American Journal of Transplantation

Jeremy S Nayagam, Samuel McGrath, Mahmoud Montasser, Michael Delaney, Tom D Cairns, Kevin J Marchbank, Steven H Sacks, H Terry Cook, Sapna Shah, Nigel Heaton, Matthew C Pickering, Abid Suddle
Hereditary complement C3 deficiency is associated with recurrent bacterial infections and proliferative glomerulonephritis. We describe a case of an adult with complete deficiency of complement C3 due to homozygous mutations in C3 gene: c.1811delT (Val604Glyfs*2), recurrent bacterial infections, crescentic glomerulonephritis and end-stage renal failure. Following isolated kidney transplantation he would remain C3 deficient with a similar, or increased, risk of infections and glomerulonephritis. As C3 is predominantly synthesised in the liver, with a small proportion of C3 monocyte-derived and kidney-derived, he proceeded to simultaneous liver-kidney transplantation...
January 23, 2020: American Journal of Transplantation
Reem Daloul, Todd Pesavento, Anthony Michaels
Since the publication of the first two novel reports demonstrating the feasibility of using Hepatitis C virus nucleic acid test positive (HCV NAT+) organs into negative recipients1,2 , evidence regarding the safety of using HCV NAT+ organs have been mounting. However, the wide implementation of such a practice hinges on the ability to ensure timely delivery of direct acting antiviral (DAA) therapy after transplantation. To date, DAA coverage by third party payers for acute HCV infection cannot be guaranteed...
January 22, 2020: American Journal of Transplantation
Ji Won Han, Dong Jin Joo, Jong Hoon Kim, Min-Seok Rha, June Young Koh, Hye Jung Park, Jae Geun Lee, Myoung Soo Kim, Soon Il Kim, Eui-Cheol Shin, Jun Yong Park, Su-Hyung Park
Treg cells are important in preventing acute rejection (AR) in solid organ transplantation, but the clinical relevance of the different kinetics early after liver transplantation (LT) in acute rejectors and non-rejectors is unclear. We analyzed peripheral blood samples of 128 LT recipients receiving basiliximab induction plus tacrolimus immunosuppression. Samples were obtained at pre-transplantation, D7, and D30 after LT. Frequency and phenotype of Tregs were analyzed by flow cytometry. The predictive value of Treg frequency at D7 was assessed for suspected acute rejection (SAR) and was validated for biopsy-proven AR (BPAR)...
January 22, 2020: American Journal of Transplantation
Tayyab S Diwan, Tiffany C Lee, Shunji Nagai, Enrico Benedetti, Andrew Posselt, Ginny Bumgardner, Sabrena Noria, Bryan A Whitson, Lloyd Ratner, David Mason, Jon Friedman, Kenneth J Woodside, Julie Heimbach
The increasing obesity epidemic has major implications in the realm of transplantation. Patients with obesity face barriers in access to transplantation as well as unique challenges in perioperative and postoperative outcomes. Due to comorbidities associated with obesity along with the underlying end-stage organ disease leading to transplantation candidacy, these patients may not even be referred for transplant evaluation, much less be waitlisted or actually undergo transplantation. However, the utilization of bariatric surgery in this population can help optimize the transplant candidacy of patients with obesity and end-stage organ disease as well as improve perioperative and postoperative outcomes...
January 21, 2020: American Journal of Transplantation
Sharad I Wadhwani, Andrew F Beck, John Bucuvalas, Laura Gottlieb, Uma Kotagal, Jennifer C Lai
Long-term outcomes remain suboptimal following pediatric liver transplantation; only one-third of children have normal biochemical liver function without immunosuppressant comorbidities 10 years post-transplant. We examined the association between an index of neighborhood socioeconomic deprivation with graft and patient survival using the Scientific Registry of Transplant Recipients. We included children <19 years who underwent liver transplantation between 1/1/2008-12/31/2013 (n=2868). Primary exposure was a neighborhood socioeconomic deprivation index-linked via patient home ZIP code-with a range of 0-1 (values nearing 1 indicate neighborhoods with greater socioeconomic deprivation)...
