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Modulation of Rab7a-mediated growth factor receptor trafficking inhibits islet beta cell apoptosis and autophagy under conditions of metabolic stress
Regenerative medicine approaches to enhancing beta cell growth and survival represent potential treatments for diabetes. It is known that growth factors such as insulin, IGF-1 and HGF support beta cell growth and survival, but in people with type 2 diabetes the destructive effects of metabolic stress predominate and beta cell death or dysfunction occurs. In this study we explore the novel hypothesis that regulation of growth factor receptor trafficking can be used to promote islet beta cell survival. Growth factor signalling is dependent on the presence of cell surface receptors. Endosomal trafficking and subsequent recycling or degradation of these receptors is controlled by the Rab GTPase family of proteins. We show that Rab7a siRNA inhibition enhances IGF-1 and HGF signalling in beta cells and increases expression of the growth factor receptors IGF-1R and c-Met. Furthermore, Rab7a inhibition promotes beta cell growth and islet survival, and protects against activation of apoptosis and autophagy pathways under conditions of metabolic stress. This study therefore demonstrates that Rab7a-mediated trafficking of growth factor receptors controls beta cell survival. Pharmaceutical Rab7a inhibition may provide a means to promote beta cell survival in the context of metabolic stress and prevent the onset of type 2 diabetes
Intraperitoneal drain placement and outcomes after elective colorectal surgery: international matched, prospective, cohort study
Despite current guidelines, intraperitoneal drain placement after elective colorectal surgery remains widespread. Drains were not associated with earlier detection of intraperitoneal collections, but were associated with prolonged hospital stay and increased risk of surgical-site infections.Background Many surgeons routinely place intraperitoneal drains after elective colorectal surgery. However, enhanced recovery after surgery guidelines recommend against their routine use owing to a lack of clear clinical benefit. This study aimed to describe international variation in intraperitoneal drain placement and the safety of this practice. Methods COMPASS (COMPlicAted intra-abdominal collectionS after colorectal Surgery) was a prospective, international, cohort study which enrolled consecutive adults undergoing elective colorectal surgery (February to March 2020). The primary outcome was the rate of intraperitoneal drain placement. Secondary outcomes included: rate and time to diagnosis of postoperative intraperitoneal collections; rate of surgical site infections (SSIs); time to discharge; and 30-day major postoperative complications (Clavien-Dindo grade at least III). After propensity score matching, multivariable logistic regression and Cox proportional hazards regression were used to estimate the independent association of the secondary outcomes with drain placement. Results Overall, 1805 patients from 22 countries were included (798 women, 44.2 per cent; median age 67.0 years). The drain insertion rate was 51.9 per cent (937 patients). After matching, drains were not associated with reduced rates (odds ratio (OR) 1.33, 95 per cent c.i. 0.79 to 2.23; P = 0.287) or earlier detection (hazard ratio (HR) 0.87, 0.33 to 2.31; P = 0.780) of collections. Although not associated with worse major postoperative complications (OR 1.09, 0.68 to 1.75; P = 0.709), drains were associated with delayed hospital discharge (HR 0.58, 0.52 to 0.66; P < 0.001) and an increased risk of SSIs (OR 2.47, 1.50 to 4.05; P < 0.001). Conclusion Intraperitoneal drain placement after elective colorectal surgery is not associated with earlier detection of postoperative collections, but prolongs hospital stay and increases SSI risk
Intraperitoneal drain placement and outcomes after elective colorectal surgery: international matched, prospective, cohort study
Many surgeons routinely place intraperitoneal drains after elective colorectal surgery. However, enhanced recovery after surgery guidelines recommend against their routine use owing to a lack of clear clinical benefit. This study aimed to describe international variation in intraperitoneal drain placement and the safety of this practice
Safety and efficacy of intraperitoneal drain placement after emergency colorectal surgery. An international, prospective cohort study
Intraperitoneal drains are often placed during emergency colorectal surgery. However, there is a lack of evidence supporting their use. This study aimed to describe the efficacy and safety of intraperitoneal drain placement after emergency colorectal surgery. Method: COMPlicAted intra-abdominal collectionS after colorectal Surgery (COMPASS) is a prospective, international, cohort study into which consecutive adult patients undergoing emergency colorectal surgery were enrolled (from 3 February 2020 to 8 March 2020). The primary outcome was the rate of intraperitoneal drain placement. Secondary outcomes included rate and time-to-diagnosis of postoperative intraperitoneal collections, rate of surgical site infections (SSIs), time to discharge and 30-day major postoperative complications (Clavien-Dindo III-V). Multivariable logistic and Cox proportional hazards regressions were used to estimate the independent association of the outcomes with drain placement. Results: Some 725 patients (median age 68.0âyears; 349 [48.1%] women) from 22 countries were included. The drain insertion rate was 53.7% (389 patients). Following multivariable adjustment, drains were not significantly associated with reduced rates (odds ratio [OR] =â1.56, 95% CI: 0.48-5.02, pâ=â0.457) or earlier detection (hazard ratio [HR] =â1.07, 95% CI: 0.61-1.90, pâ=â0.805) of collections. Drains were not significantly associated with worse major postoperative complications (ORâ=â1.26, 95% CI: 0.67-2.36, pâ=â0.478), delayed hospital discharge (HRâ=â1.11, 95% CI: 0.91-1.36, pâ=â0.303) or increased risk of SSIs (ORâ=â1.61, 95% CI: 0.87-2.99, pâ=â0.128). Conclusion: This is the first study investigating placement of intraperitoneal drains following emergency colorectal surgery. The safety and clinical benefit of drains remain uncertain. Equipoise exists for randomized trials to define the safety and efficacy of drains in emergency colorectal surgery