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American Journal of Transplantation

Michael S Mulvihill, Kannan P Samy, Qimeng A Gao, Robin Schmitz, Robert P Davis, Brian Ezekian, Francis Leopardi, Mingqing Song, Tam How, Kyha Williams, Andrew Barbas, Bradley Collins, Allan D Kirk
Naïve T cell activation requires antigen presentation combined with costimulation through CD28, both of which optimally occur in secondary lymphoid tissues such as lymph nodes and the spleen. Belatacept impairs CD28 costimulation by binding its ligands, CD80 and CD86, and in doing so, impairs de novo alloimmune responses. However, in most patients belatacept is ineffective in preventing allograft rejection when used as a monotherapy, and adjuvant therapy is required for control of costimulation-blockade resistant rejection (CoBRR)...
March 20, 2019: American Journal of Transplantation
Yui Watanabe, Marcos Galasso, Tatsuaki Watanabe, Aadil Ali, Robert Qaqish, Daisuke Nakajima, Yohei Taniguchi, Mauricio Pipkin, Lindsay Caldarone, Manyin Chen, Takashi Kanou, Cara Summers, Khaled Ramadan, Yu Zhang, Harley Chan, Thomas K Waddell, Mingyao Liu, Shaf Keshavjee, Lorenzo Del Sorbo, Marcelo Cypel
A large proportion of controlled donation after circulatory death (cDCD) donor lungs are declined because cardiac arrest does not occur in a suitable time after withdrawal of life-sustaining therapy. Improved strategies to preserve lungs after asystole may allow the recovery team to arrive after death actually occurs and enable the recovery of more lungs from cDCDs. The aim of this study was to determine the effect of donor positioning on the quality of lung preservation after cardiac arrest in a cDCD model...
March 19, 2019: American Journal of Transplantation
William H Marks, Nizam Mamode, Robert Montgomery, Mark D Stegall, Lloyd E Ratner, Lynn D Cornell, Ajda T Rowshani, Robert B Colvin, Bradley Dain, Judith A Boice, Denis Glotz
We report results of a phase 2, randomized, multicenter, open-label, two-arm study evaluating the safety and efficacy of eculizumab in preventing acute antibody-mediated rejection (AMR) in sensitized recipients of living-donor kidney transplants requiring pretransplantation desensitization (NCT01399593). In total, 102 patients underwent desensitization. Posttransplantation, 51 patients received standard of care (SOC) and 51 received eculizumab. The primary end point was week 9 posttransplantation treatment failure rate, a composite of: biopsy-proven acute AMR (Banff 2007 grades II or III; assessed by blinded central pathology); graft loss; death; or loss to follow-up...
March 19, 2019: American Journal of Transplantation
Justin R Parekh, Stuart Greenstein, Debra L Sudan, Arielle Grieco, Mark E Cohen, Bruce L Hall, Clifford Y Ko, Ryutaro Hirose
The National Surgical Quality Program (NSQIP) Transplant program was designed by transplant surgeons from the ground up to track post-transplant outcomes beyond basic recipient and graft survival. After an initial pilot phase, the program has expanded to 29 participating sites and enrolled more than 4300 recipient-donor pairs into the database, including 1444 completed liver transplant cases. In this analysis, surgical site infection (SSI), urinary tract infection (UTI) and unplanned re-operation/intervention after liver transplantation were evaluated...
March 18, 2019: American Journal of Transplantation
Benjamin Samstein, Lisa M McElroy
The imbalance between supply and demand of organs for transplant will not be fully solved by changes to the allocation system. Improved organ donation and utilization must be accomplished through critical reassessment of OPO performance as a partnership between transplant centers, OPOs and community hospitals. The continued discussion on changes to the organ distribution system should be based on patient-centeredness, enhanced transparency, improved models and metrics. Focusing too heavily on geography without consideration for the other factors at play risks oversimplification of this complex issue...
March 18, 2019: American Journal of Transplantation
Arnaud G L'Huillier, Anne I Dipchand, Vicky L Ng, Diane Hebert, Yaron Avitzur, Melinda Solomon, Bo-Yee Ngan, Derek Stephens, Angela S Punnett, Michelle Barton, Upton D Allen
Post-transplant-lymphoproliferative-disorder (PTLD) is a devastating complication of organ transplantation. In a hospital-based registry, we identified biopsy-proven cases of PTLD among children over a 15-year period and reviewed trends in PTLD rates, the sites of involvement and the associated survival rates. Cases that were included had at least 1 year of follow-up after the diagnosis of PTLD. We studied 82 patients with first-episode PTLD. Median age at diagnosis was 6.4 years (interquartile range 3.2-12...
