American Journal of Transplantation最新文献

Transplantation from donors with HCV-viremia to recipients without HCV-viremia (HCV D+/R-) is common, but no data exist for recipients with HIV or donors with HCV/HIV co-infection. We assessed outcomes of HCV D+/R- transplants within three HIV Organ Policy Equity Act studies of HIV+ abdominal transplantation to recipients with HIV between 2017-2023. Eighteen kidney and 6 liver HIV+ transplant recipients received organs from 19 donors with HCV viremia, including 7 with HCV/HIV co-infection. Median recipient age was 58 years, 96% were male, and median waitlist time was one year. All recipients had undetectable HIV RNA at time of transplant with median CD4 count 499 cells/mm³. HCV/HIV co-infected donors had median CD4 count 210 cells/mm³ and 4/7 had detectable HIV RNA. HCV treatment with direct acting antivirals was initiated at median 33 days post-transplant and sustained virologic response was achieved in 23/23 treated recipients without HCV-related adverse events; data unavailable for one participant. Kaplan-Meier survival analysis demonstrated 100% one-year and 96% three-year survival. Graft survival was 96% at one and three years. HCV D+/R- abdominal transplantation, including donors with HCV/HIV co-infection, demonstrates favorable patient and graft survival in recipients with HIV and is a viable strategy to increase organ utilization.

The proportion of deceased donor kidneys recovered for transplantation that are not transplanted reached 28% in 2023. Past research demonstrated that >90% of the non-use rate increase in the 2000s could be explained by the broadening donor pool. We used OPTN data to study kidneys recovered 2010-2023, applying causal inference methods to assess the degree to which the recent, sharp rise in the non-use rate could be explained by changes in donor clinical characteristics. Unadjusted odds of kidney non-use were 63% higher (95% CI: 56%, 70%) in 2023 vs 2018. After adjusting for donor factors, odds of non-use were only 12% (9%, 15%) higher in 2023. Both regression and propensity weighting demonstrated that 75-80% of the recent non-use rate increase can be explained by a rapidly expanding donor pool. Encouragingly, the non-use rate has not increased and remains low for above-average quality kidneys. However, the unexplained risk of non-use for kidneys in the highest kidney donor risk index quartile increased by ∼30%, potentially due to residual confounding and/or system-level, exogenous factors such as allocation policy changes. To improve placement efficiency, allocation policy should adapt to the increasingly heterogeneous donor pool by allocating kidneys differently along the donor quality spectrum.

Primary graft dysfunction (PGD) is a common complication after lung transplantation associated with poor outcomes. Although risk factors have been identified, the complex interactions between clinical variables affecting PGD risk are not well understood, which can complicate decisions about donor lung acceptance. Previously, we developed a machine learning (ML) model to predict grade 3 PGD using donor and recipient electronic health record (EHR) data, but it lacked granular information from donor lung CT scans, which are routinely assessed during offer review. In this study, we used a gated approach to determine optimal methods for analyzing donor lung CT scans among patients receiving first-time, bilateral lung transplants at a single center over 10 years. We assessed four computer vision approaches and fused the best with EHR data at three points in the ML process. A total of 160 patients had donor-lung CT scans for analysis. The best imaging-only approach employed a 3D ResNet model, yielding a median (IQR) AUROC and AUPRC of 0.63 (0.49 - 0.72) and 0.48 (0.35 - 0.6), respectively. Combining imaging with clinical data using late fusion provided the highest performance, with a median AUROC and AUPRC of 0.74 (0.59 - 0.85) and 0.61 (0.47 - 0.72), respectively.

This Phase 3 multi-center, randomized, controlled clinical trial evaluated investigational cellular product (MDR-101) to produce immune tolerance vs standard of care, in kidney transplant recipients. Adult recipients of kidneys from 2-haplotype HLA-matched living siblings were randomized 2:1 to Treatment (n=20) or Control (n=10). The MDR-101 product was from the same kidney donor. Treatment recipients received a non-myeloablative conditioning protocol with rabbit antithymocyte globulin and low-dose total lymphoid irradiation (10 fractions). MDR-101 was infused (D11). Steroids were withdrawn by D10 and mycophenolate by D39. Tacrolimus was continued until D180 and tapered to withdrawal 1-year post-transplant if donor hematopoietic mixed chimerism was ≥5%. Controls received immunosuppression per institutional standard of care. Twenty recipients received the MDR-101 infusion, none developed GVHD. Nineteen (95%) successfully discontinued all immunosuppression approximately 1-year post-kidney transplant. Fifteen (75%) reached the primary study end-point of immunosuppression-free for > 2 years. Four resumed immunosuppression: One with recurrent IgA nephropathy (IgAN) one with recurrent IgAN and rejection; one with rejection; one with borderline biopsy changes. Kidney transplant recipients receiving MDR-101 achieved donor mixed chimerism and functional immune tolerance for greater than two years with no death, graft loss, DSA or GVHD and demonstrated improved quality of life compared to standard treatment. Clinical Trial Registration - NCT03363945 (not part of word count).

In March 2023, the allocation strategy for lung transplantation (LT) underwent significant changes with the introduction of the new system, referred to as the continuous distribution (CD). The current paper describes the early impact of CD implementation on the mechanics of LT at a large tertiary care medical center. This was a retrospective study conducted across nine months before (March 2022 to November 2022) and after (March 2023 to November 2023) the implementation of the CD allocation system. The number of lung donor offers increased by 59% in the post-CD period (p=0.002). The median offers per waitlisted patient increased even more (p<0.001), leading to a significant reduction in time to transplant (p<0.001). Early clinical outcomes (median length of stay and hospital survival) were unchanged, while the cumulative length of index hospitalization was lower by 10% during the post-CD period. The cost/bed-day increased by 4.5% in a post-CD period, which converted to a 32% decrease in the contribution margin per transplant. In conclusion, the implementation of CD was associated with improved access to donor lungs, leading to favorable trends in the time to transplant while maintaining post-transplant outcomes. The CD was associated with a significant jump in the cost of LT.