No abstract

Atherosclerosis and graft arteriosclerosis are characterized by leukocytic infiltration of the vessel wall that spares the media. The mechanism(s) for medial immunoprivilege is unknown. In a chimeric humanized mouse model of allograft rejection, medial immunoprivilege was associated with expression of IDO by vascular smooth muscle cells (VSMCs) of rejecting human coronary artery grafts. Inhibition of IDO by 1-methyl-tryptophan (1-MT) increased medial infiltration by allogeneic T cells and increased VSMC loss. IFN-γ-induced IDO expression and activity in cultured human VSMCs was considerably greater than in endothelial cells (ECs) or T cells. IFN-γ-treated VSMCs, but not untreated VSMCs nor ECs with or without IFN-γ pretreatment, inhibited memory Th cell alloresponses across a semipermeable membrane in vitro. This effect was reversed by 1-MT treatment or tryptophan supplementation and replicated by the absence of tryptophan, but not by addition of tryptophan metabolites. However, IFN-γ-treated VSMCs did not activate allogeneic memory Th cells, even after addition of 1-MT or tryptophan. Our work extends the concept of medial immunoprivilege to include immune regulation, establishes the compartmentalization of immune responses within the vessel wall due to distinct microenvironments, and demonstrates a duality of stimulatory EC signals versus inhibitory VSMC signals to artery-infiltrating T cells that may contribute to the chronicity of arteriosclerotic diseases.

Morbid obesity is a barrier to kidney transplantation due to inferior outcomes, including higher rates of new-onset diabetes after transplantation (NODAT), delayed graft function (DGF), and graft failure. Laparoscopic sleeve gastrectomy (LSG) increases transplant eligibility by reducing BMI in kidney transplant candidates, but the effect of surgical weight loss on posttransplantation outcomes is unknown. Reviewing single-center medical records, we identified all patients who underwent LSG before kidney transplantation from 2011-2016 (n = 20). Post-LSG kidney recipients were compared with similar-BMI recipients who did not undergo LSG, using 2:1 direct matching for patient factors. McNemar's test and signed-rank test were used to compare groups. Among post-LSG patients, mean BMI ± standard deviation (SD) was 41.5 ± 4.4 kg/m at initial encounter, which decreased to 32.3 ± 2.9 kg/m prior to transplantation (P < .01). No complications, readmissions, or mortality occurred following LSG. After transplantation, one patient (5%) experienced DGF, and no patients experienced NODAT. Allograft and patient survival at 1-year posttransplantation was 100%. Compared with non-LSG patients, post-LSG recipients had lower rates of DGF (5% vs 20%) and renal dysfunction-related readmissions (10% vs 27.5%) (P < .05 each). Perioperative complications, allograft survival, and patient survival were similar between groups. These data suggest that morbidly obese patients with end-stage renal disease who undergo LSG to improve transplant candidacy, achieve excellent posttransplantation outcomes.

In this prospective cohort of non-HCV liver recipients receiving grafts from HCV antibody-positive/NAT-negative donors, the incidence of HCV transmission was 16%, with the highest risk conferred by donors who died of drug overdose; given the availability of safe and highly effective antiviral therapies, use of such organs could be considered to expand the donor pool. (Hepatology 2018;67:1673-1682).

The use of donation after circulatory death (DCD) liver allografts has been constrained by limitations in the duration of donor warm ischemia time (DWIT), donor agonal time (DAT), and cold ischemia time (CIT). The purpose of this study is to assess the impact of longer DWIT, DAT, and CIT on graft survival and other outcomes in DCD liver transplants. The Scientific Registry of Transplant Recipients was queried for adult liver transplants from DCD donors between 2009 and 2015. Donor, recipient, and center variables were included in the analysis. During the study period, 2107 patients underwent liver transplant with DCD allografts. In most patients, DWIT and DAT were <30 minutes. DWIT was <30 minutes in 1804 donors, between 30 and 40 minutes in 248, and >40 minutes in 37. There was no difference in graft survival, duration of posttransplant hospital length of stay, and readmission rate between DCD liver transplants from donors with DWIT <30 minutes and DWIT between 30 and 40 minutes. Similar outcomes were noted for DAT. In the multivariate analysis, DAT and DWIT were not associated with graft loss. The predictors associated with graft loss were donor age, donor sharing, CIT, recipient admission to the intensive care unit, recipient ventilator dependence, Model for End‐Stage Liver Disease score, and low‐volume transplant centers. Any CIT cutoff >4 hours was associated with increased risk for graft loss. Longer CIT was also associated with a longer posttransplant hospital stay, higher rate of primary nonfunction, and hyperbilirubinemia. In conclusion, slightly longer DAT and DWIT (up to 40 minutes) were not associated with graft loss, longer posttransplant hospitalization, or hospital readmissions, whereas longer CIT was associated with worse outcomes after DCD liver transplants.