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American Journal of Transplantation

Brian J Nankivell
Thank you for the opportunity to respond to an alternative perspective of i-IFTA presented by Drs Famulski and Halloran (1), which concentrates on a failed correlation with a singular molecular classifier in late indication-biopsies of mixed antibody-mediated rejection. Two recent cohort studies of i-IFTA started much earlier post-transplant, and both found strong correlations with TCMR that was independent of DSA (2,3). Inferences and conclusions are not directly transferrable between these different populations...
January 11, 2018: American Journal of Transplantation
Xun Luo, Joseph Leanza, Allan B Massie, Jacqueline M Garonzik-Wang, Christine E Haugen, Sommer E Gentry, Shane E Ottmann, Dorry L Segev
Currently, there is debate among the liver transplant community regarding the most appropriate mechanism for organ allocation: urgency-based (MELD) versus utility-based (survival benefit). We hypothesize that MELD and survival benefit are closely associated, and therefore, our current MELD-based allocation already reflects utility-based allocation. We used generalized gamma parametric models to quantify survival benefit of LT across MELD categories among 74,196 adult liver-only active candidates between 2006 and 2016 in the United States...
January 9, 2018: American Journal of Transplantation
Jose Miguel Pérez-Villares, Ramón Lara-Rosales, Alberto Fernández-Carmona, Patricia Fuentes-Garcia, Manuel Burgos-Fuentes, Blas Baquedano-Fernández
The scarcity of potential dead brain donors (DBD) and the persistent mismatch between supply and demand of organs for transplantation has led the transplant community to reconsider donation after circulatory death (DCD) as a strategy to increase the donor pool. Controlled donation after circulatory death (cDCD) has emerged as the most feasible way to expand the number of transplantations. In Spain, cDCD accounted for 18% of the total number of deceased donors in 2016. At present, a total of 68 hospitals in Spain have cDCD programs1 ...
January 9, 2018: American Journal of Transplantation
P Bonnafous, J Marlet, D Bouvet, E Salamé, A-C Tellier, S Guyetant, A Goudeau, H Agut, A Gautheret-Dejean, C Gaudy-Graffin
HHV-6A and HHV-6B are found as inherited and chromosomally integrated forms (iciHHV-6A and -6B) into all germinal and somatic cells and vertically transmitted in a Mendelian manner in about 1% of the population. They were occasionally shown to be horizontally transmitted through hematopoietic stem cell transplantation. Here, we present a clinical case of horizontal transmission of iciHHV-6A from donor to recipient through liver transplantation. Molecular analysis performed on three viral genes (7.2 kb) in the recipient and donor samples supports transmission of iciHHV-6A from the graft...
January 9, 2018: American Journal of Transplantation
Konrad S Famulski, Philip F Halloran
We read with interest the analysis of inflammation in areas of atrophy-scarring (i-IFTA) in renal transplant biopsies by Nankivell et al (1), concluding that this represents chronic active T cell-mediated rejection. This theme is also advocated by another recent publication (2) and by the forthcoming Banff report (3), contradicting the previous Banff consensus opinion that i-IFTA lesions are a reflection of injury and a risk for progression but not a sign of active TCMR. We write because molecular analyses do not support the conclusion that i-IFTA indicates chronic active TCMR...
January 9, 2018: American Journal of Transplantation
Z Zhang, L Liu, H Tang, W Jiao, S Zeng, Y Xu, Q Zhang, Z Sun, A Mukherjee, X Zhang, X Hu
The alterations induced in gut microbiota by tacrolimus may affect immune function and organ transplantation. Mice were treated with a high-dose of tacrolimus for 14 days. The fecal microbiota were analyzed by pyrosequencing the 16S rRNA genes, and the effect on metabolism was predicted using the sequence data. The subgroups of T cells in the serum, gut-associated lymphoid tissue and draining lymph nodes were determined by flow cytometry. Tacrolimus treatment significantly altered the relative abundance of Allobaculum, Bacteroides and Lactobacillus and CD4+ CD25hi FoxP3+ regulatory T-cells in the colonic mucosa and the circulation...
