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American Journal of Transplantation

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https://www.readbyqxmd.com/read/28102024/generating-antigen-specific-regulatory-t-cells-in-the-fast-lane
#1
EDITORIAL
Leonardo M R Ferreira, Qizhi Tang
Since the inception of therapeutic allogeneic transplantation, acceptance of transplanted allografts has depended on non-specific immunosuppression, which blunts the recipient's immune defense yet cannot fully prevent chronic rejection. What if one could induce tolerance specifically to the graft? This article is protected by copyright. All rights reserved.
January 19, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28102006/prozone-effect-can-be-single-antigen-bead-kit-manufacturer-specific
#2
LETTER
R K Battle, A A Abel, D M Turner
The practice of diluting patient serum prior to single antigen bead (SAB) testing for HLA antibodies has been reported within the literature, along with mechanisms for removing a variety of potential blocking/interference mechanisms within this assay such as the use of EDTA, DTT and hypotonic dialysis (1-4). We read with interest the case reported in this journal by Tambur, by which sample dilution can aid in the definition of HLA reactivity in terms of epitope specificity (5). This article is protected by copyright...
January 19, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28101959/comprehensive-analysis-of-transcript-changes-associated-with-allograft-rejection-combining-universal-and-selective-features
#3
Philip F Halloran, Jeffery M Venner, Konrad S Famulski
We annotated the top transcripts associated with kidney transplant rejection by p-value, either universal for all rejection or selective for T cell-mediated (TCMR) or antibody-mediated rejection (ABMR). We used eight class comparison algorithms to interrogate microarray results from 703 biopsies, 205 with rejection. The positive comparators were all rejection, TCMR, or ABMR; the negative comparators varied from normal biopsies to all non-rejecting biopsies, including other diseases. The universal algorithm, rejection vs...
January 19, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28097811/fc-silent-anti-cd154-domain-antibody-effectively-prevents-non-human-primate-renal-allograft-rejection
#4
Steven C Kim, Walter Wakwe, Laura B Higginbotham, David V Mathews, Cynthia P Breeden, Allison C Stephenson, Joe Jenkins, Elizabeth Strobert, Karen Price, Laura Price, Robert Kuhn, Haiqing Wang, Aaron Yamniuk, Suzanne Suchard, Alton B Farris, Thomas C Pearson, Christian P Larsen, Mandy L Ford, Anish Suri, Steven Nadler, Andrew B Adams
The advent of costimulation blockade provides the prospect for targeted therapy with improved graft survival in transplant patients. Perhaps the most effective costimulation blockade in experimental models is the use of reagents to block the CD40/CD154 pathway. Unfortunately, successful clinical translation of anti-CD154 therapy has not been achieved. In an attempt to develop an agent that is as effective as previous CD154 blocking antibodies but lacks the risk of thromboembolism, we evaluated the efficacy and safety of a novel anti-human CD154 domain antibody (dAb, BMS-986004)...
January 17, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28097805/complement-polymorphisms-in-kidney-transplantation-critical-in-graft-rejection
#5
L A Michielsen, A D van Zuilen, I S Muskens, M C Verhaar, H G Otten
The complement system, as part of the innate immune system, plays an important role in renal transplantation. Complement is involved in the protection against foreign organisms and clearance of apoptotic cells but can also cause injury to the renal allograft for instance via antibody binding or in ischemia reperfusion injury. Numerous polymorphisms in complement factors have been identified thus far; some of them result in different functionalities or alter complement levels. In this review, we provide an overview of the literature on the role of complement polymorphisms in renal transplantation...
January 17, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28097804/adult-living-donor-liver-transplantation-for-acute-on-chronic-liver-failure-in-high-model-for-end-stage-liver-disease-score-patients
#6
D-B Moon, S-G Lee, W-H Kang, G-W Song, D-H Jung, G-C Park, H-D Cho, E-K Jwa, W-J Kim, T-Y Ha, H-J Kim
The large volume of adult living donor liver transplantations (ALDLTs) at our center affords a unique opportunity to examine the impact of acute-on-chronic liver failure (ACLF) among high-MELD score patients. From February 1998 to March 2010, 1958 cirrhotic recipients were analyzed to study the relationship between MELD scores and ALDLT outcomes. A total of 327 high-MELD score recipients were categorized into ACLF and non-ACLF groups, and their outcomes were compared. The five-year graft and patient survival in the high MELD group were 75...