January 20, 2020: American Journal of Transplantation
Antoine Sicard, Caroline Lamarche, Madeleine Speck, May Wong, Isaac Rosado-Sánchez, Mathilde Blois, Nicolas Glaichenhaus, Majid Mojibian, Megan K Levings
Cell therapy with autologous donor-specific regulatory T cells (Tregs) is a promising strategy to minimize immunosuppression in transplant recipients. Chimeric antigen receptor (CAR) technology has recently been used successfully to generate donor-specific Tregs and overcome the limitations of enrichment protocols based on repetitive stimulations with alloantigens. However, the ability of CAR-Treg therapy to control alloreactivity in immunocompetent recipients is unknown. We first analyzed the effect of donor-specific CAR Tregs on alloreactivity in naive, immunocompetent mice receiving skin allografts...
January 19, 2020: American Journal of Transplantation
Elizabeth L Godfrey, Tahir H Malik, Jennifer C Lai, Ayse L Mindikoglu, N Thao N Galván, Ronald T Cotton, Christine A O'Mahony, John A Goss, Abbas Rana
We appreciate Kwong et al.'s utilization of Harrell's c-statistic and its ability to incorporate follow-up time as a valuable contribution to the discussion about our group's findings.1 We acknowledge that the conventional area under receiver-operating-characteristic curve concordance statistic has limitations; however, we selected the conventional c-statistic to remain methodologically consistent with the manner in which the Model for End-Stage Liver Disease (MELD) was originally designed and validated, first to predict post-TIPS survival, then when applied to ESLD generally, and finally when integrated into allocation...
January 14, 2020: American Journal of Transplantation
Alex Manara, Sam D Shemie, Stephen Large, Andrew Healey, Andrew Baker, Mitesh Badiwala, Marius Berman, Andrew J Butler, Prosanto Chaudhury, John Dark, John Forsythe, Darren H Freed, Dale Gardiner, Dan Harvey, Laura Hornby, Janet MacLean, Simon Messer, Gabriel C Oniscu, Christy Simpson, Jeanne Teitelbaum, Sylvia Torrance, Lindsay C Wilson, Christopher J E Watson
There is international variability in the determination of death. Death in donation after circulatory death (DCD) can be defined by the permanent cessation of brain circulation. Post-mortem interventions that restore brain perfusion should be prohibited as they invalidate the diagnosis of death. Retrieval teams should develop protocols that ensure the continued absence of brain perfusion during DCD organ recovery. In situ normothermic regional perfusion (NRP) or restarting the heart in the donor's body may interrupt the permanent cessation of brain perfusion since, theoretically, collateral circulations may restore it...
January 10, 2020: American Journal of Transplantation
Jennifer Verbesey, Alvin G Thomas, Matt Ronin, Jennifer Beaumont, Amy Waterman, Dorry L Segev, Stuart M Flechner, Matthew Cooper
Cooperative kidney paired donation (KPD) networks account for an increasing proportion of all living donor kidney transplants in the United States. There is sparse data on the rate of primary non-function (PNF) losses and their consequences within KPD networks. We studied National Kidney Registry (NKR) transplants (2/14/2009-12/31/2017) and quantified PNF, graft loss within 30 days of transplantation, and graft losses in the first year post-transplant and assessed potential risk factors. Of 2364 transplants, there were 38 (1...
January 10, 2020: American Journal of Transplantation
Juan S Danobeitia, Tiffany J Zens, Peter J Chlebeck, Laura J Zitur, Jose A Reyes, Michael J Eerhart, Jennifer Coonen, Saverio Capuano, Anthony M D'Alessandro, Jose R Torrealba, Daniel Burguete, Kevin Brunner, Edwin Van, Amersfoort, Yolanda Ponstein-Simarro Doorten, Cees Van Kooten, Ewa Jankowska-Gan, William Burlingham, Jeremy Sullivan, Arjang Djamali, Myron Pozniak, Yucel Yankol, Luis A Fernandez
Delayed graft function (DGF) in renal transplantation is associated with reduced graft survival and increased immunogenicity. The complement-driven inflammatory response after brain death (BD) and post-transplant reperfusion injury play significant roles in the pathogenesis of DGF. In a non-human primate model, we tested complement-blockade in BD donors to prevent DGF and improve graft survival. BD donors were maintained 20-hours, kidneys were procured and stored at 4°C for a 43-48 hours prior to implantation into ABO-compatible, non-sensitized, MHC-mismatched recipients...
