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everolimus and transplantation

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https://www.readbyqxmd.com/read/28714558/everolimus-and-reduced-calcineurin-inhibitor-therapy-in-pediatric-liver-transplant-recipients-results-from-a-multicenter-prospective-study
#1
Rainer Ganschow, Bo-Goran Ericzon, Anil Dhawan, Khalid Sharif, El-Djouher Martzloff, Barbara Rauer, Jennifer Ng, Patricia Lopez
In a 24-month, multicenter, single-arm, prospective study, 56 pediatric liver transplant patients with or without basiliximab induction were converted at 1-6 months post-transplant from standard calcineurin inhibitor (CN) therapy (± mycophenolic acid), to everolimus with reduced exposure to CNI (tacrolimus n=50, cyclosporine n=6). Steroid therapy was optional. Recruitment was stopped prematurely due to high rates of PTLD, treatment-related serious infections leading to hospitalization and premature study drug discontinuation...
July 17, 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28708648/oral-localization-of-kaposi-sarcoma-clinical-presentation-and-conservative-management
#2
Paolo Garzino-Demo, Arianna Mettus, Fabio Passalacqua, Federico Vittone, Guglielmo Ramieri
Kaposi sarcoma (KS) caused by human herpes virus type-8 is the most frequent immunosuppression-associated malignancy worldwide and its treatment is still controversial. We report on the clinical management of a patient who developed oral KS after liver transplantation. The disease appeared 1 month after the transplant and recurred after 4 months. The patient represents, to our knowledge, a rare case that was treated successfully only by shifting a conventional immunosuppressive therapy to everolimus alone.
July 13, 2017: Journal of Craniofacial Surgery
https://www.readbyqxmd.com/read/28708333/conversion-from-calcineurin-inhibitors-to-mtor-inhibitors-as-primary-immunosuppressive-drugs-in-pediatric-heart-transplantation
#3
Alfred Asante-Korang, Jennifer Carapellucci, Diane Krasnopero, Abigail Doyle, Brian Brown, Ernest Amankwah
There are only a few reports of successful use of mammalian target of rapamycin (mTORI) as primary immunosuppression in pediatric heart transplantation. Compared to calcineurin inhibitors, mTORI have less side effects, especially nephrotoxicity, infections and malignancies. A retrospective study was conducted at our institution of all 170 heart transplants from 1995-2015. Nineteen patients were switched from tacrolimus(n=15) or cyclosporin(n=4) to everolimus(n=4) or sirolimus(n=15) due to nephrotoxicity(n=5), malignancy(n=8), EBV viremia/reactive plasmacytic changes(n=5) and immune hemolytic anemia(n=1)...
July 14, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28707443/cardiac-transplant-vasculopathy
#4
EDITORIAL
Jonathan M Tobis
Transplant vasculopathy is a form of slowly progressive rejection. The interventional cardiologist plays an important role in maintaining survival of this precious commodity by performing PCI. Everolimus drug eluting stents are highly effective and have relatively low occurrence of in-stent restenosis, but transplant vasculopathy continues to progress in a diffuse pattern.
July 2017: Catheterization and Cardiovascular Interventions
https://www.readbyqxmd.com/read/28706985/clinical-utility-of-epstein-barr-virus-viral-load-monitoring-and-risk-factors-for-posttransplant-lymphoproliferative-disorders-after-kidney-transplantation-a-single-center-10-year-observational-cohort-study
#5
Erica Franceschini, Jessica Plessi, Stefano Zona, Antonella Santoro, Margherita Digaetano, Francesco Fontana, Gaetano Alfano, Giovanni Guaraldi, Patrizia Comoli, Francesca Facchini, Leonardo Potenza, William Gennari, Mauro Codeluppi, Mario Luppi, Gianni Cappelli, Inge C Gyssens, Cristina Mussini
BACKGROUND: Posttransplant lymphoproliferative disease (PTLD) is an important cause of morbidity and mortality in solid organ transplants. Epstein Barr virus (EBV) plays a major role in PTLD development. Guidelines recommend EBV viral load (VL) monitoring in high-risk populations in the first year. METHODS: Retrospective observational study in all adult patients who had at least 1 EBV-VL performed in the postkidney transplant (KT) period from January 2005 to December 2014 at the Policlinico Modena Hospital...
July 2017: Transplantation Direct
https://www.readbyqxmd.com/read/28706981/outcomes-of-liver-transplant-recipients-with-autoimmune-liver-disease-using-long-term-dual-immunosuppression-regimen-without-corticosteroid
#6
Sanjaya K Satapathy, Ollie D Jones, Jason M Vanatta, Faisal Kamal, Satish K Kedia, Yu Jiang, Satheesh P Nair, James D Eason
BACKGROUND: Liver transplant (LT) recipients with autoimmune liver disease (primary sclerosing cholangitis, primary biliary cholangitis, autoimmune hepatitis) are at increased risk of developing acute cellular rejection (ACR), and in many cases graft failure due to recurrent disease. We describe our experience with dual immunosuppression without steroid maintenance and analyze its effect on disease recurrence; ACR; patient and graft survivals; and complications, such as sepsis and de novo malignancy...