January 17, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28068455/variation-in-access-to-kidney-transplantation-across-renal-programs-in-ontario-canada
#7
K L Naylor, S N Dixon, A X Garg, S J Kim, P G Blake, G E Nesrallah, M K McCallum, C D'Antonio, A H Li, G A Knoll
In the United States, kidney transplant rates vary significantly across end-stage renal disease (ESRD) networks. We conducted a population-based cohort study to determine whether there was variability in kidney transplant rates across renal programs in a health care system distinct from the United States. We included incident chronic dialysis patients in Ontario, Canada, from 2003 to 2013 and determined the 1-, 5-, and 10-year cumulative incidence of kidney transplantation in 27 regional renal programs (similar to U...
January 9, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28066999/transplant-infectious-diseases-a-review-of-the-scientific-registry-of-transplant-recipients-published-data
#8
Camille N Kotton, Shirish Huprikar, Deepali Kumar
The Scientific Registry of Transplant Recipients (SRTR) serves to collect data on organ transplants done in the United States. Although the infectious diseases data are limited and include mostly pretransplant serologies and other non-specific infection related outcomes, such multicenter data collection allows for insightful national data and the ability to monitor trends over time. We reviewed the published concise reports for each organ type in SRTR reports containing data from 2005-2014, and summarized our findings with respect to cytomegalovirus (CMV), Epstein-Barr virus, posttransplant lymphoproliferative disorder (PTLD), hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodefiency virus (HIV), general infection, and prophylaxis...
January 9, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28066998/representing-subnormothermic-machine-perfusion-in-fatty-livers-the-complete-picture
#9
LETTER
M Vairetti, A Ferrigno, E Gringeri, U Cillo
After reading the Article "Impact of Subnormothermic Machine Perfusion Preservation in Severely Steatotic Rat Livers: A Detailed Assessment in an Isolated Setting." by Okamura et al, we wish to bring to your attention previously published results about the use of Subnormothermic Machine Perfusion (SMP) in marginal organs such as steatotic livers given that due consideration of already published data is entirely missing in the Discussion Section of Okamura et al's paper (1). This article is protected by copyright...
January 9, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28066981/disruption-of-transplant-tolerance-by-an-incognito-form-of-cd8-t-cell-dependent-memory
#10
M K Nelsen, K S Beard, R J Plenter, R M Kedl, E T Clambey, R G Gill
Several approaches successfully achieve allograft tolerance in preclinical models but are challenging to translate into clinical practice. Many clinically relevant factors can attenuate allograft tolerance induction including intrinsic genetic resistance, peri-transplant infection, inflammation, and pre-existing anti-donor immunity. The prevailing view for immune memory as a tolerance barrier is that the host harbors memory cells that spontaneously cross-react to donor MHC antigens. Such pre-existing 'heterologous' memory cells have direct reactivity to donor cells and resist most tolerance regimens...
January 9, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28066980/how-spain-reached-40-deceased-organ-donors-per-million-population
#11
REVIEW
R Matesanz, B Domínguez-Gil, E Coll, B Mahíllo, R Marazuela
With 40 donors and more than 100 transplant procedures per million population in 2015, Spain holds a privileged position worldwide in providing transplant services to its patient population. The Spanish success derives from a specific organizational approach to ensure the systematic identification of opportunities for organ donation and their transition to actual donation and to promote public support for the donation of organs after death. The Spanish results are to be highlighted in the context of the dramatic decline in the incidence of brain death and the changes in end-of-life care practices in the country since the beginning of the century...
