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American Journal of Transplantation

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https://www.readbyqxmd.com/read/28231403/view-from-the-american-society-of-reconstructive-transplantation
#1
LETTER
Suzanne V McDiarmid, Gerald Brandacher, W P Andrew Lee
The transplant community as represented by the diverse readership of the American Journal of Transplantation (AJT) may be interested in recent advances in the field of vascularized composite allotransplantation (VCA) occurring determinedly in the US and worldwide, and become enticed to contribute actively to the advancement of this innovative field. Although the first hand transplant was performed in the US in 1999, only recently has there been more widespread professional and public awareness of this new indication for transplantation to optimally restore form and function and replace like-with-like tissue in cases where conventional reconstruction is not feasible...
February 23, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28226413/thrombalexin-use-of-a-cytotopic-anticoagulant-to-reduce-thrombotic-microangiopathy-in-a-highly-sensitized-model-of-kidney-transplantation
#2
Miriam Manook, Jean Kwun, Christian Burghuber, Kannan Samy, Michael Mulvihill, Janghoon Yoon, He Xu, Andrea L MacDonald, Kyle Freischlag, Verna Curfman, Evelyn Branum, David Howell, Alton Brad Farris, Richard A Smith, Stephen Sacks, Anthony Dorling, Nizam Mamode, Stuart Knechtle
Early activation of coagulation is an important factor in the initiation of innate immunity, as characterized by thrombotic microangiopathy (TMA). In transplantation, systemic anti-coagulation is difficult due to bleeding. A novel 'cytotopic' agent, 'Thrombalexin', (TLN) combines a cell-membrane bound (mirystoyl tail) anti-thrombin (HLL peptide) which can be perfused directly to the donor organ or cells.. Thromboelastography (TEG) was used to measure time to clot formation (r-time) in both rhesus and human blood, comparing TLN vs...
February 22, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28226404/the-effect-of-cortex-medulla-proportions-on-molecular-diagnoses-in-kidney-transplant-biopsies-rejection-and-injury-can-be-assessed-in-medulla
#3
Katelynn S Madill-Thomsen, Roger C Wiggins, Farsad Eskandary, Georg A Böhmig, Philip F Halloran
Histologic assessment of kidney transplant biopsies relies on cortex rather than medulla, but for microarray studies, the proportion cortex in a biopsy is typically unknown and could affect the molecular readings. The present study aimed to develop a molecular estimate of proportion cortex in biopsies and examine its effect on molecular diagnoses. Microarrays from 26 kidney transplant biopsies divided into cortex and medulla components and processed separately showed that many of the most significant differences were in glomerular genes e...
February 22, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28226402/fluctuation-does-not-mean-variability-a-pharmacokinetic-point-of-view
#4
LETTER
Florian Lemaitre, Camille Tron, Michel Rayar
We read with interest the article by Tremblay et al. (1) recently published in the American Journal of Transplantation and wanted to congratulate them for their study. The authors reported a randomized, cross-over study comparing different formulations of tacrolimus (TAC) (immediate release (IR), extended release (ER) and the recently labelled once-daily tacrolimus formulation (LCPT)) in stable renal transplant recipients. Patients treated with IR-TAC were converted to ER-TAC with a dosage conversion factor of 1:1 on a mg basis or to LCPT with a dosage conversion factor of 1:0...
February 22, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28226199/mortality-risk-factors-among-patients-with-cirrhosis-and-a-low-%C3%A2-15-meld-sodium-score-an-analysis-of-liver-transplant-allocation-policy-using-aggregated-electronic-health-record-data
#5
K Atiemo, A Skaro, H Maddur, L Zhao, S Montag, L VanWagner, S Goel, A Kho, B Ho, R Kang, J L Holl, M M Abecassis, J Levitsy, D P Ladner
Although the MELDNa score is now used for liver transplant allocation in the United States, mortality prediction may be underestimated by the score. Using aggregated electronic health record data from 7,834 adult patients with cirrhosis, we determined whether the cause of cirrhosis/cirrhosis complications is associated with an increased risk of death among patients with a MELDNa ≤15 and whether patients with the greatest risk of death could benefit from liver transplantation (LT). Over a median follow-up of 2...
