Donor Electrocardiogram Associations With Cardiac Dysfunction, Heart Transplant Use, and Survival: The Donor Heart Study.

Background: Potential organ donors often exhibit abnormalities on electrocardiograms (ECGs) after brain death, but the physiological and prognostic significance of such abnormalities is unknown.

Objectives: This study sought to characterize the prevalence of ECG abnormalities in a nationwide cohort of potential cardiac donors and their associations with cardiac dysfunction, use for heart transplantation (HT), and recipient outcomes.

Methods: The Donor Heart Study enrolled 4,333 potential cardiac organ donors at 8 organ procurement organizations across the United States from 2015 to 2020.

Left Ventricular Dysfunction Associated With Brain Death: Results From the Donor Heart Study.

Background: Left ventricular dysfunction in potential donors meeting brain death criteria often results in nonuse of donor hearts for transplantation, yet little is known about its incidence or pathophysiology. Resolving these unknowns was a primary aim of the DHS (Donor Heart Study), a multisite prospective cohort study.

Methods: The DHS enrolled potential donors by neurologic determination of death (n=4333) at 8 organ procurement organizations across the United States between February 2015 and May 2020.

The Effect of Normothermic Machine Perfusion on the Immune Profile of Donor Liver.

Background: Normothermic machine perfusion (NMP) allows viability assessment and potential resuscitation of donor livers prior to transplantation. The immunological effect of NMP on liver allografts is undetermined, with potential implications on allograft function, rejection outcomes and overall survival. In this study we define the changes in immune profile of human livers during NMP.

Donor leukocyte trafficking during human ex vivo lung perfusion.

Background: Ex vivo lung perfusion (EVLP) is used to assess and preserve lungs prior to transplantation. However, its inherent immunomodulatory effects are not completely understood. We examine perfusate and tissue compartments to determine the change in immune cell composition in human lungs maintained on EVLP.

Challenges encountered in conducting donor-based research: Lessons learned from the Donor Heart Study.

Solid organ transplantation continues to be constrained by a lack of suitable donor organs. Advances in donor management and evaluation are needed to address this shortage, but the performance of research studies in deceased donors is fraught with challenges. Here we discuss several of the major obstacles we faced in the conduct of the Donor Heart Study-a prospective, multi-site, observational study of donor management, evaluation, and acceptance for heart transplantation.

Deceased organ donor screening for human immunodeficiency virus, hepatitis B virus and hepatitis C virus: Discordant serology and nucleic acid testing results.

Background: Before the 2014 policy change pertaining to infectious disease screening, many organ procurement organizations (OPOs) were supplementing serologic screening of deceased organ donors with nucleic acid testing (NAT) for human immunodeficiency virus (HIV-1), hepatitis B virus (HBV), and hepatitis C virus (HCV). The number of seronegative, NAT-positive donors has not been directly measured.

Methods: HIV, HBV, and HCV screening results of 11 229 donor referrals evaluated from 2010 to 2013 were obtained from 3 OPO-affiliated laboratories, capturing 35% of all donors in the United States.

Flow cytometry crossmatch reactivity with pronase-treated T cells induced by non-HLA autoantibodies in human immunodeficiency virus-infected patients.

Pronase treatment is used in the flow cytometry crossmatch (FCXM) to prevent nonspecific antibody binding on B cells. However, we have observed unexpected positive results with pronase-treated T cells in human immunodeficiency virus (HIV)-infected patients. In this study, 25 HIV-infected patients without HLA antibodies were tested with pronase-treated and nontreated cells.

Improving syphilis screening in deceased organ donors.

Background: Current U.S. policy requires screening of all deceased organ donors for syphilis infection.

Mechanism of accommodation in a sensitized human leukocyte antigen transgenic murine cardiac transplant model.

Background: Presence of donor-specific antibodies (Abs) is detrimental to posttransplant allograft function. Some sensitized recipients have successfully undergone transplantation after pretransplant conditioning regimen using plasmapheresis and/or intravenous immunoglobulin therapy, but underlying mechanisms that confer such allograft protection are undefined.

Methods: We developed a single human leukocyte antigen (HLA)-mismatched heterotopic murine heart transplant model (HLA-A2 into HLA-A2-sensitized-C57BL/6) to determine whether pretreatment of donors with low concentration of HLA class I (W6/32) or control Ab (C1.

Virtual crossmatch by identification of donor-specific anti-human leukocyte antigen antibodies by solid-phase immunoassay: a 30-month analysis in living donor kidney transplantation.

Selection of donors for kidney transplantation depends on accurate prediction of risk factors for immunologic rejection. Historically, cytotoxicity crossmatch (CXM) examining lysis of donor cells by preformed anti-human leukocyte antigen (HLA) antibodies (Abs) has been considered the best predictor of immunologic rejection. However, there is much interest in defining anti-HLA Ab specificity in recipient sera by immunoassay to predict crossmatch results and aid in donor selection.

Psychiatric disorders: are they an absolute contraindication to living donation?

