American Journal of Transplantation

No abstract text is available yet for this article.

BACKGROUND: The shortage of transplant organs remains a severe global issue. Normothermic machine perfusion (NMP) has the potential to increase organ availability, yet its efficacy is hampered by the inflammatory response during machine perfusion. METHODS: Mouse liver IRI models, discarded human liver models, and porcine marginal liver transplantation models were utilized to investigate whether FXR activation could mitigate inflammation-induced liver damage. FXR expression levels before and after reperfusion were measured...

INTRODUCTION: Normothermic machine perfusion (NMP) is increasingly considered for pre-transplant kidney quality assessment. However, fundamental questions about differences between in vivo and ex vivo renal function, as well as the impact of ischemic injury on ex vivo physiology, remain unanswered. This study utilized magnetic resonance imaging (MRI), alongside conventional parameters to explore differences between in vivo and ex vivo renal function and the impact of warm ischemia on a kidney's behavior ex vivo...

Calcineurin inhibitors (CNIs) are essential in liver transplantation (LT); however, their long-term use leads to various adverse effects. The anti-intercellular adhesion molecule-1 (ICAM-1) monoclonal antibody MD3 is a potential alternative to CNI. Despite its promising results with short-term therapy, overcoming the challenge of chronic rejection remains important. Thus, we aimed to investigate the outcomes of long-term MD3 therapy with monthly MD3 mono-maintenance in nonhuman primate LT models. Rhesus macaques underwent major histocompatibility complex-mismatched allogeneic LT...

The use of robotic surgery in transplantation is increasing, however, robotic liver transplant (RLT) remains a challenging undertaking. This is a report of the first RLT in North America and the first robotic LT using a whole graft from a deceased donor in the world. This paper describes the preparation leading to the RLT and the surgical technique of the operation. The operation was performed in a 62-year old male with hepatitis C cirrhosis and hepatocellular carcinoma (HCC) with a native MELD score of 10...

Liver transplantation (LT) is crucial for end-stage liver disease, but it is linked to infection risks. Pathobionts, microorganisms potentially harmful under specific conditions, can cause complications post-transplant. Monitoring such pathogens in fecal samples can be challenging and therefore remains underexplored post-LT. This study aimed to analyze the gut microbiome before and after LT, tracking pathobionts and correlating clinical data. The study involved 17 liver transplant recipients, 17 healthy relatives (spouses), and 13 donors...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

Recently published studies in both murine models and a meta-analysis of NHP renal transplant studies showed that anti-CD154 reagents conferred a significant survival advantage over CD40 blockers in both animal models and across multiple organs. Here we sought to compare the induction of donor-reactive Foxp3+ iTreg in mice treated with anti-CD154 vs. anti-CD40 mAb. Results indicated that while treatment with anti-CD154 resulted in a significant increase in the frequency of donor-reactive CD4+ Foxp3+ iTreg following transplantation, treatment with anti-CD40 or Cd40 deficiency failed to recapitulate this result...

Biopsy-based transcript diagnostics may identify molecular antibody-mediated rejection (AMR) when microvascular inflammation (MVI) is absent. In this single-center cohort, biopsy-based transcript diagnostics were validated in 326 kidney allograft biopsies. A total of 71 histological AMR and 35 T cell-mediated rejection (TCMR) cases were identified as molecular AMR and TCMR in 55% and 63%, respectively. Among 121 cases without MVI (glomerulitis + peritubular capillaritis = 0), 45 (37%) donor-specific antibody (DSA)-positive and 76 (63%) DSA-negative cases were analyzed...

No abstract text is available yet for this article.

Liver transplantation (LT) has emerged as an effective therapy for severe forms of acute on Chronic Liver Failure (ACLF), an entity characterized by the development of multiorgan failure and high short-term mortality. The aim of critical care management of ACLF patients is to rapidly treat precipitating events and aggressively support failing organs to ensure that patients may successfully undergo LT or, less frequently, recover. Malnutrition and sarcopenia are frequently present adversely impacting the prognosis of these patients...

