Association Between Early Immunosuppression Center Variability and One-Year Outcomes After Pediatric Liver Transplant.

Background: Despite the existence of institutional protocols, liver transplant centers often have variability in early immunosuppression practices. We aimed to measure within-center variability in early immunosuppression after pediatric liver transplant (LT) and examine its association with one-year outcomes.

Methods: We analyzed pediatric LTs from 2013 to 2018 in the United Network for Organ Sharing registry, with data aggregated by center.

A multi-platform assessment of extracellular vesicles from the plasma and urine of women with preeclampsia.

Introduction: MicroRNAs (miRNAs), packaged within extracellular vesicles (EVs), have been used to interrogate the pathogenesis of preeclampsia and to identify its biomarkers. We have previously shown that miRNA species were differentially expressed in small plasma EVs from women with preeclampsia vs healthy controls. We sought to assess the use of rapid technologies for isolation of plasma and urine EVs from parturients with preeclampsia and determine differences in the expression of selected EV miRNA species.

Impact of kidney allocation system 250 policy on 1-year graft loss.

A new deceased donor kidney allocation system (KAS250) was implemented in March 2021 that prioritizes recipients within a 250-nautical mile radius of the donor hospital. KAS250 was implemented to reduce geographic disparities in access to kidney transplantation. Studies have shown an increase in cold ischemia time (CIT) after KAS250 implementation but the impact on graft outcomes is unknown.

Distinct Pro-Inflammatory Species-Specific Transcriptional Changes in Human T Cells Following Pig Xenogeneic Stimulation.

Conventional T cell-directed immunosuppression is the mainstay of standard-of-care therapy to prevent graft rejection in clinical organ transplantation. However, it remains ineffective in preventing experimental and clinical organ xenograft rejection. Here, we explored the impact of allogeneic versus xenogeneic antigen stimulation on human T cell responses and gene profile.

Cardiac matrix-bound Nanovesicles provide insight into mechanisms of clinical heart disease progression to failure.

Aims: Remodeling of the extracellular matrix (ECM) is critical for effective wound healing and maintaining organ homeostasis. The ECM of soft tissues, including cardiac, contains embedded nanovesicles; or matrix-bound nanovesicles (MBV). The luminal cargo of MBV consists of lipids, microRNAs (miRNAs), and proteins that influence the function of immune and stromal cells.

Exercise Preconditioning of the Donor Liver Decreases Cold Ischemia/Reperfusion Injury in a Mouse Model.

Background: Liver transplantation stands as the primary treatment for end-stage liver disease, with demand surging in recent decades because of expanded indications. However, hepatic ischemia/reperfusion injury can lead to liver transplant failure in both deceased donor and living donor transplantation. This study explored whether preconditioning donor livers through exercise training (ExT) could mitigate cold ischemic injury posttransplantation.

TIM proteins and microRNAs: distinct impact and promising interactions on transplantation immunity.

Achieving sustained activity and tolerance in of allogeneic grafts after post-transplantation remains a substantial challenge. The response of the immune system to "non-self" MHC-antigenic peptides initiates a crucial phase, wherein blocking positive co-stimulatory signals becomes imperative to ensure graft survival and tolerance. MicroRNAs (miRNAs) inhibit mRNA translation or promote mRNA degradation by complementary binding of mRNA seed sequences, which ultimately affects protein synthesis.

Bridging the Gap: A Review of Pediatric to Adult Transition of Care in Liver Transplantation.

Background: With improvements in long-term graft function and survival, an increasing population of pediatric liver transplant (LT) recipients now require adult care. A process to successfully transition young adults to adult LT centers is supported in the literature with discussions on the rationale for health care transition (HCT), barriers to transition, stakeholder perspectives, and transfer readiness (TR). Results of outcomes studies are difficult to generalize and there remains no standard of care for HCT in LT.

Mitigating High-risk EBV and CMV Through Kidney Paired Donation: A Survey of Potential Donor and Recipient Candidates.

Background: High-risk cytomegalovirus (CMV) and Epstein-Barr virus (EBV) mismatches (ie, seropositive donors to seronegative recipients) among kidney transplant recipients lead to increased healthcare utilization, inferior allograft outcomes, and high mortality. We assessed the interest among prospective kidney donor and recipient candidates to participate in kidney paired donation (KPD) for averting CMV/EBV high-risk mismatches.

