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Transplantation

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https://www.readbyqxmd.com/read/28230646/effect-of-calcineurin-inhibitor-free-everolimus-based-immunosuppressive-regimen-on-albuminuria-and-glomerular-filtration-rate-after-heart-transplantation
#1
Lærke M Nelson, Arne K Andreassen, Bert Andersson, Einar Gude, Hans Eiskjær, Göran Rådegran, Göran Dellgren, Lars Gullestad, Finn Gustafsson
BACKGROUND: Albuminuria in maintenance heart transplantation (HTx) is associated with poor renal response when switching to a calcineurin inhibitor (CNI)-lowered or free immunosuppressive regimen using everolimus (EVR), but the significance of albuminuria associated with EVR treatment after early CNI withdrawal in de novo HTx is unknown. METHODS: We tested if glomerular filtration rate (mGFR, measured by CrEDTA clearance) was associated with urine albumin/creatinine ratio (UACR) post-HTx in a subgroup of patients included in the SCHEDULE trial, where de novo HTx patients (n=115) were randomized to EVR with complete CNI elimination 7-11 weeks post-HTx or standard CNI immunosuppression...
February 23, 2017: Transplantation
https://www.readbyqxmd.com/read/28230645/clinical-scale-rapid-autologous-bk-virus-specific-t-cell-line-generation-from-kidney-transplant-recipients-with-active-viremia-for-adoptive-immunotherapy
#2
Caroline Lamarche, Julie Orio, Victoria Georges-Tobar, Thomas Pincez, Mathieu Goupil, Amina Dahmani, Cedric Carli C, Ann Brasey, Lambert Busque, Jean-Sébastien Delisle
BACKGROUND: Polyomavirus-associated nephropathy (PVAN) following BK virus reactivation in kidney transplant recipients (KTR) can compromise graft survival. Lowering immunosuppression is the only established approach to prevent or treat PVAN but nonspecifically increasing host immune competence also augments rejection risk. Ex vivo T cell stimulation/expansion offers the possibility to generate BK-specific T cell lines for adoptive immunotherapy. The objective of this study was to develop and characterize a clinical scale protocol to generate BK-specific T cell lines from viremic KTR...
February 23, 2017: Transplantation
https://www.readbyqxmd.com/read/28230644/expanding-the-donor-pool-through-intensive-care-to-facilitate-organ-donation-results-of-a-spanish-multicenter-study
#3
Beatriz Domínguez-Gil, Elisabeth Coll, José Elizalde, Jaime E Herrero, Teresa Pont, Brígida Quindós, Bella Marcelo, María A Bodí, Adolfo Martínez, Agustín Nebra, Francisco Guerrero, José M Manciño, Juan Galán, Miguel Lebrón, Eduardo Miñambres, Rafael Matesanz
BACKGROUND: Intensive Care to facilitate Organ Donation (ICOD) may help to increase the donor pool. We describe the Spanish experience with ICOD. METHODS: ACCORD-Spain consisted of an audit of the donation pathway from patients dead as a result of a devastating brain injury (possible donors) in 68 hospitals during 11/1/2014-4/30/2015. We focused on possible donors whose family was interviewed to discuss organ donation once intensive care with a therapeutic purpose was deemed futile and brain death (BD) was a likely outcome...
February 23, 2017: Transplantation
https://www.readbyqxmd.com/read/28230643/mtor-inhibition-clinical-transplantation-pancreas-islet
#4
Thierry Berney, Axel Andres, Christian Toso, Pietro Majno, Jean-Paul Squifflet
This brief overview discusses the beneficial and deleterious effects of mTOR inhibitors on beta-cells, and how sirolimus- and everolimus-based immunosuppression have impacted on practices and outcomes of pancreas and islet transplantation. Sirolimus was the cornerstone of immunosuppressive regimens in islet transplantation at the turn of the millenium, but utilization of mTOR inhibitors has progressively decreased from >80% to <50% of islet transplant recipients in more recent years. For whole pancreas transplantation, mTOR inhibitors were used in approximately 20% of patients in the early 2000s, but this dropped over the years to <10% currently...
