Heterozygous mutation of chromodomain helicase DNA binding protein 8 (CHD8) is strongly associated with autism spectrum disorder (ASD) and results in dysregulated expression of neurodevelopmental and synaptic genes during brain development. To reveal how these changes affect ASD-associated cortical circuits, we studied synaptic transmission in the prefrontal cortex of a haploinsufficient Chd8 mouse model. We report profound alterations to both excitatory and inhibitory synaptic transmission onto deep layer projection neurons, resulting in a reduced excitatory:inhibitory balance, which were found to vary dynamically across neurodevelopment and result from distinct effects of reduced Chd8 expression within individual neuronal subtypes. These changes were associated with disrupted regulation of homeostatic plasticity mechanisms operating via spontaneous neurotransmission. These findings therefore directly implicate CHD8 mutation in the disruption of ASD-relevant circuits in the cortex.

BackgroundThere is currently conflicting evidence surrounding the effects of obesity on postoperative outcomes. Previous studies have found obesity to be associated with adverse events, but others have found no association. The aim of this study was to determine whether increasing body mass index (BMI) is an independent risk factor for development of major postoperative complications.MethodsThis was a multicentre prospective cohort study across the UK and Republic of Ireland. Consecutive patients undergoing elective or emergency gastrointestinal surgery over a 4‐month interval (October–December 2014) were eligible for inclusion. The primary outcome was the 30‐day major complication rate (Clavien–Dindo grade III–V). BMI was grouped according to the World Health Organization classification. Multilevel logistic regression models were used to adjust for patient, operative and hospital‐level effects, creating odds ratios (ORs) and 95 per cent confidence intervals (c.i.).ResultsOf 7965 patients, 2545 (32·0 per cent) were of normal weight, 2673 (33·6 per cent) were overweight and 2747 (34·5 per cent) were obese. Overall, 4925 (61·8 per cent) underwent elective and 3038 (38·1 per cent) emergency operations. The 30‐day major complication rate was 11·4 per cent (908 of 7965). In adjusted models, a significant interaction was found between BMI and diagnosis, with an association seen between BMI and major complications for patients with malignancy (overweight: OR 1·59, 95 per cent c.i. 1·12 to 2·29, P = 0·008; obese: OR 1·91, 1·31 to 2·83, P = 0·002; compared with normal weight) but not benign disease (overweight: OR 0·89, 0·71 to 1·12, P = 0·329; obese: OR 0·84, 0·66 to 1·06, P = 0·147).ConclusionOverweight and obese patients undergoing surgery for gastrointestinal malignancy are at increased risk of major postoperative complications compared with those of normal weight.

Objectives The role of medical students in the current COVID-19 pandemic is rapidly evolving. The aim of this review is to explore the involvement of medical students in past global health emergencies, to help inform current and future scenarios. Methods A rapid systematic review was undertaken, including articles from online databases discussing the roles, willingness and appropriateness of medical student involvement in global health emergencies. Data were extracted, appraised and written up as a narrative synthesis. This paper was registered with PROSPERO (CRD42020177231). Results 28 articles were included. Medical students played a wide variety of clinical and non-clinical roles including education and logistics, although medical assistance was the most commonly reported role. Challenges included a lack of preparedness and negative mental health impacts. 91.7% of included articles about willingness found medical students were more willing to be involved than not. Conclusion This review shows medical students are capable and willing to be involved in global health emergencies. However, there should be clear protocols for the roles that they play, taking into account the appropriateness. As a rapid review, there were study limitations and more research is required regarding the impact of these roles on medical students and the system.

Purpose This systematic review and meta-analysis directly compares joint replacement (JR) and trapeziectomy techniques to provide an update as to which surgical intervention is superior for first carpometacarpal (CMC-1) joint osteoarthritis. Methods In August 2020, MEDLINE, Embase and Web of Science were searched for eligible studies that compared these two techniques for the treatment of CMC-1 joint osteoarthritis (PROSPERO registration ID: CRD42020189728). Primary outcomes included the Disabilities of the Arm, Shoulder and Hand (DASH), QuickDASH (QDASH) and pain visual analogue scale (VAS) scores. Secondary outcomes, such as total complication, dislocation and revision surgery rates, were also measured. Results From 1909 studies identified, 14 studies (1005 patients) were eligible. Our meta-analysis found that post-operative QDASH scores were lower for patients in the JR group (five studies, p = 0.0004). Similarly, significantly better postoperative key pinch strength in favour of JR was noted (three studies, p = 0.001). However, pain (VAS) scores were similar between the two groups (five studies, p = 0.21). Moreover, JR techniques had significantly greater odds of overall complications (12 studies; OR 2.12; 95% CI 1.13–3.96, p = 0.02) and significantly greater odds of revision surgery (9 studies; OR 5.14; 95% CI 2.06–12.81, p = 0.0004). Conclusion Overall, based on very low- to moderate-quality evidence, JR treatments may result in better function with less disability with comparable pain (VAS) scores; however, JR has greater odds of complications and greater odds of requiring revision surgery. More robust RCTs that compare JR and TRAP with standardised outcome measures and long-term follow-up would add to the overall quality of evidence.

