Effect of donor genotype on patient survival after liver transplant: a retrospective cohort study.

Background: Several genetic variants are associated with chronic liver disease. The role of these variants in outcomes after liver transplantation (LT) is uncertain. The aim of this study was to determine if donor genotype at risk-associated variants in (rs738409 C>G, p.

Normothermic machine perfusion for older transplant recipients.

Introduction: Elderly patients (≥65 years old) are increasingly undergoing liver transplantation and are more likely to be removed from the waitlist. Normothermic machine perfusion (NMP) holds promise in expanding the number of livers available for transplant and improving outcomes for marginal donors and recipients. We aimed to determine the impact of NMP on outcomes in elderly recipients at our institution and nationally using the UNOS database.

No Stone Left Unturned: Utilization of an Organ Procurement Organization Donor Surgeon at Procurement Reduces Discards of Marginal Liver Allografts.

Background: The recent trend of organ procurement organizations (OPOs) employing independent surgeons for organ procurement has been developed with the goal of improving the supply of suitable organs for transplantation. We investigated the effects that the addition of an OPO-employed, organ-procurement specialist has on liver allograft discard rate, marginal organ utilization, and graft survival.

Methods: Organ Procurement and Transplant Network and OPO data were retrospectively studied between April 1, 2014' and July 31, 2019' within the Southwest Transplant Alliance donor service area.

Outcomes of Simultaneous Liver-Kidney Transplantation Using Kidneys of Deceased Donors With Acute Kidney Injury.

Outcomes from simultaneous liver-kidney transplantation (SLKT) when using kidneys from donors with acute kidney injury (AKI) have not been studied. We studied 5344 SLKTs between May 1, 2007, and December 31, 2019, by using Organ Procurement and Transplantation Network registry data supplemented with United Network for Organ Sharing-DonorNet data. Designating a donor as having AKI required by definition that the following criteria were met: (1) the donor's condition aligned with the Kidney Disease: Improving Global Outcomes (KDIGO) international consensus guidelines and the terminal serum creatinine (Scr) level was ≥1.

Impact of Portable Normothermic Blood-Based Machine Perfusion on Outcomes of Liver Transplant: The OCS Liver PROTECT Randomized Clinical Trial.

Importance: Ischemic cold storage (ICS) of livers for transplant is associated with serious posttransplant complications and underuse of liver allografts.

Objective: To determine whether portable normothermic machine perfusion preservation of livers obtained from deceased donors using the Organ Care System (OCS) Liver ameliorates early allograft dysfunction (EAD) and ischemic biliary complications (IBCs).

Design, Setting, And Participants: This multicenter randomized clinical trial (International Randomized Trial to Evaluate the Effectiveness of the Portable Organ Care System Liver for Preserving and Assessing Donor Livers for Transplantation) was conducted between November 2016 and October 2019 at 20 US liver transplant programs.

Trends in utilization of deceased donor kidneys based on hepatitis C virus status and impact of public health service labeling on discard.

Background: Kidneys from deceased donors infected with hepatitis C virus (HCV) are underutilized. Most HCV virus-infected donors are designated as Public Health Service increased donors (PHS-IR). Impact of PHS and HCV designations on discard is not well studied.

Somatic Mutations Increase Hepatic Clonal Fitness and Regeneration in Chronic Liver Disease.

Normal tissues accumulate genetic changes with age, but it is unknown if somatic mutations promote clonal expansion of non-malignant cells in the setting of chronic degenerative diseases. Exome sequencing of diseased liver samples from 82 patients revealed a complex mutational landscape in cirrhosis. Additional ultra-deep sequencing identified recurrent mutations in PKD1, PPARGC1B, KMT2D, and ARID1A.

Two-stage liver transplant for ruptured hepatic adenoma: A case report.

Background: Only one case of liver transplantation for hepatic adenoma has previously been reported for patients with rupture and uncontrolled hemorrhage. We present the case of a massive ruptured hepatic adenoma with persistent hemorrhagic shock and toxic liver syndrome which resulted in a two-stage liver transplantation. This is the first case of a two-stage liver transplantation performed for a ruptured hepatic adenoma.

A Cellular Anatomy of the Normal Adult Human Prostate and Prostatic Urethra.

A comprehensive cellular anatomy of normal human prostate is essential for solving the cellular origins of benign prostatic hyperplasia and prostate cancer. The tools used to analyze the contribution of individual cell types are not robust. We provide a cellular atlas of the young adult human prostate and prostatic urethra using an iterative process of single-cell RNA sequencing (scRNA-seq) and flow cytometry on ∼98,000 cells taken from different anatomical regions.

Survey of Liver Transplantation Practices for Severe Acute Alcoholic Hepatitis.

Liver transplantation (LT) has a demonstrated survival benefit in select patients with severe acute alcoholic hepatitis (SAH) who do not respond to steroids, but prior studies suggest low adoption among US LT centers. Our study explored current perceptions and practice patterns of LT for SAH in the United States. We administered a Web-based survey to medical directors of US LT centers between May and October of 2017 to characterize practice patterns and perceptions of LT for SAH.

SIMULTANEOUS LIVER KIDNEY TRANSPLANTATION IN LIVER TRANSPLANT CANDIDATES WITH RENAL DYSFUNCTION: IMPORTANCE OF CREATININE LEVELS, DIALYSIS, AND ORGAN QUALITY IN SURVIVAL.

Background: The survival benefit from simultaneous liver-kidney transplantation (SLK) over liver transplant alone (LTA) in recipients with moderate renal dysfunction is not well understood. Moreover, the impact of deceased donor organ quality in SLK transplant survival has not been well described in the literature.

