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.

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.

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Treatment of tendon injuries is challenging. To develop means to augment tendon regeneration, we have previously prepared a soluble, low immunogenic (DNA‐free), tendon extracellular matrix fraction (tECM) by urea extraction of juvenile bovine tendons, which is capable of enhancing transforming growth factor‐β (TGF‐β) mediated tenogenesis in human adipose‐derived stem cells (hASCs). Here, we aimed to elucidate the mechanism of tECM‐driven hASC tenogenic differentiation in vitro, focusing on the integrin and TGF‐β/SMAD pathways. Our results showed that tECM promoted hASC proliferation and tenogenic differentiation in vitro based on tenogenesis‐associated markers. tECM also induced higher expression of several integrin subunits and TGF‐β receptors, and nuclear translocation of p‐SMAD2 in hASCs. Pharmacological inhibition of integrin‐ECM binding, focal adhesion kinase (FAK) signaling, or TGF‐β signaling independently led to compromised pro‐tenogenic effects of tECM and actin fiber polymerization. Additionally, integrin blockade inhibited tECM‐driven TGFBR2 expression, while inhibiting TGF‐β signaling decreased tECM‐mediated expression of integrin α1, α2, and β1 in hASCs. Together, these findings suggest that the strong pro‐tenogenic bioactivity of tECM is regulated via integrin/TGF‐β signaling crosstalk. Understanding how integrins interact with signaling by TGF‐β and/or other growth factors (GFs) within the tendon ECM microenvironment will provide a rational basis for an ECM‐based approach for tendon repair.

Background Tak Province, at the Thai–Myanmar border, is one of three high malaria incidence areas in Thailand. This study aimed to describe and identify possible factors driving the spatiotemporal trends of disease incidence from 2012 to 2015. Methods Climate variables and forest cover were correlated with malaria incidence using Pearson’s r . Statistically significant clusters of high (hot spots) and low (cold spots) annual parasite incidence per 1000 population (API) were identified using Getis-Ord Gi* statistic. Results The total number of confirmed cases declined by 76% from 2012 to 2015 ( Plasmodium falciparum by 81%, Plasmodium vivax by 73%). Incidence was highly seasonal with two main annual peaks. Most cases were male (62.75%), ≥ 15 years (56.07%), and of Myanmar (56.64%) or Thai (39.25%) nationality. Median temperature (1- and 2-month lags), average temperature (1- and 2-month lags) and average relative humidity (2- and 3-month lags) correlated positively with monthly total, P. falciparum and P. vivax API. Total rainfall in the same month correlated with API for total cases and P. vivax but not P. falciparum . At sub-district level, percentage forest cover had a low positive correlation with P. falciparum , P. vivax , and total API in most years. There was a decrease in API in most sub-districts for both P. falciparum and P. vivax . Sub-districts with the highest API were in the Tha Song Yang and Umphang Districts along the Thai–Myanmar border. Annual hot spots were mostly in the extreme north and south of the province. Conclusions There has been a large decline in reported clinical malaria from 2012 to 2015 in Tak Province. API was correlated with monthly climate and annual forest cover but these did not account for the trends over time. Ongoing elimination interventions on one or both sides of the border are more likely to have been the cause but it was not possible to assess this due to a lack of suitable data. Two main hot spot areas were identified that could be targeted for intensified elimination activities. Electronic supplementary material The online version of this article (10.1186/s12936-019-2871-2) contains supplementary material, which is available to authorized users.