January 10, 2020: American Journal of Transplantation
Ankit Bharat
Lung transplantation, while increasingly being offered to an expanding list of end-stage lung diseases, still suffers from poor long-term outcomes due to the development of allograft rejection. Regulatory Foxp3+ T cells have emerged as important modulators of lung transplant tolerance (1). Bronchus-associated lymphoid tissue (BALT), enriched in Foxp3+ T cells as well as B cells, develops following lung transplantation. While some studies have implicated BALT in the pro-inflammatory host response and allograft rejection, others have shown that BALT promotes tolerance, predominantly through the accumulation of Foxp3+ T cells (2, 3)...
January 9, 2020: American Journal of Transplantation
Kiran Bambha, Alexandra Shingina, Jennifer L Dodge, Kevin O'Connor, Sue Dunn, Jennifer Prinz, Mark Pabst, Kathy Nilles, Lena Sibulesky, Scott W Biggins
U.S. deceased donor solid organ transplantation (dd-SOT) depends upon an individual's/family's altruistic willingness to donate organs after death; however, there is a shortage of deceased organ donors in the U.S. Informing individuals of their own lifetime risk of needing dd-SOT could reframe the decision-making around organ donation after death. Using United Network for Organ Sharing (UNOS) data (2007-2016), this cross-sectional study identified: (i)deceased organ donors; (ii)individuals wait-listed for dd-SOT (liver, kidney, pancreas, heart, lung, intestine); (iii)dd-SOT recipients...
January 9, 2020: American Journal of Transplantation
Brendan Parent, Nader Moazami, Stephen Wall, Julius Carillo, Zachary Kon, Deane Smith, B Corbett Walsh, Arthur Caplan
Controlled heart donation after circulatory determination of death (cDCD) is well-established internationally with good outcomes and could be adopted in the United States to increase heart supply if ethical and logistical challenges are comprehensively addressed. The most effective and resource-efficient method for mitigating warm ischemia after circulatory arrest is normothermic regional perfusion (NRP) in situ. This strategy requires restarting circulation after declaration of death according to circulatory criteria, which appears to challenge the legal circulatory death definition requiring irreversible cessation...
January 8, 2020: American Journal of Transplantation
V Forni Ogna, A Ogna, J Haba-Rubio, G Nowak, J-P Venetz, D Golshayan, M Matter, M Burnier, M Pascual, R Heinzer
Fluid overload has been associated with a high prevalence of sleep apnea (SA) in patients with end-stage kidney disease (ESKD). In this prospective study, we hypothesized that improvement of kidney function and hydration status after kidney transplantation (Tx) may result in an improvement of SA severity. A total of 196 patients on the kidney Tx waiting list were screened for SA using home nocturnal polysomnography (PSG) to measure the apnea-hypopnea index (AHI), and underwent bioimpedance to assess body composition...
January 8, 2020: American Journal of Transplantation
Naoya Yamada, Tadayoshi Karasawa, Taiichi Wakiya, Ai Sadatomo, Homare Ito, Ryo Kamata, Sachiko Watanabe, Takanori Komada, Hiroaki Kimura, Yukihiro Sanada, Yasunaru Sakuma, Koichi Mizuta, Nobuhiko Ohno, Naohiro Sata, Masafumi Takahashi
Hepatic ischemia-reperfusion (I/R) injury is a major problem in liver transplantation (LT). Although hepatocyte cell death is the initial event in hepatic I/R injury, the underlying mechanism remains unclear. In the present study, we retrospectively analyzed the clinical data of 202 pediatric living donor LT and found that a high serum ferritin level, a marker of iron overload, of the donor is an independent risk factor for liver damage after LT. Since ferroptosis has been recently discovered as an iron-dependent cell death that is triggered by a loss of cellular redox homeostasis, we investigated the role of ferroptosis in a murine model of hepatic I/R injury, and found that liver damage, lipid peroxidation, and upregulation of the ferroptosis marker Ptgs2 were induced by I/R, and all of these manifestations were markedly prevented by the ferroptosis-specific inhibitor ferrostatin-1 (Fer-1) or α-tocopherol...
