Establishing and Validating a Biomolecular Signature of Ischemia/Reperfusion Injury in a Porcine Pancreas Allotransplantation Model.

Background: Despite considerable advancement in surgical and immunological management in pancreas transplantation, graft pancreatitis remains a feared complication after pancreas transplantation. Identification of molecular mechanisms of underlying ischemia/reperfusion injury (IRI) in pancreas transplantation could, therefore, pave the path for targeted therapy to improve surgical outcomes. The aim of the study was to identify and validate the genes differentially expressed in the early period (24 h) of graft reperfusion in pancreas transplantation.

Opportunities and challenges with the implementation of normothermic machine perfusion in kidney transplantation.

End stage kidney disease and dialysis are lifetime limiting and lifestyle-defining conditions with enormous costs to the health care system. Despite a severe organ shortage, thousands of organs that are retrieved for transplantation go to waste every year because of the presumed inadequacy of organ quality and/or the limited organ preservation time. Normothermic kidney machine perfusion (NMP) holds the potential to resolve this through improved preservation, prolonged preservation time, kidney quality assessment, reconditioning and treatment.

SBRT for bridging and downstaging HCC before transplant.

Background & Aims: Stereotactic body radiotherapy (SBRT) has emerged as a bridging/downstaging therapy for patients with hepatocellular carcinoma (HCC) awaiting liver transplantation (LT). This study evaluates the safety and outcomes of the use of SBRT in such patients.

Methods: A retrospective review was conducted from 2004 to 2019 on 88 adult patients with HCC receiving SBRT as bridging/downstaging therapy.

Metabolomic Insight into Donation After Circulatory-Death Kidney Grafts in Porcine Autotransplant Model: Normothermic Ex Vivo Kidney Perfusion Compared with Hypothermic Machine Perfusion and Static Cold Storage.

Organ shortage is a major challenge in transplantation, prompting the use of extended criteria donor grafts. These require improved preservation techniques and reliable methods to assess graft function. This study aimed to evaluate changes in the kidney metabolome following three preservation methods: normothermic ex vivo kidney perfusion (NEVKP), hypothermic machine perfusion (HMP) and static cold storage (SCS) in porcine autotransplant models.

Delineating the Metabolic Phenotype of Biopsy-Derived Kidney Cells.

Kidney transplantation is the optimal treatment for end-stage kidney disease; however, transplanted kidneys are often lost prematurely, with up to 50% graft loss at 10 years post-transplant. One of the major causes of premature graft loss is the injury sustained by the graft at the time of transplantation, known as ischemia-reperfusion injury (IRI). Delayed graft function (DGF), defined as the need for dialysis in the first week post-transplant, is a manifestation of severe IRI that shows functional and histologic features of acute kidney injury (AKI).

Comparing outcomes of deceased-donor and living-donor liver transplants in patients with PVT.

Portal vein thrombosis (PVT) complicates liver transplantation (LT) by hindering portal flow restoration. Some centers still consider PVT a contraindication for living-donor LT (LDLT) due to technical challenges compared to deceased-donor LT (DDLT). We retrospectively analyzed adults undergoing LT with main PVT between 2006 and 2023, excluding tumor thrombi and re-LT.

Mitochondrial Transplantation Reduces Injury and Improves Liver Function in a Porcine Model of Hemi-hepatic Ischemia/Reperfusion.

Objective: To assess mitochondrial transplantation (MitoTx) via portal vein infusion to reduce liver ischemia-reperfusion injury (I/R) in a survival porcine model.

Summary Background Data: MitoTx has been shown to alleviate I/R injury in various organs.

Methods: Male Yorkshire pigs (38±1 kg) were subjected to 2 hours of ischemia in the left hemi-liver (left portal-triad clamping), and at the beginning of reperfusion (marked as t=0 h), animals received a 1-hour infusion of autologous mitochondria (MT, 7×10^9/kg) or saline (controls) via the portal vein.

Normothermic Ex Vivo Machine Perfusion Mitigates Apoptosis in a Porcine Model of Pancreas Transplantation.