March 18, 2019: American Journal of Transplantation
Markus J Barten, Stephan W Hirt, Jens Garbade, Christoph Bara, Andreas O Doesch, Christoph Knosalla, Carola Grinninger, Jörg Stypmann, Christian Sieder, Han B Lehmkuhl, Martina Porstner, Uwe Schulz
In the 12-month, open-label MANDELA study, patients were randomized at month 6 after heart transplantation to (i) convert to calcineurin inhibitor (CNI)-free immunosuppression with everolimus (EVR), mycophenolic acid and steroids (CNI-free, n=71), or to (ii) continue reduced-exposure CNI, with EVR and steroids (EVR/redCNI, n=74). Tacrolimus was administered in 48.8% of EVR/redCNI patients and 52.6% of CNI-free patients at radomization. Both strategies improved and stabilized renal function based on the primary endpoint (estimated GFR at month 18 post-transplant post-randomization) with superiority of the CNI-free group versus EVR/redCNI : mean 64...
March 18, 2019: American Journal of Transplantation
Heather Wasik, Cozumel Pruette, Rebecca Ruebner, Mara McAdams-DeMarco, Sheng Zhou, Alicia Neu, Dorry Segev, Allan Massie
Pediatric kidney transplant (KT) candidates often have multiple potential living donors (LD); no evidence-based tool exists to compare potential LD, or to decide between marginal LD vs deceased donor (DD) kidney transplantation (KT). We developed a pediatric living kidney donor profile index (P-LKDPI) on the same scale as the DD KDPI by using Cox regression to model the risk of all-cause graft loss as a function of living donor characteristics and DD KDPI. HLA-B mismatch (aHR per mismatch=1.04 1.271.55 ), HLA-DR mismatch (aHR per mismatch=1...
March 15, 2019: American Journal of Transplantation
Albert Holvast, Gursah Kats-Ugurlu, Frank A J A Bodewes, Ruben H J de Kleine, Robert J Porte, Adrienne H Brouwers, Hubert P J van der Doef
Secondary protein-losing enteropathy (PLE) is a rare complication following pediatric liver transplantation (LT), mostly related to venous outflow obstruction of the liver. Here, we discuss a thus far unknown cause of secondary PLE following pediatric LT. A 7-months old boy underwent LT with biliary anastomosis using a Roux-en-Y jejunal loop. Eleven months later he developed PLE. Routine diagnostic work-up was negative. No hepatic outflow obstruction was detected during catheterization. Although the hepatic venous pressure gradient was slightly increased (10 mmHg), there were no clinical signs of portal hypertension...
March 14, 2019: American Journal of Transplantation
Moira H D Bruintjes, Esmee V van Helden, Marjan de Vries, Lieke Wirken, Andrea Wm Evers, Henriët van Middendorp, Heinrich Kloke, Frank C H d'Ancona, Johan F Langenhuijsen, Monique A H Steegers, Michiel C Warlé
Chronic postsurgical pain (CPSP) following laparoscopic donor nephrectomy (LDN) is a disregarded topic. In this cross-sectional study, all consecutive patients who underwent a LDN at the Radboudumc (2003-2016) were approached for participation. Five hundred and twelve living kidney donors were included and asked to complete two questionnaires, including the Mc Gill Pain questionnaire and the RAND Short Form-36 Health Status Inventory (RAND SF-36) regarding their health-related quality of life (HRQoL). The mean prevalence of CPSP following LDN was 5...
March 14, 2019: American Journal of Transplantation
Jeff Reeve, Georg A Böhmig, Farsad Eskandary, Gunilla Einecke, Gaurav Gupta, Katelynn Madill-Thomsen, Martina Mackova, Philip F Halloran
We previously reported a system for assessing rejection in kidney transplant biopsies using microarray-based gene expression data, the Molecular Microscope® Diagnostic System (MMDx). The present study was designed to optimize the accuracy and stability of MMDx diagnoses by replacing single machine learning classifiers with ensembles of diverse classifier methods. We also examined the use of automated report sign-outs and the agreement between multiple human interpreters of the molecular results. Ensembles generated diagnoses that were both more accurate than the best individual classifiers, and nearly as stable as the best, consistent with expectations from the machine learning literature...
March 13, 2019: American Journal of Transplantation
Danae Bixler, Pallavi Annambholta, Winston E Abara, Melissa G Collier, Jefferson Jones, Tonya Mixson-Hayden, Sridhar V Basavaraju, Sumathi Ramachandran, Saleem Kamili, Anne Moorman
We evaluated clinical outcomes among organ recipients with donor-derived hepatitis B virus (HBV) or hepatitis C virus (HCV) infections investigated by CDC from 2014-2017 in the United States. We characterized new HBV infections in organ recipients if donors tested negative for total anti-HBc, HBsAg and HBV DNA, and new recipient HCV infections if donors tested negative for anti-HCV and HCV RNA. Donor risk behaviors were abstracted from next-of-kin interviews and medical records. During 2014-2017, seven new recipient HBV infections associated with seven donors were identified; six (86%) recipients survived...
