Peri-operative SARS-CoV-2 infection increases postoperative mortality. The aim of this study was to determine the optimal duration of planned delay before surgery in patients who have had SARS-CoV-2 infection. This international, multicentre, prospective cohort study included patients undergoing elective or emergency surgery during October 2020. Surgical patients with pre-operative SARS-CoV-2 infection were compared with those without previous SARS-CoV-2 infection. The primary outcome measure was 30-day postoperative mortality. Logistic regression models were used to calculate adjusted 30-day mortality rates stratified by time from diagnosis of SARS-CoV-2 infection to surgery. Among 140,231 patients (116 countries), 3127 patients (2.2%) had a pre-operative SARS-CoV-2 diagnosis. Adjusted 30-day mortality in patients without SARS-CoV-2 infection was 1.5% (95%CI 1.4-1.5). In patients with a pre-operative SARS-CoV-2 diagnosis, mortality was increased in patients having surgery within 0-2 weeks, 3-4 weeks and 5-6 weeks of the diagnosis (odds ratio (95%CI) 4.1 (3.3-4.8), 3.9 (2.6-5.1) and 3.6 (2.0-5.2), respectively). Surgery performed ≥ 7 weeks after SARS-CoV-2 diagnosis was associated with a similar mortality risk to baseline (odds ratio (95%CI) 1.5 (0.9-2.1)). After a ≥ 7 week delay in undertaking surgery following SARS-CoV-2 infection, patients with ongoing symptoms had a higher mortality than patients whose symptoms had resolved or who had been asymptomatic (6.0% (95%CI 3.2-8.7) vs. 2.4% (95%CI 1.4-3.4) vs. 1.3% (95%CI 0.6-2.0), respectively). Where possible, surgery should be delayed for at least 7 weeks following SARS-CoV-2 infection. Patients with ongoing symptoms ≥ 7 weeks from diagnosis may benefit from further delay.

Abstract-Two active metabolites of the angiotensin type 1 (AT 1 ) receptor blocker losartan have been described previously, EXP3174 and EXP3179. Whereas EXP3174 is the main antihypertensive AT 1 receptor-blocking metabolite, the role of EXP3179 is widely unknown. Recently, a subgroup of AT 1 receptor blockers has been identified as ligands for the peroxisome proliferator-activated receptor ␥ (PPAR-␥ he Losartan Intervention For End point reduction in hypertension (LIFE) study has shown that hypertensive patients receiving the angiotensin type 1 receptor blocker (ARB) losartan have a 25% lower rate of new-onset diabetes than patients treated with the ␤-blocker atenolol. 1 Although these data suggest a possible antidiabetic action of losartan, the molecular mechanisms are widely unknown.We and others recently demonstrated that a subset of ARBs, including losartan, induces the activity of a nuclear hormone receptor named peroxisome proliferator-activated receptor ␥ (PPAR-␥) by partial agonism. 2,3 The direct activation of the ligand-binding domain of PPAR-␥ by ARBs is independent of their angiotensin type 1 receptor (AT 1 R) blocking actions. 3 PPAR-␥ functions as a transcriptional regulator in adipose tissue where it regulates multiple genes involved in lipid and glucose metabolism. 4 Activated by synthetic full agonists like thiazolidinediones/glitazones, PPAR-␥ markedly improves whole-body insulin sensitivity resulting in decreased levels of fasting plasma glucose, fasting plasma insulin, and plasma triglycerides. 5 Thus, PPAR-␥ activation by ARBs presents a promising molecular mechanism for metabolic actions of these compounds.Losartan induced PPAR-␥ activity only at high concentrations in vitro. 3 Losartan is hepatically metabolized by the cytochrome-P450 pathway and exerts its antihypertensive actions in vivo predominantly by its main metabolite, EXP3174 (Figure 1). 6,7 During hepatic metabolization of losartan, additional active metabolites are produced, including EXP3179 (Figure 1). This metabolite has a significant molecular homology with indomethacin, an antiinflammatory cyclooxygenase (COX) inhibitor, and mediates a variety of AT 1 R-independent, pleiotropic functions (eg, inhibition of platelet aggregation, endothelial adhesion molecule expression, etc). 7 Indomethacin has been also identified as an activator of PPAR-␥. 8 Given the structural homology of indomethacin and EXP3179, it is likely that EXP3179 has