February 22, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28224698/determinants-of-the-magnitude-of-interaction-between-tacrolimus-and-voriconazole-posaconazole-in-solid-organ-recipients
#6
Thomas Vanhove, Hanneke Bouwsma, Luuk Hilbrands, Jesse J Swen, Isabel Spriet, Pieter Annaert, Bart Vanaudenaerde, Geert Verleden, Robin Vos, Dirk R J Kuypers
Administration of azole antifungals to tacrolimus-treated solid organ recipients results in a major drug-drug interaction characterized by increased exposure to tacrolimus. The magnitude of this interaction is highly variable but cannot currently be predicted. We performed a retrospective analysis of 126 solid organ recipients (95 lung, 31 kidney) co-treated with tacrolimus and voriconazole (n=100) or posaconazole (n=26). Predictors of the change in tacrolimus dose-corrected trough concentrations (C/D) between baseline and tacrolimus - azole co-therapy were assessed using linear mixed modeling...
February 21, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28199785/assessment-of-tocilizumab-anti-il-6-receptor-monoclonal-as-a-potential-treatment-for-chronic-antibody-mediated-rejection-and-transplant-glomerulopathy-in-hla-sensitized-renal-allograft-recipients
#7
Jua Choi, Olivier Aubert, Ashley Vo, Alexandre Loupy, Mark Haas, Dechu Puliyanda, Irene Kim, Sabrina Louie, Alexis Kang, Alice Peng, Joe Kahwaji, Nancy Reinsmoen, Mieko Toyoda, Stanley C Jordan
Extending the functional integrity of renal allografts is the primary goal of transplant medicine. Development of donor-specific antibodies (DSAs) post-transplant leads to chronic active antibody-mediated rejection (cABMR) and transplant glomerulopathy (TG), resulting in the majority of graft losses in the U.S. This reduces the quality & length of life for patients and increases cost. There are no approved treatments for cABMR. Evidence suggests the pro-inflammatory cytokine interleukin 6 (IL-6) may play an important role in DSA generation and cABMR...
February 15, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28199784/allosensitization-following-bone-graft
#8
Eoin D O'Sullivan, Richard K Battle, Sharon Zahra, John F Keating, Lorna P Marson, David M Turner
It is recognised that patients may become sensitized to donor-specific HLA antigens as a result of previous antigenic exposures, classically through previous transplantation, pregnancy or blood transfusion. We present an unusual case of a patient who unexpectedly developed a range of anti-HLA antibodies following orthopaedic surgery where a bone graft was deployed intraoperatively. We describe the case of a 52-year-old male awaiting a renal transplantation, undergoing elective orthopaedic surgery requiring a small volume bone graft...
February 15, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28199780/cytomegalovirus-responsive-cd8-t-cells-expand-after-solid-organ-transplantation-in-the-absence-of-cmv-disease
#9
Lauren E Higdon, Jennifer Trofe-Clark, Sai Liu, Kenneth B Margulies, Malaya K Sahoo, Emily Blumberg, Benjamin A Pinsky, Jonathan S Maltzman
Cytomegalovirus (CMV) is a major cause of morbidity and mortality in solid-organ transplant recipients. Approximately 60% of adults are CMV seropositive indicating previous exposure. Following resolution of primary infection, CMV remains in a latent state. Reactivation is controlled by memory T cells in healthy individuals; transplant recipients have reduced memory T cell function due to chronic immunosuppressive therapies. In this study, CD8(+) T cell responses to CMV polypeptides IE-1 and pp65 were analyzed in sixteen CMV seropositive renal and cardiac transplant recipients longitudinally pre- and post-transplant...
February 15, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28199773/the-road-to-hla-antibody-evaluation-do-not-rely-on-mfi
#10
H Clifford Sullivan, Robert S Liwski, Robert A Bray, Howard M Gebel
Technological advances in HLA laboratory testing undoubtedly improved the sensitivity and specificity of HLA antibody assessment, but not without introducing a set of challenges regarding data interpretation. In particular, the introduction of solid-phase single antigen bead (SAB) antibody assessment brought the belief that mean fluorescence intensity (MFI) was a quantifiable value. As such, MFI levels heavily influenced HLA antibody reporting, monitoring and clinical practice. However, given that SAB testing was neither intended for nor approved to be quantifiable, is the use of MFI in current clinical and laboratory practice valid? What, if anything, does this numerical value actually reveal about the pathogenic potential of the antibody? What are the pitfalls and caveats associated with reporting MFI? Herein, we travel the road to HLA antibody assessment and explore the reliability of MFI values to make clinical decisions...
