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.
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.
A prospective survey performed in UK neurosurgical units performed from 23 March 2020 until 24 April 2020.
Regional neurosurgical units outside London (as the pandemic was more advanced at time of study).
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 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.
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.
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.
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/).
Introduction: Low dose ionising radiation such as from CT scans carries a low but cumulative risk of cancer and children are particularly sensitive. Children with VP Shunts often undergo multiple CT ...scans. We developed a CT protocol with reduced radiation for paediatric patients with shunts and compared it with the current practice in the other neurosurgical units in the UK and ROI by conducting a nationwide survey.
Methods: An email questionnaire was send to the superintendent radiographer in every Neurosurgical unit in the UK and the ROI.
Results: The response rate was 70%. Only 5 (19%) of the responding units used a dedicated CT shunt protocol with reduced radiation. Radiation was reduced by lowering the tube current. In comparison, our protocol uses a combination of less tube current and fewer slices. This reduced the radiation exposure of a CT head significantly with sufficient image quality to make a diagnosis.
Conclusion: Radiation from CT for paediatric shunt patients scans can and should be reduced. This can be achieved by using reduced radiation protocols. A national paediatric CT shunt protocol could lead to significant reduction in effective radiation dose.
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.
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.
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.
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.
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 (
= 304) and 2019 (
= 868). The current and future impact on UK neurosurgical operative activity has implications for service delivery and neurosurgical training.
Inhibition of cardiac K channels by local anesthetic may contribute to QTc interval prolongation of the electrocardiogram and induction of ventricular arrhythmia. The transient outward current Ito ...has been identified as a toxicologically relevant target of bupivacaine. S(-)-ropivacaine has been developed as a safer alternative to bupivacaine. The effects of S(-)-ropivacaine on Ito have not been investigated. In human ventricular myocardium, Ito is formed by Kv4.3 and KChIP2.2 subunits. Therefore, the aim of this study was to establish the effects of S(-)-ropivacaine on human Kv4.3/KChIP2.2 channels.
Kv4.3/KChIP2.2 complementary DNA cloned from human heart was transiently transfected in Chinese hamster ovary cells. The pharmacologic effects of S(-)-ropivacaine were investigated with the patch clamp method.
Ropivacaine inhibited Kv4.3/KChIP2.2 channels in a concentration-dependent, stereospecific, and reversible manner. The IC50 value of S(-)-ropivacaine for inhibition of the charge conducted by Kv4.3/KChIP2.2 channel was 117 +/- 21 microm (n = 30). The local anesthetic accelerated macroscopic current decline with an IC50 value of 77 +/- 11 microm (n = 30). It shifted the midpoint of channel activation into the depolarizing direction, and it slowed recovery from inactivation without altering steady state inactivation. Kv4.3 channels are more sensitive to the inhibitory effect than Kv4.3/KChIP2.2 channels.
: The results are consistent with the idea that ropivacaine, by blocking Kv4.3/KChIP2.2 from the open state, interferes with the gating modifying effects of KChIP2.2 on Kv4.3 channels. Inhibition of Kv4.3/KChIP2.2 channels by the local anesthetic may contribute to the deterioration of cardiac function during events of intoxication.
Following a previous review
1
of our experience managing HGG and finding that carefully selected elderly (age ≥65 years) patients benefit from radical treatment we decided to re-audit our practice. ...This retrospective audit concerns patients with a histological or radiological diagnosis of HGG over four non-consecutive years, 2011 onwards. Patients were identified via the trust cancer management systems. Survival data was calculated for patients presenting in 2011, 2013 & 2015. 147 patients were identified, 71 of them elderly. The overall median age was 64 years. In 2011 23 patients presented to the MDT (39% of which were elderly), 44 in 2013 (52% elderly), 31 in 2015 (52% elderly) and 49 in 2017 (47% elderly). The median age of the elderly patient group was 67 in 2011, 72 in 2013, 70 in 2015 and 72 in 2017. Most patients underwent debulking +/- adjuvant radio-chemotherapy: 74% of the younger and 66% of the older patients. The median survival was 12 months for younger and 5 months for older patients. Patients who had debulking surgery +/-adjuvant radio-chemotherapy had a 13 and 6 months survival, respectively. Although the percentage of elderly patients referred to the MDT did not increase, the median age of the elderly patient group has increased over the years. Two thirds of elderly patients received aggressive treatment, which was unchanged to our practice in 2007. Median survival times for HGG did not improve compared to our previous audit. Performance status at presentation may be in an important factor in patient selection
2
but better measurements of “frailty” in the elderly population are required to assist in management decisions.
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Mukerji et al. J Neurooncol. 2008 Feb;86(3):329–36: Treating high grade gliomas in the elderly: the end of ageism?
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Arvold & Reardon Clin Interv Aging. 2014 Feb21;9:357–67: Treatment options for glioblastoma in the elderly patient.
Abstract
Background
A growing body of clinical data highlights the prognostic importance of achieving gross total resection (GTR) in patients with glioblastoma. The aim of this study was to determine ...nationwide practice and attitudes towards achieving GTR and dealing with residual enhancing disease.
Methods
The study was in 2 parts: an electronic questionnaire sent to United Kingdom neuro-oncology surgeons to assess surgical practice followed by a 3-month prospective, multicenter observational study of current neurosurgical oncology practice.
Results
Twenty-seven surgeons representing 22 neurosurgical units completed the questionnaire. Prospective data were collected for 113 patients from 15 neurosurgical units. GTR was deemed to be achieved at time of surgery in 82% (91/111) of cases, but in only 45% (36/80) on postoperative MRI. Residual enhancing disease was deemed operable in 16.3% (13/80) of cases, however, no patient underwent early repeat surgery for residual enhancing disease. The most commonly cited reason (38.5%, 5/13) was perceived lack of clinical benefit.
Conclusion
There is a subset of patients for whom GTR is thought possible, but not achieved at surgery. For these patients, early repeat resection may improve overall survival. Further prospective surgical research is required to better define the prognostic implications of GTR for residual enhancing disease and examine the potential benefit of this early re-intervention.
Case report
We present the case of an 11-year-old boy who was suffering distinct trigeminal neuralgia. At the age of 3 years, the patient had contracted a severe Epstein–Barr virus infection and ...developed mild meningoencephalitis. Magnetic resonance imaging scans showed a slight enhancement in the pontomesencephalic cistern as well as a neurovascular conflict at the right trigeminal nerve. Intraoperatively, thickened fibrous tissue was found that was attached to both the trigeminal nerve and the superior cerebellar artery. Microvascular decompression using Gore Tex as tissue implant brought immediate relief.
Discussion
Trigeminal neuralgia in pediatric patients is very rare. We present a case of typical trigeminal neuralgia in a child, demonstrating the pathogenesis of the neurovascular conflict due to subarachnoidal adhesions after meningoencephalitis.
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