American Journal of Transplantation

Due to the breadth of factors that might affect kidney transplant decisions to accept an organ or wait for another, presumably "better" offer, a high degree of heterogeneity in decision-making exists among transplant surgeons and hospitals. These decisions do not typically include objective predictions regarding the future availability of equivalent or better-quality organs, nor the likelihood of patient death while waiting for another organ. To investigate the impact of displaying such predictions on organ donation decision making, we conducted a statistically designed experiment involving 53 kidney transplant professionals, where kidney organ offers were presented via an online application and systematically altered to observe effects on decision making...

In July 2022, the Scientific Registry of Transplant Recipients (SRTR) hosted an innovative, multistakeholder consensus conference to identify information and metrics desired by stakeholders in the transplantation system, including patients, living donors, caregivers, deceased donor family members, transplant professionals, organ procurement organization professionals, payers, and regulators. Crucially, patients, caregivers, living donors, and deceased donor family members were included in all aspects of this conference, including serving on the planning committee, participating in preconference focus groups and learning sessions, speaking at the conference, moderating conference sessions and breakout groups, and shaping the conclusions...

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Data on the potential benefits and risks of induction therapy in pediatric liver transplantation (LT) are limited. This was a retrospective cohort study of 2,748 pediatric LT recipients at 26 children's hospitals between 1/1/2006-5/31/2017 using data from the Pediatric Health Information System (PHIS) linked to the United Network for Organ Sharing database. Induction regimen was obtained from PHIS day-by-day pharmacy resource utilization. Cox proportional hazards evaluated the association of induction regimen (none/corticosteroid-only, non-depleting, depleting) on patient and graft survival...

Advanced heart failure (AHF) therapy allocation is vulnerable to bias related to subjective assessments and poor group dynamics. Our objective was to determine whether an implementation strategy for AHF team members could feasibly contribute to organizational and culture change supporting equity in AHF allocation. Using pretest-posttest design, the strategy included an 8-week multi-component training on bias reduction, standardized numerical social assessments, and enhanced group dynamics at an AHF center. Evaluations of organizational and cultural change included pretest-posttest AHF team member surveys, transcripts of AHF meetings to assess group dynamics using a standardized scoring system, and posttest interviews guided by framework for implementing a complex strategy...

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Anatomical variations of left hepatic vein (LHV) are observed in nearly a third of left lateral segment (LLS) donors in living donor liver transplantation (LDLT). There is paucity of studies and no structured algorithm for customised outflow reconstruction in LLS grafts with variant anatomy. Analysis of a prospectively collected database of 296 LLS paediatric LDLT was done to identify different venous drainage patterns of segments 2 (V2) and 3 (V3). LHV anatomy was classified into three types: type 1(n=270, 91...

Liver transplantation in patients with end-stage liver disease and co-existing hemophilia A has been described. Controversy exists over perioperative management of patients with factor (F) VIII inhibitor predisposing to hemorrhage. We describe the case of a 58-year-old male with a history of hemophilia A and FVIII inhibitor eradicated with rituximab prior to living donor liver transplantation, without recurrence of inhibitor. We also provide perioperative management recommendations from our successful multidisciplinary approach...

Despite data demonstrating increased utilization of kidneys from hepatitis C virus (HCV)-infected donors, it is unknown whether: 1) this is due to an increase in the donor pool or improved organ utilization, and 2) data from early pilot trials was temporally associated with changes in organ utilization. We used data from the Organ Procurement and Transplantation Network of all kidney donors and recipients of kidney transplants from 1/1/2015-3/31/2022 to evaluate temporal changes using Joinpoint regression. Our primary analyses compared donors based on their HCV viremic status (HCV-infected vs...

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Damage to the gastrointestinal tract following allogeneic hematopoietic stem cell transplantation is a significant contributor to the severity and perpetuation of graft-versus-host disease. In preclinical models and clinical trials, we showed that infusing high numbers of regulatory T-cells reduces graft-versus-host disease incidence. Despite no change in in vitro suppressive function, transfer of ex vivo expanded regulatory T-cells transduced to overexpress G-protein coupled receptor 15 or C-C Motif Chemokine Receptor 9, specific homing receptors for colon or small intestine, respectively, lessened graft-versus-host disease severity in mice...

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To date, plasma cell (PC) targeted therapies have been limited by suboptimal PC depletion and antibody rebound. We hypothesized this is in part due to PC residence in protective bone marrow (BM) microenvironments. The purpose of this proof-of-concept study was to examine the effects of the CXCR4 antagonist, plerixafor, on PC BM residence, its safety profile (alone and in combination with the proteasome inhibitor, bortezomib), and the transcriptional impact on BMPCs in HLA-sensitized kidney transplant candidates...

In testing the prognostic value of the occurrence of an intervening event (clinical event that occurs post-transplant), 3 proper statistical methodologies for testing its prognostic value exist (time dependent covariate, landmark, and semi-Markov modelling methods). However, time-dependent bias has appeared in many clinical reports, whereby the intervening event is statistically treated as a baseline variable (as if it occurred at transplant). Using a single-center cohort of 445 intestinal transplant cases to test the prognostic value of 1st acute cellular rejection (ACR) and severe (grade of) ACR on the hazard rate of developing graft loss, we demonstrate how the inclusion of such time-dependent bias can lead to severe underestimation of the true hazard ratio (HR)...

In heart transplantation, the use of biomarkers to detect the risk of rejection has been evolving. In this setting, it is becoming less clear as to what is the most reliable test or combination of tests to detect rejection and to assess the state of the alloimmune response. Therefore, a virtual expert panel was organized in heart and kidney transplantation to evaluate emerging diagnostics and how they may be best utilized to monitor and manage transplant patients. This manuscript covers the heart content of the conference and is a work product of the American Society of Transplantation's Thoracic and Critical Care Community of Practice...

Liver transplantation risks transferring a genetic defect in metabolic pathways, including the urea cycle. We present a case of pediatric liver transplantation complicated by metabolic crisis and early allograft dysfunction (EAD) in a previously healthy unrelated deceased donor. Allograft function improved with supportive care and retransplantation was avoided. Because the hyperammonemia suggested an enzymatic defect in the allograft, genetic testing from donor-derived DNA revealed a heterozygous mutation in the ASL gene, which encodes the urea cycle enzyme argininosuccinate lyase...

The growing accessibility and falling costs of genetic sequencing techniques has expanded the utilization of genetic testing in clinical practice. For living kidney donation, genetic evaluation has been increasingly used to identify genetic kidney disease in potential candidates, especially in those of younger ages. However, genetic testing on asymptomatic living kidney donors remains fraught with many challenges and uncertainties. Not all transplant practitioners are aware of the limitations of genetic testing, are comfortable with selecting testing methods, comprehending test results, or providing counsel, and many do not have access to a renal genetic counselor or a clinical geneticist...

Instant blood-mediated inflammatory reaction (IBMIR) is initiated by innate immune responses that cause substantial islet loss following intraportal transplantation. Thrombomodulin (TM) is a multifaceted innate immune modulator. We report the generation of a chimeric form of this molecule with streptavidin (SA-TM) for transient display on the surface of islets modified with biotin to mitigate IBMIR. SA-TM protein expressed in insect cells showed the expected structural and functional features. SA-TM converted protein C into activated protein C, blocked phagocytosis of xenogeneic cells by mouse macrophages, and inhibited neutrophil activation...

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