Development and optimisation of in vitro sonodynamic therapy for glioblastoma

Sonodynamic therapy (SDT) is currently on critical path for glioblastoma therapeutics. SDT is a non-invasive approach utilising focused ultrasound to activate photosensitisers like 5-ALA to impede tumour growth. Unfortunately, the molecular mechanisms underlying the therapeutic functions of SDT remain enigmatic. This is primarily due to the lack of intricately optimised instrumentation capable of modulating SDT delivery to glioma cells in vitro. Consequently, very little information is available on the effects of SDT on glioma stem cells which are key drivers of gliomagenesis and recurrence. To address this, the current study has developed and validated an automated in vitro SDT system to allow the application and mapping of focused ultrasound fields under varied exposure conditions and setup configurations. The study optimizes ultrasound frequency, intensity, plate base material, thermal effect, and the integration of live cells. Indeed, in the presence of 5-ALA, focused ultrasound induces apoptotic cell death in primary patient-derived glioma cells with concurrent upregulation of intracellular reactive oxygen species. Intriguingly, primary glioma stem neurospheres also exhibit remarkably reduced 3D growth upon SDT exposure. Taken together, the study reports an in vitro system for SDT applications on tissue culture-based disease models to potentially benchmark the novel approach to the current standard-of-care.</p

Prospective, multicentre study of external ventricular drainage-related infections in the UK and Ireland.

OBJECTIVES: External ventricular drain (EVD) insertion is a common neurosurgical procedure. EVD-related infection (ERI) is a major complication that can lead to morbidity and mortality. In this study, we aimed to establish a national ERI rate in the UK and Ireland and determine key factors influencing the infection risk. METHODS: A prospective multicentre cohort study of EVD insertions in 21 neurosurgical units was performed over 6 months. The primary outcome measure was 30-day ERI. A Cox regression model was used for multivariate analysis to calculate HR. RESULTS: A total of 495 EVD catheters were inserted into 452 patients with EVDs remaining in situ for 4700 days (median 8 days; IQR 4-13). Of the catheters inserted, 188 (38%) were antibiotic-impregnated, 161 (32.5%) were plain and 146 (29.5%) were silver-bearing. A total of 46 ERIs occurred giving an infection risk of 9.3%. Cox regression analysis demonstrated that factors independently associated with increased infection risk included duration of EVD placement for ≥8 days (HR=2.47 (1.12-5.45); p=0.03), regular sampling (daily sampling (HR=4.73 (1.28-17.42), p=0.02) and alternate day sampling (HR=5.28 (2.25-12.38); p<0.01). There was no association between catheter type or tunnelling distance and ERI. CONCLUSIONS: In the UK and Ireland, the ERI rate was 9.3% during the study period. The study demonstrated that EVDs left in situ for ≥8 days and those sampled more frequently were associated with a higher risk of infection. Importantly, the study showed no significant difference in ERI risk between different catheter types

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/)

COVID-19 and Spontaneous Resolution of Lumbar Disc Prolapse:A Retrospective Cohort Study of Patients Awaiting Microdiscectomy

INTRODUCTION: Between individual patients with lumbar disc prolapse (LDP), the natural course of disease is significantly variable. Spontaneous resolution is reported to occur in up to 70% of cases. However, we currently cannot predict for whom and when this will occur. Neurosurgical intervention is indicated for LDP patients with non-tolerable pain after at least 8-12 weeks of conservative management, or significant neurological deficit. Channelling essential resources in the National Health Service (NHS) to fight the COVID-19 pandemic led to the postponement of most elective operations, including microdiscectomy. This left many LDP patients previously considered to be surgical candidates with conservative-only options in the interim. To our knowledge, we are the first centre to report the specific impact of the peri- and post-pandemic period on waiting list times, delayed elective microdiscectomy, and the incidence of spontaneous LDP resolution.METHODS: Retrospective case series of a prospectively collected electronic departmental database identified LDP patients that would have been impacted by the COVID-19 pandemic at some point in their care pathway (March 2020 - February 2022). Further information was obtained from electronic patient records.RESULTS: 139 LDP patients were listed for elective microdiscectomy at the time of postponement of elective surgery. Over a third of LDP patients (n=47, 33.8%), in shared decision with the responsible neurosurgeon, had their re-scheduled microdiscectomy cancelled due to clinical improvement (14.1%), radiological regression (6.5%) or both (12.2%).CONCLUSION: Our single-centre retrospective analysis revealed that for over a third of LDP patients, the prolonged post-pandemic waiting list times for elective microdiscectomy resulted in their surgery not taking place either due to spontaneous clinical improvement or proven radiological regression. Considering this, a prolonged conservative approach to LDP may be appropriate in some patients - allowing time for natural resolution, whilst avoiding perioperative risks.</p

A prospective, multicentre study of external ventricular drainage-related infections in the United Kingdom and Ireland

Objectives External Ventricular Drain (EVD) insertion is a common neurosurgical procedure. EVD- related infection (ERI) is a major complication that can lead to morbidity and mortality. In this study, we aimed to establish a national ERI rate in the United Kingdom (UK) and Ireland and determine key factors influencing the infection risk. Methods A prospective multi-centre cohort study of EVD insertions in 21 neurosurgical units was performed over 6 months. The primary outcome measure was 30-day ERI. A Cox Regression Model was used for multivariate analysis to calculate Hazard Ratios (HR). Results A total of 495 EVD catheters were inserted into 452 patients with EVDs remaining in-situ for 4700 days (median 8 days; interquartile range 4-13). Of the catheters inserted, 188 (38%) were antibiotic-impregnated, 161 (32.5%) were plain and 146 (29.5%) were silver-bearing. A total of 46 ERIs occurred giving an infection risk of 9.3%. Cox regression analysis demonstrated that factors independently associated with increased infection risk included duration of EVD placement for ≥8 days [HR=2.47 (1.12-5.45); p=0.03], regular sampling (daily sampling [HR=4.73 (1.28-17.42), p=0.02] and alternate day sampling [HR=5.28 (2.25-12.38); p<0.01]). There was no association between catheter type or tunnelling distance and ERI. Conclusions In the UK and Ireland, the ERI rate was 9.3% during the study period. The study demonstrated that EVDs left in situ for ≥8 days and those sampled more frequently were associated with a higher risk of infection. Importantly, the study showed no significant difference in ERI risk between different catheter types

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

Delaying surgery for patients with a previous SARS-CoV-2 infection

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