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American Journal of Transplantation

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https://www.readbyqxmd.com/read/30431704/geographic-disparities-in-lung-transplant-rates
#1
Martin Kosztowski, Sheng Zhou, Errol Bush, Robert S Higgins, Dorry L Segev, Sommer E Gentry
In November 2017, an emergency change to the lung allocation policy eliminated the donation service area (DSA) as the first geographic tier of allocation in response to a lawsuit from a New York City lung transplant candidate. The lawsuit claimed that DSA borders are arbitrary and that allocation should be based on medical priority. We investigated whether deceased-donor lung transplant (LT) rates differed substantially between DSAs in the United States prior to the policy change. We estimated LT rates per active person-year using multilevel Poisson regression and empirical Bayes methods...
November 15, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/30431703/cytomegalovirus-mismatch-still-negatively-affects-patient-and-graft-survival-in-the-era-of-routine-prophylactic-and-preemptive-therapy-a-paired-kidney-analysis
#2
N Leeaphorn, N Garg, N Thamcharoen, E V Khankin, F Cardarelli, M Pavlakis
The impact of CMV serostatus on kidney transplant outcomes in an era when CMV prophylactic and preemptive strategies are used routinely is not clearly established. Using UNOS/OPTN data, recipients with first deceased donor kidney transplant (≥18 years, 2010-2015) were stratified into 4 groups in the main cohort: D-/R-, D+/R-, D+/R+, and D-/R+. In a paired kidney cohort, we identified 2,899 pairs of D- kidney transplant with discordance of recipient serostatus (D-/R- vs D-/R+) and 4,567 pairs of D+ kidney transplant with discordance of recipient serostatus (D+/R- vs D+/R+)...
November 15, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/30417964/do-we-still-need-to-demonstrate-the-survival-benefit-of-pancreas-transplantation
#3
LETTER
Pedro Ventura-Aguiar, Joana Ferrer, Jordi Rovira, Fritz Diekmann
In this issue of the American Journal of Transplantation, Fridell et al1 et al retrospectively analyze the outcomes of pancreas transplant recipients from OPTN database. In summary, receiving a pancreas graft increased patient survival when compared to those who remained on the waiting list (WL) for a simultaneous kidney pancreas (SPK). Though these results are not unexpected for SPK recipients, the authors highlight a survival advantage in those who received a kidney transplant, and later a pancreas after kidney (PAK)...
November 12, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/30417539/molecular-phenotype-of-kidney-transplant-indication-biopsies-with-inflammation-in-scarred-areas
#4
Philip F Halloran, Arthur Matas, Bertram L Kasiske, Katelynn Madill-Thomsen, Martina Mackova, Konrad S Famulski
In kidney transplant biopsies, inflammation in areas of atrophy-fibrosis (i-IFTA) is associated with increased risk of failure, presumably because inflammation is evoked by recent parenchymal injury from rejection or other insults, but some cases also have rejection. The present study explored the frequency of rejection in i-IFTA, by histology Banff 2015 and microarray-based molecular diagnostic system (MMDx). In unselected indication biopsies (108 i-IFTA, 73 uninflamed IFTA (i0-IFTA), and 53 no IFTA), i-IFTA biopsies were later, more scarred, and had more antibody-mediated rejection (ABMR) by histology (28%) and MMDx (45%)...
November 12, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/30417522/long-term-psychosocial-outcomes-after-nondirected-donation-a-single-center-experience
#5
C Jacobs, D Berglund, J Wiseman, C Garvey, D Larson, M Voges, C Radecki Breitkopf, H N Ibrahim, A J Matas
Short-term studies have demonstrated that nondirected donors (NDDs) have similar psychosocial outcomes to those donating directly, but long-term studies have not been done. NDDs at our center were surveyed regarding motivation; support during donation; stresses related to donation; regret; financial resources used for donation; preferences about communication with the recipient; and cost reimbursement. Of 100 NDDs done at our center in the last 20 years, 95 remain in contact with us, and 77 responded to our survey (mean 6...