Little information has been published about the suitability of candidates for living organ donation who have a past or current psychiatric diagnosis. A retrospective review of 445 living donor kidney transplants performed at Barnes-Jewish Hospital's transplant center from 1995 to 2005 disclosed 42 donor candidates with such a history, prompting detailed psychological evaluation. Although 41 candidates (10% of the donor pool) met criteria for 1 or more psychiatric diagnoses, none were considered psychologically unfit for donation.

Living donor renal transplantation in the presence of donor-specific human leukocyte antigen antibody detected by solid-phase assay.

Presensitization of donor human leukocyte antigens (HLA) demonstrated through a positive crossmatch is detrimental to allograft function and best avoided through donor exclusion. The clinical significance of alloantibody detectable by sensitive solid-phase assay is not completely defined and is the focus of this study. Pretransplant sera from 64 consecutive living-donor renal transplant recipients were screened by enzyme-linked immunosorbent assay (ELISA) and Luminex assays.

A significant role for histocompatibility in human islet transplantation.

Background: In recent years, transplantation of islets and pancreas has become a viable option for patients debilitated with type I diabetes. The success of islet transplantation has been attributed to the ability to isolate high quality islets for transplantation and capacity to maintain the recipient's immunosuppressive levels within a specific target range following transplantation. The purpose of this study was to determine the role of pretransplant sensitization to human leukocyte antigen (HLA) in islet transplantation.

HLA class I antibody mediated accommodation of endothelial cells via the activation of PI3K/cAMP dependent PKA pathway.

Allografts transplanted across ABO incompatibility or human leucocyte antigen (HLA)-sensitization undergoes antibody (Ab) mediated hyperacute rejection. Depleting anti-graft Ab from the recipient by plasmapheresis prior to transplantation can prevent this Ab-mediated rejection. Under these conditions, allografts have been shown to function even when the Ab rebound in the recipients.

Liver transplantation for hepatocellular carcinoma: expanding special priority to include stage III disease.

Hypothesis: After liver transplantation, patients with stage III hepatocellular carcinoma (HCC) experience survivals similar to those of patients with less advanced disease and of matched control subjects.

Design: Retrospective review of prospectively collected database.

Setting: University hospital.

Hospital-independent organ recovery from deceased donors: a two-year experience.

Early experience with deceased donor (DD) organ recovery outside of the hospital setting was found to be safe, efficient and cost effective. A 2-year experience under current practice protocols implemented to further process improvements is now reviewed. From December 1, 2001 to December 31, 2003, 123 criteria eligible DDs were transferred from local and regional hospitals to the Mid-America Transplant Services (MTS) facility for organ and tissue recovery.

Cyclosporine minimization and cost reduction in renal transplant recipients receiving a C2-monitored, cyclosporine-based quadruple immunosuppressive regimen.

Background: Targeting 2-hr postdose cyclosporine (C2) levels to 1,000 to 1,700 mg/dL during the first 6 months after renal transplantation is recommended for triple immunosuppressive regimens. This trial determines whether lower C2 levels could be targeted safely in de novo kidney transplant recipients under a quadruple regimen compared with a similar cohort monitored with trough (C0) levels.

Methods: This single-center, sequential, cohort-designed trial included patients who received Thymoglobulin, corticosteroids, an antimetabolite, and cyclosporine monitored by C2 (n=50) or C0 (n=50).

Pirfenidone inhibits obliterative airway disease in a murine heterotopic tracheal transplant model.

Background: Chronic lung allograft rejection in the form of bronchiolitis obliterans syndrome and its histopathologic correlate, obliterative bronchiolitis (OB), are a major source of morbidity and mortality after lung transplantation. Murine heterotopic tracheal transplants into fully allogeneic mismatched recipients develop obliterative airway disease (OAD), which is a suitable model of OB. Using this murine heterotopic tracheal allograft model, we evaluated the effect of pirfenidone, a novel antifibrotic agent, on the development of OAD.

Cadaveric-donor organ recovery at a hospital-independent facility.

Background: Of the many logistic issues addressed throughout the cadaveric organ donation process, timely access to the operating theater for surgical recovery of organs and tissues can be one of the most problematic. Delay in recovery adds to cost, risks organ viability, and compounds donor family anguish with compromise to donation consent.

Methods: From March 1 to November 30, 2001, 25 cadaveric donors were selected and successfully transferred from local donor critical care units to an off-site facility, which was constructed, equipped, and staffed to allow surgical recovery of organs and tissues.

Prospective, pilot, open-label, short-term study of conversion to leflunomide reverses chronic renal allograft dysfunction.

Leflunomide (LEF) is a synthetic isoxazole derivative with anti-inflammatory and antiviral properties, which has been reported to prevent acute rejection and delay progression of chronic allograft nephropathy (CAN) in animal models. We performed a pilot, crossover trial in 22 renal transplant recipients who were converted from azathioprine (AZA) or mycophenolate mofetil (MMF) to LEF in an effort to slow progression of renal dysfunction [deteriorating renal function (n = 5), cyclosporine (CyA) nephrotoxicity (n = 4) or biopsy-proven CAN (n = 13)]. Baseline maintenance immunosuppression consisted of CyA, AZA or MMF and prednisone.