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https://www.readbyqxmd.com/read/27907919/the-impact-of-health-care-appointment-non-adherence-on-graft-outcomes-in-kidney-transplantation
#1
David J Taber, James N Fleming, Cory E Fominaya, Mulugeta Gebregziabher, Kelly J Hunt, Titte R Srinivas, Prabhakar K Baliga, John W McGillicuddy, Leonard E Egede
BACKGROUND: Non-adherence to medication is a well-studied and known cause of late allograft loss, but it is difficult to measure and prospectively monitor. The aim of this study was to assess if appointment non-adherence was correlated with medication non-adherence and a predictor of graft outcomes. METHODS: This was a longitudinal cohort study that used the National United States Renal Data System and veterans affairs health records data with time-to-event analyses conducted to assess the impact on graft and patient survival...
December 2, 2016: American Journal of Nephrology
https://www.readbyqxmd.com/read/27903231/new-analogues-of-mycophenolic-acid
#2
Agnieszka Głowacka, Michal Prejs, Grzegorz Cholewinski, Krystyna Dzierzbicka
Mycophenolic acid (MPA) possesses antibacterial, antifungal, antiviral, immunosuppressive and anticancer properties. It is a non-competitive and reversible inhibitor of dehydrogenase inosine-5'-monophosphate (IMPDH) [1,2]. This compound belongs to the immunosuppressive drugs used for the prevention of both acute and chronic transplant rejection [3]. Until now clinically have been used two derivatives of MPA: mycophenolate mofetil (MMF, CellCept) and mycophenolate sodium (MPS, Myfortic). They cause, similar to MPA, although at lower degree, the side effects such as vomiting, abdominal pain, diarrhea, nausea, gastrointestinal, urogenital tract, blood or nervous system disorders...
November 29, 2016: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/27898719/myocardial-gene-expression-profiling-to-predict-and-identify-cardiac-allograft-acute-cellular-rejection-the-get-study
#3
Diane Bodez, Hakim Hocini, Nicolas Tchitchek, Pascaline Tisserand, Nicole Benhaiem, Caroline Barau, Mounira Kharoubi, Aziz Guellich, Soulef Guendouz, Costin Radu, Jean-Paul Couetil, Bijan Ghaleh, Jean-Luc Dubois-Randé, Emmanuel Teiger, Luc Hittinger, Yves Levy, Thibaud Damy
AIMS: Serial invasive endomyocardial biopsies (EMB) remain the gold standard for acute cellular rejection (ACR) diagnosis. However histological grading has several limitations. We aimed to explore the value of myocardial Gene Expression Profiling (GEP) for diagnosing and identifying predictive biomarkers of ACR. METHODS: A case-control study nested within a retrospective heart transplant patients cohort included 126 patients with median (IQR) age 50 (41-57) years and 111 (88%) males...
2016: PloS One
https://www.readbyqxmd.com/read/27898464/donor-derived-exosomes-the-trick-behind-the-semidirect-pathway-of-allorecognition
#4
Adrian E Morelli, William Bracamonte-Baran, William J Burlingham
PURPOSE OF REVIEW: The passenger leukocyte hypothesis predicts that after transplantation, donor antigen-presenting cells (APCs) from the graft present donor MHC molecules to directly alloreactive T cells in lymphoid organs. However, in certain transplantation models, recent evidence contradicts this long-standing concept. New findings demonstrate that host, instead of donor, APCs play a prominent role in allosensitization against donor MHC molecules via the semidirect pathway. A similar mechanism operates in development of T-cell split tolerance to noninherited maternal antigens...
November 24, 2016: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/27898463/transplantation-tolerance-after-allograft-rejection
#5
Michelle L Miller, Maria-Luisa Alegre, Anita S Chong
PURPOSE OF REVIEW: Although elusive for many decades, transplantation tolerance can now be achieved in the clinic. This has prompted follow-up investigations into its stability and longevity, as well as into barriers to its induction, which include memory T and B cells. RECENT FINDINGS: Clinical observations reveal that transplantation tolerance can be induced in adult recipients and that even episodes of acute rejection do not preclude successful weaning from immunosuppression to reveal tolerance...