February 23, 2017: Transplantation
https://www.readbyqxmd.com/read/28230642/strategies-to-obtain-diverse-and-specific-human-monoclonal-antibodies-from-transgenic-animals
#5
Marianne Brüggemann, Michael J Osborn, Biao Ma, Roland Buelow
Techniques to obtain large quantities of antigen-specific monoclonal antibodies, mAbs, were first established in the 1970s when Georges Köhler and César Milstein immortalized antibody-producing mouse B-lymphocytes by fusion with myeloma cells (http://www.whatisbiotechnology.org/exhibitions/milstein). Combined with the expression of human antibodies in transgenic animals, this technique allowed upon immunization the generation of highly specific fully human mAbs for therapeutic applications. Apart from being extremely beneficial, mAbs are a huge success commercially...
February 23, 2017: Transplantation
https://www.readbyqxmd.com/read/28230641/peritransplant-energy-changes-and-their-correlation-to-outcome-after-human-liver-transplantation
#6
Bote G Bruinsma, James H Avruch, Gautham V Sridharan, Pepijn D Weeder, Marie Louise Jacobs, Kerry Crisalli, Beth Amundsen, Robert J Porte, James F Markmann, Korkut Uygun, Heidi Yeh
BACKGROUND: The ongoing shortage of donor livers for transplantation and the increased use of marginal livers necessitate the development of accurate pretransplant tests of viability. Considering the importance energy status during transplantation, we aimed to correlate peritransplant energy cofactors to posttransplant outcome and subsequently model this in an ex vivo setting. METHODS: Sequential biopsies were taken from 19 donor livers postpreservation, as well as 30 min after portal venous (PVR) and hepatic arterial reperfusion (HAR) and analyzed by LC-MS for energetic cofactors (ATP/ADP/AMP, NADH/NAD, NADPH/NADP, FAD, GSSG/GSH)...
February 23, 2017: Transplantation
https://www.readbyqxmd.com/read/28230639/mammalian-target-of-rapamycin-inhibition-clinical-transplantation-liver
#7
Björn Nashan
The evidence base concerning use of mammalian target of rapamycin (mTOR) inhibitor therapy after liver transplantation is evolving rapidly, clarifying their benefits and disadvantages in different clinical scenarios. The H2304 trial showed that starting everolimus at 1 month posttransplant, with reduced tacrolimus, achieves a sustained improvement in renal function versus standard tacrolimus-based therapy, with at least equivalent immunosuppressive efficacy. Randomized studies evaluating early discontinuation of CNI therapy after introduction of an mTOR inhibitor consistently demonstrated a substantial improvement in renal function versus standard CNI therapy...
February 23, 2017: Transplantation
https://www.readbyqxmd.com/read/28230638/mtor-inhibition-cardiovascular-diseases-dyslipidemia-and-atherosclerosis
#8
Ammar Kurdi, Wim Martinet, Guido R Y De Meyer
Inhibitors of the mechanistic target of rapamycin (mTOR) have unique anti-atherosclerotic effects such as depletion of plaque macrophages, induction of autophagy and activation of cholesterol efflux. However, a common side effect of their use is dyslipidemia, a well-known risk factor for atherosclerosis. Indeed, mTOR inhibitors prevent lipid storage, increase LDL cholesterol levels and activate lipolysis. Although the net effect of mTOR inhibition seems favorable, the use of cholesterol lowering drugs to manage dyslipidemia remains the most recommended strategy...
February 23, 2017: Transplantation
https://www.readbyqxmd.com/read/28230637/mtor-inhibition-and-cardiovascular-diseases-cardiac-hypertrophy
#9
Ernesto Paoletti
Left ventricular hypertrophy (LVH) is highly prevalent in kidney transplant recipients, and is associated with poor clinical outcome. Immunosuppressive agents might affect LVH behavior after kidney transplantation. This review is an appraisal of available data regarding LVH in renal transplantation and especially of studies that evaluated LVH response to treatment. In particular, the role of mammalian target of rapamycin inhibitors adopted as immunosuppressive agents in kidney transplantation is reviewed in the light of recent studies that have shown LVH regression induced by this class of medications in kidney transplant recipients with posttransplant cardiomyopathy...
February 23, 2017: Transplantation
https://www.readbyqxmd.com/read/28230636/mtor-inhibition-clinical-transplantation-kidney
#10
Stuart M Flechner
No abstract text is available yet for this article.
February 23, 2017: Transplantation
https://www.readbyqxmd.com/read/28230640/disparities-in-waitlist-and-posttransplantation-outcomes-in-liver-transplant-registrants-and-recipients-18-24-years-old-analysis-of-the-unos-database
#11
Noelle H Ebel, Evelyn K Hsu, Kristin Berry, Simon P Horslen, George N Ioannou
BACKGROUND: We evaluated liver transplantation waitlist and posttransplantation outcomes in 18-24 year olds compared to both younger (0-17 year old) and older (25-34 year old) registrants and recipients. METHODS: Utilizing national data from the United Network for Organ Sharing, competing risk, Cox regression and Kaplan-Meier analyses were performed on first-time liver transplant registrants (n=13,979) and recipients (n=8,718) ages 0-34 years old between 2002 to 2015...