January 9, 2018: American Journal of Transplantation
Jesse D Schold, Kenneth A Andreoni, Anil K Chandraker, Robert S Gaston, Jayme E Locke, Amit K Mathur, Timothy Pruett, Abbas Rana, Lloyd E Ratner, Laura D Buccini
Outcomes of patients receiving solid organ transplants in the United States are systematically aggregated into bi-annual Program-Specific Reports (PSRs) detailing risk-adjusted survival by transplant center. Recently, the Scientific Registry of Transplant Recipients(SRTR) issued 5-tier ratings evaluating centers based on risk-adjusted one-year graft survival. Our primary aim was to examine the reliability of 5-tier ratings over time. Using ten consecutive PSRs for adult kidney transplant centers from June,2012 to December,2016(n=208) we applied 5-tier ratings to center outcomes and evaluated ratings over time...
January 9, 2018: American Journal of Transplantation
A H Querard, F Le Borgne, A Dion, M Giral, G Mourad, V Garrigue, L Rostaing, N Kamar, A Loupy, C Legendre, E Morelon, F Buron, Y Foucher, E Dantan
From a prospective and multicentric French cohort, we proposed an external validation study for the Expanded Criteria Donor (ECD), based on 4833 kidney recipients transplanted for the first time between 2000 and 2014. We estimated the subject-specific effect from a multivariable Cox model. We confirmed a 1.75-fold (95%CI from 1.53 to 2.00, p<0.0001) increase in graft failure risk if a given patient received an ECD graft compared to a graft from a donor with standard criteria (SCD). Complementarily, we estimated the population-average effect using propensity scores...
January 9, 2018: American Journal of Transplantation
E Nordheim, R Horneland, E M Aandahl, K Grzyb, L Aabakken, V Paulsen, K Midtvedt, A Hartmann, T Jenssen
The surgical technique with duodeno- duodenal enteroanastomosis of pancreas transplants allows for representative endoscopic ultrasound guided needle biopsies of the donor duodenum and the pancreas graft. We assessed whether histological findings in transplanted donor duodenal biopsies can indicate rejection in the transplanted pancreas. From September 2012, a duodeno-duodenal enteroanastomosis has been default technique for pancreas transplantations at our center. In 67 recipients we prospectively examined 113 endoscopic ultrasound- guided procedures with representative biopsies from the duodenum- and the pancreas grafts (97 per protocol and 16 on indication)...
January 9, 2018: American Journal of Transplantation
Monal Sharma, Wei Liu, Sudhir Perincheri, Muthukumar Gunasekaran, T Mohanakumar
Long-term success of heart transplantation is hindered by humoral and cell-mediated immune responses. We studied preexisting antibodies to two cardiac self-antigens, myosin and vimentin, and exosomes induced by antibodies to self-antigens in eliciting immune responses to cardiac grafts. After syngeneic heterotopic murine heart transplantation, rabbit anti-myosin or normal rabbit immunoglobulin was administered at days 0 or 7. Sera were collected after heartbeat cessation and cellular infiltration was analyzed, and exosomes were isolated from sera...
January 9, 2018: American Journal of Transplantation
Piero Ruggenenti, Giuseppe Remuzzi
Graft survival in 37 recipients of one or two histologically evaluated kidneys from octogenarian donors with a KDPI of 96-100% was similar to that observed in 198 recipients of non-histologically evaluated single grafts from <60-year-old donors with a KDPI of 0-95%.1 Ekser and coworkers2 consistently reported 91% 5-year graft survival in 100 recipients of dual transplants of histologically evaluated kidneys from >60-year-old donors with cerebrovascular death and a KDPI of >85%. Thus, both studies, as well as previous reports in a similar context,3 converge to indicate that kidneys from >60-year-old donors with a KDPI of >85% can safely be used, provided their kidneys are selected and allocated on the basis of pre-transplant histological findings...
January 9, 2018: American Journal of Transplantation
Lorenzo Norsa, Girish Gupte, Esther Ramos Boluda, Francisca Joly, Olivier Corcos, Jacques Pirenne, Gustaf Herlenius, Florence Lacaille
A multicenter Europe-wide single point study in intestinal transplantation (ITx) centers was conducted to identify and describe patients surviving for more than 10 years after ITx in childhood. The health and nutritional status, care requirements and psychosocial status were recorded. Among 120 transplanted before 2005, 38 patients with a functioning graft were included. Thirty (79%) had an exclusive oral diet, 7 (18%) complimentary enteral nutrition for eating disorders, one a combination of parenteral and enteral nutrition...
January 9, 2018: American Journal of Transplantation
Timothy Sullivan
In their recent study (1), Sawinski et al present compelling evidence of the potential harms of HIV protease inhibitors (PIs) following kidney transplantation. In this study, PI use was associated with an increased risk of both allograft loss and death. As the authors note, the link between graft failure and PI use can be attributed to the major interaction between PIs and calcineurin inhibitors (CNIs), which likely results in high rates of acute rejection and CNI toxicity. This article is protected by copyright...
