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everolimus and transplantation

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https://www.readbyqxmd.com/read/29151264/renal-protection-strategies-after-heart-transplantation
#1
REVIEW
Daniel Reichart, Hermann Reichenspurner, Markus Johannes Barten
Renal dysfunction caused by calcineurin inhibitor (CNI) nephrotoxicity occurs often and contributes significantly to late mortality after heart transplantation (HTx). Over the last decades, this has prompted many clinical studies in an effort to develop kidney-protecting immunosuppressive strategies including delayed CNI start, minimization, withdrawal or even de-novo CNI avoidance. In the past, these strategies often failed due to the lack of efficacy. Since 2009, novel CNI-reducing strategies are under investigation...
November 19, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/29112898/development-and-validation-of-an-analytical-method-using-uplc-ms-ms-to-quantify-everolimus-in-dried-blood-spots-in-the-oncology-setting
#2
Lotte M Knapen, Yvo de Beer, Roger J M Brüggemann, Leo M Stolk, Frank de Vries, Vivianne C G Tjan-Heijnen, Nielka P van Erp, Sander Croes
While the therapeutic drug monitoring (TDM) of everolimus has been routinely performed for over 10 years in solid organ transplantation medicine, in order to optimize the balance between effectiveness and toxicity, it is yet uncommon in the treatment of malignancies. The aim of this study was to develop and validate a bioanalytical method to quantify everolimus in dried blood spots (DBS) to facilitate TDM for the oncology outpatient setting. The hematocrit effect of everolimus was investigated. An 7.5mm disk from the central part of the DBS was punched, followed by the extraction of everolimus from the DBS by methanol/acetonitrile (80/20%) spiked with deuterium-labelled everolimus as internal standard...
October 29, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29111569/the-influence-of-immunosuppressants-on-direct-acting-antiviral-therapy-is-dependent-on-hepatitis-c-virus-genotype
#3
Alexandra Frey, Katja Piras-Straub, Andreas Walker, Jörg Timm, Guido Gerken, Kerstin Herzer
BACKGROUND: Direct-acting antivirals (DAA) have substantially increased sustained virological response rates after liver transplantation, with improved tolerance compared to interferon-based therapy. The influence of immunosuppressive agents on the efficacy of DAAs has not been clarified. METHODS: Subgenomic HCV replicons for genotype (GT) 1b, 2b, 3a and 4a were treated with the mammalian target of rapamycin (mTOR) inhibitors everolimus and sirolimus or with the calcineurin inhibitors (CNI) cyclosporine or tacrolimus, either alone or in combination with selected DAAs...
November 7, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/29095297/everolimus-for-pediatric-patients-with-acute-graft-versus-host-disease-after-hematopoietic-stem-cell-transplantation-a-pilot-study
#4
Yu-Hua Chao, Yin-Chen Chang, Han-Ping Wu, Ching-Tien Peng, Te-Fu Weng, Kang-Hsi Wu
Acute graft-versus-host disease (aGVHD) is a significant cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Due to the poor prognosis for patients not responding to first-line steroids treatment, improvements in aGVHD therapy are needed. Everolimus is a promising candidate that combines immunosuppressive properties with anti-neoplastic effects. Here, we retrospectively reviewed the efficacy of everolimus with steroids as primary treatment in 13 patients with grade II to grade IV aGVHD after HSCT...
November 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29075123/immunosuppressants-and-new-onset-gallstone-disease-in-patients-having-undergone-renal-transplantation
#5
Fu-Chao Liu, Pei-Chi Ting, Jr-Rung Lin, Huang-Ping Yu
BACKGROUND: There are very few reports describing the development of gallstone disease after renal transplantation (GSDART) in Asia. The aim of this population-based study was to explore the prevalence, predictive factors, and outcomes of newly developed GSDART. The relationship between immunosuppressant and GSDART was also explored. PATIENTS AND METHODS: Renal transplantation (RT) recipients were identified from the National Health Insurance Research Database of Taiwan during January 1998-December 2012...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/29067525/hypernatremia-and-acute-pancreatitis-in-chronic-kidney-disease-back-to-the-salt-mines-questions
#6
Marie de Tersant, Thérésa Kwon, Marie-Alice Macher, Anne Maisin, Georges Deschênes, Olivier Niel
BACKGROUND: Acute pancreatitis can be a life-threatening complication in patients with chronic kidney disease (CKD), especially in kidney transplant recipients. CASE DIAGNOSIS/TREATMENT: The patient was 7 years old when he received renal transplantation for CKD secondary to posterior urethral valves. Two years later, he presented with severe necrotizing pancreatitis (Ranson's score 5, Balthazar's score 8). Viral and genetic testing came back negative; pancreatitis was attributed to the patient's treatments (prednisone, trimethoprim-sulfamethoxazole, and everolimus)...
