the outcomes of endoscopic third ventriculostomy (ETV) and ventriculoperitoneal shunt (VPS) in the treatment of paediatric hydrocephalus. METHODS: We searched PubMed, MEDLINE, and Cochrane Central Register of Controlled Trials databases for articles published from 2000 to May 2023 (last search date May 6, 2023). Keywords searched included "endoscopic third ventriculostomy", "ventriculoperitoneal shunting", "paediatric population", and "outcomes". Using random-effects models, we compared success rates and complications of ETV and VPS. The primary outcome was ETV vs.VPS success rates, and the secondary outcome was post-treatment complications. Included studies reported on treatment success and complication rates. RESULTS: Out of 126 articles, 8 RCTs and 1 prospective study were included. Six studies reported primary outcome data (806 patients identified: 464 in ETV group, 342 in VPS group). Combined success rates were 81.8% (n = 283/346) for ETV and 86.7% (n = 182/210) for VPS (median follow-up 41 months). There was no difference in success rates between ETV and VPS groups (risk ratio 0.84, 95% confidence interval 0.80-0.90, I2 = 0%, p = 0.93). Combined complication rates were 4.6% (n = 16/346) in the ETV group and 27.1% (n = 57/210) in the VPS group. ETV had a lower rate of postoperative complications (risk ratio 0.76, 95% confidence interval 0.42-1.38, I2 = 53%, p = 0.04). CONCLUSIONS: Both ETV and VPS are viable surgical options for the management of paediatric hydrocephalus with similar success rates when used as first-line treatment. However, our study concluded that VPS results in a higher complication rate. REGISTRATION: This systematic review and meta-analysis was formally registered in the PROSPERO International database under the registration number CRD42023452907 on the 29th of August 2023.

Nanoparticle drug delivery to target breast cancer brain metastasis: Current and future trends.

Breast cancer brain metastasis (BCBM) is rapidly becoming an impediment to continuing survival gains seen in breast cancer patients. Drug delivery across the blood-brain barrier is the main issue hindering systemic therapy against BCBM. This review details recent advances in nanoparticle (NP) drug delivery systems to target BCBM. Their primary benefits are: enhanced circulating and intra-BCBM drug biodistribution, BCBM targeting through NP functionalization, opportunities for gene manipulation and their theragnostic applications. Multiple NPs have been synthesized to deliver therapeutic HER2 blockade, which is particularly important given HER2-positive breast cancer's tendency to form BCBM. Finally, we review the clinical context in which NP-based therapeutics have been investigated in BCBM patients. While a breakthrough in improving patient outcomes remain awaited, these clinical trials represent positive steps in the changing attitude towards BCBM as a treatable illness. Although multiple challenges remain in the clinical translation of BCBM-directed NP therapies, ongoing research in the field offers promising avenues for novel targeting of this devastating disease.

Gliomas: Genetic alterations, mechanisms of metastasis, recurrence, drug resistance, and recent trends in molecular therapeutic options.

Glioma is the most common intracranial tumor with poor treatment outcomes and has high morbidity and mortality. Various studies on genomic analyses of glioma found a variety of deregulated genes with somatic mutations including TERT, TP53, IDH1, ATRX, TTN, etc. The genetic alterations in the key genes have been demonstrated to play a crucial role in gliomagenesis by modulating important signaling pathways that alter the fundamental intracellular functions such as DNA damage and repair, cell proliferation, metabolism, growth, wound healing, motility, etc. The SPRK1, MMP2, MMP9, AKT, mTOR, etc., genes, and noncoding RNAs (miRNAs, lncRNAs, circRNAs, etc.) were shown mostly to be implicated in the metastases of glioma. Despite advances in the current treatment strategies, a low-grade glioma is a uniformly fatal disease with overall median survival of âˆ¼ 5-7 years while the patients bearing high-grade tumors display poorer median survival of âˆ¼ 9-10 months mainly due to aggressive metastasis and therapeutic resistance. This review discusses the spectrum of deregulated genes, molecular and cellular mechanisms of metastasis, recurrence, and its management, the plausible causes for the development of therapy resistance, current treatment options, and the recent trends in malignant gliomas. Understanding the pathogenic mechanisms and advances in molecular genetics would aid in the novel diagnosis, prognosis, and translation of pathogenesis-based treatment opportunities which could pave the way for precision medicine in glioma.

