Adeno-associated virus-mediated transduction of PD-L1 in a rodent lung transplant model.

Acute cellular rejection is a key contributor to chronic lung allograft dysfunction following transplantation; while treatable, traditional immunosuppressive therapies are associated with significant side effects. Gene therapy offers an approach to modulate recipient immune responses while minimizing the toxicity of conventional immunosuppressive therapy. In this study, we evaluated adenoassociated virus (AAV)-mediated programmed death-ligand (PD-L)1 overexpression, an inhibitory ligand of T cells, in a rat single-lung transplant model.

Proceedings of the 29th Annual Congress of the International Liver Transplantation Society.

The 2024 Annual Congress of the International Liver Transplantation Society (ILTS) was from May 1-4 in Houston, Texas, USA, under the theme "Liver Disease and Transplantation: Breaking Barriers and Exploring New Frontiers." In addition to a robust scientific program, the congress also hosted a hands-on cadaveric robotic liver surgery course, a machine perfusion workshop, and a transesophageal echocardiography course. In this report, the ILTS Vanguard and Basic Sciences Committees present a summary of the congress proceedings.

Evolving adeno-associated viruses for gene transfer to the kidney via cross-species cycling of capsid libraries.

The difficulty of delivering genes to the kidney has limited the translation of genetic medicines, particularly for the more than 10% of the global population with chronic kidney disease. Here we show that new variants of adeno-associated viruses (AAVs) displaying robust and widespread transduction in the kidneys of mice, pigs and non-human-primates can be obtained by evolving capsid libraries via cross-species cycling in different kidney models. Specifically, the new variants, AAV.

Transforming the logistics of liver transplantation with normothermic machine perfusion: Clinical impact versus cost.

Normothermic machine perfusion (NMP) facilitates the utilization of marginal liver allografts. It remains unknown whether clinical benefits offset additional costs in the real-world setting. We performed a comparison of outcomes and hospitalization costs for donor livers preserved by NMP versus static cold storage at a high-volume center.

Risk Factors for Invasive Surgical Site Infections Among Adult Single Liver Transplant Recipients at Duke University Hospital in the Period 2015-2020.

Background: Invasive primary surgical site infections (IP-SSI) are a severe complication of liver transplant surgery. Identification of risk factors for IP-SSI is critical to IP-SSI prevention.

Methods: All adult single liver transplants performed at Duke University Hospital in the period 2015-2020 were reviewed for IP-SSI occurring within 90 d of transplant.

Optimizing DCD Liver Grafts With Prolonged Warm Ischemic Time Using Stabilized Plasmin in a Static Cold Storage Orthotopic Rat Liver Transplant Model.

Background: The clinical success of liver transplantation has led to increased demand, requiring further expansion of the donor pool. Therapeutic interventions to optimize organs from donation after circulatory death (DCD) have significant potential to mitigate the organ shortage. Dysfunction in DCD liver grafts is mediated by microvascular thrombosis during the warm ischemic period, and strategies that reduce this thrombotic burden may improve graft function.

Subnormothermic Oxygenated Machine Perfusion (24 h) in DCD Kidney Transplantation.

Background: Ex vivo kidney perfusion is an evolving platform that demonstrates promise in preserving and rehabilitating the kidney grafts. Despite this, there is little consensus on the optimal perfusion conditions. Hypothermic perfusion offers limited functional assessment, whereas normothermic perfusion requires a more complex mechanical system and perfusate.

Contemporary trends and outcomes after liver transplantation and resection for intrahepatic cholangiocarcinoma.

Background: Liver transplantation (LT) has been shown to be superior to resection in highly selected patients with perihilar cholangiocarcinoma (CCA), yet has traditionally been contraindicated for intrahepatic CCA (iCCA). Herein, we aimed to examine contemporary trends and outcomes for surgical resection and LT for iCCA.

Methods: The National Cancer Database was queried for patients presenting with stage I-III iCCA between 2010 and 2018 who underwent resection or LT.

Adeno-associated virus mediates gene transduction after static cold storage treatment in rodent lung transplantation.

Objective: Adeno-associated virus is a clinically used gene therapy vector but has not been studied in lung transplantation. We sought to determine the efficacy of adeno-associated virus delivery during static cold storage via the airway versus the pulmonary artery before lung transplantation in a rodent model.

Methods: Lewis rat lung grafts were treated with a dose of 8e8 or 4e9 viral genome/μL recombinant adeno-associated virus subtype-9 vectors containing firefly luciferase genomes administered via the pulmonary artery or airway during cold storage.

Gene delivery followed by ex vivo lung perfusion using an adeno-associated viral vector in a rodent lung transplant model.

Objective: Ex vivo lung perfusion has emerged as a platform for organ preservation, evaluation, and restoration. Gene delivery using a clinically relevant adeno-associated vector during ex vivo lung perfusion may be useful in optimizing donor allografts while the graft is maintained physiologically active. We evaluated the feasibility of adeno-associated vector-mediated gene delivery during ex vivo lung perfusion in a rat transplant model.

Sterile inflammation in liver transplantation.

Sterile inflammation is the immune response to damage-associated molecular patterns (DAMPs) released during cell death in the absence of foreign pathogens. In the setting of solid organ transplantation, ischemia-reperfusion injury results in mitochondria-mediated production of reactive oxygen and nitrogen species that are a major cause of uncontrolled cell death and release of various DAMPs from the graft tissue. When properly regulated, the immune response initiated by DAMP-sensing serves as means of damage control and is necessary for initiation of recovery pathways and re-establishment of homeostasis.

AAV9-mediated gene delivery to liver grafts during static cold storage in a rat liver transplant model.

Introduction: Recombinant adeno-associated virus (rAAV) is a novel strategy used clinically for gene delivery, but has not been characterized in the context of organ transplantation. We sought to determine the efficacy of rAAV-mediated gene delivery during static cold storage (SCS) prior to liver transplantation.

Methods: A triple-plasmid transfection protocol was used to produce rAAV subtype-9 vectors containing firefly luciferase genomes in HEK293 cells.

Incidence of Postreperfusion Hyperfibrinolysis in Liver Transplantation by Donor Type and Observed Treatment Strategies.

Background: Hyperfibrinolysis is a possible complication during liver transplantation, particularly immediately after reperfusion.

Methods: We performed a retrospective study to examine the incidence, treatment, and resolution of postreperfusion hyperfibrinolysis in patients undergoing liver transplantation at Duke University Hospital from 2015 to 2020.

Results: Out of 535 patients undergoing liver transplantation, 21 or 3.