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Background: In controlled donation after circulatory determination of death (DCD), it is common to administer premortem heparin to potential donors. This practice remains controversial because there is limited evidence for it and there is the possibility of inducing hemorrhage. To our knowledge, no previous studies have assessed the effects of heparin timing and dose on graft function., Methods: We performed a multicentre cohort study of consecutive DCD donors and the recipients of their organs. Anticoagulation administration was considered early if given near the time of withdrawal of life-sustaining measures and late if delayed until the onset of donor hypoxemia (oxygen saturation < 70%) or hypotension (systolic blood pressure < 60 mm Hg or mean blood pressure < 50 mm Hg). The anticoagulation dose was considered high if it was 300 units/kg or greater., Results: Donor anticoagulation data were available for 301 kidney, 75 liver and 46 lung recipients. Heparin was administered in 92% of cases and was most commonly withheld in donors with cerebrovascular causes of death ( p = 0.01). Administration was late in 59% and the dose was low in 27%. Among kidney recipients, there were no significant differences in need for dialysis, glomerular filtration rate over the first year after transplantation or graft survival on the basis of whether or not the donor received heparin, the timing of heparin administration or the dose of heparin. Among liver recipients, alkaline phosphatase concentrations over the first year were significantly higher among recipients who received organs from donors to whom lower doses of heparin had been administered., Conclusion: Premortem heparin is widely used in DCD cases, but there is variability in timing and dose, which was not associated with kidney outcomes in this study. Donor anticoagulation may have a greater impact in preventing biliary complications following liver transplantation., Competing Interests: Competing interests: None declared., (© 2022 CMA Impact Inc. or its licensors.)

Aim: To investigate the effect of 20-hydroxyecdysone on steroidogenic pathway genes and plasma progesterone, and its potential impact on vascular functions., Methods: Chimeric mice with humanized liver were treated with 20-hydroxyecdysone for 3 days, and hepatic steroidogenic pathway genes and plasma progesterone were measured by transcriptomics and GC-MS/MS, respectively. Direct effects on muscle and mesenteric arterioles were assessed by myography., Results: CYP17A1 was downregulated in 20-hydroxyecdysone-treated mice compared with untreated group (p = 0.04), with an insignificant increase in plasma progesterone. Progesterone caused vasorelaxation which was blocked by 60 mM KCl, but unaffected by nitric oxide synthase inhibition., Conclusion: In the short term, 20-hydroxyecdysone mediates CYP17A1 downregulation without a significant increase in plasma progesterone, which has a vasodilatory effect involving inhibition of voltage-dependent calcium channels, and the potential to enhance 20-hydroxyecdysone vasorelaxation., (© 2022 The Authors.)

Background & Aims: Association between sarcopenia and mortality in cirrhosis is well recognised; however, little is known about the clinical implications of adipose tissue radiodensity, indicative of biological features. This study aimed to determine an association between high subcutaneous adipose tissue (SAT) radiodensity and survival, compare the prevalence of high SAT radiodensity between healthy population and patients with cirrhosis, and identify an association between computed tomography (CT)-measured SAT radiodensity and histological characteristics., Methods: Adult patients with cirrhosis (n = 786) and healthy donors (n = 129) with CT images taken as part of the liver transplant (LT) assessment were included. Abdominal SAT biopsies (1-2 g) were harvested from the incision site at the time of LT from 12 patients with cirrhosis., Results: The majority of patients were male (67%) with a mean model for end-stage liver disease (MELD) score of 15 ± 8. SAT radiodensity above -83 HU in females (sub-distribution hazard ratio [sHR] 1.84, 95% CI 1.20-2.85, p  = 0.006) and higher than -74 HU in males (sHR 1.51, 95% CI 1.05-1.18, p  = 0.02) was associated with the highest mortality risk after adjusting for confounders in competing risk analysis. The frequency of high SAT radiodensity was 26% for those with cirrhosis, compared with 2% in healthy donors ( p <0.001). An inverse correlation was found between SAT radiodensity and the mean cross-sectional area of SAT adipocytes ( r  = -0.67, p  = 0.02). Shrunken, smaller adipocytes with expanded interstitial space were predominant in patients with high SAT radiodensity, whereas larger adipocytes with a thin rim of cytoplasm were observed in patients with low SAT radiodensity (744 ± 400 vs. 1,521 ± 1,035 μm 2 , p <0.001)., Conclusion: High SAT radiodensity frequently presents and is associated with a higher mortality in cirrhosis. SAT morphological rearrangement in patients with high SAT radiodensity might indicate diminished lipid stores and alterations in tissue characteristics., Lay Summary: Poor quality of subcutaneous adipose tissue (fat under the skin) is associated with higher mortality in patients with end-stage liver disease. Fat cells are smaller in patients with poor adipose tissue quality., Competing Interests: The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2022 The Author(s).)