February 22, 2017: Transplantation
https://www.readbyqxmd.com/read/28221244/hla-amino-acid-polymorphisms-and-kidney-allograft-survival
#12
Malek Kamoun, Keith P McCullough, Martin Maiers, Marcelo A Fernandez Vina, Hongzhe Li, Valerie Teal, Alan B Leichtman, Robert M Merion
BACKGROUND: The association of HLA mismatching with kidney allograft survival has been well established. We examined whether amino acid mismatches at the antigen recognition site of HLA molecules represent independent and incremental risk factors for kidney graft failure (GF) beyond those mismatches assessed at the antigenic (2-digit) specificity. METHODS: Data on 240,024 kidney transplants performed between 1987 and 2009 were obtained from the Scientific Registry of Transplant Recipients...
February 18, 2017: Transplantation
https://www.readbyqxmd.com/read/28212220/hcv-antiviral-therapy-in-liver-transplant-candidates-and-recipients-with-renal-insufficiency
#13
Elizabeth C Verna, Robert S Brown
Hepatitis C virus (HCV) remains the leading indication for liver transplant in much of the world, and has traditionally been associated with diminished posttransplant survival due to recurrent HCV-related liver disease. This field has been dramatically changed by the advent of safe and effective directly active antiviral (DAA) therapy, such that most patients can be cured in the pre or posttransplant setting. In addition, there are now DAA regimens specifically approved for use in patients with severe renal insufficiency...
February 16, 2017: Transplantation
https://www.readbyqxmd.com/read/28207639/predictors-of-waitlist-mortality-in-portopulmonary-hypertension
#14
Hilary M DuBrock, David S Goldberg, Norman L Sussman, Sonja D Bartolome, Zakiyah Kadry, Reena J Salgia, David C Mulligan, Walter K Kremers, Steven M Kawut, Michael J Krowka, Richard N Channick
BACKGROUND: The current Organ Procurement Transplantation Network (OPTN) policy grants Model for End Stage Liver Disease (MELD) exception points to patients with portopulmonary hypertension (POPH), but potentially important factors, such as severity of liver disease and pulmonary hypertension, are not included in the exception score, and may affect survival. The purpose of this study was to identify significant predictors of waitlist mortality in patients with POPH. METHODS: We performed a retrospective cohort study of patients in the OPTN database with hemodynamics consistent with POPH [defined as mean pulmonary arterial pressure (mPAP) >25mmHg and pulmonary vascular resistance (PVR) ≥240 dynes-s-cm] who were approved for a POPH MELD exception between 2006 and 2014...
February 15, 2017: Transplantation
https://www.readbyqxmd.com/read/28207638/association-of-local-intrapulmonary-production-of-antibodies-specific-to-donor-major-histocompatibility-complex-class-i-with-the-progression-of-chronic-rejection-of-lung-allografts
#15
Ei Miyamoto, Hideki Motoyama, Masaaki Sato, Akihiro Aoyama, Toshi Menju, Kei Shikuma, Terumasa Sowa, Akihiko Yoshizawa, Masao Saito, Akihiro Takahagi, Satona Tanaka, Mamoru Takahashi, Keiji Ohata, Takeshi Kondo, Kyoko Hijiya, Toyofumi F Chen-Yoshikawa, Hiroshi Date
BACKGROUND: Antibody-mediated rejection may lead to chronic lung allograft dysfunction, but antibody-mediated rejection may develop in the absence of detectable donor-specific antibody (DSA) in recipient serum. This study investigated whether humoral immune responses develop not only systemically but locally within rejected lung allografts, resulting in local production of DSA. METHODS: Lewis rats received orthotopic left lung transplantation from Lewis (syngeneic control) or Brown-Norway (major histocompatibility complex-mismatched allogeneic) donor rats...
