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Abstract Whole-exome sequencing (WES), a ground-breaking technology, has emerged as a linchpin in neurology and neurosurgery, offering a comprehensive elucidation of the genetic landscape of various neurological disorders. This transformative methodology concentrates on the exonic portions of DNA, which constitute approximately 1% of the human genome, thus facilitating an expedited and efficient sequencing process. WES has been instrumental in advancing our understanding of neurodegenerative diseases, neuro-oncology, cerebrovascular disorders, and epilepsy by revealing rare variants and novel mutations and providing intricate insights into their genetic complexities. This has been achieved while maintaining a substantial diagnostic yield, thereby offering novel perspectives on the pathophysiology and personalized management of these conditions. The utilization of WES boasts several advantages over alternative genetic sequencing methodologies, including cost-effectiveness, reduced incidental findings, simplified analysis and interpretation process, and reduced computational demands. However, despite its benefits, there are challenges, such as the interpretation of variants of unknown significance, cost considerations, and limited accessibility in resource-constrained settings. Additionally, ethical, legal, and social concerns are raised, particularly in the context of incidental findings and patient consent. As we look to the future, the integration of WES with other omics-based approaches could help revolutionize the field of personalized medicine through its implications in predictive models and the development of targeted therapeutic strategies, marking a significant stride toward more effective and clinically oriented solutions. Graphical Abstract

Abstract Complications are plausible events during surgical operations. Surgical complications profoundly impact surgeons, often called “second victims” of adverse events. These complications trigger a range of emotional and psychological responses, including guilt, anxiety, heightened empathy, and the looming threat of burnout. Moreover, the toll extends to physical health, with chronic stress and sleep disturbances taking their toll. Surgeons’ social lives are not immune to the fallout, and their career satisfaction may wane, pushing some towards defensive medicine practices. While mentorship, counselling, and peer support are crucial support mechanisms, they encounter barriers such as time constraints and the fear of negative perceptions. This paper suggests practical recommendations, including comprehensive wellness programmes, a streamlined badge card system for easy access to resources, and mindfulness training to mitigate stress and burnout. Recognising and proactively addressing these multifaceted impacts is imperative for cultivating a resilient medical community capable of providing optimal patient care.

Abstract Chromosomal instability (CIN) is a pivotal factor in gliomas, contributing to their complexity, progression, and therapeutic challenges. CIN, characterized by frequent genomic alterations during mitosis, leads to genetic abnormalities and impacts cellular functions. This instability results from various factors, including replication errors and toxic compounds. While CIN’s role is well documented in cancers like ovarian cancer, its implications for gliomas are increasingly recognized. CIN influences glioma progression by affecting key oncological pathways, such as tumor suppressor genes (e.g., TP53), oncogenes (e.g., EGFR), and DNA repair mechanisms. It drives tumor evolution, promotes inflammatory signaling, and affects immune interactions, potentially leading to poor clinical outcomes and treatment resistance. This review examines CIN’s impact on gliomas through a narrative approach, analyzing data from PubMed/Medline, EMBASE, the Cochrane Library, and Scopus. It highlights CIN’s role across glioma subtypes, from adult glioblastomas and astrocytomas to pediatric oligodendrogliomas and astrocytomas. Key findings include CIN’s effect on tumor heterogeneity and its potential as a biomarker for early detection and monitoring. Emerging therapies targeting CIN, such as those modulating tumor mutation burden and DNA damage response pathways, show promise but face challenges. The review underscores the need for integrated therapeutic strategies and improved bioinformatics tools like CINdex to advance understanding and treatment of gliomas. Future research should focus on combining CIN-targeted therapies with immune modulation and personalized medicine to enhance patient outcomes.

Bladder cancer is the tenth most prevalent malignancy worldwide, with a significant mortality burden. Urothelial carcinoma (UC) is the most common histological subtype, and treatment options are guided by whether the disease is muscle-invasive (MIBC) or non-muscle-invasive (NMIBC), with subsequent risk group stratification. The growing popularity of immune checkpoint inhibitors (ICIs) to treat MIBC and NMIBC as either monotherapy or combined with intravesical agents, may radically change the treatment paradigm of UC. Current treatments for NMBIC includes intravesical chemotherapy after trans-urethral resection of the bladder tumour, intravesical bacillus Calmette-Guerin (BCG) or radical cystectomy. Cisplatin-based chemotherapy is widely regarded as the first-line treatment for metastatic UC due to its beneficial response and survival rates when compared to alternative therapies. However, up to 70 % of metastatic UC patients are ineligible, and the prognosis of these patients remains poor, with a median survival of 13–16 months. For NMIBC and MIBC, ICIs provide a promising alternative for cisplatin-ineligible patients. In UC, ICIs including atezolizumab, nivolumab, avelumab, and pembrolizumab are Food and Drug Administration (FDA)-approved for monotherapy, and have demonstrated promising results, particularly in those who cannot receive cisplatin-based chemotherapy, and as a second-line treatment option for recurrent UC following platinum-based chemotherapy. It is important to consider that some patients may experience adverse events (AEs) with limited clinical benefit. Infusion-related reactions and immune-mediated AEs (imAEs) such as colitis, endocrinopathies, hepatitis, pneumonitis, interstitial lung disease, renal dysfunction, nephritis, cutaneous and neurological toxicities must be monitored for. Currently, there is no clear consensus on the role of a ‘two-year stopping rule’ in reducing the risk of imAEs, with further research on the optimal treatment duration of ICIs required. With increased ICI use, vigilance regarding their side effects is imperative. This review aims to provide an updated overview of ICI toxicities in bladder cancer, to assist clinicians in their therapeutic decision-making, with consideration of patient characteristics and the clinical context.