January 7, 2020: American Journal of Transplantation
Elena Pérez-Nadales, Belén Gutiérrez-Gutiérrez, Alejandra M Natera, Edson Abdala, Maira Reina Magalhães, Alessandra Mularoni, Francesco Monaco, Ligia Camera Pierrotti, Maristela Pinheiro Freire, Ranganathan N Iyer, Seema Metha, Elisa Grazia Calvi, Mario Tumbarello, Marco Falcone, Mario Fernández-Ruiz, José María Costa-Mateo, Meenakshi M Rana, Tania Mara Varejão Strabelli, Mical Paul, María Carmen Fariñas, Wanessa Trindade Clemente, Emmanuel Roilides, Patricia Muñoz García, Laurent Dewispelaere, Belén Loeches, Warren Lowman, Ban Hock Tan, Rosa Escudero-Sánchez, Marta Bodro Marimont, Paolo Antonio Grossi, Fabio Soldani, Filiz Gunseren, Nina Nestorova, Álvaro Pascual, Luis Martínez-Martínez, José María Aguado, Jesús Rodríguez-Baño, Julián Torre-Cisneros
Treatment of carbapenemase-producing Enterobacterales bloodstream infections (CPE-BSI) in solid-organ transplant recipients (SOT) is challenging. The objective of this study was to develop a specific score to predict mortality in SOT recipients with CPE-BSI. A multinational, retrospective (2004-2016) cohort study (INCREMENT-SOT, NCT02852902) was performed. The main outcome variable was 30-day all-cause mortality. The INCREMENT-SOT-CPE score was developed using logistic regression. The global cohort included 216 patients...
December 31, 2019: American Journal of Transplantation
Emily Bethea, Ashwini Arvind, Jenna Gustafson, Karin Andersson, Daniel Pratt, Irun Bhan, Michael Thiim, Kathleen Corey, Patricia Bloom, Jim Markmann, Heidi Yeh, Nahel Elias, Shoko Kimura, Leigh Anne Dageforde, Alex Cuenca, Tatsuo Kawai, Kassem Safa, Winfred Williams, Hannah Gilligan, Meghan Sise, Jay Fishman, Camille Kotton, Arthur Kim, Christin Marks, Sarah Shao, Mariesa Cote, Linda Irwin, Paul Myoung, Raymond T Chung
The practice of transplanting hepatitis C (HCV)-infected livers into HCV-uninfected recipients has not previously been recommended in transplant guidelines, in part because of concerns over uncontrolled HCV infection of the allograft. Direct-acting antivirals (DAAs) provide an opportunity to treat donor derived HCV-infection, and should be administered early in the post-transplant period. However, evidence on the safety and efficacy of an immediate DAA treatment approach, including how to manage logistical barriers surrounding timely DAA procurement, are required prior to broader use of HCV-positive donor organs...
December 30, 2019: American Journal of Transplantation
Ankit Bharat
Lung allografts suffer from a high incidence of acute as well as chronic rejection. Due to exposure to the external milieu, lung allografts are also uniquely susceptible to damage from noxious stimuli. The diagnosis of allograft injury and differentiation from rejection requires transbronchial biopsy which is associated with severe complications, such as pneumothorax and bleeding, and is frequently inaccurate due to the heterogeneity observed in histopathology. The study by Halloran et al (1) attempts to operationalize machine learning based microarray analysis of pre-validated rejection-associated transcripts within mucosal biopsies, in lieu of transbronchial biopsies, to improve diagnostic accuracy and safety...
December 30, 2019: American Journal of Transplantation
Christopher O C Bellamy, Sandrine Prost
That allograft biopsies are still needed reflects that histopathology outperforms other modalities in difficult settings, because the underlying truth in a tissue sample cannot be recapitulated with other approaches. The unique advantage of tissue sections is the retention of spatial relationships to molecular level.
December 30, 2019: American Journal of Transplantation
Francisco M Marty, Per T Ljungman, Roy F Chemaly, Hong Wan, Valerie L Teal, Joan R Butterton, Wendy W Yeh, Randi Y Leavitt, Cyrus S Badshah
Letermovir, a cytomegalovirus (CMV) terminase-complex inhibitor, is indicated for prophylaxis of CMV infection and disease in adult CMV-seropositive recipients of allogeneic hematopoietic cell transplantation (HCT). In a phase III, double-blind, randomized trial, letermovir significantly reduced the risk of clinically significant CMV infection (CS-CMVi) vs placebo through Week 24 post-HCT. This analysis investigated outcomes in participants with detectable CMV DNA at randomization, who were excluded from the primary efficacy analysis...
December 28, 2019: American Journal of Transplantation
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