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.

Chemical profiling of both fruit and aerial part extracts of Euphorbia abyssinica via ultra-performance liquid chromatography−mass spectrometry (UPLC-MS) showed them to be a rich source of diverse compounds. A total of 39 compounds in both extracts including flavonoids and phenolic compounds were identified as predominant metabolites. The antioxidant activity of both extracts was evaluated using three different in vitro assays (DPPH, ABTS, and FRAP assays). The E. abyssinica fruit extract demonstrated more potent activity compared to the aerial part extract (IC 50 of 85.1 ± 1.07 and 562.3 ± 1.01 μg/mL, respectively) in the DPPH assay. Furthermore, using ABTS and FRAP assays, the antioxidant capacities of the fruit extract were 1063.03 ± 37.8 and 1476.5 ± 95.6, respectively, calculated as μM Trolox equivalent/mg extract. One of the existing markers for cancer chemoprevention is the induction of phase II detoxifying enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1), which plays a vital role in cytoprotection against oxidative damage. The extracts were assessed to test their chemopreventive potential via NQO1 enzyme induction. The methanolic extract of fruits demonstrated a concentration-dependent increase in the cancer chemopreventive marker enzyme NQO1 at the protein expression level in a murine hepatoma cell line (Hepa1c1c7). The interaction with Kelch-like ECH-associated protein 1 (KEAP1) is an essential transcription factor that controls the expression of the NQO1 enzyme. The demonstrated induction of NQO1 by the fruit extract is consistent with a molecular docking study of the effect of dereplicated compounds on the KEAP1 target. Among the dereplicated compounds, hesperidin, naringin, and rutin have been established as promising inducer compounds for the chemopreventive marker NQO1. Our results highlight the E. abyssinica fruit extract as a future chemopreventive lead.

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