Abstract Multiple Sclerosis (MS) is a complex autoimmune disorder that significantly impacts the central nervous system, leading to a range of complications. While intracranial haemorrhage (ICH) is a rare but highly morbid complication, more common CNS complications include progressive multifocal leukoencephalopathy (PML) and other CNS infections. This severe form of stroke, known for its high morbidity and mortality rates, presents a critical challenge in the management of MS. The use of disease-modifying drugs (DMDs) in treating MS introduces a nuanced aspect to patient care, with certain medications like Dimethyl Fumarate and Fingolimod showing potential in reducing the risk of ICH, while others such as Alemtuzumab and Mitoxantrone are associated with an increased risk. Understanding the intricate relationship between these DMDs, the pathophysiological mechanisms of ICH, and the individualised aspects of each patient's condition is paramount. Factors such as genetic predispositions, existing comorbidities, and lifestyle choices play a crucial role in tailoring treatment approaches, emphasising the importance of a personalised, vigilant therapeutic strategy. The necessity for ongoing and detailed research cannot be overstated. It is crucial to explore the long-term effects of DMDs on ICH occurrence and prognosis in MS patients, aiming to refine clinical practices and promote patient-centric, informed therapeutic decisions. This approach ensures that the management of MS is not only comprehensive but also adaptable to the evolving understanding of the disease and its treatments.

ABSTRACT Background and Aims The diagnosis and management of soft tissue sarcoma (STS) in sub‐Saharan Africa (SSA) present significant challenges. Positive outcomes in STS treatment include achieving negative margins, improved quality of life, and reduced recurrence rates, while negative outcomes involve incomplete resection, local recurrence, and surgical complications. This review aims to examine the current state of STS management in SSA, identify key challenges, and propose potential solutions to improve patient outcomes. Methods A comprehensive review of the literature using PubMed/MEDLINE, Google Scholar, and Scopus, focusing on English‐language studies examining the management of STS in SSA. Inclusion criteria centered on studies reporting on surgical interventions, outcomes, and healthcare challenges in the region. Articles lacking sufficient data, non‐English sources, conference abstracts, and duplicates were excluded. Results Findings highlight several obstacles in the management of STS in SSA, including limited multidisciplinary teams, inadequate healthcare infrastructure, financial constraints, and lack of standardized treatment protocols. Key themes such as diagnostic capacity and resource allocation were identified as significant barriers. Conclusion Improving STS outcomes in SSA requires investment in healthcare infrastructure, professional development, enhanced funding, and collaborative research. Addressing these gaps is crucial to achieving better surgical management and improving survival rates for patients with STS in SSA.

Abstract Introduction The prevalence of abdominal injuries in war and conflict zones, particularly in low‐ and middle‐income countries (LMICs), presents a significant healthcare challenge. These injuries, often resulting from explosive devices, firearms, and shrapnel, lead to high morbidity and mortality rates due to delayed diagnoses, inadequate medical infrastructure, and limited access to specialised care. This review aims to summarise the literature on conflict‐related abdominal injuries in LMICs, highlighting the impact of such trauma on healthcare systems and patient outcomes, and suggesting strategies for improvement. Methods A comprehensive narrative review was conducted, focusing on studies from contemporary and historical conflict‐ridden nations. Databases such as PubMed, EMBASE, Google Scholar, the Cochrane Library, and Scopus were searched using specific keywords. Inclusion criteria encompassed various study designs and both paediatric and adult populations, with studies providing raw data prioritised. Exclusions included non‐English articles, non‐peer‐reviewed studies, and those not reporting outcomes or involving high‐income countries. Results The review identified significant challenges in managing war‐related abdominal trauma in LMICs, including a shortage of healthcare personnel and infrastructure, socio‐political barriers, and research gaps. Clinical implications of such injuries include elevated mortality rates, with surgical and nonsurgical management outcomes varying significantly. Positive advancements in diagnostics and surgical techniques have improved survival rates, yet the need for further infrastructural and workforce enhancements remains critical. Conclusion Abdominal trauma in conflict‐affected LMICs necessitates focused efforts to improve healthcare delivery, including targeted funding for infrastructure and equipment, development of training programs for trauma specialists, and increased humanitarian aid. Bridging research gaps and fostering collaborative efforts are essential for advancing the management of abdominal trauma and enhancing patient outcomes in these challenging environments.

