The screening and management of pituitary dysfunction following traumatic brain injury in adults: British Neurotrauma Group guidance.

Pituitary dysfunction is a recognised, but potentially underdiagnosed complication of traumatic brain injury (TBI). Post-traumatic hypopituitarism (PTHP) can have major consequences for patients physically, psychologically, emotionally and socially, leading to reduced quality of life, depression and poor rehabilitation outcome. However, studies on the incidence of PTHP have yielded highly variable findings. The risk factors and pathophysiology of this condition are also not yet fully understood. There is currently no national consensus for the screening and detection of PTHP in patients with TBI, with practice likely varying significantly between centres. In view of this, a guidance development group consisting of expert clinicians involved in the care of patients with TBI, including neurosurgeons, neurologists, neurointensivists and endocrinologists, was convened to formulate national guidance with the aim of facilitating consistency and uniformity in the care of patients with TBI, and ensuring timely detection or exclusion of PTHP where appropriate. This article summarises the current literature on PTHP, and sets out guidance for the screening and management of pituitary dysfunction in adult patients with TBI. It is hoped that future research will lead to more definitive recommendations in the form of guidelines

Oncolytic reovirus as a combined antiviral and anti-tumour agent for the treatment of liver cancer

Objective: Oncolytic viruses (OVs) represent promising, proinflammatory cancer treatments. Here, we explored whether OV-induced innate immune responses could simultaneously inhibit HCV while suppressing hepatocellular carcinoma (HCC). Furthermore, we extended this exemplar to other models of virus-associated cancer. Design and results: Clinical grade oncolytic orthoreovirus (Reo) elicited innate immune activation within primary human liver tissue in the absence of cytotoxicity and independently of viral genome replication. As well as achieving therapy in preclinical models of HCC through the activation of innate degranulating immune cells, Reo-induced cytokine responses efficiently suppressed HCV replication both in vitro and in vivo. Furthermore, Reo-induced innate responses were also effective against models of HBV-associated HCC, as well as an alternative endogenous model of Epstein–Barr virus-associated lymphoma. Interestingly, Reo appeared superior to the majority of OVs in its ability to elicit innate inflammatory responses from primary liver tissue. Conclusions: We propose that Reo and other select proinflammatory OV may be used in the treatment of multiple cancers associated with oncogenic virus infections, simultaneously reducing both virus-associated oncogenic drive and tumour burden. In the case of HCV-associated HCC (HCV-HCC), Reo should be considered as an alternative agent to supplement and support current HCV-HCC therapies, particularly in those countries where access to new HCV antiviral treatments may be limited

Global overview of the management of acute cholecystitis during the COVID-19 pandemic (CHOLECOVID study)

There was no funding support for this study. Disclosure. The authors declare no conflict of interest.Peer reviewedPublisher PD

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Identification of Surgeon Burnout via a Single-Item Measure

BackgroundBurnout is endemic in surgeons in the UK and linked with poor patient safety and quality of care, mental health problems, and workforce sustainability. Mechanisms are required to facilitate the efficient identification of burnout in this population. Multi-item measures of burnout may be unsuitable for this purpose owing to assessment burden, expertise required for analysis, and cost.AimsTo determine whether surgeons in the UK reporting burnout on the 22-item Maslach Burnout Inventory (MBI) can be reliably identified by a single-item measure of burnout.MethodsConsultant (n = 333) and trainee (n = 217) surgeons completed the MBI and a single-item measure of burnout. We applied tests of discriminatory power to assess whether a report of high burnout on the single-item measure correctly classified MBI cases and non-cases.ResultsThe single-item measure demonstrated high discriminatory power on the emotional exhaustion burnout domain: the area under the curve was excellent for consultants and trainees (0.86 and 0.80), indicating high sensitivity and specificity. On the depersonalisation domain, discrimination was acceptable for consultants (0.76) and poor for trainees (0.69). In contrast, discrimination was acceptable for trainees (0.71) and poor for consultants (0.62) on the personal accomplishment domain.ConclusionsA single-item measure of burnout is suitable for the efficient assessment of emotional exhaustion in consultant and trainee surgeons in the UK. Administered regularly, such a measure would facilitate the early identification of at-risk surgeons and swift intervention, as well as the monitoring of group-level temporal trends to inform resource allocation to coincide with peak periods

Burnout Among Surgeons in the UK During the COVID-19 Pandemic: A Cohort Study

BackgroundSurgeon burnout has implications for patient safety and workforce sustainability. The aim of this study was to establish the prevalence of burnout among surgeons in the UK during the COVID-19 pandemic.MethodsThis cross-sectional online survey was set in the UK National Health Service and involved 601 surgeons across the UK of all specialities and grades. Participants completed the Maslach Burnout Inventory and a bespoke questionnaire. Outcome measures included emotional exhaustion, depersonalisation and low personal accomplishment, as measured by the Maslach Burnout Inventory-Human Services Survey (MBI-HSS).ResultsA total of 142 surgeons reported having contracted COVID-19. Burnout prevalence was particularly high in the emotional exhaustion (57%) and depersonalisation (50%) domains, while lower on the low personal accomplishment domain (15%). Burnout prevalence was unrelated to COVID-19 status; however, the greater the perceived impact of COVID-19 on work, the higher the prevalence of emotional exhaustion and depersonalisation. Degree of worry about contracting COVID-19 oneself and degree of worry about family and friends contacting COVID-19 was positively associated with prevalence on all three burnout domains. Across all three domains, burnout prevalence was exceptionally high in the Core Trainee 1–2 and Specialty Trainee 1–2 grades.ConclusionsThese findings highlight potential undesirable implications for patient safety arising from surgeon burnout. Moreover, there is a need for ongoing monitoring in addition to an enhanced focus on mental health self-care in surgeon training and the provision of accessible and confidential support for practising surgeons