February 15, 2017: Transplantation
https://www.readbyqxmd.com/read/28207637/the-efficacy-of-a-prevascularized-retrievable-poly-d-l-lactide-co-%C3%AE%C2%B5-caprolactone-subcutaneous-scaffold-as-transplantation-site-for-pancreatic-islets
#16
Alexandra M Smink, Shiri Li, Don T Hertsig, Bart J de Haan, Leendert Schwab, Aart A van Apeldoorn, Eelco de Koning, Marijke M Faas, Jonathan R T Lakey, Paul de Vos
BACKGROUND: The liver as transplantation site for human pancreatic islets is a harsh microenvironment for islets and it lacks the ability to retrieve the graft. A retrievable, extrahepatic transplantation site that mimics the pancreatic environment is desired. Ideally this transplantation site should be located subdermal for easy surgical-access but this never resulted in normoglycemia. Here we describe the design and efficacy of a novel prevascularized, subcutaneously implanted, retrievable poly (D,L-lactide-co-ε-caprolactone) (PDLLCL) scaffold...
February 15, 2017: Transplantation
https://www.readbyqxmd.com/read/28207636/association-between-pretransplant-cancer-and-survival-in-kidney-transplant-recipients
#17
Dag Olav Dahle, Tom Grotmol, Torbjørn Leivestad, Anders Hartmann, Karsten Midtvedt, Anna V Reisæter, Geir Mjøen, Hege K Pihlstrøm, Hege Næss, Hallvard Holdaas
BACKGROUND: Kidney transplantation in recipients with a previous malignancy is often deferred 2-5 years after cancer treatment due to fear of cancer recurrence. In Norway, the required waiting period has been 1 year. METHODS: We compared patient and graft survival of recipients with pretransplant cancer to the outcomes of matched recipients without such cancer (comparators) using Cox regression. RESULTS: From 1963 to 2010, 377 of 5867 recipients (6...
February 15, 2017: Transplantation
https://www.readbyqxmd.com/read/28207635/kidney-transplantation-rates-across-glomerulonephritis-subtypes-in-the-united-states
#18
Michelle M O'Shaughnessy, Sai Liu, Maria E Montez-Rath, Richard A Lafayette, Wolfgang C Winkelmayer
BACKGROUND: Whether kidney transplantation rates differ by glomerulonephritis (GN) subtype remains largely unknown. METHODS: Using the US Renal Data System, we identified all adult patients with ESRD attributed to 1 of 6 GN subtypes who initiated dialysis in the US (1996-2013). Patients with diabetic nephropathy (DN) and autosomal-dominant polycystic kidney disease (ADPKD) served as "external" non-GN comparators. Using Cox proportional hazards regression, with death considered a competing risk, we estimated hazard ratios [HRs (95% confidence intervals)] for first kidney transplantation, controlling for year, demographics, comorbidities, socioeconomic factors, and Organ Procurement Organization (OPO)...
February 15, 2017: Transplantation
https://www.readbyqxmd.com/read/28207634/ethnic-background-is-a-potential-barrier-to-living-donor-kidney-transplantation-in-canada-a-single-center-retrospective-cohort-study
#19
Istvan Mucsi, Aarushi Bansal, Olusegun Famure, Yanhong Li, Margot Mitchell, Amy D Waterman, Marta Novak, S Joseph Kim
BACKGROUND: We examined if African or Asian ethnicity was associated with lower access to kidney transplantation (KT) in a Canadian setting. METHODS: Patients referred for KT to the Toronto General Hospital from January 1, 2003 to December 31, 2012, who completed social work assessment, were included (n=1769). The association between ethnicity and the time from referral to completion of KT evaluation or receipt of a KT were examined using Cox proportional hazards models...
February 15, 2017: Transplantation
https://www.readbyqxmd.com/read/28207633/acute-liver-failure-injury-related-to-drug-reaction-with-eosinophilia-and-systemic-symptoms-outcomes-and-prognostic-factors
#20
Philippe Ichai, Astrid Laurent-Bellue, Faouzi Saliba, David Moreau, Camille Besch, Claire Francoz, Laurence Valeyrie-Allanore, Sylvie Roussin Bretagne, Marc Boudon, Teresa Maria Antonini, Florent Artru, Gabriella Pittau, Olivier Roux, Daniel Azoulay, Eric Levesque, François Durand, Catherine Guettier, Didier Samuel
BACKGROUND: Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS) is a rare severe adverse drug induced reaction with multiorgan involvement. The outcome and prediction of those patients who develop severe acute liver injury (sALI) or acute liver failure (ALF) remain little known. METHODS: A multicenter retrospective study of patients admitted with a diagnosis of DRESS-related sALI or ALF. Histological review was performed on liver core biopsies from native livers...
February 15, 2017: Transplantation
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