Methods: We surveyed 51 potential living donors and 102 kidney recipient candidates presenting for their evaluation visit at the University of Pittsburgh Medical Center between October 2022 and May 2023.

FCGR2C Q and FCGR3A V alleles jointly associate with worse natural killer cell-mediated antibody-dependent cellular cytotoxicity and microvascular inflammation in kidney allograft antibody-mediated rejection.

Natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC) is a major mechanism of humoral allograft injury. FCGR3A V/F polymorphism influences ADCC activity. Additionally, NK cell FcγRIIc expression, dictated by the Q/STP polymorphism, was never investigated in kidney transplantation.

Drug delivery strategies for local immunomodulation in transplantation: Bridging the translational gap.

Drug delivery strategies for local immunomodulation hold tremendous promise compared to current clinical gold-standard systemic immunosuppression as they could improve the benefit to risk ratio of life-saving or life-enhancing transplants. Such strategies have facilitated prolonged graft survival in animal models at lower drug doses while minimizing off-target effects. Despite the promising outcomes in preclinical animal studies, progression of these strategies to clinical trials has faced challenges.

Economic evaluation of weight loss and transplantation strategies for kidney transplant candidates with obesity.

Novel antiobesity medications, particularly glucagon-like peptide-1 receptor agonists (GLP-1RAs), have expanded weight loss (WL) options for kidney transplantation (KT) candidates with obesity beyond lifestyle modifications and bariatric surgery. However, varying effectiveness, risk profiles, and costs make strategy choices challenging. To aid decision-making, we used a Markov model to examine the cost-effectiveness of different WL strategies over a 10-year horizon.

Expedited liver transplantation as first-line therapy for severe alcohol hepatitis: ELFSAH; deferring corticosteroids in the sickest subset of patients.

Background & Aims: Severe alcohol-associated hepatitis (SAH) represents a lethal subset of alcohol-associated liver disease. Although corticosteroids are recommended by guidelines, their efficacy and safety remain questionable and so liver transplantation (LT) has been increasingly utilized. The timing and indication of corticosteroid use, specifically in patients being considered for LT requires further clarification.

Liver transplantation provides survival benefit at all levels of frailty: From the Multicenter Functional Assessment in Liver Transplantation Study.

Background And Aims: Offering LT to frail patients may reduce waitlist mortality but may increase post-LT mortality. LT survival benefit is the concept of balancing these risks. We sought to quantify the net survival benefit with LT by liver frailty index (LFI).

The transformative potential of artificial intelligence in solid organ transplantation.

Solid organ transplantation confronts numerous challenges ranging from donor organ shortage to post-transplant complications. Here, we provide an overview of the latest attempts to address some of these challenges using artificial intelligence (AI). We delve into the application of machine learning in pretransplant evaluation, predicting transplant rejection, and post-operative patient outcomes.

Lymphotoxin β receptor and tertiary lymphoid organs shape acute and chronic allograft rejection.

Solid organ transplantation remains the life-saving treatment for end-stage organ failure, but chronic rejection remains a major obstacle to long-term allograft outcomes and has not improved substantially. Tertiary lymphoid organs (TLOs) are ectopic lymphoid structures that form under conditions of chronic inflammation, and evidence from human transplantation suggests that TLOs regularly form in allografts undergoing chronic rejection. In this study, we utilized a mouse renal transplantation model and manipulation of the lymphotoxin αβ/lymphotoxin β receptor (LTαβ/LTβR) pathway, which is essential for TLO formation, to define the role of TLOs in transplantation.

Clinically relevant cut-points for changes in the Liver Frailty Index are associated with waitlist mortality in patients with cirrhosis.

Physical frailty is a critical determinant of mortality in patients with cirrhosis and can be objectively measured using the Liver Frailty Index (LFI), which is potentially modifiable. We aimed to identify LFI cut-points associated with waitlist mortality. Ambulatory adults with cirrhosis without HCC awaiting liver transplantation from 9 centers from 2012 to 2021 for ≥3 months with ≥2 pre-liver transplantation LFI assessments were included.