July 2017: Transplantation Direct
https://www.readbyqxmd.com/read/28670871/clinical-practice-patterns-are-relatively-uniform-between-pediatric-heart-transplant-centers-a-survey-based-assessment
#7
Chesney Castleberry, Sonja Ziniel, Christopher Almond, Scott Auerbach, Seth A Hollander, Ashwin K Lal, Matthew Fenton, Elfriede Pahl, Joseph W Rossano, Melanie D Everitt, Kevin P Daly
Clinical practice variations are a barrier to the study of pediatric heart transplants and coordination of multicenter RCTs in this patient population. We surveyed centers to describe practice patterns, understand areas of variation, and willingness to modify protocol. Pediatric heart transplant centers were identified, and one survey was completed per center. Simple descriptive statistics were used. The response rate was 77% (40 responses from 52 contacted centers, 37 with complete responses). Median center volume of respondents was eight transplants/year (IQR 3-19)...
July 3, 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28662293/retrospective-evaluation-of-the-efficacy-and-safety-of-belatacept-with-thymoglobulin-induction-and-maintenance-everolimus-a-single-center-clinical-experience
#8
D Wojciechowski, S Chandran, J Yang, M Sarwal, F Vincenti
Belatacept use has been constrained by higher rates of acute rejection. We hypothesized that belatacept with low dose rATG and initial mycophenolate maintenance with conversion to everolimus at 1 month post-transplant ± corticosteroids would improve efficacy and maintain safety. Retrospective single center analysis of the first 44 low immunologic risk kidney transplant recipients treated with this regimen. The cohort was 59% male, mean age at transplant of 57 years. Diabetes was the most common cause of ESRD (39%)...
June 29, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28662279/impact-of-early-conversion-from-cyclosporin-to-everolimus-on-left-ventricular-mass-index-a-randomized-controlled-trial
#9
Anoushka Krishnan, Armando Teixeira-Pinto, Doris Chan, Aron Chakera, Gursharan Dogra, Neil Boudville, Ashley Irish, Kelly Morgan, Jessica Phillips, Germaine Wong, Wai H Lim
This is an 18-month prospective, randomized controlled trial (RCT) designed to compare the effect of early conversion from cyclosporin to everolimus/ mycophenolic acid (E-MPA) between 3-4 months post-transplant to cyclosporin/mycophenolic acid (CsA-MPA) on left ventricular mass index (LVMI) at 3 and 18 months post-transplant (primary outcome). Secondary outcomes included estimated glomerular filtration rate (eGFR), viral infection and adverse events. Twenty-four patients were randomized in a 1:1 ratio to E-MPA or CsA-MPA groups...
June 29, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28661568/everolimus-induced-nephrotic-syndrome-precipitated-by-interaction-with-voriconazole-in-a-patient-with-hodgkin-s-lymphoma
#10
P N Tran, L C Pinter-Brown
WHAT IS KNOWN AND OBJECTIVES: Everolimus is a small molecule that inhibits the mammalian target of rapamycin (mTOR) and is used for treatment of various solid tumours and renal transplant rejection prophylaxis. Whereas everolimus-induced proteinuria was previously observed in 3%-36% renal transplant recipients, nephrotic syndrome was not reported in cancer patients taking everolimus. However, nephrotic syndrome was reported in patients taking sirolimus. CASE SUMMARY: We report the case of a 32-year-old female with relapsed Hodgkin's lymphoma who was on everolimus for 5 years and developed nephrotic syndrome about 2 months after initiation of voriconazole...
June 29, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28641881/peripheral-blood-regulatory-t-cell-counts-as-a-predictive-biomarker-for-the-outcome-of-kidney-transplant-a-systematic-review
#11
Francisco Herrera-Gómez, Mónica Vásquez-Seoane, Waldo Del Aguila, Débora Martín-García, Álvaro Maurtua-Briseño Meiggs, Anunciación González-López, Beatriz Andrés-Martín, Álvaro Nava-Rebollo, Fernando Casquero-Fernández, Pilar Pascual-Núñez, Jesús Grande-Villoria, Jesús Bustamante-Bustamante, Carlos Ochoa-Sangrador, Claude Lambert, Alicia Mendiluce-Herrero
BACKGROUND AND OBJECTIVE: Circulating regulatory T cells could become a suitable biomarker for kidney recipients. The objective of this study was to evaluate the effect of mammalian target of rapamycin (mTOR) inhibitors on regulatory T cell numbers, and the clinical interest of this effect. MATERIAL AND METHODS: Systematic review of published and unpublished studies. Worldwide databases or repositories. Randomised controlled trials and cohort studies comparing regulatory T cell counts and rejection episodes between patients with and without mTOR inhibitors were searched...