Spine surgery is continually evolving, with the application of new technologies often serving as a catalyst for improved clinical outcomes. Exoscope-assisted spinal surgery has recently emerged as a notable technological advancement offering a refined approach to visualisation, thereby potentially contributing to improved surgical precision, reduced complication rates, and optimised patient outcomes. The application of exoscopes have improved spine surgeries such as spinal fusion procedures, decompression surgeries, instrumentation surgeries, minimally invasive and complex surgeries. These improvements include enhanced visualisation, improved ergonomics, improved surgical precision, reduced operation times and postoperative infection rates. The integration of robotics in exoscope-assisted spine surgery enables autofocus function, ensuring the integrity of the sterile field, providing superior image quality, resolution, and three-dimensional perception. However, challenges such as decrease in depth perception and the lack of long-term follow-up data hinder its widespread adoption. Ethical considerations regarding patient safety, technology dependency, and health inequity add another dimension to these challenges. Despite these challenges, exoscope-assisted spine surgery holds significant potential for transforming clinical practice and improving patient outcomes. This review seeks to provide a concise overview of the benefits and limits of exoscope-assisted spine surgeries, while highlighting its challenges and ethical considerations. Addressing these limitations by conducting large-scale clinical trials and exploring the integration of artificial intelligence (AI) could assist in realising the potential of exoscopes in spine surgery.”

Abstract Introduction Artificial intelligence (AI) is transforming oncology and surgery by improving diagnostics, personalizing treatments, and enhancing surgical precision. Patients appreciate AI for its potential to provide accurate prognoses and tailored therapies. However, AI's implementation raises ethical concerns, data privacy issues, and the need for transparent communication between patients and health care providers. This study aims to understand patients' perspectives on AI integration in oncology and surgery to foster a balanced and patient‐centered approach. Methods The study utilized a comprehensive literature review and analysis of existing research on AI applications in oncology and surgery. The focus was on examining patient perceptions, ethical considerations, and the potential benefits and risks associated with AI integration. Data was collected from peer‐reviewed journals, conference proceedings, and expert opinions to provide a broad understanding of the topic. The perspectives of patients was also emphasized to highlight the nuances of their acceptance and concerns regarding AI in their health care. Results Patients generally perceive AI in oncology and surgery as beneficial, appreciating its potential for more accurate diagnoses, personalized treatment plans, and improved surgical outcomes. They particularly value AI's role in providing timely and precise diagnostics, which can lead to better prognoses and reduced anxiety. However, concerns about data privacy, ethical implications, and the reliability of AI systems were prevalent. Consequently, trust in AI and health care providers was deemed as a crucial factor for patient acceptance. Additionally, the need for transparent communication and ethical safeguards was also highlighted to address these concerns effectively. Conclusion The integration of AI in oncology and surgeryholds significant promise for enhancing patient care and outcomes. Patients view AI as a valuable tool that can provide accurate prognoses and personalized treatments. However, addressing ethical concerns, ensuring data privacy, and building trust through transparent communication are essential for successful AI integration. Future initiatives should focus on refining AI algorithms, establishing robust ethical guidelines, and enhancing patient education to harmonize technological advancements with patient‐centered care principles.

Abstract Using the particular nature of melanoma mutanomes to develop medicines that activate the immune system against specific mutations is a game changer in immunotherapy individualisation. It offers a viable solution to the recent rise in resistance to accessible immunotherapy alternatives, with some patients demonstrating innate resistance to these drugs despite past sensitisation to these agents. However, various obstacles stand in the way of this method, most notably the practicality of sequencing each patient's mutanome, selecting immunotherapy targets, and manufacturing specific medications on a large scale. With the robustness and advancement in research techniques, artificial intelligence (AI) is a potential tool that can help refine the mutanome-based immunotherapy for melanoma. Mutanome-based techniques are being employed in the development of immune-stimulating vaccines, improving current options such as adoptive cell treatment, and simplifying immunotherapy responses. Although the use of AI in these approaches is limited by data paucity, cost implications, flaws in AI inference capabilities, and the incapacity of AI to apply data to a broad population, its potential for improving immunotherapy is limitless. Thus, in-depth research on how AI might help the individualisation of immunotherapy utilising knowledge of mutanomes is critical, and this should be at the forefront of melanoma management.

