Banff Histopathological Consensus Criteria for Preimplantation Kidney Biopsies.

The Banff working group on preimplantation biopsy was established to develop consensus criteria (best practice guidelines) for the interpretation of preimplantation kidney biopsies. Digitally scanned slides were used (i) to evaluate interobserver variability of histopathologic findings, comparing frozen sections with formalin-fixed, paraffin-embedded tissue of wedge and needle core biopsies, and (ii) to correlate consensus histopathologic findings with graft outcome in a cohort of biopsies from international medical centers. Intraclass correlations (ICCs) and univariable and multivariable statistical analyses were performed.

IGF-1 and Chondroitinase ABC Augment Nerve Regeneration after Vascularized Composite Limb Allotransplantation.

Impaired nerve regeneration and inadequate recovery of motor and sensory function following peripheral nerve repair remain the most significant hurdles to optimal functional and quality of life outcomes in vascularized tissue allotransplantation (VCA). Neurotherapeutics such as Insulin-like Growth Factor-1 (IGF-1) and chondroitinase ABC (CH) have shown promise in augmenting or accelerating nerve regeneration in experimental models and may have potential in VCA. The aim of this study was to evaluate the efficacy of low dose IGF-1, CH or their combination (IGF-1+CH) on nerve regeneration following VCA.

Subclinical Rejection in Renal Transplantation: Reappraised.

Short-term outcomes in renal transplantation have improved significantly in the past few years. However, the improvement in long-term outcomes has been modest. The reasons for graft failure beyond the first year of transplantation have been attributed to several different factors.

SIRT1 Disruption in Human Fetal Hepatocytes Leads to Increased Accumulation of Glucose and Lipids.

There are unprecedented epidemics of obesity, such as type II diabetes and non-alcoholic fatty liver diseases (NAFLD) in developed countries. A concerning percentage of American children are being affected by obesity and NAFLD. Studies have suggested that the maternal environment in utero might play a role in the development of these diseases later in life.

Re-Examining Risk of Repeated HLA Mismatch in Kidney Transplantation.

Kidney retransplantation is a risk factor for decreased allograft survival. Repeated mismatched HLA antigens between first and second transplant may be a stimulus for immune memory responses and increased risk of alloimmune damage to the second allograft. Historical data identified a role of repeated HLA mismatches in allograft loss.

Liver transplantation for treatment of severe S-adenosylhomocysteine hydrolase deficiency.

A child with severe S-adenosylhomocysteine hydrolase (AHCY) deficiency (AHCY c.428A>G, p.Tyr143Cys; c.

Kidney Transplant Survival: Transforming Early Post-Transplant Opportunities to Long-Term Success.

Substantial strides have been made in improving the short-term success after kidney transplantation. Although there has been some progress, there has not been a robust improvement with respect to long-term outcomes. However, there remain many potentially modifiable transplant-specific risks to long-term patient and graft survival.

Multi-institutional Study of Outcomes After Pediatric Heart Transplantation: Candidate Gene Polymorphism Analysis of ABCC2.

Objectives: Earlier studies have indicated that the pharmacokinetics of mycophenolic acid (MPA) is influenced by polymorphisms of ABCC2, which encodes for the membrane transporter MRP2. The ABCC2 rs717620 A allele has been associated with enterohepatic recirculation of MPA, and our previous work had correlated the discontinuance of MPA with this allele in pediatric heart transplant patients. Therefore, we hypothesized that the ABCC2 rs717620 A allele would be associated with poorer outcomes including rejection with hemodynamic compromise (RHC), graft failure, and death in the pediatric heart transplant (PHTx) population receiving MPA.

Immunologic human renal allograft injury associates with an altered IL-10/TNF-α expression ratio in regulatory B cells.

Human B cells with immunoregulatory properties in vitro (Bregs) have been defined by the expression of IL-10 and are enriched in various B-cell subsets. However, proinflammatory cytokine expression in B-cell subsets is largely unexplored. We examined the cytokine profiles of human PBMCs and found that subsets of CD24(hi)CD38(hi) transitional B cells (TrBs), CD24(hi)CD27(+) memory B cells, and naïve B cells express IL-10 and the proinflammatory cytokine TNF-α simultaneously.

A switch in the source of ATP production and a loss in capacity to perform glycolysis are hallmarks of hepatocyte failure in advance liver disease.

Background & Aims: The cause of hepatic failure in the terminal stages of chronic injury is unknown. Cellular metabolic adaptations in response to the microenvironment have been implicated in cellular breakdown.

Methods: To address the role of energy metabolism in this process we studied mitochondrial number, respiration, and functional reserve, as well as cellular adenosine-5'-triphosphate (ATP) production, glycolytic flux, and expression of glycolysis related genes in isolated hepatocytes from early and terminal stages of cirrhosis using a model that produces hepatic failure from irreversible cirrhosis in rats.

Gene polymorphisms impact the risk of rejection with hemodynamic compromise: a multicenter study.

Background: Rejection with hemodynamic compromise (RHC) is associated with high mortality in heart recipients. This study investigates the association between genetic polymorphisms and RHC in pediatric heart recipients.

Methods: Data from 532 pediatric heart recipients from six centers in the Pediatric Heart Transplant Study were analyzed for time to RHC by recipient race, age at transplantation, and genotype at 13 genetic polymorphisms (TNF-α A-308G, IL-6 G-174C, INF-γ T+874A, IL-10 G-1082A, C-819T, and C-592A; FAS A-670G, FASL C-843T, and ACE I/D; and VEGF A-2578C, C-1451T, C+405G, and -2549 I/D).

Barriers to the successful treatment of liver disease by hepatocyte transplantation.