June 19, 2017: Medicina Clínica
https://www.readbyqxmd.com/read/28640529/effect-of-everolimus-versus-calcineurin-inhibitors-on-quality-of-life-in-heart-transplant-recipients-during-a-3-year-follow-up-results-of-a-randomized-controlled-trial-schedule
#12
A Relbo Authen, I Grov, K Karason, F Gustafsson, H Eiskjaer, G Rådegran, E Gude, K Jansson, G Dellgren, D Solbu, S Arora, A K Andreassen, L Gullestad
The SCHEDULE trial was a 12-month, randomized, open-label, parallel-group trial that compared everolimus (EVR; n=56) to conventional CsA (n=59) immunosuppression. Previously, we reported that EVR outperformed CsA in improving renal function and coronary artery vasculopathy, despite a higher rejection rate with EVR. The present study aimed to compare the effects of these treatments on quality of life (QoL). Within 5 postoperative days, patients (mean age 50±13 years, 27% women) were randomized to EVR or a standard CsA dosage (CsA group)...
June 22, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28624108/modification-of-immunosuppressive-therapy-as-risk-factor-for-complications-after-liver-transplantation
#13
REVIEW
Paolo De Simone, Paola Carrai, Laura Coletti, Davide Ghinolfi, Stefania Petruccelli, Franco Filipponi
Management of complications post-liver transplantation (LT) includes immunosuppressive manipulations with the aim to reduce the overall burden of immunologic suppression and compensate for renal, cardiovascular, metabolic toxicities, and for the increased oncologic risk. Two approaches can be implemented to reduce immunosuppression-related adverse events: upfront schedules tailored to the pretransplant individual patient's risk profile versus downstream modifications in the event of immunosuppression-related complications...
April 2017: Best Practice & Research. Clinical Gastroenterology
https://www.readbyqxmd.com/read/28605781/everolimus-with-cyclosporine-withdrawal-or-low-exposure-cyclosporine-in-kidney-transplantation-from-month-3-a-multicentre-randomized-trial
#14
Klemens Budde, Martin Zeier, Oliver Witzke, Wolfgang Arns, Frank Lehner, Markus Guba, Johannes Jacobi, Volker Kliem, Petra Reinke, Ingeborg A Hauser, Bruno Vogt, Rolf Stahl, Thomas Rath, Michael Duerr, Eva-Maria Paulus, Christoph May, Martina Porstner, Claudia Sommerer
Background.: Randomized trials have shown that early adoption of everolimus-based immunosuppressive regimens without a calcineurin inhibitor (CNI) improves long-term kidney graft function, but the optimal strategy for CNI minimization remains uncertain. Methods.: In a prospective, randomized, multicentre, 12-month trial, 499 de novo kidney transplant patients were randomized at Month 3 to (i) remain on standard CNI (cyclosporine) therapy with mycophenolic acid, (ii) convert to everolimus with mycophenolic acid or (iii) start everolimus with reduced CNI and no mycophenolic acid (clinical trials registry: ClinicalTrials...
June 1, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28581202/switch-to-an-everolimus-facilitated-cyclosporine-a-sparing-immunosuppression-improves-glycemic-control-in-selected-kidney-transplant-recipients
#15
Florian Kälble, Jörg Seckinger, Matthias Schaier, Christian Morath, Vedat Schwenger, Martin Zeier, Claudia Sommerer
BACKGROUND: Mammalian target of rapamycin inhibitors (mToRi) allow calcineurin inhibitor (CNI) sparing therapy in renal transplant recipients with possible beneficial effects on the long-term allograft function and cardiovascular risk. The influence of mToRi on glucose metabolism is still under discussion. METHODS: In a retrospective analysis, renal allograft recipients switched from a cyclosporine A (CsA) to an everolimus (EVR) based immunosuppression in the first year after transplantation were compared with patients on continued CsA treatment...
June 5, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28551032/recommendations-for-the-use-of-everolimus-in-de-novo-kidney-transplantation-false-beliefs-myths-and-realities
#16
Julio Pascual, Fritz Diekmann, Constantino Fernández-Rivera, Gonzalo Gómez-Marqués, Alex Gutiérrez-Dalmau, María José Pérez-Sáez, Asunción Sancho-Calabuig, Federico Oppenheimer
The immunosuppressive combination most commonly used in de novo kidney transplantation comprises a calcineurin inhibitor (CI), tacrolimus, a mycophenolic acid derivative and steroids. The evidence which underlies this practice is based in the Symphony trial with controlled follow-up of one year, in which no comparator group included the combination CI-mTOR inhibitor. Different high-quality clinical trials support the use of everolimus as a standard immunosuppressive drug associated with reduced exposure of a CI in kidney transplantation...
