Effects of temperature on survival, moulting, and expression of neuropeptide and mTOR signalling genes in juvenile Dungeness crab (Metacarcinus magister)

Mechanistic target of rapamymcin (mTOR) is a highly conserved protein kinase that controls cellular protein synthesis and energy homeostasis. We hypothesize that mTOR integrates intrinsic signals (moulting hormones) and extrinsic signals (thermal stress) to regulate moulting and growth in decapod crustaceans. The effects of temperature on survival, moulting and mRNA levels of mTOR signalling genes (Mm-Rheb, Mm-mTOR, Mm-AMPKα, Mm-S6K and Mm-AKT) and neuropeptides (Mm-CHH and Mm-MIH) were quantified in juvenile Metacarcinus magister. Crabs at different moult stages (12, 19 or 26 days postmoult) were transferred from ambient temperature (∼15°C) to temperatures between 5 and 30°C for up to 14 days. Survival was 97–100% from 5 to 20°C, but none survived at 25 or 30°C. Moult stage progression accelerated from 5 to 15°C, but did not accelerate further at 20°C. In eyestalk ganglia, Mm-Rheb, Mm-AMPKα and Mm-AKT mRNA levels decreased with increasing temperatures. Mm-MIH and Mm-CHH mRNA levels were lowest in the eyestalk ganglia of mid-premoult animals at 20°C. In the Y-organ, Mm-Rheb mRNA levels decreased with increasing temperature and increased during premoult, and were positively correlated with haemolymph ecdysteroid titre. In the heart, moult stage had no effect on mTOR signalling gene mRNA levels; only Mm-Rheb, Mm-S6K and Mm-mTOR mRNA levels were higher in intermoult animals at 10°C. These data suggest that temperature compensation of neuropeptide and mTOR signalling gene expression in the eyestalk ganglia and Y-organ contributes to regulate moulting in the 10 to 20°C range. The limited warm compensation in the heart may contribute to mortality at temperatures above 20°C

Rivaroxaban with or without aspirin in stable cardiovascular disease

BACKGROUND: We evaluated whether rivaroxaban alone or in combination with aspirin would be more effective than aspirin alone for secondary cardiovascular prevention. METHODS: In this double-blind trial, we randomly assigned 27,395 participants with stable atherosclerotic vascular disease to receive rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg once daily). The primary outcome was a composite of cardiovascular death, stroke, or myocardial infarction. The study was stopped for superiority of the rivaroxaban-plus-aspirin group after a mean follow-up of 23 months. RESULTS: The primary outcome occurred in fewer patients in the rivaroxaban-plus-aspirin group than in the aspirin-alone group (379 patients [4.1%] vs. 496 patients [5.4%]; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.86; P<0.001; z=−4.126), but major bleeding events occurred in more patients in the rivaroxaban-plus-aspirin group (288 patients [3.1%] vs. 170 patients [1.9%]; hazard ratio, 1.70; 95% CI, 1.40 to 2.05; P<0.001). There was no significant difference in intracranial or fatal bleeding between these two groups. There were 313 deaths (3.4%) in the rivaroxaban-plus-aspirin group as compared with 378 (4.1%) in the aspirin-alone group (hazard ratio, 0.82; 95% CI, 0.71 to 0.96; P=0.01; threshold P value for significance, 0.0025). The primary outcome did not occur in significantly fewer patients in the rivaroxaban-alone group than in the aspirin-alone group, but major bleeding events occurred in more patients in the rivaroxaban-alone group. CONCLUSIONS: Among patients with stable atherosclerotic vascular disease, those assigned to rivaroxaban (2.5 mg twice daily) plus aspirin had better cardiovascular outcomes and more major bleeding events than those assigned to aspirin alone. Rivaroxaban (5 mg twice daily) alone did not result in better cardiovascular outcomes than aspirin alone and resulted in more major bleeding events

Global attitudes in the management of acute appendicitis during COVID-19 pandemic: ACIE Appy Study

Background: Surgical strategies are being adapted to face the COVID-19 pandemic. Recommendations on the management of acute appendicitis have been based on expert opinion, but very little evidence is available. This study addressed that dearth with a snapshot of worldwide approaches to appendicitis. Methods: The Association of Italian Surgeons in Europe designed an online survey to assess the current attitude of surgeons globally regarding the management of patients with acute appendicitis during the pandemic. Questions were divided into baseline information, hospital organization and screening, personal protective equipment, management and surgical approach, and patient presentation before versus during the pandemic. Results: Of 744 answers, 709 (from 66 countries) were complete and were included in the analysis. Most hospitals were treating both patients with and those without COVID. There was variation in screening indications and modality used, with chest X-ray plus molecular testing (PCR) being the commonest (19\ub78 per cent). Conservative management of complicated and uncomplicated appendicitis was used by 6\ub76 and 2\ub74 per cent respectively before, but 23\ub77 and 5\ub73 per cent, during the pandemic (both P < 0\ub7001). One-third changed their approach from laparoscopic to open surgery owing to the popular (but evidence-lacking) advice from expert groups during the initial phase of the pandemic. No agreement on how to filter surgical smoke plume during laparoscopy was identified. There was an overall reduction in the number of patients admitted with appendicitis and one-third felt that patients who did present had more severe appendicitis than they usually observe. Conclusion: Conservative management of mild appendicitis has been possible during the pandemic. The fact that some surgeons switched to open appendicectomy may reflect the poor guidelines that emanated in the early phase of SARS-CoV-2

Evaluation of a quality improvement intervention to reduce anastomotic leak following right colectomy (EAGLE): pragmatic, batched stepped-wedge, cluster-randomized trial in 64 countries

Background Anastomotic leak affects 8 per cent of patients after right colectomy with a 10-fold increased risk of postoperative death. The EAGLE study aimed to develop and test whether an international, standardized quality improvement intervention could reduce anastomotic leaks. Methods The internationally intended protocol, iteratively co-developed by a multistage Delphi process, comprised an online educational module introducing risk stratification, an intraoperative checklist, and harmonized surgical techniques. Clusters (hospital teams) were randomized to one of three arms with varied sequences of intervention/data collection by a derived stepped-wedge batch design (at least 18 hospital teams per batch). Patients were blinded to the study allocation. Low- and middle-income country enrolment was encouraged. The primary outcome (assessed by intention to treat) was anastomotic leak rate, and subgroup analyses by module completion (at least 80 per cent of surgeons, high engagement; less than 50 per cent, low engagement) were preplanned. Results A total 355 hospital teams registered, with 332 from 64 countries (39.2 per cent low and middle income) included in the final analysis. The online modules were completed by half of the surgeons (2143 of 4411). The primary analysis included 3039 of the 3268 patients recruited (206 patients had no anastomosis and 23 were lost to follow-up), with anastomotic leaks arising before and after the intervention in 10.1 and 9.6 per cent respectively (adjusted OR 0.87, 95 per cent c.i. 0.59 to 1.30; P = 0.498). The proportion of surgeons completing the educational modules was an influence: the leak rate decreased from 12.2 per cent (61 of 500) before intervention to 5.1 per cent (24 of 473) after intervention in high-engagement centres (adjusted OR 0.36, 0.20 to 0.64; P &lt; 0.001), but this was not observed in low-engagement hospitals (8.3 per cent (59 of 714) and 13.8 per cent (61 of 443) respectively; adjusted OR 2.09, 1.31 to 3.31). Conclusion Completion of globally available digital training by engaged teams can alter anastomotic leak rates. Registration number: NCT04270721 (http://www.clinicaltrials.gov)