Abstract Single-cell ribonucleic acid sequencing (scRNA-seq) has emerged as a transformative technology in neurological and neurosurgical research, revolutionising our comprehension of complex neurological disorders. In brain tumours, scRNA-seq has provided valuable insights into cancer heterogeneity, the tumour microenvironment, treatment resistance, and invasion patterns. It has also elucidated the brain tri-lineage cancer hierarchy and addressed limitations of current models. Neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis have been molecularly subtyped, dysregulated pathways have been identified, and potential therapeutic targets have been revealed using scRNA-seq. In epilepsy, scRNA-seq has explored the cellular and molecular heterogeneity underlying the condition, uncovering unique glial subpopulations and dysregulation of the immune system. ScRNA-seq has characterised distinct cellular constituents and responses to spinal cord injury in spinal cord diseases, as well as provided molecular signatures of various cell types and identified interactions involved in vascular remodelling. Furthermore, scRNA-seq has shed light on the molecular complexities of cerebrovascular diseases, such as stroke, providing insights into specific genes, cell-specific expression patterns, and potential therapeutic interventions. This review highlights the potential of scRNA-seq in guiding precision medicine approaches, identifying clinical biomarkers, and facilitating therapeutic discovery. However, challenges related to data analysis, standardisation, sample acquisition, scalability, and cost-effectiveness need to be addressed. Despite these challenges, scRNA-seq has the potential to transform clinical practice in neurological and neurosurgical research by providing personalised insights and improving patient outcomes.

Hereditary spastic paraplegia is a genetically heterogeneous neurodegenerative disorder characterised primarily by muscle stiffness in the lower limbs. Neurodegenerative disorders are conditions that result from cellular and metabolic abnormalities, many of which have strong genetic ties. While ageing is a known contributor to these changes, certain neurodegenerative disorders can manifest early in life, progressively affecting a person’s quality of life. Hereditary spastic paraplegia is one such condition that can appear in individuals of any age. In hereditary spastic paraplegia, a distinctive feature is the degeneration of long nerve fibres in the corticospinal tract of the lower limbs. This degeneration is linked to various cellular and metabolic processes, including mitochondrial dysfunction, remodelling of the endoplasmic reticulum membrane, autophagy, abnormal myelination processes and alterations in lipid metabolism. Additionally, hereditary spastic paraplegia affects processes like endosome membrane trafficking, oxidative stress and mitochondrial DNA polymorphisms. Disease-causing genetic loci and associated genes influence the progression and severity of hereditary spastic paraplegia, potentially affecting various cellular and metabolic functions. Although hereditary spastic paraplegia does not reduce a person’s lifespan, it significantly impairs their quality of life as they age, particularly with more severe symptoms. Regrettably, there are currently no treatments available to halt or reverse the pathological progression of hereditary spastic paraplegia. This review aims to explore the metabolic mechanisms underlying the pathophysiology of hereditary spastic paraplegia, emphasising the interactions of various genes identified in recent network studies. By comprehending these associations, targeted molecular therapies that address these biochemical processes can be developed to enhance treatment strategies for hereditary spastic paraplegia and guide clinical practice effectively.

Craniosynostosis, marked by premature cranial suture fusion, necessitates prompt intervention to avert developmental, neurological, and aesthetic issues. While high-income countries have advanced in managing this condition, low- and middle-income countries grapple with substantial healthcare access disparities. This narrative review explores current craniosynostosis management in low- and middle-income countries. The review focused on studies published between 2008 and 2023. The focus was neurosurgical outcomes, and the search utilised databases like PubMed, EMBASE, Google Scholar, the Cochrane Library and Scopus, incorporating specific keywords and phrases. An in-depth analysis of 21 included studies reveals noteworthy positive outcomes, including low mortality, successful corrections and sustained efficacy. These advancements stem from enhanced pre-operative strategies, surgical techniques and postoperative care. Nonetheless, challenges persist, encompassing complications, mortality, reoperations, and treatment disparities, particularly in low- and middle-income countries constrained by financial and expertise limitations. The enhancement of clinical practice and the formulation of effective policies in the future entail several key strategies. These include the reinforcement of specialised healthcare infrastructure and diagnostic capabilities, the ongoing training and retention of neurosurgeons, the improvement of funding mechanisms, and the promotion of equitable access. Additionally, a crucial focus is placed on fortifying paediatric neurosurgical care in low- and middle-income countries. The recommendations underscore the importance of collaborative initiatives, the development of specialised healthcare infrastructure, and the implementation of strategic policies to not only advance pediatric neurosurgical care but also to address existing gaps in management.