November 24, 2016: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/27898462/recent-advances-in-allograft-vasculopathy
#6
Jonathan Merola, Daniel D Jane-Wit, Jordan S Pober
PURPOSE OF REVIEW: Despite considerable advances in controlling acute rejection, the longevity of cardiac and renal allografts remains significantly limited by chronic rejection in the form of allograft vasculopathy. This review discusses recently reported mechanistic insights of allograft vasculopathy pathogenesis as well as recent clinical evaluations of new therapeutic approaches. RECENT FINDINGS: Although adaptive immunity is the major driver of allograft vasculopathy, natural killer cells mediate vasculopathic changes in a transplanted mouse heart following treatment with donor-specific antibody (DSA)...
November 24, 2016: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/27893617/differential-role-of-b-cells-and-il-17-versus-ifn-%C3%AE-during-early-and-late-rejection-of-pig-islet-xenografts-in-mice
#7
Hee Kap Kang, Shusen Wang, Anil Dangi, Xiaomin Zhang, Amar Singh, Lei Zhang, James M Rosati, Wilma Suarez-Pinzon, Xuelian Deng, Xiaoyan Chen, Edward B Thorp, Bernhard J Hering, Stephen D Miller, Xunrong Luo
BACKGROUND: Xenogeneic islet transplantation is an emerging therapeutic option for diabetic patients. However, immunological tolerance to xenogeneic islets remains a challenge. METHODS: The current study used a pig-to-mouse discordant xenogeneic islet transplant model to examine anti-donor xenogeneic immune responses during early and late rejection, and to determine experimental therapeutic interventions that promote durable pig islet xenograft survival. RESULTS: We found that during early acute rejection of pig islet xenografts, the rejecting hosts exhibited a heavy graft infiltration with B220 B cells and a robust anti-pig antibody production...
November 23, 2016: Transplantation
https://www.readbyqxmd.com/read/27893614/the-presence-of-pretransplant-hla-antibodies-does-not-impact-the-development-of-chronic-lung-allograft-dysfunction-or-clad-related-death
#8
Oscar E Zazueta, Sara E Preston, Anna Moniodis, Sabrina Fried, Miae Kim, Keri Townsend, Isabelle Wood, Steve Boukedes, Indira Guleria, Phillip Camp, Souheil El-Chemaly, Ivan O Rosas, Anil Chandraker, Edgar Milford, Hilary J Goldberg
BACKGROUND: Development of Donor-specific Antibodies (DSA) after lung transplantation is associated with antibody mediated rejection (AMR), acute cellular rejection, and bronchiolitis obliterans syndrome (BOS); however, the significance of circulating antibodies before transplant remains unclear. METHODS: We performed a retrospective cohort study including recipients of primary lung transplants between 2008 and 2012.We assessed the impact of circulating human leukocyte (HLA) and noncytotoxic Donor Specific antibodies (DSA) detected before transplant on development of Chronic Lung Allograft Dysfunction (CLAD) or CLAD related death...
November 23, 2016: Transplantation
https://www.readbyqxmd.com/read/27891189/variations-in-dna-methylation-of-interferon-gamma-and-programmed-death-1-in-allograft-rejection-after-kidney-transplantation
#9
Karin Boer, L Elly A de Wit, Fleur S Peters, Dennis A Hesselink, Leo J Hofland, Michiel G H Betjes, Caspar W N Looman, Carla C Baan
BACKGROUND: The role of DNA methylation in the regulation of the anti-donor-directed immune response after organ transplantation is unknown. Here, we studied the methylation of two mediators of the immune response: the pro-inflammatory cytokine interferon γ (IFNγ) and the inhibitory receptor programmed death 1 (PD1) in naïve and memory CD8+ T cell subsets in kidney transplant recipients receiving immunosuppressive medication. Both recipients experiencing an episode of acute allograft rejection (rejectors) as well as recipients without rejection (non-rejectors) were included...
2016: Clinical Epigenetics
https://www.readbyqxmd.com/read/27889299/safety-and-efficacy-outcomes-3-years-after-switching-to-belatacept-from-a-calcineurin-inhibitor-in-kidney-transplant-recipients-results-from-a-phase-2-randomized-trial
#10
Josep M Grinyó, Maria Del Carmen Rial, Josefina Alberu, Steven M Steinberg, Roberto C Manfro, Georgy Nainan, Flavio Vincenti, Charlotte Jones-Burton, Nassim Kamar
BACKGROUND: In a phase 2 study, kidney transplant recipients of low immunologic risk who switched from a calcineurin inhibitor (CNI) to belatacept had improved kidney function at 12 months postconversion versus those continuing CNI therapy, with a low rate of acute rejection and no transplant loss. STUDY DESIGN: 36-month follow-up of the intention-to-treat population. SETTING & PARTICIPANTS: CNI-treated adult kidney transplant recipients with stable transplant function (estimated glomerular filtration rate [eGFR], 35-75mL/min/1...