SARS-CoV-2 has been associated with an increased rate of venous thromboembolism in critically ill patients. Since surgical patients are already at higher risk of venous thromboembolism than general populations, this study aimed to determine if patients with peri-operative or prior SARS-CoV-2 were at further increased risk of venous thromboembolism. We conducted a planned sub-study and analysis from an international, multicentre, prospective cohort study of elective and emergency patients undergoing surgery during October 2020. Patients from all surgical specialties were included. The primary outcome measure was venous thromboembolism (pulmonary embolism or deep vein thrombosis) within 30 days of surgery. SARS-CoV-2 diagnosis was defined as peri-operative (7 days before to 30 days after surgery); recent (1-6 weeks before surgery); previous (≥7 weeks before surgery); or none. Information on prophylaxis regimens or pre-operative anti-coagulation for baseline comorbidities was not available. Postoperative venous thromboembolism rate was 0.5% (666/123,591) in patients without SARS-CoV-2; 2.2% (50/2317) in patients with peri-operative SARS-CoV-2; 1.6% (15/953) in patients with recent SARS-CoV-2; and 1.0% (11/1148) in patients with previous SARS-CoV-2. After adjustment for confounding factors, patients with peri-operative (adjusted odds ratio 1.5 (95%CI 1.1-2.0)) and recent SARS-CoV-2 (1.9 (95%CI 1.2-3.3)) remained at higher risk of venous thromboembolism, with a borderline finding in previous SARS-CoV-2 (1.7 (95%CI 0.9-3.0)). Overall, venous thromboembolism was independently associated with 30-day mortality ). In patients with SARS-CoV-2, mortality without venous thromboembolism was 7.4% (319/4342) and with venous thromboembolism was 40.8% (31/76). Patients undergoing surgery with peri-operative or recent SARS-CoV-2 appear to be at increased risk of postoperative venous thromboembolism compared with patients with no history of SARS-CoV-2 infection. Optimal venous thromboembolism prophylaxis and treatment are unknown in this cohort of patients, and these data should be interpreted accordingly.

Objective: To evaluate whether intraoperative subcutaneous wound irrigation with 0.04% polyhexanide can reduce surgical site infection (SSI) in elective laparotomies compared to saline. Background: SSI is a common complication after gastrointestinal surgery. To date, there is a lack of evidence whether subcutaneous wound irrigation is beneficial in terms of reduction of SSI. Methods: The RECIPE trial was an investigator initiated single-center, single-blind prospective, randomized controlled trial with 2 parallel treatment groups, comparing wound irrigation with 0.9% saline to antiseptic 0.04% polyhexanide solution in elective laparotomies. Primary endpoint was the rate of SSI within 30 days postoperatively according to Centers for Disease Control and Prevention criteria. Results: Between February 02, 2015, and May 23, 2018, 456 patients were randomly assigned to saline (n = 228) or polyhexanide (n = 228). Final cohort for analysis comprised 393 patients (202 in the saline and 191 in the polyhexanide group). Overall rate of SSI was 28.2%, n = 111. Simple analysis with cross tabulation revealed that significantly fewer SSIs occurred in the polyhexanide group: n = 70 (34.7%) versus n = 41 (21.5%); P = 0.004. In a multiple logistic regression model the factor wound irrigation with polyhexanide [odds ratio (OR) 0.44; 95% confidence interval (CI) 0.27–0.72; P = 0.001) was associated with risk reduction of SSI. Preoperative anemia (OR 2.08; 95% CI 1.27–3.40; P = 0.004) and more than 5 prior abdominal operations compared to none (OR 8.51; 95% CI 2.57–28.21; P < 0.001) were associated with SSI. Conclusions: Intraoperative subcutaneous wound irrigation with antiseptic 0.04% polyhexanide solution is effective in reducing SSI after elective laparotomies.