February 15, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28199762/improving-the-diagnostic-criteria-for-primary-liver-graft-non-function-in-adults-utilizing-standard-and-transportable-laboratory-parameters-an-outcome-based-analysis
#11
Mohammad A B Al-Freah, Mark J W McPhail, Elena Dionigi, Matthew R Foxton, Georg Auzinger, Mohamed Rela, Julia A Wendon, John G O'Grady, Michael A Heneghan, Nigel D Heaton, William Bernal
Current diagnostic criteria for primary non-function (PNF) of liver grafts are based on clinical experience rather than statistical methods. A retrospective, single centre study was conducted of all adults (n=1,286) who underwent primary liver transplant 2000-2008 in our centre. Laboratory variable during the first post-liver transplant week were analysed. Forty two patients (3.7%) had 2-week graft failure. Transplant albumin, day-1 AST, day-1 lactate, day-3 bilirubin, day-3 INR and day-7 AST were independently associated with PNF on multivariate logistic regression...
February 15, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28188681/mhealth-in-solid-organ-transplant-the-time-is-now
#12
J N Fleming, D J Taber, J McElligott, J W McGillicuddy, F Treiber
Despite being in existence for over 40 years, the application of telemedicine has lagged significantly in comparison to its generated interest. One detractor has been the immobile design of most historic telemedicine interventions and the relative deficiency of smartphones in the general populace. Recently, the exponential increase in smartphone ownership and familiarity have provided the potential for the development of mobile health (mHealth) interventions that can realistically be mirrored in clinical applications...
February 11, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28188678/prophylactic-ureteric-stents-in-renal-transplant-recipients-a-multicentre-randomised-controlled-trial-of-early-versus-late-removal
#13
Pareeta Patel, Irene Rebollo-Mesa, Elizabeth Ryan, Manish D Sinha, Stephen D Marks, Neal Banga, Iain C Macdougall, Michelle C Webb, Geoff Koffman, Jonathon Olsburgh
Prophylactic ureteric stenting in renal transplantation reduces major urological complications (MUCs). There is however morbidity related to the indwelling duration of a stent, we aimed to determine the optimal duration for stents in this clinical setting. Patients (aged 2-75 years) from 6 UK hospitals undergoing renal transplantation were recruited and randomly assigned, to either early stent removal at 5 days (without cystoscopy) or late at 6 weeks post-transplantation (with cystoscopy). The primary outcome was a composite of stent-related complications defined as pain, visible haematuria, migration, fragmentation, and urinary tract infections (UTIs) within 3 months of transplantation...
February 11, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28188676/hemoglobin-based-oxygen-carrier-rescues-double-transplant-patient-from-life-threatening-anemia
#14
M F Gomez, O Aljure, G Ciancio, M Lynn
This is a case of a 46-year-old male, Jehovah's Witness kidney-pancreas transplant recipient found to have early in the postoperative period, splenic vein thrombosis requiring heparin infusion. Two days later, he developed severe symptomatic anemia (Hb < 6 g/dL). Standard medical therapy for bloodless surgical patients with severe anemia was instituted. Nevertheless, the patient's hemoglobin concentration continued to decline to critical levels (2 g/dL). Transfusion of allogeneic blood products was not an option, prompting use of a hemoglobin-based oxygen carrier (HBOC)...
February 11, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28188669/orthogonal-comparison-of-molecular-signatures-of-kidney-transplants-with-subclinical-and-clinical-acute-rejection-equivalent-performance-is-agnostic-to-either-technology-or-platform
#15
S M Kurian, E Velazquez, R Thompson, T Whisenant, S Rose, N Riley, F Harrison, T Gelbart, J J Friedewald, J Charrette, S Brietigam, J Peysakhovich, M R First, M M Abecassis, D R Salomon
We performed orthogonal technology comparisons of concurrent peripheral blood and biopsy tissue samples from 69 kidney transplant recipients, who underwent a comprehensive algorithm-driven clinical phenotyping. The sample cohort included patients with normal protocol biopsies and stable transplant function (TX, n=25), subclinical acute rejection (subAR, n=23), and clinical acute rejection (cAR, n=21). Comparisons between microarray and RNA sequencing (RNA-seq) signatures were performed, demonstrating a strong correlation between the blood and tissue compartments for both technology platforms...