Management of patients with hepatic failure and liver-based metabolic disorders is complex and expensive. Hepatic failure results in impaired coagulation, altered consciousness and cerebral function, a heightened risk of multiple organ system failure, and sepsis [1]. Such manifold problems are only treatable today and for the foreseeable future by transplantation.

Critical role of interferon regulatory factor-1 in murine liver transplant ischemia reperfusion injury.

Interferon regulatory factor-1 (IRF-1) is a transcription factor that regulates gene expression during immunity. We hypothesized that IRF-1 plays a pivotal role in liver transplant (LTx) ischemia/reperfusion (I/R) injury. Mouse orthotopic LTx was conducted after 24 hours cold storage in University of Wisconsin (UW) solution in wildtype (WT) C57BL/6 and IRF-1 knockout (KO) mice.

Lymphoproliferative disorders and de novo malignancies in intestinal and multivisceral recipients: improved outcomes with new outlooks.

Background: Early experience with intestinal and multivisceral transplantation was plagued with high risk of rejection and posttransplant lymphoproliferative disorders (PTLD). To improve outcome, innovative management and immunosuppressant strategies were sequentially evolved.

Methods: With initiation of the program in 1990, serial monitoring of Epstein-Barr-Viral load was introduced in 1994 with adoption of preemptive antiviral therapy.

Genotypic variation and phenotypic characterization of granzyme B gene polymorphisms.

Background: Granzyme B has been associated with allograft rejection in solid organ transplantation. Single nucleotide polymorphisms (SNPs) in the granzyme B gene might impact its expression. The aims of this study were (1) to establish the frequency of two granzyme B SNPs (A-295G; Q-55R) in pediatric heart transplant (PHTx) recipients and (2) to determine their phenotypic expression in healthy individuals.

Clinical impact of cytokine and growth factor genetic polymorphisms in thoracic organ transplantation.

Demographic and clinical risk factors may only partially predict short- and long-term outcomes after thoracic transplantation. The interindividual variability seen in rejection profiles could be related to the recipient's or donor's genetic background. Rejection, either acute or chronic, elicits an alloimmune response that involves a complex network of cytokines, growth factors, adhesion molecules, and other molecules, which may modulate the immune response toward rejection or, conversely, mediate graft acceptance.

Effect of cytokine and pharmacogenomic genetic polymorphisms in transplantation.

Consolidating the information that we have on pharmacogenetics and on cytokine genetics to produce patient-oriented individualized drug regimens is an important challenge in transplantation medicine. Using a multi-variant approach based on genetic profile and other relevant clinical factors a score system may be developed to predict the severity of rejection, infection, or other complications associated with transplantation. The ultimate goal of these studies is to improve patient outcome through individualized drug regimens.

Genetic polymorphisms impact the risk of acute rejection in pediatric heart transplantation: a multi-institutional study.

Objective: The objective of this study was to determine the association between the genetic polymorphisms of proinflammatory and regulatory cytokines and long-term rates of repeat and late acute rejection episodes in pediatric heart transplant (PHTx) recipients.

Methods: Three hundred twenty-three PHTx recipients: 205 White non-Hispanic, 43 Black non-Hispanic, and 75 Hispanic were analyzed for time to first repeat and late acute rejection episodes by race, age at transplantation, and gene polymorphism (interleukin [IL]-6, -174 G/C, IL-10, -1082 G/A, -819 C/T, 592 C/A; vascular endothelial growth factor (VEGF) -2578 C/A, -460 C/T, +405 C/G; tumor necrosis factor alpha (TNF-alpha)-308 G/A).

Results: Recipient black race and older age at transplant were risk factors for both repeat and late rejections, though black race was more significantly related to late rejection (P=0.

Outcomes after transplantation of deceased-donor kidneys with rising serum creatinine.

The increasing number of candidates for kidney transplantation and relatively unchanged deceased-donor pool has led to expansion in the criteria for donor acceptability. Outcomes of kidneys from donors with progressively rising creatinine values have not been reported. Patients transplanted between September 2003 and August 2006 with kidneys from donors with peak creatinine levels >2.

Recovery of functional memory T cells in lung transplant recipients following induction therapy with alemtuzumab.

Profound T-cell depletion with the monoclonal antibody alemtuzumab facilitates reduced maintenance immunosuppression in abdominal and lung transplantation. While the phenotype of the post-depletional T cells has been characterized, little is known about their function. In the present study, global and CMV-specific T-cell function was assessed longitudinally in 23 lung transplant (LTx) recipients using T-cell assays (ImmuKnow and T Cell Memory, Cylex, Columbia, MD) during the first year posttransplant after induction therapy.

Effects of lipodystrophy on quality of life and depression in HIV-infected men on HAART.

The aim of the study was a prospective assessment of the possible consequences of a diagnosis of lipodystrophy on health-related quality of life (HRQL) and depressive symptomatology in HIV-seropositive men who have sex with men. A standardized physical assessment for lipodystrophy was introduced within a prospective study in April 1999. Over a 2-year follow- up, 37 HIV-seropositive men who met the criteria for lipodystrophy were longitudinally compared to 92 HIV-seropositive men without lipodystrophy and 88 HIV-seronegative men on measures of HRQL and depression.

Pathophysiologic observations and histopathologic recognition of the portal hyperperfusion or small-for-size syndrome.

In an attempt to more completely define the histopathologic features of the portal vein hyperperfusion or small-for-size syndrome (PHP/SFSS), we strictly identified 5 PHP/SFSS cases among 39 (5/39; 13%) adult living donor liver transplants (ALDLT) completed between 11/01 and 09/03. Living donor segments consisting of 3 right lobes, 1 left lobe, and 1 left lateral segment, with a mean allograft-to-recipient weight ratio (GRWR) of 1.0 +/- 0.