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.

Background and Aim The purpose of the present study was to determine the effects of IL-37 on liver cells and on liver inflammation induced by hepatic ischemia/reperfusion (I/R). Materials and methods Mice were subjected to I/R. Some mice received recombinant IL-37 (IL-37) at the time of reperfusion. Serum levels of alanine amino transferase, liver myeloperoxidase content were assessed. Serum and liver TNFα, MIP-2 and KC were also assessed. Hepatic reactive oxygen species (ROS) levels were assessed. For in vitro experiments, isolated hepatocytes and Kupffer cells were treated with IL-37 and inflammatory stimulants. Cytokine and chemokine production by these cells were assessed. Primary hepatocytes were induced cell injury and treated with IL-37 concurrently. Hepatocyte cytotoxicity and Bcl-2 expression were determined. Isolated neutrophils were treated with TNFα and IL-37 and neurtrophil activation and respiratory burst were assessed. Results IL-37 reduced hepatocyte injury and neutrophil accumulation in the liver after I/R. These effects were accompanied by reduced serum levels of TNFα and MIP-2 and hepatic ROS levels.IL-37 significantly reduced MIP-2 and KC productions from LPS-stimulated hepatocytes and Kupffer cells. IL-37 significantly reduced cell death and increased Bcl-2 expression in hepatocytes. IL-37 significantly suppressed TNFα induced-neutrophil activation. Conclusions IL-37 is protective against hepatic I/R injury. These effects are related to the ability of IL-37 to reduce proinflammatory cytokine and chemokine production by hepatocytes and Kupffer cells as well as having a direct protective effect on hepatocytes. In addition, IL-37 contributes to reduce liver injury through suppression of neutrophil activity.

IL-33 is a recently identified member of the IL-1 family that binds to the receptor, ST2L. In the current study, we sought to determine if IL-33 is an important in the hepatic response to I/R. Male C57BL/6 mice were subjected to 90 minutes of partial hepatic ischemia followed by up to 8 hours of reperfusion. Some mice received recombinant IL-33 (IL-33) intraperitoneally prior to surgery or anti-ST2 antibody intraperitoneally at the time of reperfusion. Primary hepatocytes and Kupffer cells were isolated and treated with IL-33 to assess the effects of IL-33 on inflammatory cytokine production. Primary hepatocytes were treated with IL-33 to assess the effects of IL-33 on the mediators for cell survival in hepatocytes. IL-33 protein expression increased within 4 hours after reperfusion and remained elevated for up to 8 hours. ST2L protein expression was detected in normal liver and was upregulated within 1hr and peaked at 4hrs after I/R. ST2L was primarily expressed by hepatocytes, with little to no expression by Kupffer cells. IL-33 significantly reduced hepatocellular injury and liver neutrophil accumulation at 1 hour and 8 hours after reperfusion. In addition, IL-33 treatment increased liver activation of NF-κB, p38 mitogen activated protein kinase (MAPK), Cyclin D1 and Bcl-2, but reduced serum levels of CXC chemokines. In vitro experiments demonstrated that IL-33 significantly reduced hepatocyte cell death, due to increased NF-κB activation and Bcl-2 expression in hepatocytes. Conclusion: The data suggest that IL-33 is an important endogenous regulator of hepatic I/R injury. It appears that IL-33 has direct protective effects on hepatocytes, associated with activation of NF-κB, p38 MAPK, Cyclin D1 and Bcl-2 that limits liver injury and reduces the stimulus for inflammation.

The rate and causes of hospital readmissions after liver transplantation (LT) remain largely unknown in the United States. Adult patients (n 5 11,937; 43.1% of all LT cases) undergoing LT from 2007 to 2011 were examined with a linkage of the University HealthSystem Consortium and Scientific Registry of Transplant Recipients databases to determine the incidence and risk factors for 30-day readmissions and utilization metrics 90 days after LT. The overall 30-day hospital readmission rate after LT was 37.9%, with half of patients admitted within 7 days after discharge. Readmitted patients had worse overall graft and patient survival with a 2-year follow-up. Multivariate analysis identified risk factors associated with 30-day hospital readmission, including a higher Model for End-Stage Liver Disease score, diabetes at LT, dialysis dependence, a high donor risk index allograft, and discharge to a rehabilitation facility. After adjustments for donor, recipient, and geographic factors in a hierarchical model, we found significant variation in readmission rates among hospitals ranging from 26.3% to 50.8% (odds ratio, 0.53-1.90). In the 90-day analysis after LT, readmissions accounted for $43,785 of added costs in comparison with patients who were not readmitted in the first 90 days. This is the first national report showing that more than one-third of LT recipients are readmitted to their center within 30 days and that readmissions are associated with center variation and increased resource utilization. Liver Transpl 21:953-960, 2015. V C 2015 AASLD.

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