November 12, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/30414349/hla-dr-dq-molecular-mismatch-a-prognostic-biomarker-for-primary-alloimmunity
#6
Chris Wiebe, Vasilis Kosmoliaptsis, Denise Pochinco, Ian W Gibson, Julie Ho, Patricia E Birk, Aviva Goldberg, Martin Karpinski, Jamie Shaw, David N Rush, Peter W Nickerson
Alloimmune risk stratification in renal transplantation has lacked the necessary prognostic biomarkers to personalize recipient care or optimize clinical trials. HLA molecular mismatch improves precision compared to traditional antigen mismatch but has not been studied in detail at the individual molecule level. This study evaluated 664 renal transplant recipients and correlated HLA-DR/DQ single molecule eplet mismatch with serologic, histologic, and clinical outcomes. Compared to traditional HLA-DR/DQ whole antigen mismatch HLA-DR/DQ single molecule eplet mismatch improved the correlation with de novo donor-specific antibody (dnDSA) development (AUC 0...
November 10, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/30414243/multicenter-investigation-of-the-reliability-and-validity-of-the-live-donor-assessment-tool-as-an-enhancement-to-the-psychosocial-evaluation-of-living-donors
#7
Yoon Won Amy Kook, Akhil Shenoy, Julia Hunt, Farrah Desrosiers, Janna S Gordon-Elliott, Sheila Jowsey-Gregoire, Joyce A Trompeta, Margo Vandrovec, Sandra Weinberg, Weijia Fan, Dianne LaPointe Rudow
The Live Donor Assessment Tool (LDAT) is the first psychosocial assessment tool developed to standardize live donor psychosocial evaluations. A multi-center study was conducted to explore reliability and validity of the LDAT and determine its ability to enhance the psychosocial evaluation beyond its center of origin. Four transplant programs participated, each with their own team of evaluators and unique demographics. Liver and kidney living donors (LDs) undergoing both standard psychosocial evaluation and LDAT from June 2015 to September 2016 were studied...
November 10, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/30412654/long-term-outcomes-of-eculizumab-treated-positive-crossmatch-recipients-allograft-survival-histologic-findings-and-natural-history-of-the-donor-specific-antibodies
#8
Carrie A Schinstock, Andrew J Bentall, Byron H Smith, Lynn D Cornell, Matthew Everly, Manish J Gandhi, Mark D Stegall
We aimed to determine long-term outcomes for eculizumab-treated, positive crossmatch (+XM) kidney transplant recipients compared with +XM and age-matched negative crossmatch (-XM) controls. We performed an observational retrospective study and examined allograft survival, histologic findings, long-term B-cell flow cytometric XM (BFXM), and allograft-loss-associated factors. The mean (SD) posttransplant follow-up was 6.3 (2.5) years in the eculizumab group; 7.6 (3.5), +XM control group; 7.9 (2.5), -XM control group...
November 9, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/30412648/is-the-hub-and-spoke-model-of-care-delivery-a-possible-answer-to-geographical-variation-in-liver-transplant-outcomes
#9
LETTER
D Tai, C Timehin, D Patch, D Thorburn, R H Westbrook
We read with interest the United Kingdom (UK) transplant registry analysis article by Webb et al on the proximity to transplant center and outcome among Liver Transplant (LT) patients (1). The negative correlation between travel time to the LT center and subsequent access to organs and mortality is of great concern. This article is protected by copyright. All rights reserved.
November 9, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/30411840/refinement-of-humoral-rejection-effector-mechanisms-to-identify-specific-pathogenic-histological-lesions-with-different-graft-outcomes
#10
LETTER
Oriol Bestard, Josep Grinyó
In this issue, Senev and colleagues reported a large retrospective study of kidney transplant patients (n=935), in whom the impact on graft outcome of the histological phenotype of antibody-mediated rejection following the 2015 Banff classification (ABMRh ) was investigated according to the presence or absence of circulating HLA-DSA (DSApos ABMRh and DSAneg ABMRh , respectively) (1). Additionally, authors assessed if C4d-positivity in peritubular capillaries (PTCs) could be used as a surrogate for circulating DSA, as proposed by the 2017 Banff classification...