March 12, 2019: American Journal of Transplantation
Neil Mehta, Jennifer L Dodge, Ryutaro Hirose, John P Roberts, Francis Y Yao
All patients with hepatocellular carcinoma (HCC) meeting United Network for Organ Sharing (UNOS) T2 criteria currently receive the same listing priority for liver transplantation (LT). A previous study from our center identified a subgroup with a very low risk of waitlist dropout who may not derive immediate LT benefit. To evaluate this issue at a national level, we analyzed within the UNOS database 2052 patients with T2 HCC receiving priority listing from 2011-2014 in long wait time regions 1, 5, and 9. Probabilities of waitlist dropout were 18...
March 12, 2019: American Journal of Transplantation
Mary G Bowring, Ashton A Shaffer, Allan B Massie, Andrew Cameron, Niraj Desai, Mark Sulkowski, Jacqueline Garonzik-Wang, Dorry L Segev
Several single-center reports of using HCV-viremic organs for HCV-uninfected (HCV-) recipients were recently published. We sought to characterize national utilization of HCV-exposed donors for HCV- recipients (HCV D+/R-) in kidney transplantation (KT) and liver transplantation (LT). Using SRTR data (4/1/2015-12/2/2018) and Gini coefficients, we studied center-level clustering of 1,193 HCV D+/R- KTs and LTs. HCV-viremic (NAT+) D+/R- KTs increased from 1/month in 2015 to 22/month in 2018 (LTs: 0/month to 12/month)...
March 12, 2019: American Journal of Transplantation
Nobuki Ishida, Kohei Ishiyama, Yoshihiro Saeki, Yuka Tanaka, Hideki Ohdan
The activation of natural killer (NK) cells in the liver inhibits engraftment of intraportally transplanted islets. We attempted to modulate the activity of NK cells by co-transplanting mesenchymal stem cells (MSCs) with islets in mice. We first investigated the ability of MSCs to secrete prostaglandin E2 (PGE2), a predominant inhibitor of NK cell function, in various combinations of inflammatory cytokines. Notably, we found that PGE2 production was partially delayed in MSCs activated by inflammatory cytokines in vitro, whereas liver NK cells were activated early after islet transplantation in vivo...
March 12, 2019: American Journal of Transplantation
Caner Süsal, Bernd Döhler
Intra-patient variability (IPV) of tacrolimus trough level has been associated with poor outcome after kidney transplantation. These findings were derived from single center analyses and restricted mainly to measurements early after transplantation. We analyzed in a multicenter effort whether high IPV of tacrolimus levels at post-transplant years 1, 2 and 3 was associated with impaired clinical outcome. More than 6,600 patients who received a deceased donor kidney transplant during 2000-2014 and had a functioning graft for >3 years were studied...
March 12, 2019: American Journal of Transplantation
Anna Valujskikh
The life-saving procedure of organ transplantation inevitably involves major cell stress and tissue injury within the transplanted organ caused by ischemia, reperfusion and subsequent assault by the recipient immune system. These processes lead to the generation and release of danger-associated-molecular patterns, or DAMPs, that can be recognized by both immune and non-immune cells resulting in their activation. Biochemically diverse DAMPs can be expressed by stressed cells on plasma membrane or in the secreted form, released from damaged extracellular matrix, or derive from dead and damaged cells (1)...
March 11, 2019: American Journal of Transplantation
Thomas M Egan, John Jacob Requard
Gentry and Segev claim the OPTN contractor's responsibilities should be re-structured "to achieve policy coherence and infrastructure excellence". We comment on their recommendations, and submitting a competing OPTN contract bid. The authors detail the timeline HRSA used to collect information from interested parties, and the abbreviated response time to a radically different Scope of Work (SOW) posted with the Request for Proposal (RFP). We founded a not-for-profit corporation, Organs for Life (OFL), to explore submitting a competing bid for the OPTN contract...
March 11, 2019: American Journal of Transplantation
Joseph T Brooks, Jorge Ortiz
We read with interest the article by Montgomery et al. regarding bariatric surgery for obese, prospective living kidney donors.1 The authors argued that the continued increase in rates of obesity in the United States directly impacts not only the potential living kidney donor (LKD) population, but also donor and recipient outcomes following living kidney donation. This article is protected by copyright. All rights reserved.
March 10, 2019: American Journal of Transplantation
Vanessa Grubbs
When 33 year-old RP went to his transplant evaluation appointment in 2004, he was told he was nearing the top of the waitlist. He had been on dialysis for 5 years, but was 32 years away from being eligible for Medicare's lifetime immunosuppressant coverage after transplant. He recalls the financial counselor saying, "Even after your insurance pays, you will still have to pay $215 every month for the medications. Can you afford that?". This article is protected by copyright. All rights reserved.
March 8, 2019: American Journal of Transplantation
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