October 24, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/29064613/everolimus-associated-perianal-ulcers-in-an-eight-month-old-heart-transplant-recipient
#7
Marco S Spehl, Thilo Fleck, Franziska Schauer, Frank Meiss, Brigitte Stiller
mTOR inhibitors have a wide spectrum of therapeutic applications in adults and children. Little is known, however, about serious adverse effects in children undergoing mTOR inhibitor therapy. Oral ulcers are common and sometimes severe, but no other gastrointestinal involvement has been reported so far. Here we present a case of everolimus-associated perianal ulcers in an eight-month-old infant, 3 months after heart transplantation, which necessitated the drug's discontinuation. In a thorough series of diagnostic tests, we identified no other cause for the progressive perianal ulceration...
October 24, 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/29045503/maintenance-therapy-following-induction-chemoimmunotherapy-in-patients-with-diffuse-large-b-cell-lymphoma-current-perspective
#8
N M Reddy, C Thieblemont
Background: Maintenance therapy has proven efficacy in indolent non-Hodgkin lymphoma (NHL), yet its role in diffuse large B-cell lymphoma (DLBCL) is an area of ongoing investigation. While DLBCL is potentially curable, >30% of patients relapse following front-line therapy and have a poor prognosis, especially those with refractory disease. Maintenance therapy holds promise to maintain response post-induction. Patients and methods: Keyword searches were carried out in PubMed and congress abstracts of 'diffuse large B-cell lymphoma' and 'maintenance' and focused on phase II/III studies of maintenance following front-line induction...
November 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28966983/late-recurrence-of-hepatocellular-carcinoma-after-liver-transplantation
#9
Julia A Zhang, Sandi A Kwee, Linda L Wong
AIMS: Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide and liver transplant (LT) prolongs survival. However, 15-20% will experience recurrent HCC, most occurring within 2 years of LT. HCC patients with late recurrences (>5 years after LT) may have distinctive clinical/biological characteristics. METHODS: A retrospective review was conducted of 88 patients who underwent LT for HCC between 1993-2015, analyzing demographics, clinical factors, explant pathology, and outcome...
2017: Hepatoma Research
https://www.readbyqxmd.com/read/28930797/optimizing-the-safety-profile-of-everolimus-by-delayed-initiation-in-de-novo-heart-transplant-recipients-results-of-the-prospective-randomized-study-everheart
#10
Luciano Potena, Carlo Pellegrini, Francesco Grigioni, Cristiano Amarelli, Ugolino Livi, Massimo Maccherini, Gabriella Masciocco, Giuseppe Faggian, Paola Lilla Della Monica, Gino Gerosa, Nicola Marraudino, Marco Corda, Massimo Boffini
BACKGROUND: Although everolimus potentially improves long-term heart transplantation (HTx) outcomes, its early postoperative safety profile had raised concerns and needs optimization. METHODS: This 6-month, open-label, multicenter randomized trial was designed to compare the cumulative incidence of a primary composite safety endpoint comprising wound healing delays, pericardial effusion (PCEs), pleural effusion (PLEs) needing drainage, and renal insufficiency events (estimated glomerular filtration rate [eGFR] ≤30/mL/min/1...