The Impact of Surgical Resection and Adjuvant Therapy on Survival in Pediatric Patients with Atypical Teratoid/Rhabdoid Tumor: Systematic Review and Pooled Survival Analysis.

BACKGROUND: Atypical teratoid/rhabdoid tumor (ATRT) is a rare malignant neoplasm in the pediatric population. ATRT is characterized by rhabdoid cells combined with the loss of either the INI1 (integrase interactor 1) or BRG1 (Brahma-related gene-1) protein. OBJECTIVE: To systematically review and analyze patient and tumor characteristics, prognosis, and impact of treatment on survival in pediatric patients with ATRT confirmed by alterations in INI1 or BRG1. This systematic review is the first to include only pediatric cases of ATRT confirmed with either INI1 or BRG1 alterations. METHODS: MEDLINE was searched using the terms "atypical teratoid/rhabdoid tumor" AND "paediatric/pediatric." Cases were included if confirmed by loss of INI1 or BRG1. The extracted dataset was analyzed using descriptive statistics, log-rank test, and Kaplan-Meier survival analysis via SPSS. RESULTS: A total of 38 articles were included in this study. The average age at diagnosis was 3 years. The most common locations reported are the supratentorial region and cerebral hemispheres. Ninety-three patients were reported to show evidence of dissemination. The average overall survival was 29 months. A significant difference in survival was noted between the tumor location groups, particularly worse outcomes for patients with spinal ATRT (P < 0.001). Extent of resection and adjuvant therapy were significant for survival (χ2 = 10.107, P = 0.018 and χ2 = 20.38, P < 0.0001, respectively). CONCLUSIONS: ATRT of the central nervous system in pediatric populations is a rare neoplasm associated with a poor prognosis in most patients. Future studies should be directed to find a standardized treatment protocol.

Molecular Mechanisms of PD-1 and PD-L1 Activity on a Pan-Cancer Basis: A Bioinformatic Exploratory Study.

Immune checkpoint blockade targeting PD-1 (PDCD1)/PD-L1 (CD274) is increasingly used for multiple cancers. However, efficacy and adverse-related events vary significantly. This bioinformatic study interrogated molecular differences pertaining to PDCD1/CD274 and their correlated genes on a pan-cancer basis to identify differences between cancer types. Patient RNA-seq data from fifteen cancer types were accessed on cBioPortal to determine the role of PDCD1/CD274 in patient survival and to identify positively and negatively correlated genes, which were also assessed for clinical relevance. Genes correlating with PDCD1/CD274 across multiple cancers were taken forward for drug repurposing via DRUGSURV and microRNA analysis using miRDB and miRabel. MicroRNAs were also screened for clinical relevance using OncomiR. Forty genes were consistently correlated with PDCD1/CD274 across multiple cancers, with the cancers themselves exhibiting a differential role for the correlated genes in terms of patient survival. Esophageal and renal cancers in particular stood out in this regard as having a unique survival profile. Forty-nine putative microRNAs were identified as being linked to the PDCD1/CD274 network, which were taken forward and further assessed for clinical relevance using OncomiR and previously published literature. One hundred and thirty significant survival associations for 46 microRNAs across fourteen groups of cancers were identified. Finally, a total of 23 putative repurposed drugs targeting multiple components of the PDCD1/CD274 network were identified, which may represent immunotherapeutic adjuvants. Taken together, these results shed light on the varying PDCD1/CD274 networks between individual cancers and signpost a need for more cancer-specific investigations and treatments.