January 9, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28039960/preventive-strategies-against-cytomegalovirus-and-incidence-of-%C3%AE-herpesvirus-infections-in-olid-organ-transplant-recipients-a-nationwide-cohort-study
#12
Cecilia Martin-Gandul, Susanne Stampf, Delphine Héquet, Nicolas J Mueller, Alexia Cusini, Christian van Delden, Nina Khanna, Katia Boggian, Cédric Hirzel, Paola Soccal, Hans H Hirsch, Manuel Pascual, Pascal Meylan, Oriol Manuel
We assessed the impact of antiviral preventive strategies on the incidence of herpes-simplex virus (HSV) and varicella-zoster virus (VZV) infections in a nationwide cohort of transplant recipients. Risk factors for the development of HSV/VZV infection were assessed by Cox PH regression. We included 2781 patients (56% kidney, 20% liver, 10% lung, 7.3% heart, 6.7% others). Overall, 1264 (45%) patients received antiviral prophylaxis [(val)ganciclovir (n=1126) or (val)acyclovir (n=138)]. Incidences for HSV and VZV infections were 28...
December 31, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/28039954/costimulation-blockade-emerging-hope-for-patients-in-large-markets-only
#13
LETTER
J S Gill, P Halloran, T Jevnikar, E Cole, D Rush, G Knoll
We were excited to read of the long term results and emerging applications of belatacept in the articles led by Durrbach(1) , Wen(2) , Ebcioglu(3) and others(4) in the November 2016 issue of AJT. These exciting advances prompt us to raise the issue of the lack of access to belatacept in Canada. Cynically we might suggest a special Canadian version of the cover was needed entitled "Costimulation Blockade Emerges - except in Canada." This article is protected by copyright. All rights reserved.
December 31, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/28039910/bk-polyomavirus-genomic-integration-and-large-t-antigen-expression-evolving-paradigms-in-human-oncogenesis
#14
Daniel J Kenan, Piotr A Mieczkowski, Eva Latulippe, Isabelle Côté, Harsharan K Singh, Volker Nickeleit
Human polyomaviruses are ubiquitous, with primary infections typically occurring during childhood and subsequent latency that may last a lifetime. Polyomavirus-mediated disease has been described in immunocompromised patients; its relationship to oncogenesis is poorly understood. Here we present deep sequencing data from a high grade BK virus-associated tumor expressing large T antigen. The carcinoma arose in a kidney allograft six years after transplantation. We identified a novel genotype-1a BK polyomavirus (termed "Chapel Hill BK polyomavirus-2″) that was integrated into the BRE gene in chromosome 2 of tumor cells...
December 31, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/28035752/the-effect-of-mhc-antigen-matching-between-donors-and-recipients-on-skin-tolerance-of-vascularized-composite-allografts
#15
K Shanmugarajah, H Powell, D A Leonard, C Mallard, A Albritton, E Harrington, M A Randolph, E Farkash, D H Sachs, J M Kurtz, C L Cetrulo
The emergence of skin-containing vascularized composite allografts (VCAs) has provided impetus to understand factors affecting rejection/tolerance of skin. VCA tolerance can be established in miniature swine across haploidentical MHC barriers using mixed chimerism. As the deceased donor pool for VCAs does not permit MHC antigen matching, clinical VCAs are transplanted across varying MHC disparities. Here, we investigated whether sharing of MHC class I or class II antigens between donors and recipients influences VCA skin tolerance...
December 30, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/28035732/ranolazine-for-refractory-angina-in-a-heart-transplant-recipient-with-cardiac-allograft-vasculopathy
#16
LETTER
D F Yeung, M Toma, M K Davis, A Ignaszewski
Cardiac allograft vasculopathy (CAV) is a leading cause of long-term mortality in patients who have undergone cardiac transplantation. Because of allograft denervation, these patients rarely present with typical chest pain. Nevertheless, reinnervation is possible and allows angina to develop in the presence of myocardial ischemia. This article is protected by copyright. All rights reserved.