September 19, 2017: Transplantation
https://www.readbyqxmd.com/read/28923653/effects-of-the-mammalian-target-of-rapamycin-inhibitor-everolimus-on-hepatitis-c-virus-replication-in%C3%A2-vitro-and-in%C3%A2-vivo
#11
A Frey, E-M Ecker, K Piras-Straub, A Walker, T G Hofmann, J Timm, B B Singer, G Gerken, K Herzer
BACKGROUND: The influence of immunosuppressants on hepatitis C virus (HCV) re-infection after liver transplantation, particularly mammalian target of rapamycin inhibitors, remains unclear. The aim of our study was to analyze the influence of everolimus (EVR) on HCV replication activity in the context of underlying molecular mechanisms, with focus on the pro-myelocytic leukemia protein (PML). METHODS: HCV viral load was recorded in 40 patients with post-transplant HCV re-infection before and 8 weeks after introduction of EVR...
October 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28923623/mycophenolate-mofetil-withdrawal-with-conversion-to-everolimus-to-treat-bk-virus-infection-in-kidney-transplant-recipients
#12
D Wojciechowski, S Chandran, A Webber, R Hirose, F Vincenti
BACKGROUND: BK virus (BKV) is a significant post-transplant infection. Mammalian target of rapamycin inhibitors (mTORis) reduce BKV large T antigen expression in vitro and are associated with lower rates of BKV infection when used as de novo immunosuppression in clinical studies. METHODS: We performed a prospective, single-center, randomized, open label pilot trial to evaluate the impact of mycophenolate mofetil (MMF) withdrawal with conversion to the mTORi everolimus versus a 50% reduction of the MMF dose for the treatment of BKV infection after kidney transplantation...
October 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28923619/ten-year-follow-up-of-pharmacokinetics-guided-very-early-cyclosporine-minimization-synchronized-with-everolimus-initiation-in-de-novo-kidney-transplantation
#13
V Sumethkul, P Tankee, S Worawichawong, S Jirasiritham
BACKGROUND: Minimization of calcineurin inhibitor (CNI) from the 1st week after kidney transplantation (KT) may reduce the risk of CNI nephrotoxicity. METHODS: Ten de novo KT recipients who received full exposure cyclosporine (CsA) and prednisolone as initial therapy were enrolled. Initial CsA minimization was 50% and started at day 7 after KT. This was synchronized with everolimus (EVL) initiation. Target trough level of EVL was 3-8 ng/mL. Pharmacokinetics studies of CsA and EVL were studied at week 4...
October 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28923615/effective-and-safe-reduction-of-conventional-immunosuppressants-using-everolimus-in-maintenance-kidney-transplant-recipients
#14
K Nanmoku, A Kurosawa, T Kubo, T Shinzato, T Shimizu, T Kimura, T Yagisawa
BACKGROUND: Adverse events due to conventional immunosuppressive therapy decrease both graft and patient survival. We aimed to establish a new protocol using everolimus (EVR) to safely minimize conventional immunosuppressants in maintenance kidney transplant recipients. METHODS: A total of 86 consecutive kidney transplant recipients with no complications were maintained with triple-drug combination therapy (conventional group). In case of complications, the administration of very low-dose tacrolimus (C0: 5...
October 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28878864/use-of-everolimus-in-liver-transplantation
#15
REVIEW
Mei-Ling Yee, Hui-Hui Tan
In recent years, the use of mammalian target of rapamycin inhibitors has gained traction in their use as alternative or adjunct immunosuppressants in the post-liver transplantation (LT) setting. The efficacy of everolimus (EVR) in de novo LT is established and a reasonable time to initiate EVR is 30 d from LT surgery. Initiating EVR early post-LT allows for calcineurin inhibitor (CNI) reduction, thus reducing nephrotoxicity in LT recipients. However, data is inadequate on the appropriate timing for conversion from CNI to EVR maintenance in order to achieve optimal renoprotective effect without compromising drug efficacy...
August 18, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28873970/immunosuppressive-agents-in-adult-kidney-transplantation-in-the-national-health-service-a-model-based-economic-evaluation
#16
Tristan M Snowsill, Jason Moore, Ruben E Mujica Mota, Jaime L Peters, Tracey L Jones-Hughes, Nicola J Huxley, Helen F Coelho, Marcela Haasova, Chris Cooper, Jenny A Lowe, Jo L Varley-Campbell, Louise Crathorne, Matt J Allwood, Rob Anderson
Background: Immunosuppression is required in kidney transplantation to prevent rejection and prolong graft survival. We conducted an economic evaluation to support England's National Institute for Health and Care Excellence in developing updated guidance on the use of immunosuppression, incorporating new immunosuppressive agents, and addressing changes in pricing and the evidence base. Methods: A discrete-time state transition model was developed to simulate adult kidney transplant patients over their lifetime...