Heterozygous mutation of chromodomain helicase DNA binding protein 8 (CHD8) is strongly associated with autism spectrum disorder (ASD) and results in dysregulated expression of neurodevelopmental and synaptic genes during brain development. To reveal how these changes affect ASD-associated cortical circuits, we studied synaptic transmission in the prefrontal cortex of a haploinsufficient Chd8 mouse model. We report profound alterations to both excitatory and inhibitory synaptic transmission onto deep layer projection neurons, resulting in a reduced excitatory:inhibitory balance, which were found to vary dynamically across neurodevelopment and result from distinct effects of reduced Chd8 expression within individual neuronal subtypes. These changes were associated with disrupted regulation of homeostatic plasticity mechanisms operating via spontaneous neurotransmission. These findings therefore directly implicate CHD8 mutation in the disruption of ASD-relevant circuits in the cortex.

Background: Patient selection for critical care admission must balance patient safety with optimal resource allocation. This study aimed to determine the relationship between critical care admission, and postoperative mortality after abdominal surgery. Methods: This prespecified secondary analysis of a multicentre, prospective, observational study included consecutive patients enrolled in the DISCOVER study from UK and Republic of Ireland undergoing major gastrointestinal and liver surgery between October and December 2014. The primary outcome was 30-day mortality. Multivariate logistic regression was used to explore associations between critical care admission (planned and unplanned) and mortality, and intercentre variation in critical care admission after emergency laparotomy. Results: Of 4529 patients included, 37.8% (n¼1713) underwent planned critical care admissions from theatre. Some 3.1% (n¼86/2816) admitted to ward-level care subsequently underwent unplanned critical care admission. Overall 30-day mortality was 2.9% (n¼133/4519), and the risk-adjusted association between 30-day mortality and critical care admission was higher in unplanned [odds ratio (OR): 8.65, 95% confidence interval (CI): 3.51e19.97) than planned admissions (OR: 2.32, 95% CI: 1.43e3.85). Some 26.7% of patients (n¼1210/4529) underwent emergency laparotomies. After adjustment, 49.3% (95% CI: 46.8e51.9%, P<0.001) were predicted to have planned critical care admissions, with 7% (n¼10/145) of centres outside the 95% CI. Conclusions: After risk adjustment, no 30-day survival benefit was identified for either planned or unplanned postoperative admissions to critical care within this cohort. This likely represents appropriate admission of the highest-risk patients. Planned admissions in selected, intermediate-risk patients may present a strategy to mitigate the risk of unplanned admission. Substantial inter-centre variation exists in planned critical care admissions after emergency laparotomies.

Introduction: Radical cystectomy (RC) is historically considered the gold standard treatment for muscle invasive and high-risk non-muscle invasive bladder cancer.However, this technique leaves the majority of patients of both sexes with poor sexual and urinary function. Organ-sparing cystectomy (OSC) techniques are emerging as an alternative to the standard procedure to preserve these functions, without compromising the oncological outcomes. We present a systematic review and metaanalysis of the published literature.Methods: MEDLINE, Embase and Web of Science were systematically searched for eligible studies on 6 April 2021. Primary outcomes studied were both oncological outcomes, specifically overall recurrence, and functional outcomes, specifically sexual function, and daytime and nighttime continence. Odds ratios (OR) with 95% confidence intervals (95% CI) were calculated. The PROSPERO registration reference number was CRD42018118897.Results: From 13 894 identified abstracts, 19 studies (1886 male and 305 female patients) were eligible for inclusion in this review. These studies included patients who underwent either whole prostate, prostate capsule, seminal vesicle, nerve, uterus, ovary, vagina and fallopian tube sparing techniques. Four studies included only female patients.Thirteen studies reported oncological outcomes, and overall recurrence rate was similar between the two groups (five studies; OR 0.73; 95% CI 0.38-1.40, p = 0.34).Thirteen studies reported on male sexual function. In men, OSC had significantly

Aim The challenge of managing first carpometacarpal (CMC-1) joint osteoarthritis is the lack of guidance on which surgical intervention is superior. This systematic review and meta-analysis compares joint replacement (JR) and trapeziectomy techniques to provide an update. Method In August 2020, MEDLINE, Embase and Web of Science were searched for eligible studies that compared these two techniques for the treatment of CMC-1 joint osteoarthritis (PROSPERO registration ID: CRD42020189728). Primary outcomes included the Disabilities of the Arm, Shoulder and Hand (DASH), QuickDASH and pain visual analogue scale (VAS) scores. Secondary outcomes, such as total complication, dislocation, and revision surgery rates, were also measured. Results From 1909 studies identified, 14 studies (1005 patients) were eligible. Our meta-analysis found that post-operative QuickDASH score was lower for patients in the JR group, indicating decreased disability following this technique (5 studies, p = 0.0002). However, pain VAS scores were similar between the two groups (5 studies, p = 0.22). Interestingly, JR techniques had significantly greater odds of overall complications (12 studies; OR 2.27; 95% CI 1.17-4.40, p = 0.02) and significantly greater odds of revision surgery (9 studies; OR 5.14; 95% CI 2.06-12.81, p = 0.0004). Conclusions Overall, based on low to moderate quality evidence, we found that JR treatments may result in better function with less disability with comparable pain (VAS) scores; however, JR has greater odds of complications and greater odds of requiring revision surgery. More robust RCTs that compare JR and TRAP with standardised outcome measures and long-term follow-up would add to the overall quality of evidence.