Background: Pancreas transplantation is one of the most effective treatment options for individuals diagnosed with complicated diabetes. However, the pancreas has one of the strictest acceptance criteria and the highest discard rate of any organ after retrieval. Normothermic ex vivo perfusion (NEVP) has emerged as a promising strategy to evaluate and potentially improve the quality of pancreatic grafts before transplantation.

Living Donor Liver Transplantation for Alcohol-related Liver Disease: An Intention-to-treat Analysis.

Background: Alcohol-associated liver disease (ALD) is the leading indication for liver transplantation (LT) in the Western world. Although 6 mo of abstinence is no longer a criterion for patients with ALD, the outcomes of living donor LT (LDLT) versus deceased donor LT (DDLT) are not well established.

Methodss: We performed an intention-to-treat analysis to evaluate the impact of listing and pursuing primary LDLT (pLDLT) compared with primary DDLT (pDDLT).

Deceased donor liver utilisation and assessment: Consensus guidelines from the European Liver and Intestine Transplant Association.

Over the past two decades, the application of machine perfusion (MP) in human liver transplantation has moved from the realm of clinical exploration to routine clinical practice. Both in situ and ex situ perfusion strategies are feasible, safe, and may offer improvements in relevant post-transplant outcomes. An important utility of these strategies is the ability to transplant grafts traditionally considered too risky to transplant using conventional cold storage alone.

Feasibility and Optimization of Donation Advisor: a Decision Support Tool for Deceased Organ Donation and Transplantation.

Background: This study aimed to evaluate the ability of Donation Advisor (DA), a validated clinical decision support tool that uses continuous monitoring, variability analysis, and predictive models, to (i) predict likelihood of successful donation after circulatory determination of death (DCD) before withdrawal of life-sustaining measures (WLSM), and (ii) describe ischemia during WLSM in DCD patients.

Methods: Eligible patients were screened at the 5 sites where DA was implemented. DA reports were generated in real time but shown to clinicians after the donation was complete (noninterventional).

Factor V Serves as an Early Biomarker for Graft Loss After Liver Transplant: A Prospective Evaluation.

Background: Low post-operative day (POD) 1 Factor V has been retrospectively associated with graft loss after liver transplantation when stratified by a cutoff of 0.36 U/mL. We aimed to validate this prospectively.

Evolving Trends in the Management of Duodenal Leaks After Pancreas Transplantation: A Single-Centre Experience.

Duodenal leaks (DL) contribute to most graft losses following pancreas transplantation. However, there is a paucity of literature comparing graft preservation approach versus upfront graft pancreatectomy in these patients. We reviewed all pancreas transplants performed in our institution between 2000 and 2020 and identified the recipients developing DL to compare based on their management: percutaneous drainage vs.

Development and Assessment of a Deceased Donor Organ Recovery Workshop for Surgical Fellows.

Objective: To assess the impact of a deceased donor organ procurement training workshop on the transplant fellow's confidence and proficiency in organ recovery. This pilot workshop was designed to address the current gap in the transplant fellow's training in North America.

Design: Participants' confidence and competence in deceased donor organ recovery were assessed pre- and postworkshop (immediate, 1- and 6-month) using a survey questionnaire.

Normothermic ex vivo kidney perfusion preserves mitochondrial and graft function after warm ischemia and is further enhanced by AP39.

We previously reported that normothermic ex vivo kidney  perfusion (NEVKP) is superior in terms of organ protection compared to static cold storage (SCS), which is still the standard method of organ preservation, but the mechanisms are incompletely understood. We used a large animal kidney autotransplant model to evaluate mitochondrial function during organ preservation and after kidney transplantation, utilizing live cells extracted from fresh kidney tissue. Male porcine kidneys stored under normothermic perfusion showed preserved mitochondrial function and higher ATP levels compared to kidneys stored at 4 °C (SCS).