Methods: The Scientific Registry of Transplant Recipients was studied for adult recipients receiving LTA (N=2,700) or SLK (N=1,361) transplantation with moderate renal insufficiency between 2003 and 2013.

Acute Rejection Rates and Graft Outcomes According to Induction Regimen among Recipients of Kidneys from Deceased Donors Treated with Tacrolimus and Mycophenolate.

Background And Objectives: IL-2 receptor antagonist (IL2-RA) is recommended as a first-line agent for induction therapy in renal transplantation. However, this remains controversial in deceased donor renal transplantation (DDRT) maintained on tacrolimus (TAC)/mycophenolic acid (MPA) with or without steroids.

Design, Setting, Participants, & Measurements: We studied the United Network for Organ Sharing Registry for patients receiving DDRT from 2000 to 2012 maintained on TAC/MPA at transplantation hospital discharge (n=74,627) to compare outcomes of IL2-RA and other induction agents.

Utilization of hepatitis B core antibody-positive donor liver grafts.

Background: The inclusion of hepatitis B core antibody-positive (HBcAb+) liver donors is a strategy utilized to increase organ availability. This study examined HBcAb+ transplantation practices to identify specific factors influencing outcomes.

Methods: Twenty-five HBcAb+ liver transplants were identified retrospectively among 868 adult transplants performed between 1 January 1997 and 31 December 2009.

Regulatory T cells suppress antigen-driven CD4 T cell reactivity following injury.

Injury initiates local and systemic host responses and is known to increase CD4 Treg activity in mice and humans. This study uses a TCR transgenic T cell adoptive transfer approach and in vivo Treg depletion to determine specifically the in vivo influence of Tregs on antigen-driven CD4 T cell reactivity following burn injury in mice. We report here that injury in the absence of recipient and donor Tregs promotes high antigen-driven CD4 T cell expansion and increases the level of CD4 T cell reactivity.

A case of external iliac arteriovenous fistula and high-output cardiac failure after endovenous laser treatment of great saphenous vein.

Valvular incompetence in the great saphenous vein (GSV) is the most common cause of superficial venous insufficiency and symptomatic varicose vein development. Recently, less invasive modalities such as foam sclerotherapy, radiofrequency ablation (RFA), and endovenous laser treatment (EVLT) have gained popularity in the treatment of saphenofemoral junction and saphenous truncal incompetence over the traditional approach of surgical ligation and stripping. Here, we present the case of a 32-year-old woman who underwent EVLT and was diagnosed subsequently with ipsilateral external iliac arteriovenous (AV) fistula and high-output cardiac failure.

Murine dendritic cell antigen-presenting cell function is not altered by burn injury.

Severe injury disrupts normal immune regulation causing a transient hyperinflammatory reaction and suppressed adaptive immune function. This report addresses the potential contribution of dendritic cells (DC) to changes in adaptive immune function after injury by specifically measuring injury-induced changes in splenic DC numbers and subsets, cell-surface markers, TLR responses, and APC function. Using a mouse burn injury model, we found that injury did not markedly alter the relative percentage of lymphoid, myeloid, or plasmacytoid DC in the spleens of burn-injured mice.

Injury enhances resistance to Escherichia coli infection by boosting innate immune system function.

Major injury is widely thought to predispose the injured host to opportunistic infections. This idea is supported by animal studies showing that major injury causes reduced resistance to polymicrobial sepsis induced by cecal ligation and puncture. Although cecal ligation and puncture represents a clinically relevant sepsis model, we wanted to test whether injury might also lead to greater susceptibility to peritoneal infection caused by a single common pathogen, Escherichia coli.

Comparison of longitudinal leukocyte gene expression after burn injury or trauma-hemorrhage in mice.

A primary objective of the large collaborative project entitled "Inflammation and the Host Response to Injury" was to identify leukocyte genes that are differentially expressed after two different types of injury in mouse models and to test the hypothesis that both forms of injury would induce similar changes in gene expression. We report here the genes that are expressed in white blood cells (WBCs) and in splenocytes at 2 h, 1 day, 3 days, and 7 days after burn and sham injury or trauma-hemorrhage (T-H) and sham T-H. Affymetrix Mouse Genome 430 2.

Increased CD4+ CD25+ T regulatory cell activity in trauma patients depresses protective Th1 immunity.

Objectives: We recently reported increased CD4 CD25 T regulatory (Treg) activity after burn injury in mice. This study sought to determine if Tregs mediate the reduction in TH1-type immunity after serious injury in man and if Treg function is altered by injury.

Methods: Peripheral blood was withdrawn from 19 consenting adult patients (35.

Platelet depletion in mice increases mortality after thermal injury.

Platelets play a fundamental role in maintaining hemostasis and have been shown to participate in innate and adaptive immunity. However, the role of platelets in the immune response to injury remains undefined. We tested the importance of platelets in the host response to serious injury in a newly developed platelet-deficient mouse model.

Enhanced TLR4 reactivity following injury is mediated by increased p38 activation.

Severe injury primes the innate-immune system for increased Toll-like receptor 4 (TLR4)-induced proinflammatory cytokine production by macrophages. In this study, we examined changes in TLR4 signaling pathways in splenic macrophages from burn-injured or sham mice to determine the molecular mechanism(s) responsible for the increased TLR4 responsiveness. Using flow cytometry and specific antibodies, we first looked for injury-induced changes in the expression levels of several TLR-associated signaling molecules.