July 1, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28846559/sofosbuvir-based-regimens-in-hiv-hcv-coinfected-patients-after-liver-transplantation-results-from-the-anrs-co23-cupilt-study
#17
Teresa Maria Antonini, Audrey Coilly, Emilie Rossignol, Claire Fougerou-Leurent, Jérôme Dumortier, Vincent Leroy, Aurélie Veislinger, Sylvie Radenne, Danielle Botta-Fridlund, François Durand, Pauline Houssel-Debry, Nassim Kamar, Valérie Canva, Philippe Perré, Victor De Ledinghen, Alexandra Rohel, Alpha Diallo, Anne-Marie Taburet, Didier Samuel, Georges-Philippe Pageaux, Jean-Charles Duclos-Vallée
BACKGROUND: A recurrence of hepatitis C virus after liver transplantation affects survival in HIV/HCV coinfected patients. This study assessed the efficacy and safety of sofosbuvir-based regimens in HIV/HCV coinfected patients following liver transplantation. METHODS: 29 HIV/HCV coinfected transplanted patients receiving tacrolimus, cyclosporine or everolimus-based immunosuppressive therapy were enrolled in the CUPILT cohort. Their antiviral treatment combined sofosbuvir, daclatasvir with or without ribavirin (n=10/n=6), or sofosbuvir, ledipasvir with or without ribavirin (n=2/n=11)...
August 24, 2017: Transplantation
https://www.readbyqxmd.com/read/28845376/sirolimus-associated-pruritus-case-report-and-review
#18
Joyce Y Cheng, Philip R Cohen
Sirolimus is an immunosuppressant drug used to prevent organ rejection in transplant patients. We describe a man with sirolimus-associated pruritus and review the features of this adverse event in other individuals receiving this drug. The patient was a 67-year-old heart transplant recipient receiving sirolimus as part of his immunosuppressive regimen. He developed severe pruritus over the distal extremities, face, and earlobes six months after starting the drug. The symptoms became progressively worse as he continued to receive this medication...
June 27, 2017: Curēus
https://www.readbyqxmd.com/read/28817434/everolimus-is-associated-with-less-weight-gain-than-tacrolimus-2-years-following-liver-transplantation-results-of-a-randomized-multicenter-study
#19
Michael Charlton, Mary Rinella, Dharmesh Patel, Kevin McCague, Julie Heimbach, Kymberly Watt
BACKGROUND: Weight gain early after transplant is a risk factor for posttransplant metabolic syndrome (PTMS), cardiovascular events, and renal insufficiency. The impact of mTOR inhibition on posttransplant weight gain and the development of PTMS components postliver transplantation were examined in a randomized, controlled study. METHODS: Following a run-in period, patients (N = 719) were randomized at 30±5 days posttransplant in a 1:1:1 ratio to 3 treatment groups: (i) everolimus (EVR) + reduced tacrolimus (TAC)(n=245); (ii) TAC control (n=243) or (iii) TAC elimination (n=231)...
August 15, 2017: Transplantation
https://www.readbyqxmd.com/read/28804814/factors-associated-with-cardiovascular-target-organ-damage-in-children-after-renal-transplantation
#20
Bianca Borchert-Mörlins, Daniela Thurn, Bernhard M W Schmidt, Anja K Büscher, Jun Oh, Tanja Kier, Elena Bauer, Sabrina Baig, Nele Kanzelmeyer, Markus J Kemper, Rainer Büscher, Anette Melk
BACKGROUND: Cardiovascular disease is the second-most common cause of death in pediatric renal transplant recipients. The aim of this study was to evaluate subclinical cardiovascular target organ damage defined as the presence of arterio- and atherosclerotic lesions and cardiac remodeling and to analyze contributing risk factors in a large cohort of children after renal transplantation (RT). METHODS: A total of 109 children aged 13.1 ± 3.3 years who had undergone RT at one of three German transplant centers were enrolled in this study...
November 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
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