November 23, 2016: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/27888576/total-recall-can-we-reshape-t-cell-memory-by-lymphoablation
#11
Michael Nicosia, Anna Valujskikh
Despite recent advances in immunosuppression, donor-reactive memory T cells remain a serious threat to successful organ transplantation. To alleviate damaging effects of preexisting immunologic memory, lymphoablative induction therapies are used as a part of standard care in sensitized recipients. However, there is accumulating evidence that memory T cells have advantages over their naïve counterparts in surviving depletion and expanding under lymphopenic conditions. This may at least partially explain the inability of existing lymphoablative strategies to improve long term allograft outcome in sensitized recipients, despite well-documented decrease in the frequency of early acute rejection episodes...
November 26, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/27888556/evaluate-quality-of-kidneys-from-dcd-ecd-donors-by-parameters-of-machine-perfusion
#12
Guodong Chen, Chang Wang, Yi Zhao, Longhui Qiu, Xiaopeng Yuan, Jiang Qiu, Changxi Wang, Xiaoshun He, Lizhong Chen
AIM: To investigate whether the parameters of machine perfusion could predict the quality of kidneys from donation after circulatory death(DCD) donors and expanded criteria donors (ECD) . METHODS: 58 kidneys from DCD/ECD donors were harvested in our hospital from July 2011 to August 2014. All kidneys were preserved with machine perfusion(Life Port), and parameters of machine perfusion were collected. All kidneys were biopsied before transplantation. The primary endpoints were delayed graft function(DGF), graft loss and patient death...
November 26, 2016: Nephrology
https://www.readbyqxmd.com/read/27888551/selective-targeting-of-high-affinity-lfa-1-does-not-augment-costimulation-blockade-in-a-nonhuman-primate-renal-transplantation-model
#13
K P Samy, D A Anderson, D J Lo, M S Mulvihill, M Song, A B Farris, B S Parker, A L MacDonald, C Lu, T A Springer, S C Kachlany, K A Reimann, T How, F V Leopardi, K S Franke, K D Williams, B H Collins, A D Kirk
Costimulation blockade (CoB) via belatacept is a lower morbidity alternative to calcineurin inhibitor (CNI)-based immunosuppression. However, it has higher rates of early acute rejection. These early rejections are mediated in part by memory T cells, which have reduced dependence on the pathway targeted by belatacept, and increased adhesion molecule expression. One such molecule is Leukocyte Function Associated Antigen (LFA)-1. LFA-1 exists in two forms, a commonly expressed, low-affinity form, and a transient, high-affinity form, expressed only during activation...
November 26, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/27888534/early-steroid-withdrawal-results-in-improved-patient-and-graft-survival-and-lower-risk-of-post-transplant-cardiovascular-risk-profiles-a-single-center-10-year-experience
#14
Reynold Lopez-Soler, Ryan Chan, Jessica Martinolich, Lisa Park, Ashar Ata, Nikolaos Chandolias, David Conti
Long term use of steroids results in predictable secondary effects that can lead to increased morbidity and mortality. In this study, we present 10 years' worth of data of early steroid withdrawal (ESW) immunosuppression consisting of Mycophenolate, Sirolimus, and Tacrolimus. From 2003 to 2013, 563 kidney transplant recipients were weaned off steroids prior to discharge. We compared outcomes with that of our 65 historical controls maintained on steroids. We analyzed graft and patient survival and determined the incidence of steroid-related comorbidities such as hypertension, hypercholesterolemia, diabetes, coronary artery disease, and weight gain...
November 26, 2016: Clinical Transplantation
https://www.readbyqxmd.com/read/27887740/outcomes-of-renal-transplantation-in-patients-with-bipolar-affective-disorder-and-schizophrenia-a-national-retrospective-cohort-study
#15
Mary I Butler, Deirdre McCartan, Anne Cooney, Patrick O Kelly, Izhar Ahmed, Dilly Little, Siobhan MacHale, Peter Conlon
BACKGROUND: Patients with severe psychiatric disorders such as schizophrenia and bipolar affective disorder (BPAD) have in the past been excluded from organ transplantation programs based on their psychiatric illness. However, there is little data on the outcomes of renal transplantation in these patients and little evidence to support such exclusion. METHODS: We reviewed the database of the Irish National Renal Transplant Programme and identified all patients with a history of BPAD or schizophrenia who had received a transplant over a 28-year period...