Recent solid-phase microextraction-based analytical approaches for the profiling of biliary bile acids in pre-transplant assessments of liver grafts subjected to normothermic ex vivo liver perfusion.

Background: Liver transplantation is the definitive treatment for end-stage liver failure, but the scarcity of donor organs remains a significant challenge. Leveraging organs from extended criteria donors (ECD) offers a potential avenue to address worldwide shortages, though these organs are more susceptible to post-reperfusion injury. This study explores the use of normothermic ex vivo liver perfusion (NEVLP) as a method for organ preservation - an approach that sustains liver metabolism and facilitates pre-transplant assessments of organ viability via bile analysis.

Pancreas transplantation with grafts obtained from donation after cardiac death or donation after brain death results in comparable outcomes.

Introduction: Pancreas organ shortages and long recipient waitlist times are critical components that limit recipients from receiving a pancreas transplant. Over the last decade, our center has been using donation after cardiac death (DCD) donors as an adjunct to donation after brain death (DBD) donors to expand the organ pool. The aim of this study was to compare recipient and graft survival between DCD and DBD recipients.

Indocyanine green fluorescence quantification during normothermic ex situ perfusion for the assessment of porcine liver grafts after circulatory death.

Current graft evaluation during normothermic ex situ liver perfusion lacks real-time parameters for predicting posttransplant hepatocyte and biliary function. Indocyanine green (ICG) imaging has been widely used in liver surgery, enabling the visualization of hepatic uptake and excretion through bile using near-infrared light. In this research, porcine livers under various ischemic conditions were examined during a 5-hour normothermic ex situ liver perfusion procedure, introducing ICG at 1 hour through the hepatic artery.

Impact of early surgical complications on kidney transplant outcomes.

Background: Kidney transplantation (KT) improves clinical outcomes of patients with end stage renal disease. Little has been reported on the impact of early post-operative surgical complications (SC) on long-term clinical outcomes following KT. We sought to determine the impact of vascular complications, urological complications, surgical site complications, and peri-graft collections within 30 days of transplantation on patient survival, graft function, and hospital readmissions.

The impact of normothermic and hypothermic preservation methods on kidney lipidome-comparative study using chemical biopsy with microextraction probes.

Introduction: Normothermic kidney perfusion (NEVKP) is designed to replicate physiological conditions to improve graft outcomes. A comparison of the impact of hypothermic and normothermic preservation techniques on graft quality was performed by lipidomic profiling using solid-phase microextraction (SPME) chemical biopsy as a minimally invasive sampling approach.

Methods: Direct kidney sampling was conducted using SPME probes coated with a mixed-mode extraction phase in a porcine autotransplantation model of the renal donor after cardiac death, comparing three preservation methods: static cold storage (SCS), NEVKP, and hypothermic machine perfusion (HMP).

A cell-free nutrient-supplemented perfusate allows four-day ex vivo metabolic preservation of human kidneys.

The growing disparity between the demand for transplants and the available donor supply, coupled with an aging donor population and increasing prevalence of chronic diseases, highlights the urgent need for the development of platforms enabling reconditioning, repair, and regeneration of deceased donor organs. This necessitates the ability to preserve metabolically active kidneys ex vivo for days. However, current kidney normothermic machine perfusion (NMP) approaches allow metabolic preservation only for hours.

Correction: Won et al. Ex Vivo Perfusion Using a Mathematical Modeled, Controlled Gas Exchange Self-Contained Bioreactor Can Maintain a Mouse Kidney for Seven Days. 2022, , 1822.

In the original publication [...

Pursuing living donor liver transplantation improves outcomes of patients with autoimmune liver diseases: An intention-to-treat analysis.

Living donor liver transplantation (LDLT) offers the opportunity to decrease waitlist time and mortality for patients with autoimmune liver disease (AILD), autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis. We compared the survival of patients with a potential living donor (pLDLT) on the waitlist versus no potential living donor (pDDLT) on an intention-to-treat basis. Our retrospective cohort study investigated adults with AILD listed for a liver transplant in our program between 2000 and 2021.