Lung transplantation continues to have lower rates of long-term graft survival compared to other organs. Additionally, lung utilization rates from brain-dead donors (BDDs) remain substantially lower compared to other solid organs, despite a growing need for lung transplantation and significant risk of waitlist mortality. This study aims to examine the effects of using a combination of the recently described novel lung donor acceptability score (LUNDON) and the newly adopted recipient lung composite allocation score (CAS) to guide transplantation...

The first-generation Molecular Microscope® (MMDx) system for heart transplant endomyocardial biopsies used expression of rejection-associated transcripts (RATs) to diagnose T cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR) but also detected acute injury. However, the ideal system should detect rejection without being influenced by injury, to permit analysis of the relationship between rejection and parenchymal injury. To achieve this, we developed a new rejection classification in an expanded cohort of 3230 biopsies: 1641 from INTERHEART (ClinicalTrials...

Neutrophils exacerbate pulmonary ischemia-reperfusion injury (IRI) resulting in poor short and long-term outcomes for lung transplant recipients. Glycolysis powers neutrophil activation, but it remains unclear if neutrophil-specific targeting of this pathway will inhibit IRI. Lipid nanoparticles containing the glycolysis flux inhibitor 2-deoxyglucose (2-DG) were conjugated to neutrophil-specific Ly6G antibodies (NP-Ly6G(2-DG)). Intravenously administered NP-Ly6G(2-DG) to mice exhibited high specificity for circulating neutrophils...

Donation after circulatory death(DCD) could account for the largest expansion of the donor allograft pool in the contemporary era. However, the organ yield and associated costs of Normothermic Regional Perfusion(NRP) compared to Super-Rapid Recovery(SRR) with ex-situ Normothermic Machine Perfusion(NMP), remain unreported. The Organ Procurement and Transplantation Network (December 2019-June 2023) was analyzed to determine the number of organs recovered per donor. A cost analysis was performed based on our institution's experience since 2022...

Quality metrics are ubiquitous in healthcare in the United States and entrenched in the field of transplantation, including mandatory public reporting of both Organ Procurement Organization(OPO) and transplant center performance. There have been numerous iterations in scope and implications of quality reporting for transplant providers, including those by CMS, the Organ Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients. Notably, after years of evaluating transplant center performance as part of their Conditions of Participation for transplant centers, CMS discontinued the use of one-year post-transplant outcomes for assessment of transplant center performance in 2019...

This study aimed to dissect the relationship between specific gut commensal bacterial subgroups, their functional metabolic pathways, and their impact on skin allograft outcome and alloimmunity. We previously showed that oral broad-spectrum antibiotic pre-treatment in mice delayed skin, heart and lung allograft rejection and dampened alloimmune responses. Here, rationally designed antibiotic combinations targeting major bacterial groups were used to elucidate their individual contribution to modulating alloimmune responses...

The excess mortality of COVID-19 solid organ transplant recipients (SOTRs) throughout the pandemic remains unclear. This prospective cohort study based on the Japanese nationwide registry included 1,632 SOTRs diagnosed with COVID-19 between February 1, 2020, and July 31, 2022, categorized based on dominant phases of variants of concern (VOC): Waves 1-3 (Beta), 4 (Alpha), 5 (Delta), 6 (Omicron BA.1/BA.2), and 7 (Omicron BA.5). Excess mortality of COVID-19-affected SOTRs was analyzed by calculating standardized mortality ratios (SMRs)...

As an alternative to static cold storage (SCS), advanced perfusion techniques such as normothermic regional perfusion (NRP) and ex-situ perfusion (normothermic or hypothermic) have emerged as a way to improve the ischemic injury suffered by DCD livers. Multiple studies have been published that have demonstrated superior post-DCD liver transplant outcomes when using advanced perfusion compared to SCS. In particular, these studies have shown lower rates of ischemic cholangiopathy with advanced perfusion. In addition to the improved post-liver transplant outcomes, studies have also demonstrated higher rates liver utilization from DCD donors when advanced perfusion is used compared to SCS...