Investigating the effects of arginine methylation inhibitors on microdissected brain tumour biopsies maintained in a miniaturised perfusion system.

Arginine methylation is a post-translational modification that consists of the transfer of one or two methyl (CH3) groups to arginine residues in proteins. Several types of arginine methylation occur, namely monomethylation, symmetric dimethylation and asymmetric dimethylation, which are catalysed by different protein arginine methyltransferases (PRMTs). Inhibitors of PRMTs have recently entered clinical trials to target several types of cancer, including gliomas (NCT04089449). People with glioblastoma (GBM), the most aggressive form of brain tumour, are among those with the poorest quality of life and likelihood of survival of anyone diagnosed with cancer. There is currently a lack of (pre)clinical research on the possible application of PRMT inhibitors to target brain tumours. Here, we set out to investigate the effects of clinically-relevant PRMT inhibitors on GBM biopsies. We present a new, low-cost, easy to fabricate perfusion device that can maintain GBM tissue in a viable condition for at least eight days post-surgical resection. The miniaturised perfusion device enables the treatment of GBM tissue with PRMT inhibitors ex vivo, and we observed a two-fold increase in apoptosis in treated samples compared to parallel control experiments. Mechanistically, we show thousands of differentially expressed genes after treatment, and changes in the type of arginine methylation of the RNA binding protein FUS that are consistent with hundreds of differential gene splicing events. This is the first time that cross-talk between different types of arginine methylation has been observed in clinical samples after treatment with PRMT inhibitors.

Prognostic factors following resection of intracranial metastases.

Background: The aim of this study was to identify prognostic factors associated with resection of intracranial metastases. Methods: A retrospective case series including patients who underwent resection of cranial metastases from March 2014 to April 2021 at a single center. This identified 112 patients who underwent 124 resections. The median age was 65 years old (24-84) and the most frequent primary cancers were nonsmall cell lung cancer (56%), breast adenocarcinoma (13%), melanoma (6%), and colorectal adenocarcinoma (6%). Postoperative MRI with contrast was performed within 48 hours in 56% of patients and radiation treatment was administered in 41%. GraphPad Prism 9.2.0 was used for the survival analysis. Results: At the time of data collection, 23% were still alive with a median follow-up of 1070 days (68-2484). The 30- and 90-day, and 1- and 5-year overall survival rates were 93%, 83%, 35%, and 17%, respectively. The most common causes of death within 90 days were as follows: unknown (32%), systemic or intracranial disease progression (26%), and pneumonia (21%). Age and extent of neurosurgical resection were associated with overall survival (P < 0.05). Patients aged >70 had a median survival of 5.4 months compared with 9.7, 11.4, and 11.4 for patients <50, 50-59, and 60-69, respectively. Gross-total resection achieved an overall survival of 11.8 months whereas sub-total, debulking, and unclear extent of resection led to a median survival of 5.7, 7.0, and 9.0 months, respectively. Conclusion: Age and extent of resection are potential predictors of long-term survival.

Neurosurgery activity levels in the United Kingdom and republic of Ireland during the first wave of the covid-19 pandemic - a retrospective cross-sectional cohort study.

The impact of Covid-19 on surgical patients worldwide has been substantial. In the United Kingdom (UK) and the Republic of Ireland (RoI), the first wave of the pandemic occurred in March 2020. The aims of this study were to: (1) evaluate the volume of neurosurgical operative activity levels, Covid-19 infection rate and mortality rate in April 2020 with a retrospective cross-sectional cohort study conducted across 16 UK and RoI neurosurgical centres, and (2) compare patient outcomes in a single institution in April-June 2020 with a comparative cohort in 2019. Across the UK and RoI, 818 patients were included. There were 594 emergency and 224 elective operations. The incidence rate of Covid-19 infection was 2.6% (21/818). The overall mortality rate in patients with a Covid-19 infection was 28.6% (6/21). In the single centre cohort analysis, an overall reduction in neurosurgical operative activity by 65% was observed between 2020 (n = 304) and 2019 (n = 868). The current and future impact on UK neurosurgical operative activity has implications for service delivery and neurosurgical training.

Impact of COVID-19 pandemic on surgical neuro-oncology multi-disciplinary team decision making: a national survey (COVID-CNSMDT Study).

OBJECTIVES: Pressures on healthcare systems due to COVID-19 has impacted patients without COVID-19 with surgery disproportionally affected. This study aims to understand the impact on the initial management of patients with brain tumours by measuring changes to normal multidisciplinary team (MDT) decision making. DESIGN: A prospective survey performed in UK neurosurgical units performed from 23 March 2020 until 24 April 2020. SETTING: Regional neurosurgical units outside London (as the pandemic was more advanced at time of study). PARTICIPANTS: Representatives from all units were invited to collect data on new patients discussed at their MDT meetings during the study period. Each unit decided if management decision for each patient had changed due to COVID-19. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome measures included number of patients where the decision to undergo surgery changed compared with standard management usually offered by that MDT. Secondary outcome measures included changes in surgical extent, numbers referred to MDT, number of patients denied surgery not receiving any treatment and reasons for any variation across the UK. RESULTS: 18 units (75%) provided information from 80 MDT meetings that discussed 1221 patients. 10.7% of patients had their management changed-the majority (68%) did not undergo surgery and more than half of this group not undergoing surgery had no active treatment. There was marked variation across the UK (0%-28% change in management). Units that did not change management could maintain capacity with dedicated oncology lists. Low volume units were less affected. CONCLUSION: COVID-19 has had an impact on patients requiring surgery for malignant brain tumours, with patients receiving different treatments-most commonly not receiving surgery or any treatment at all. The variations show dedicated cancer operating lists may mitigate these pressures. STUDY REGISTRATION: This study was registered with the Royal College of Surgeons of England's COVID-19 Research Group (https://www.rcseng.ac.uk/coronavirus/rcs-covid-research-group/).

Pineal cyst surveillance in adults - a review of 10 years' experience.

Objective: Pineal cysts are common benign incidental findings in adults. There are no commonly accepted criteria for follow up or indications for intervention. We looked at our outcomes for this condition to explore their natural history and review our surveillance criteria.Method: Retrospective review of multidisciplinary team meetings at a tertiary neurosurgical centre over 10 years. Data relating to demographics, presenting symptoms, maximum diameter, duration of surveillance, final diagnosis and overall outcome were extracted from electronic patient records and available MRI. Data were analysed using IBM SPSS version 24.Result: Seventy-seven pineal cysts were identified. Female to male ratio was 1.43, female mean age was 38.6 and male mean age was 50.4. An increase in referral frequency was observed over the study period (mean increase of 1.4 cases per year). Presenting symptoms of headache in 45% and visual and hearing symptoms in 38.5% were recorded and baseline mean maximum diameter was 13.4mm. 20 patients were discharged on presentation, 54 were booked for at least one follow-up scan with a median follow up period of 14 months. The mean change in maximum diameter was 0.04mm over 18 months. Three patients (3.9%) underwent endoscopic biopsy and CSF diversion for cysts all more than 20mm with radiological evidence of hydrocephalus. In 100% of cases, the initial MDT diagnosis and final diagnosis were concordant.Conclusions: No patient under surveillance required surgical treatment and those managed surgically were symptomatic with large cysts and hydrocephalus on presentation. A majority of pineal cysts remained unchanged during the MRI follow-up, therefore our review suggests that routine follow-up of pineal cysts is not necessary in the absence of unusual radiological characteristics or related clinical symptoms.