September 20, 2016: Psychosomatics
https://www.readbyqxmd.com/read/27887677/outcome-disparities-between-african-americans-and-caucasians-in-contemporary-kidney-transplant-recipients
#16
David J Taber, Leonard E Egede, Prabhakar K Baliga
BACKGROUND: Racial disparities in African-American (AA) kidney transplant have persisted for nearly 40 years, with limited data available on the scope of this issue in the contemporary era of transplantation. METHODS: Descriptive retrospective cohort study of US registry data including adult solitary kidney transplants between Jan 1, 2005 to Dec 31, 2009. RESULTS: 60,695 recipients were included; 41,426 Caucasians (68%) and 19,269 AAs (32%)...
November 18, 2016: American Journal of Surgery
https://www.readbyqxmd.com/read/27885144/treatment-of-multiple-myeloma-in-a-heart-transplant-recipient-focus-on-the-immunomodulatory-effects-of-lenalidomide
#17
Lola Xie, Bartosz Jozwik, Phillip Weeks, L Maximilian Buja, Robert Brown, Sriram Nathan, Keshava Rajagopal, Christina Paruthi, Biswajit Kar, Pranav Loyalka, Indranee Rajapreyar
Malignancy following solid organ transplant remains a significant threat to the survival of cardiac transplant recipients. Plasma cell dyscrasias including multiple myeloma have been encountered in this population, and medication treatments traditionally used to treat these disorders demonstrate immunomodulatory effects that may have implications on the transplanted allograft. Lenalidomide is an immunomodulatory agent that has been used to treat plasma cell disorders, including light-chain amyloidosis (AL) and multiple myeloma, and represents such a class of medications in which the risks and benefits in the solid organ transplant population remain to be fully elucidated...
November 24, 2016: Progress in Transplantation
https://www.readbyqxmd.com/read/27882068/transplantation-of-deceased-donor-livers-with-elevated-levels-of-serum-transaminases-at-shiraz-transplant-center
#18
Nasir Fakhar, Saman Nikeghbalian, Kourosh Kazemi, Ali Reza Shamsayeefar, Siavash Gholami, Amir Kasraianfard, Seyed Ali Malek-Hosseini
BACKGROUND: The current organ shortage has prompted the use of marginal organs. We conducted this retrospective study to present our experience with transplanting deceased donor livers with elevated levels of serum transaminases and to explain whether elevated levels of serum transaminases in donors affect allograft function and survival of the recipients. METHODS: Data of deceased donor livers and patients, who underwent liver transplantation from March 2013 to March 2015 at Shiraz center for organ transplantation, was reviewed...
October 2016: Hepatitis Monthly
https://www.readbyqxmd.com/read/27878627/right-ventricular-dysfunction-as-an-echocardiographic-measure-of-acute-rejection-following-heart-transplantation-in-children
#19
Sanjeev Aggarwal, Jennifer Blake, Swati Sehgal
Noninvasive biomarkers of acute allograft rejection (AAR) following orthotopic heart transplantation (OHT) are needed. The aim of this study was to investigate the accuracy of echocardiographic (ECHO) right ventricular (RV) global functional and resistance indices in the detection of AAR. This retrospective chart review included children with biopsy-proven AAR (grade ≥ 2R cellular or CD4 + antibody-mediated rejection) following OHT and an ECHO within 12 h of the biopsy. ECHO measures: (a) ratio of systolic to diastolic duration (S/D), (b) RV myocardial performance index (MPI) and (c) tricuspid regurgitant gradient to RV outflow tract velocity time integral ratio (TRG/VTI), were derived at baseline, during AAR and at two follow-ups...
November 23, 2016: Pediatric Cardiology
https://www.readbyqxmd.com/read/27878210/t-regulatory-cell-mediated-immunotherapy-for-solid-organ-transplantation-a-clinical-perspective
#20
Mohammad Afzal Khan
T regulatory cells (Tregs) play a vital role in suppressing heightened immune responses, and thereby promote a state of immunological tolerance. Tregs modulate both innate and adaptive immunity, which make them a potential candidate for cell-based immunotherapy to suppress uncontrolled activation of graft specific inflammatory cells and their toxic mediators. These grafts specific inflammatory cells (T effector cells) and other inflammatory mediators (Immunoglobulins, active complement mediators) are mainly responsible for graft vascular deterioration followed by acute/chronic rejection...
November 22, 2016: Molecular Medicine
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