January 9, 2018: American Journal of Transplantation
D Bobylev, J Salman, W Sommer, F Ius, T Siemeni, M Avsar, C Kühn, A Niehaus, J Gottlieb, A Haverich, I Tudorache, G Warnecke
Scarcity of donors leads transplant surgeons to consider extended-criteria lungs and occasionally to accept the unlikely. Here we report a case of successful single lung transplantation from a donor 8 months after double lung transplantation. This article is protected by copyright. All rights reserved.
January 4, 2018: American Journal of Transplantation
Daniel R Kaul
Unexpected donor-derived infections (DDI) are relatively uncommon events complicating less than 1% of solid organ transplants (1). Disease can be severe, however, with malignancies and agents that infect the central nervous system carrying a particularly high risk of adverse outcomes (2). In most cases, this risk is managed by a combination of clinical assessment and pre-procurement donor testing. This article is protected by copyright. All rights reserved.
January 4, 2018: American Journal of Transplantation
Mounia S Braza, Patricia Conde, Mercedes Garcia, Isabel Cortegano, Manisha Brahmachary, Venu Pothula, Francois Fay, Peter Boros, Sherry A Werner, Florent Ginhoux, Willem J M Mulder, Jordi Ochando
The colony-stimulating factor 1 (CSF1) regulates the differentiation and function of tissue macrophages and determines the outcome of the immune response. The molecular mechanisms behind CSF1-mediated macrophage development remain to be elucidated. Here we demonstrate that neutrophil-derived CSF1 controls macrophage polarization and proliferation, which is necessary for the induction of tolerance. Inhibiting neutrophil production of CSF1 or preventing macrophage proliferation, using targeted nanoparticles loaded with the cell cycle inhibitor simvastatin, abrogates the induction of tolerance...
January 4, 2018: American Journal of Transplantation
Robert Ettenger, Renata Albrecht, Rita Alloway, Ozlem Belen, Marc W Cavaillé-Coll, Marie A Chisholm-Burns, Mary Amanda Dew, William E Fitzsimmons, Peter Nickerson, Graham Thompson, Pujita Vaidya
The Food and Drug Administration (FDA) held a public meeting and scientific workshop in September 2016 to obtain perspectives from solid organ transplant recipients, family caregivers, and other patient representatives. The morning sessions focused on the impact- of organ transplantation on patients' daily lives and the spectrum of activities undertaken to maintain grafts. Participants described the physical, emotional, and social impacts of their transplant on daily life. They also discussed their post-transplant treatment regimens, including the most burdensome side effects and their hopes for future treatment...
December 30, 2017: American Journal of Transplantation
Jesse D Schold, Jayme E Locke
Population health has been broadly defined as "health outcomes of a group of individuals, including the distribution of such outcomes within the group." (1) Increasingly, population health has gained prominence and impact with emergence of Accountable Care Organizations that serve populations across transitions of care and different providers (often extended to communities). Population health has also been a focus of healthcare reform and development of policies and interventions aimed at simultaneously improving quality and reducing costs...
December 30, 2017: American Journal of Transplantation
Rebecca Craig-Schapiro, Besma Nejim, Isibor Arhuidese, Mahmoud B Malas
While studies demonstrate poor outcomes of lower extremity revascularization in end-stage renal disease patients, little is known about results in renal transplant patients. We analyzed 2-year primary patency and limb salvage outcomes and associated risk factors of transplant (N=202) and non-transplant patients (N=25,274) in the Vascular Quality Initiative database undergoing infrainguinal bypass from 2003-2016. Multivariable Cox regression analysis and coarsened exact matching with many-to-one were employed...
December 29, 2017: American Journal of Transplantation
R N Smith, M Matsunami, B A Adam, I A Rosales, T Oura, A B Cosimi, T Kawai, M Mengel, R B Colvin
Tolerance induction to prevent allograft rejection is a long standing clinical goal. However, convincing and dependable tolerance identification remains elusive. Hypothesizing that intragraft RNA expression is informative in both rejection and tolerance, we profile intra-renal allograft RNA expression in a mixed chimerism renal allograft model of Cynomolgus monkeys and identify biologically significant tolerance. Analysis of 67 genes identified three dominant factors, each with a different pattern of gene expressions, relating to T cell mediated rejection (TCMR), chronic antibody mediated rejection (CAMR), or Tolerance...
December 29, 2017: American Journal of Transplantation
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