February 11, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28173625/bet-proteins-an-approach-to-future-therapies-in-transplantation
#16
Beatriz Suarez-Álvarez, Ramón M Rodríguez, Marta Ruiz-Ortega, Carlos López-Larrea
In order to develop new efficient therapies for organ transplantation it is essential to acquire a comprehensive knowledge of the molecular mechanisms and processes, such as immune activation, chronic inflammation and fibrosis that lead to rejection and long-term graft loss. Recent efforts have shed some light on the epigenetic regulation associated with these processes. In this context, the bromo and extraterminal (BET) family of bromodomain proteins (BRD2, BRD3, BRD4 and BRDT) have emerged as major epigenetic players, connecting chromatin structure with gene expression changes...
February 7, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28173620/proteasome-inhibitor-carfilzomib-based-therapy-for-antibody-mediated-rejection-of-the-pulmonary-allograft-use-and-short-term-findings
#17
Christopher R Ensor, Samuel A Yousem, Marilyn Marrari, Matthew R Morrell, Massimo Mangiola, Joseph M Pilewski, Jonathan D'Cunha, Stephen R Wisniewski, Raman Venkataramanan, Adriana Zeevi, John F McDyer
We present this observational study of lung transplant recipients (LTR) treated with Carfilzomib (CFZ)-based therapy for antibody-mediated rejection (AMR) of the lung. Patients were considered responders to CFZ if C1q-fixing ability of their immunodominant (ID) DSA was suppressed after treatment. Treatment consisted of CFZ plus plasma exchange and immunoglobulins. Fourteen LTRs underwent CFZ for 20 ID DSA AMR. Ten (71.4%) of LTRs responded to CFZ. DSA IgG MFI fell from 7664 (IQR 3230-11874) to 1878 (653-7791) after therapy (p=0...
February 7, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28168823/opo-strategies-to-prevent-unintended-use-of-kidneys-exported-for-high-pra-98-cpra-recipients
#18
A S Paramesh, N Neidlinger, M Salvatore, A Smith, A Friedman, W Payne, T Taber, C Wright
Since the advent of the Kidney Allocation System (KAS), matched candidates with high (>98%) panel reactive antibody (hPRA) are given priority over local candidates with lower PRA. This often leads to exporting of kidneys. Data for these kidneys is not detailed on routine reports. Twenty two organ procurement organizations prospectively submitted data from 8/2015 - 7/2016, describing allocation practices of kidneys to hPRA patients and outcomes of these kidneys. 520 out of 6924 procured kidneys were exported for hPRA recipients...
February 6, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28168821/metrics-and-data-analysis-in-transplantation-quality-improvement-via-transparency
#19
EDITORIAL
J A Fishman
Transparency in clinical data has been identified as a driver of improved clinical outcomes in transplantation by many including Porter (1). Transparency in this context includes the broad availability of outcomes data including clinical outcomes adjusted for risk, the costs of care, and the experience of the center in providing those services - as a basis for comparing the "value" of healthcare services at various clinical centers. At the same time, and perhaps of greater importance, dramatic advances in transplant immunology and immunosuppression, microbiologic diagnosis and therapy, surgical techniques, organ procurement and allocation, and in clinical management of complex patients have been major drivers of improved transplant outcomes...
February 6, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28141921/a-tale-of-two-pathways-renewing-the-promise-of-anti-cd40l-blockade
#20
EDITORIAL
A W Thomson, M B Ezzelarab
Amongst the most promising alternative immunosuppressive strategies to overcome the limitations of calcineurin inhibition in organ transplantation has for some time, been the blockade of co-stimulatory pathways that are essential for naïve T cell activation. The most important and best characterized of these are the CD80/86-CD28/CTLA4 and CD40-CD40L(CD154) ligand-receptor pathways. More than twenty years ago, compelling reports (1) showed that selective blocking of these pathways was highly effective in promoting long-term allograft acceptance/tolerance in rodents...
January 31, 2017: American Journal of Transplantation
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