Obesity-related insulin resistance is driven by low-grade chronic inflammation of metabolic tissues. In the liver, non-alcoholic fatty liver disease (NAFLD) is associated with hepatic insulin resistance and systemic glucose dysregulation. However, the immunological factors supporting these processes are poorly understood. We found that the liver accumulates pathogenic CD8+ T cell subsets which control hepatic insulin sensitivity and gluconeogenesis during diet-induced obesity in mice. In a cohort of human patients, CD8+ T cells represent a dominant intrahepatic immune cell population which links to glucose dysregulation. Accumulation and activation of these cells are largely supported by type I interferon (IFN-I) responses in the liver. Livers from obese mice upregulate critical interferon regulatory factors (IRFs), interferon stimulatory genes (ISGs), and IFNα protein, while IFNαR1−/− mice, or CD8-specific IFNαR1−/− chimeric mice are protected from disease. IFNαR1 inhibitors improve metabolic parameters in mice, while CD8+ T cells and IFN-I responses correlate with NAFLD activity in human patients. Thus, IFN-I responses represent a central immunological axis that governs intrahepatic T cell pathogenicity during metabolic disease.
A program was established within our regional procurement organization to permit evaluation of altruistic living donors (LD) interested in nondirected kidney or liver segment donation prior to transplant center referral.During the initial 30 months of program operations, 731 donor inquiries were received of which 131 individuals called back after review of mailed information materials. Forty-seven candidates initiated and 19 completed the evaluation process. Seven underwent donation to include six kidneys and one liver segment, five are actively pending donation, five were excluded from donation following transplant center evaluation and two took no further action after their intended liver recipients received deceased donor (DD) transplants. Psychological evaluation of these 19 candidates found them to be free of psychopathology, highly cooperative and self-directed. They did not exhibit attentionseeking or religious motivations for their actions. All seven donors and recipients continue to do well postoperatively. This evaluation program has made possible largescale screening and education of prospective altruistic LD within the general population and also provides a unique opportunity to further our understanding of those individuals interested in living-nondirected donation.
The coronavirus disease 2019 (COVID‐19) pandemic is a rapidly changing circumstance with dramatic policy changes and universal efforts to deal with the initial crisis and minimize its consequences. To identify changes to organ donation and transplantation during this time, an anonymous web‐based survey was distributed to 19 select organ procurement organizations (OPOs) throughout the United States comparing 90‐day activity during March‐May 2020 and March‐May 2019. Seventeen OPOs responded to the survey (response rate of 89.5%). Organ authorization decreased by 11% during the current pandemic (n = 1379 vs n = 1552, P = .0001). Organ recovery for transplantation fell by 17% (P = .0001) with a further 18% decrease in the number of organs transplanted (P = .0001). Donor cause of death demonstrated a 4.5% decline in trauma but a 35% increase in substance abuse cases during the COVID‐19 period. All OPOs reported significant modifications in response to the pandemic, limiting the onsite presence of staff and transitioning to telephonic approaches for donor family correspondence. Organ donation during the current climate has seen significant changes and the long‐term implications of such shifts remain unclear. These trends during the COVID‐19 era warrant further investigation to address unmet needs, plan for a proportionate response to the virus and mitigate the collateral impact.
The use of procurement biopsies in deceased donor kidney acceptance is controversial. We analyzed Scientific Registry of Transplant Recipients data (n = 59 328 allografts, 2014-2018) to describe biopsy practices across US organ procurement organizations (OPOs) and examine relationships with discards, using hierarchical modeling to account for OPO and donor factors. Median odds ratios (MORs) provide the median of the odds that allografts with identical reported traits would be biopsied or discarded from 2 randomly drawn OPOs. Biopsies were obtained for 52.7% of kidneys. Biopsy use rose in a graded manner with kidney donor profile index (KDPI).Biopsy rates differed significantly among OPOs (22.8% to 77.5%), even after adjustment for KDPI and other donor factors. Discard rates also varied from 6.6% to 32.1% across OPOs. After adjustment for donor factors and OPO, biopsy was associated with more than 3 times the likelihood of discard (adjusted odds ratio [ 95%LCL aOR 95%UCL ], 3.29 3.51 3.76 ). This association was most pronounced for low-risk (KDPI <20) kidneys (aOR, 5.45 6.47 7.69 ), with minimal impact at KDPI >85 (aOR, 0.88 1.15 1.51 ). Adjusted MORs for kidney discard and biopsy were greatest for low-risk kidneys. Reducing the rate of unnecessary biopsy and improving the accuracy of histologic assessments in higher KDPI organs may help reduce graft discard rates. K E Y W O R D Sbiopsy, clinical research/practice, donors and donation: deceased, health services and outcomes research, kidney transplantation/nephrology, organ procurement, organ procurement and allocation, Scientific Registry for Transplant Recipients (SRTR)
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