December 30, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/28029219/defining-the-tipping-point-in-surgical-performance-for-laparoscopic-donor-nephrectomy-among-transplant-surgery-fellows-a-risk-adjusted-cumulative-summation-learning-curve-analysis
#17
O K Serrano, A S Bangdiwala, D M Vock, D Berglund, T B Dunn, E B Finger, T L Pruett, A J Matas, R Kandaswamy
UNOS recommends that fellowship-trained surgeons participate in 15 LDN to be considered proficient. ASTS mandates 12 LDN during abdominal transplant surgery fellowship (ATSF). We performed a retrospective intraoperative case analysis to create a risk-adjusted cumulative summation (RACUSUM) model to assess the learning curve (LC) of novice TSF (nTSF). Between January 2000 and December 2014, 30 nTSF rotated on the Organ Procurement Rotation (OPR) of our ASTS-approved ATSF. Measures of surgical performance included: 1) intraoperative time (ORT), 2) estimated blood loss (EBL), and 3) incidence of intraoperative complications (IOC)...
December 28, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/28027625/early-conversion-from-calcineurin-inhibitor-to-everolimus-based-therapy-following-kidney-transplantation-results-of-the-randomized-elevate-trial
#18
Johan W de Fijter, Hallvard Holdaas, Ole Øyen, Jan-Stephan Sanders, Sankaran Sundar, Frederike J Bemelman, Claudia Sommerer, Julio Pascual, Yingyos Avihingsanon, Cholatip Pongskul, Frederic Oppenheimer, Lorenzo Toselli, Graeme Russ, Zailong Wang, Patricia Lopez, Jossy Kochuparampil, Josep M Cruzado, Markus van der Giet
In a 24-month, multicenter, open-label, randomized trial, 715 de novo kidney transplant recipients were randomized at 10-14 weeks to convert to everolimus (n=359) or remain on standard calcineurin inhibitor (CNI) therapy (n=356; 231 tacrolimus; 125 cyclosporine), all with mycophenolic acid and steroids. The primary endpoint, change in estimated GFR from randomization to month 12, was similar for everolimus versus CNI: mean (SE) 0.3(1.5)mL/min/1.73(2) versus -1.5(1.5)mL/min/1.73(2) (p=0.116). At month 24, mean (SD) estimated GFR was 62...
December 27, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/28027623/expression-of-a-chimeric-antigen-receptor-specific-for-donor-hla-class-i-enhances-the-potency-of-human-regulatory-t-cells-in-preventing-human-skin-transplant-rejection
#19
Dominic A Boardman, Christina Philippeos, Gilbert O Fruhwirth, Mohammad A A Ibrahim, Rosalind F Hannen, Dianne Cooper, Federica M Marelli-Berg, Fiona M Watt, Robert I Lechler, John Maher, Lesley A Smyth, Giovanna Lombardi
Regulatory T cell (Treg) therapy using recipient-derived Tregs expanded ex vivo is currently being investigated clinically by us and others as a means of reducing allograft rejection following organ transplantation. Data from animal models has demonstrated that adoptive transfer of allospecific Tregs offers greater protection from graft rejection compared to polyclonal Tregs. Chimeric antigen receptors (CAR) are clinically-translatable synthetic fusion proteins which can redirect the specificity of T cells towards designated antigens...
December 27, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/28024112/left-sided-living-kidney-donation-leads-to-transiently-reduced-adrenocortical-responsiveness
#20
F Burn, C Schirpenbach, M Bidlingmaier, M Reincke, D Vetter, D Weishaupt, J G Brockmann, M K Müller, M Weber, F Dahm, A Nocito
Living kidney donation is safe and established, but can lead to long-term complications such as chronic fatigue. Since the adrenal vein is usually transected during left-sided donor nephrectomy - which is not necessary on the right- we hypothesized that venous congestion might lead to an impairment of adrenal function, offering a possible explanation. In this prospective open label, mono-centric cohort study adrenal function was compared in left- and right-sided living kidney donors. The primary endpoint was plasma cortisol response to low-dose ACTH stimulation...
December 26, 2016: American Journal of Transplantation
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