May 24, 2017: Nefrología: Publicación Oficial de la Sociedad Española Nefrologia
https://www.readbyqxmd.com/read/28548030/everolimus-inhibited-multiple-isoforms-of-udp-glucuronosyltransferases-ugts
#17
Zuo Du, Guang Wang, Yun-Feng Cao, Cui-Min Hu, Kun Yang, Yong-Zhe Liu, Chun-Ze Zhang, Wei-Hua Zhang, Zhi-Tu Zhu, Hong-Zhi Sun, Xiao-Yu Sun, Mo Hong, Zhong-Ze Fang
1. Everolimus is an inhibitor of mammalian target of rapamycin (mTOR) and has been clinically utilized to prevent the rejection of organ transplants. This study aims to determine the inhibition of everolimus on the activity of phase II drug-metabolizing enzymes UDP-glucuronosyltransferases (UGTs). 2. The results showed that 100 uM of everolimus exerted more than 80% inhibition towards UGT1A1, -1A3, and -2B7. UGT1A3 and UGT2B7 were selected to elucidate the inhibition mechanism, and in silico docking showed that hydrogen bonds and hydrophobic interactions mainly contributed to the strong binding of everolimus towards the activity cavity of UGT1A3 and UGT2B7...
May 26, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28546531/supplementary-administration-of-everolimus-reduces-cardiac-systolic-function-in-kidney-transplant-recipients
#18
Kazuma Tsujimura, Morihito Ota, Kiyoshi Chinen, Kiyomitsu Nagayama, Masato Oroku, Morikuni Nishihira, Yoshiki Shiohira, Masami Abe, Kunitoshi Iseki, Hideki Ishida, Kazunari Tanabe
BACKGROUND The effect of everolimus, one of the mammalian targets of rapamycin inhibitors, on cardiac function was evaluated in kidney transplant recipients. MATERIAL AND METHODS Seventy-six participants who underwent kidney transplant between March 2009 and May 2016 were retrospectively reviewed. To standardize everolimus administration, the following criteria were used: (1) the recipient did not have a donor-specific antigen before kidney transplantation; (2) the recipient did not have proteinuria and uncontrollable hyperlipidemia after kidney transplantation; and (3) acute rejection was not observed on protocol biopsy 3 months after kidney transplantation...
May 26, 2017: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/28542523/impact-of-maintenance-immunosuppressive-therapy-on-the-fecal-microbiome-of-renal-transplant-recipients-comparison-between-an-everolimus-and-a-standard-tacrolimus-based-regimen
#19
Gianluigi Zaza, Alessandra Dalla Gassa, Giovanna Felis, Simona Granata, Sandra Torriani, Antonio Lupo
BACKGROUND: The gut microbiome is the full set of microbes living in the gastrointestinal tract and is emerging as an important dynamic/fluid system that, if altered by environmental, dietetic or pharmacological factors, could considerably influence drug response. However, the immunosuppressive drug-induced modifications of this system are still poorly defined. METHODS: We employed an innovative bioinformatics approach to assess differences in the whole-gut microbial metagenomic profile of 20 renal transplant recipients undergoing maintenance treatment with two different immunosuppressive protocols...
2017: PloS One
https://www.readbyqxmd.com/read/28511172/donor-specific-anti-human-leukocyte-antigens-antibodies-acute-rejection-renal-function-and-histology-in-kidney-transplant-recipients-receiving-tacrolimus-and-everolimus
#20
Alexandra Ferreira, Claudia Felipe, Marina Cristelli, Laila Viana, Geovana Basso, Suelen Stopa, Juliana Mansur, Mayara Ivani, Adrieli Bessa, Priscila Ruppel, Wilson Aguiar, Erika Campos, Maria Gerbase-DeLima, Henrique Proença, Helio Tedesco-Silva, José Medina-Pestana
BACKGROUND: This analysis compared efficacy, renal function, and histology in kidney transplant recipients receiving tacrolimus (TAC) combined with everolimus (EVR) or mycophenolate (MPS). METHODS: This was a retrospective analysis from a randomized trial in kidney transplant recipients who received a single 3 mg/kg dose of rabbit antithymocyte globulin (r-ATG), TAC, EVR, and prednisone (PRED; r-ATG/EVR, n = 85), basiliximab (BAS), TAC, EVR, and PRED (BAS/EVR, n = 102) or BAS, TAC, MPS, and PRED (BAS/MPS, n = 101)...
2017: American Journal of Nephrology
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