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.

Cyclic ADP-ribose (cADP-ribose) 1 is synthesized from ␤-NAD ϩ , an abundant intracellular substrate, by ADP-ribosyl cyclase in sea urchin eggs and in mammalian cells (1, 2). Pharmacological studies suggest that cADP-ribose is an endogenous modulator of ryanodine-sensitive Ca 2ϩ release channels (3-10). If cADP-ribose acts as an intracellular second messenger, ADPribosyl cyclase, as an effector enzyme, should be activated or inhibited in response to stimulation by hormones or neurotransmitters, which should simultaneously be associated with a transient decrease in the intracellular NAD ϩ concentration ([NAD ϩ ] i ) and an increase in cADP-ribose concentration (11).ADP-ribosyl cyclase seems to be present in both cytosolic and membrane-bound forms (1, 2, 12). The mammalian membranebound form of ADP-ribosyl cyclase has been identified as a cellsurface antigen, CD38 (13-19) and .Recently, it has been shown that the formation of cADPribose is regulated by nitric oxide or cGMP (21-23) and that nitric oxide or cGMP is increased by stimulation with agonists (24, 25). These findings suggest the hypothesis that the regulation of the cADP-ribose level is located far downstream in the signal transduction cascade from receptors (11). An alternative hypothesis is that the cADP-ribose formation is regulated by ADP-ribosyl cyclase through the direct action of G proteins activated by receptors within the surface membrane, as already shown for the formation of cyclic AMP, inositol 1,4,5-trisphosphate, and diacylglycerol (26 -28). To test this hypothesis, we used NG108-15 neuroblastoma ϫ glioma hybrid cells (29), in which signal transduction from receptors to effectors has been extensively characterized (29,30). In particular, in NGPM1-27 cells (31), which overexpress muscarinic acetylcholine receptors (mAChRs), it has been shown that intracellular NAD ϩ or NAD ϩ metabolites are involved in signal transduction from m1 mAChRs to K ϩ channels (32,33). In this context, such neuronal cell lines have advantages for analyzing receptor-ADP-ribosyl cyclase coupling in detail.For measurement of ADP-ribosyl cyclase, high pressure liquid chromatography (HPLC) is commonly used to separate cADP-ribose-related compounds (1,2,8,14,15,17,19,34,35). However, since it takes 30 -60 min to process one sample, it is essential to develop a much more rapid method that can allow processing of multiple samples at once. There are two papers that describe ADP-ribosyl cyclase assay by TLC (21,36), in which NAD ϩ migrates faster than cADP-ribose. The methods used in those reports seem to be affected by large amounts of radiolabeled substrates. We here developed a TLC method that overcomes this problem and allows separation of cADP-ribose in up to 19 samples within 40 -50 min. Our TLC method was first tested on COS-7 cells overexpressing human CD38 and was shown to be applicable for measuring ADP-ribosyl cyclase activity. We demonstrate that crude cell membranes of NG108-15 cells possess ADP-ribosyl cyclase activity and that such activity is activated or inhibi...

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.

O's-PNI may represent a useful indicator of the occurrence of complications and length of hospital stay, and may influence overall survival at 6 mo postsurgery. Nutritional management during the perioperative period could therefore contribute to satisfactory outcomes following esophagectomy in esophageal cancer patients.

BackgroundThe aim of the present study was to investigate the age-specific prognostic factors in patients who underwent gastrectomy for gastric cancer.MethodsThe medical records of 366 patients with gastric cancer who underwent surgical resection at our hospital between January 2007 and December 2014 were retrospectively reviewed. Of the 366 patients, 117 were aged 75 years or older and 249 were aged 74 years or younger. All factors that were identified as significant using univariate analysis were included in the multivariate analysis.ResultsThe median follow-up duration was 52.9 months (range, 1.0–117.5 months). We found that in patients aged 75 years or older, postoperative complications and the extent of cancer were independent prognostic factors of overall survival and disease-free survival. In contrast, in patients aged 74 years or younger, only the lymph node status and postoperative chemotherapy were independent prognostic factors for overall survival and disease-free survival, respectively.ConclusionsPathological outcomes and postoperative complications are important prognostic factors for survival in patients aged 75 years or older with gastric cancer, whereas pathological outcomes and postoperative chemotherapy are important prognostic factors for survival in patients aged 74 years or younger. Because the prevention of postoperative complications may contribute to improvements in the prognosis of elderly patients with gastric cancer, we suggest that it is necessary to consider limited surgery instead of radical surgery, depending on the patient’s general condition and co-morbidities.