Molecular Pathogenesis of Glioblastoma in Adults and Future Perspectives: A Systematic Review.

Glioblastoma (GBM) is the most common and malignant tumour of the central nervous system. Recent appreciation of the heterogeneity amongst these tumours not only changed the WHO classification approach, but also created the need for developing novel and personalised therapies. This systematic review aims to highlight recent advancements in understanding the molecular pathogenesis of the GBM and discuss related novel treatment targets. A systematic search of the literature in the PubMed library was performed following the PRISMA guidelines for molecular pathogenesis and therapeutic advances. Original and meta-analyses studies from the last ten years were reviewed using pre-determined search terms. The results included articles relevant to GBM development focusing on the aberrancy in cell signaling pathways and intracellular events. Theragnostic targets and vaccination to treat GBM were also explored. The molecular pathophysiology of GBM is complex. Our systematic review suggests targeting therapy at the stemness, p53 mediated pathways and immune modulation. Exciting novel immune therapy involving dendritic cell vaccines, B-cell vaccines and viral vectors may be the future of treating GBM.

Why are neurosurgeons sued? A single-center, half-decade review.

Purpose:The burden of medicolegal claims in neurosurgery is increasing in the UK. Trepidation associated with malpractice claims has the potential to negatively impact surgical practice and patient safety. What are the causes of these claims and can we address them? The aim of this study was to identify the incidence and total burden of litigation claims related to neurosurgery in a London tertiary center.Methods:We retrospectively reviewed all consecutive cases of claims in neurosurgery that were reported to NHSR between March 2013 and April 2018 by St George's Hospital legal department. This was an extension of previous study by Mukherjee et al., who studied the medicolegal claims in our institution in the preceding 9-year period (2004-2013).Results:There were 18 litigation claims against neurosurgery. Claims were reviewed for clinical event, cause, likelihood of pay-out and legal outcome. Eleven claims were settled in court and seven were settled without court proceeding. All claims were spinal cases, 56% emergency admissions. Causes included faulty surgical technique (39%), delayed treatment (33%), delayed diagnosis/misdiagnosis (17%), and lack of information (11%) with a likelihood of financial success of 43%, 67%, 33%, and 100%, respectively. The highest median pay-outs were for lack of information (£2.8 million) and faulty surgical technique (£1 million). When compared to the preceding 9-year period, there a modest reduction in claims per year, despite an increase in workload. Distribution of litigation causes remained similar but overall financial burden was higher.Conclusion:Spinal surgery has the highest malpractice claim risk in neurosurgical practice. Our review shows that faulty surgical technique is the leading cause of neurosurgical claims. Claims against lack of information, although less frequent, resulted in the highest median pay-out. This study reinforces previously published data that good surgical technique and thorough process of informed consent may reduce litigation in neurosurgery.

Intracranial Subarachnoid Haemorrhage Caused by Cervical Spinal Dural Arteriovenous Fistulas: Case Report.

Cervical spinal vascular abnormalities commonly present with progressive myelopathy as a result of venous congestion. They are not very prone to bleed and tend to be underdiagnosed due to their subtle clinical presentation. We came across a rare case of intracranial subarachnoid haemorrhage caused by cervical spinal dural fistula in the Imperial College Healthcare NHS Trust Hospitals/UK in June 2020. We diagnosed the patient under strict evidence base medicine guidance, which otherwise would have been missed. We discussed the case in several multidisciplinary team (MDT) meetings, and patient was treated under the joint care of the neurology and neurosurgical teams. Patient made a full recovery and discharged home with no neurological defects or complications. Here, we reported this case with all the evidence we gathered from our MDT discussion. We hope our experience would help improve the diagnosis and management protocol for future patients with a similar condition.

An Expanded Role for the RFX Transcription Factor DAF-19, with Dual Functions in Ciliated and Nonciliated Neurons.

Regulatory Factor X (RFX) transcription factors (TFs) are best known for activating genes required for ciliogenesis in both vertebrates and invertebrates. In humans, eight RFX TFs have a variety of tissue-specific functions, while in the worm Caenorhabditis elegans, the sole RFX gene, daf-19, encodes a set of nested isoforms. Null alleles of daf-19 confer pleiotropic effects including altered development with a dauer constitutive phenotype, complete absence of cilia and ciliary proteins, and defects in synaptic protein maintenance. We sought to identify RFX/daf-19 target genes associated with neuronal functions other than ciliogenesis using comparative transcriptome analyses at different life stages of the worm. Subsequent characterization of gene expression patterns revealed one set of genes activated in the presence of DAF-19 in ciliated sensory neurons, whose activation requires the daf-19c isoform, also required for ciliogenesis. A second set of genes is downregulated in the presence of DAF-19, primarily in nonsensory neurons. The human orthologs of some of these neuronal genes are associated with human diseases. We report the novel finding that daf-19a is directly or indirectly responsible for downregulation of these neuronal genes in C. elegans by characterizing a new mutation affecting the daf-19a isoform (tm5562) and not associated with ciliogenesis, but which confers synaptic and behavioral defects. Thus, we have identified a new regulatory role for RFX TFs in the nervous system. The new daf-19 candidate target genes we have identified by transcriptomics will serve to uncover the molecular underpinnings of the pleiotropic effects that daf-19 exerts on nervous system function.