November 9, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/30411502/opposite-acute-potassium-and-sodium-shifts-during-transplantation-of-hypothermic-machine-perfused-donor-livers
#11
Laura C Burlage, Lara Hessels, Rianne van Rijn, Alix P M Matton, Masato Fujiyoshi, Aad P van den Berg, Koen Reyntjens, Peter Meyer, Marieke T de Boer, Ruben H J de Kleine, Maarten W Nijsten, Robert J Porte
Liver transplantation is frequently associated with hyperkalemia, especially after graft reperfusion. Dual hypothermic oxygenated machine perfusion (DHOPE) reduces ischemia/reperfusion injury and improves graft function, compared to conventional static cold storage (SCS). We examined the effect of DHOPE on ex situ and in vivo shifts of potassium and sodium. Potassium and sodium shifts were derived from balance measurements in a preclinical study of livers that underwent DHOPE (n=6) or SCS alone (n=9), followed by ex situ normothermic reperfusion...
November 9, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/30411495/development-and-validation-of-an-optimized-prediction-of-mortality-for-candidates-awaiting-liver-transplantation
#12
Dimitris Bertsimas, Jerry Kung, Nikolaos Trichakis, Yuchen Wang, Ryutaro Hirose, Parsia A Vagefi
Since 2002, the Model for End-Stage Liver Disease (MELD) has been used to rank liver transplant candidates. However, despite numerous revisions, MELD allocation still does not allow for equitable access to all waitlisted candidates. An Optimized Prediction of Mortality (OPOM) was developed (http://www.opom.online) utilizing machine learning Optimal Classification Tree models trained to predict a candidate's three-month waitlist mortality or removal utilizing the Standard Transplant Analysis and Research (STAR) dataset...
November 9, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/30408329/mitochondrial-membrane-potential-and-delayed-graft-function-following-kidney-transplantation
#13
Jacqueline M Garonzik-Wang, Bonnie E Lonze, Jessica M Ruck, Xun Luo, Allan B Massie, Keith Melancon, James F Burdick, Dorry L Segev, Zhaoli Sun
Delayed graft function (DGF) complicates 20-40% of deceased-donor kidney transplants and is associated with increased length of stay and subsequent allograft failure. Accurate prediction of DGF risk for a particular allograft could influence organ allocation, patient counseling, and post-operative planning. Mitochondrial dysfunction, a reported surrogate of tissue health in ischemia-perfusion injury, might also be a surrogate for tissue health after organ transplantation. To understand the potential of MMP in clinical decision-making, we analyzed whether lower mitochondrial membrane potential (MMP), a measure of mitochondrial dysfunction, was associated with DGF...
November 8, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/30378766/neutrophil-extracellular-trap-fragments-stimulate-innate-immune-responses-that-prevent-lung-transplant-tolerance
#14
Davide Scozzi, Xingan Wang, Fuyi Liao, Liu Zhiyi, Jihong Zhu, Katy Pugh, Mohsen Ibrahim, Hsi-Min Hsiao, Mark J Miller, Yizhan Guo, Thalachallour Mohanakumar, Alexander S Krupnick, Daniel Kreisel, Andrew E Gelman
Neutrophil extracellular traps (NETs) have been shown to worsen acute pulmonary injury including after lung transplantation. The breakdown of NETs by DNAse-1 can help restore lung function, but whether there is an impact on allograft tolerance remains less clear. Using intravital 2-photon microscopy, we analyzed the effects of DNAse-1 on NETs in mouse orthotopic lung allografts damaged by ischemia-reperfusion injury. Although DNAse-1 treatment rapidly degrades intragraft NETs the consequential release of NET fragments induces prolonged interactions between infiltrating CD4+ T cells and donor-derived antigen presenting cells...
October 31, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/30378753/restructuring-the-optn-contract-to-achieve-policy-coherence-and-infrastructure-excellence
#15
Sommer E Gentry, Dorry L Segev
The OPTN went up for competitive bid again this year, yet this contract has been held by only one entity since its inception. The OPTN's scope has grown steadily, and now embraces several disparate missions: to operate the computing and coordination infrastructure that maintains waiting lists and makes organ offers in priority order, to regulate transplant centers and OPOs, to follow and protect living donors, and to decide organ allocation policy in concert with the many voices of the transplant community...
