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.
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.
View Article and Find Full Text PDFIntroduction: 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.
Background: Subnormothermic machine perfusion (SNMP) of liver grafts is currently less clinically developed than normothermic and hypothermic approaches, but may have logistical advantages. At intermediate temperatures, the oxygen demand of the graft is low enough to be satisfied with an acellular perfusate, obviating the need for oxygen carrying molecules. This intermediate metabolic rate, however, is sufficient to support the production of bile, which is emerging as an important indicator of graft injury and viability.
View Article and Find Full Text PDFThe impact of HLA matching on graft survival has been well characterized in renal transplantation, with a higher degree of matching associated with superior graft survival. Additionally, living donor grafts are known to confer superior survival compared to those from deceased donors. The purpose of this study is to report our multi-decade institutional experience and outcomes for patients who received HLA-identical living donor grafts, which represent the most favorable scenario in kidney transplantation.
View Article and Find Full Text PDFNormothermic machine perfusion (NMP) provides clinicians an opportunity to assess marginal livers before transplantation. However, objective criteria and point-of-care (POC) biomarkers to predict risk and guide decision making are lacking. In this investigation, we characterized trends in POC biomarkers during NMP and compared primate donation after circulatory death (DCD) livers with short and prolonged warm ischemic injury.
View Article and Find Full Text PDFBackground: Livers from "nonideal" but acceptable donors are underutilized; however, organ procurement organization (OPO) metrics do not assess how OPO-specific practices contribute to these trends. In this analysis, we evaluated nonideal liver donor avoidance or risk aversion among OPOs and within US donation service areas (DSAs).
Methods: Adult donors in the United Network for Organ Sharing registry who donated ≥1 organ for transplantation between 2007 and 2019 were included.
Ex vivo lung perfusion (EVLP) is a novel lung preservation strategy that facilitates the use of marginal allografts; however, it is more expensive than static cold storage (SCS). To understand how preservation method might affect postoperative costs, we compared outcomes and index hospitalization costs among matched EVLP and SCS preserved lung transplant (LTx) recipients at a single, high-volume institution. A total of 22 EVLP and 66 matched SCS LTx recipients were included; SCS grafts were further stratified as either standard-criteria (SCD) or extended-criteria donors (ECD).
View Article and Find Full Text PDFBackground: Six hours was historically regarded as the limit of acceptable ischemic time for lung allografts. However, broader sharing of donor lungs often necessitates use of allografts with ischemic time >6 hours. We characterized the association between ischemic time ≥8 hours and outcomes after lung transplantation using a contemporary cohort from a high-volume institution.
View Article and Find Full Text PDFBackground: Selection of the optimal treatment modality for primary liver cancers remains complex, balancing patient condition, liver function, and extent of disease. In individuals with preserved liver function, liver resection remains the primary approach for treatment with curative intent but may be associated with significant mortality. The purpose of this study was to establish a simple scoring system based on Model for End-stage Liver Disease (MELD) and extent of resection to guide risk assessment for liver resections.
View Article and Find Full Text PDFUnlabelled: Explantation of native viscera in multivisceral transplant candidates, particularly in those with extensive portomesenteric thrombosis (PMT), carries considerable morbidity due to extensive vascularized adhesions. Preemptive visceral angioembolization has been previously described as a technique to minimize excessive blood loss during mobilization of the native viscera but is not well described specifically in patients with extensive PMT.
Methods: In a series of 5 patients who underwent mutivisceral transplant for PMT from June 2015 to November 2018, we performed preoperative superior mesenteric, splenic, and hepatic artery embolization to reduce blood loss during explanation and evaluated the blood loss and blood product utilization, as well as 30-day rates of infectious complications.
Historically in the United States, kidneys for simultaneous liver-kidney transplantation (SLKT) candidates were allocated with livers, prioritizing SLKT recipients over much of the kidney waiting list. A 2017 change in policy delineated renal function criteria for SLKT and implemented a safety net for kidney-after-liver transplantation. We compared the use and outcomes of SLKT and kidney-after-liver transplant with the 2017 policy.
View Article and Find Full Text PDFObjective: Ex vivo lung perfusion has emerged as a novel technique to safely preserve lungs before transplantation. Recent studies have demonstrated an accumulation of inflammatory molecules in the perfusate during ex vivo lung perfusion. These proinflammatory molecules, including damage-associated molecular patterns and inflammatory cytokines, may contribute to acute and chronic allograft dysfunction.
View Article and Find Full Text PDFBackground: "Textbook outcome" (TO) is a novel composite quality measure that encompasses multiple postoperative endpoints, representing the ideal "textbook" hospitalization for complex surgical procedures. We defined TO for kidney transplantation using a cohort from a high-volume institution.
Methods: Adult patients who underwent isolated kidney transplantation at our institution between 2016 and 2019 were included.
Liver grafts from pediatric donors represent a small fraction of grafts transplanted into adult recipients, and their use in adults requires special consideration of donor size to prevent perioperative complications. In the past, graft weight or volume ratios have been adopted from the living donor liver transplant literature to guide clinicians; however, these metrics are not regularly available to surgeons accepting deceased donor organs. In this study, we evaluated all pediatric-to-adult liver transplants in the United Network for Organ Sharing Standard Transplant Analysis and Research database from 1987 to 2019, stratified by donor age and donor-recipient height mismatch ratio (HMR; defined as donor height/recipient height).
View Article and Find Full Text PDFBackground: Outcomes after kidney transplantation (KTx) remain limited by delayed graft function (DGF) and acute rejection. Non-invasive biomarkers may help identify patients at increased risk for these events. We examined the association between the systemic immune-inflammation index (SII), a novel inflammatory biomarker, and outcomes after KTx and evaluated its ability to predict post-transplant prognosis.
View Article and Find Full Text PDFLight-controlled sequential photolysis from a single nanoparticle is a challenge for controlled release. A wavelength-selective sequential photolysis from single gold nanoparticles is reported for the first time. In particular, it is also demonstrated that such nanoparticle can be used to sequentially release two payloads in living cells.
View Article and Find Full Text PDFObjective: We sought to compare kidney transplantation outcomes between Veterans Affairs (VA) and non-VA transplant centers.
Summary Background Data: Transplant care at the VA has previously been scrutinized due to geographic and systematic barriers. The recently instituted MISSION Act entered effect June 6th, 2019, which enables veteran access to surgical care at civilian hospitals if certain eligibility criteria are met.
Transpl Infect Dis
December 2020
There is an accumulating body of literature surrounding the impact of COVID-19 infection in solid organ transplant recipients. The aim of this review was to summarize the existing literature specifically in kidney transplant (KTx) recipients, with an emphasis on the epidemiology, clinical presentation, laboratory findings, post-operative outcomes, and therapeutic strategies currently employed. We identified thirty-seven studies published between January 1, 2020, and June 10, 2020, that were included in our analysis.
View Article and Find Full Text PDFThe cellular mechanisms underlying impaired function of aged liver grafts have not been fully elucidated, but mitochondrial dysfunction appears to be contributory. Sirtuin1 has been identified as a key mediator of mitochondrial recovery following ischemia-reperfusion injury. The purpose of this study was to determine whether differences exist in sirtuin-1 expression/activity in old vs.
View Article and Find Full Text PDF