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The UK neurosurgical community has a track record of delivering high-quality, practice-changing clinical research studies, facilitated by a robust clinical research infrastructure and close collaborations between neurosurgical centers. More recently, these large-scale studies have been conceived, developed, and delivered by neurosurgical trainees, working under the umbrella of the British Neurosurgical Trainee Research Collaborative (BNTRC). In this paper, we outline the current landscape of large-scale neurosurgical studies in the UK, focusing on the role of trainees in facilitating this research. Importantly, we focus on our experience of trainee-led studies, including the development of the network, current challenges, and future directions. We believe that a similar model can be applied in different settings and countries, which will drive up the quality of neurosurgical research, ultimately benefiting future neurosurgical patients.

OBJECTIVESymptomatic chronic subdural hematoma (CSDH) will become an increasingly common presentation in neurosurgical practice as the population ages, but quality evidence is still lacking to guide the optimal management for these patients. The British Neurosurgical Trainee Research Collaborative (BNTRC) was established by neurosurgical trainees in 2012 to improve research by combining the efforts of trainees in each of the United Kingdom (UK) and Ireland's neurosurgical units (NSUs). The authors present the first study by the BNTRC that describes current management and outcomes for patients with CSDH throughout the UK and Ireland. This provides a resource both for current clinical practice and future clinical research on CSDH.METHODSData on management and outcomes for patients with CSDH referred to UK and Ireland NSUs were collected prospectively over an 8-month period and audited against criteria predefined from the literature: NSU mortality < 5%, NSU morbidity < 10%, symptomatic recurrence within 60 days requiring repeat surgery < 20%, and unfavorable functional status (modified Rankin Scale score of 4–6) at NSU discharge < 30%.RESULTSData from 1205 patients in 26 NSUs were collected. Bur-hole craniostomy was the most common procedure (89%), and symptomatic recurrence requiring repeat surgery within 60 days was observed in 9% of patients. Criteria on mortality (2%), rate of recurrence (9%), and unfavorable functional outcome (22%) were met, but morbidity was greater than expected (14%). Multivariate analysis demonstrated that failure to insert a drain intraoperatively independently predicted recurrence and unfavorable functional outcome (p = 0.011 and p = 0.048, respectively). Increasing patient age (p < 0.00001), postoperative bed rest (p = 0.019), and use of a single bur hole (p = 0.020) independently predicted unfavorable functional outcomes, but prescription of high-flow oxygen or preoperative use of antiplatelet medications did not.CONCLUSIONSThis is the largest prospective CSDH study and helps establish national standards. It has confirmed in a real-world setting the effectiveness of placing a subdural drain. This study identified a number of modifiable prognostic factors but questions the necessity of some common aspects of CSDH management, such as enforced postoperative bed rest. Future studies should seek to establish how practitioners can optimize perioperative care of patients with CSDH to reduce morbidity as well as minimize CSDH recurrence. The BNTRC is unique worldwide, conducting multicenter trainee-led research and audits. This study demonstrates that collaborative research networks are powerful tools to interrogate clinical research questions.

We aim to describe the outcomes after chronic subdural hematoma drainage (CSDH) management in a large cohort of patients on antithrombotic drugs, either antiplatelets or anticoagulants, at presentation and to inform clinical decision making on the timing of surgery and recommencement of these drugs. We used data from a previous UK-based multi-center, prospective cohort study. Outcomes included recurrence within 60 days, functional outcome at discharge, and thromboembolic event during hospital stay. We performed Cox regression on recurrence and multiple logistic regression on functional outcome. There were 817 patients included in the analysis, of which 353 (43.2%) were on an antithrombotic drug at presentation. We observed a gradual reduction in risk of recurrence for patients during the 6 weeks post-CSDH surgery. Neither antiplatelet nor anticoagulant drug use influenced risk of CSDH recurrence (hazard ratio, 0.93; 95% confidence interval [CI], 0.58-1.48; p = 0.76) or persistent/worse functional impairment (odds ratio, 1.08; 95% CI, 0.76-1.55; p = 0.66). Delaying surgery after cessation of antiplatelet drug did not affect risk of bleed recurrence. There were 15 in-hospital thromboembolic events recorded. Events were more common in the group pre-treated with antithrombotic drugs (3.3%) compared to the non-antithrombotic group (0.9%). Patients on an antithrombotic drug pre-operatively were at higher risk of thromboembolic events with no excess risk of bleed recurrence or worse functional outcome after CSDH drainage. The data did not support delaying surgery in patients on antithrombotic therapy. In the absence of a randomized controlled trial, early surgery and early antithrombotic recommencement should be considered in those at high risk of thromboembolic events.

Increasing age and lower pre-operative Glasgow coma score (GCS) are associated with worse outcome after surgery for chronic subdural haematoma (CSDH). Only few studies have quantified outcomes specific to the very elderly or comatose patients. We aim to examine surgical outcomes in these patient groups. We analysed data from a prospective multicentre cohort study, assessing the risk of recurrence, death, and unfavourable functional outcome of very elderly (≥ 90 years) patients and comatose (pre-operative GCS ≤ 8) patients following surgical treatment of CSDH. Seven hundred eighty-five patients were included in the study. Thirty-two (4.1%) patients had pre-operative GCS ≤ 8 and 70 (8.9%) patients were aged ≥ 90 years. A higher proportion of comatose patients had an unfavourable functional outcome (38.7 vs 21.7%; p = 0.03), although similar proportion of comatose (64.5%) and non-comatose patients (61.8%) functionally improved after surgery (p = 0.96). Compared to patients aged

Originally identified as collapse-inducing and repellent proteins for neuronal processes, semaphorins are now implicated in a diverse array of cellular responses, contributing not only to embryonic development, but also to the maintenance of tissue integrity in the adult organism. In addition, semaphorins play a role in the pathological context. Some Semaphorins can act at a distance, facilitating the navigation of cells or axonal process, whilst others evoke responses in a contact-dependent fashion. The intracellular signaling mechanisms employed by the semaphorins are beginning to be determined, and much work in recent years implicates a host of intracellular kinases in mediating Semaphorin function. These include the tyrosine kinase Fyn and the serine/threonine kinases Cdk5, GSK3, MAPK, and LIMK, and the lipid kinase PI3K. What follows is a review of this work with respect to their functions in mediating specific semaphorin-induced responses.

Current devices for measuring muscle contraction in vivo have limited accuracy in establishing and re-establishing the optimum muscle length. They are variable in the reproducibility to determine the muscle contraction at this length, and often do not maintain precise conditions during the examination. Consequently, for clinical testing only semi-quantitative methods have been used. We present a newly developed myograph, an accurate measuring device for muscle contraction, consisting of three elements. Firstly, an element for adjusting the axle of the device and the physiological axis of muscle contraction; secondly, an element to accurately position and reposition the extremity of the muscle; and thirdly, an element for the progressive pre-stretching and isometric locking of the target muscle. Thus it is possible to examine individual in vivo muscles in every pre-stretched, specified position, to maintain constant muscle-length conditions, and to accurately re-establish the conditions of the measurement process at later sessions. In a sequence of experiments the force of contraction of the muscle at differing stretching lengths were recorded and the forces determined. The optimum muscle length for maximal force of contraction was established. In a following sequence of experiments with smaller graduations around this optimal stretching length an increasingly accurate optimum muscle length for maximal force of contraction was determined. This optimum length was also accurately re-established at later sessions. We have introduced a new technical solution for valid, reproducible in vivo force measurements on every possible point of the stretching curve. Thus it should be possible to study the muscle contraction in vivo to the same level of accuracy as is achieved in tests with in vitro organ preparations.