October 31, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/30378751/synthetic-poly-ethylene-glycol-based-microfluidic-islet-encapsulation-reduces-graft-volume-for-delivery-to-highly-vascularized-and-retrievable-transplant-site
#16
Jessica D Weaver, Devon M Headen, Maria M Coronel, Michael D Hunckler, Haval Shirwan, Andrés J García
Transplantation of hydrogel-encapsulated allogeneic islets has been explored to reduce or eliminate the need for chronic systemic immunosuppression by creating a physical barrier which prevents direct antigen presentation. Although successful in rodents, translation of alginate microencapsulation to large animals and humans has been hindered by large capsule sizes (≥500 μm diameter) that result in suboptimal nutrient diffusion in the intraperitoneal space. We developed a microfluidic encapsulation system which generates synthetic poly(ethylene glycol) (PEG)-based microgels with smaller diameters (310 ± 14 μm) that improve encapsulated islet insulin responsiveness over alginate capsules and allow transplantation within vascularized tissue spaces, thereby reducing islet mass requirements and graft volumes...
October 31, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/30378749/impact-of-mbl2-gene-polymorphisms-on-the-risk-of-infection-in-solid-organ-transplant-recipients-a-systematic-review-and-meta-analysis
#17
Mario Fernández-Ruiz, Estela Giménez, David Lora, José María Aguado, Manuel Pascual, Oriol Manuel
Mannose-binding lectin (MBL) is a soluble pattern recognition molecule involved in complement activation. Single nucleotide polymorphisms (SNPs) in the MBL2 gene have been associated with susceptibility to infection, although data in solid organ transplant recipients remains inconclusive. This meta-analysis was primarily aimed at investigating the association between post-transplant bacterial and fungal infection and variant alleles of MBL2 gene SNPs in the promoter/5' untranslated region and exon 1. Cytomegalovirus (CMV) infection and/or disease were considered secondary outcomes...
October 31, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/30378739/spectrum-of-chronic-lung-allograft-pathology-in-a-mouse-minor-mismatched-orthotopic-lung-transplant-model
#18
Tereza Martinu, Hisashi Oishi, Stephen C Juvet, Marcelo Cypel, Mingyao Liu, Gerald J Berry, David M Hwang, Shaf Keshavjee
Chronic lung allograft dysfunction (CLAD) is a fatal condition that limits survival after lung transplantation (LTx). The pathological hallmark of CLAD is obliterative bronchiolitis (OB). A subset of patients present with a more aggressive CLAD phenotype, called restrictive allograft syndrome (RAS), characterized by lung parenchymal fibrosis (PF). The mouse orthotopic single LTx model has proven relevant to the mechanistic study of allograft injury. The minor-alloantigen- mismatched strain combination using C57BL/10(B10) donors and C57BL/6(B6) recipients reportedly leads to OB...
October 31, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/30378738/on-the-elusive-tcr-specificity-of-thymic-regulatory-t-cells
#19
Christian LeGuern, Sharon Germana
Therapies using thymus-derived regulatory T cells (Tregs) are promising strategies for preventing autoimmunity or graft rejection. The efficacy of these approaches is, however, contingent on a better understanding of Treg mode of action, especially about factors controlling their activation in vivo. Although key parameters of Treg suppression have been identified, little information is available on Treg activation in vivo via the TCR. In the light of recent studies using TCR transgenic mouse models as well as unpublished data, we discuss evidence in support of the view that Treg TCR specificities are not necessarily highly diverse, that the accessibility of Treg selective antigens controls Treg development and that peptides derived from MHC class II (MHC-II) could be prevailing antigens involved in Treg selection...
October 31, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/30378723/liver-transplantation-for-hcv-non-viremic-recipients-with-hcv-viremic-donors
#20
Allison J Kwong, Anji Wall, Marc Melcher, Uerica Wang, Aijaz Ahmed, Aruna Subramanian, Paul Y Kwo
In the context of organ shortage, the opioid epidemic, and effective direct-acting antiviral (DAA) therapy for hepatitis C (HCV), more HCV-infected donor organs may be used for liver transplantation. Current data regarding outcomes after donor-derived HCV in previously non-viremic liver transplant recipients are limited. Clinical data for adult liver transplant recipients with donor-derived HCV infection from March 2017 to January 2018 at our institution were extracted from the medical record. Ten patients received livers from donors known to be infected with HCV based on positive nucleic acid testing (NAT)...
October 31, 2018: American Journal of Transplantation
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