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Everolimus transplantation

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https://www.readbyqxmd.com/read/28425200/high-dose-calcineurin-inhibitor-free-everolimus-as-a-maintenance-regimen-for-heart-transplantation-may-be-a-risk-factor-for%C3%A2-pneumocystis-pneumonia
#1
Yu-Ning Hu, Nan-Yao Lee, Jun-Neng Roan, Chi-Hsin Hsu, Chwan-Yao Luo
BACKGROUND: Everolimus reduces the incidence of cardiac-allograft vasculopathy (CAV) and is less renally toxic than are calcineurin inhibitors (CNIs). We evaluated the safety of CNI-free everolimus for post-heart transplant (HTx) patients. METHODS: We retrospectively reviewed the records of 36 consecutive patients who had undergone an HTx between January 2006 and December 2013 in National Cheng Kung University Hospital. All patients initially had been treated with the standard tacrolimus regimen...
April 20, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/28416360/primary-hepatic-angiosarcoma-and-liver-transplantation-radiological-surgical-histological-findings-and-clinical-outcome
#2
M Tran Minh, A Mazzola, F Perdigao, F Charlotte, G Rousseau, F Conti
Angiosarcoma is a rare type of soft tissue sarcoma that accounts for less than 1% of all sarcomas and only 2% of all primary hepatic tumours. Thorotrast, arsenic, and vinyl chloride monomer are frequently listed as occupational exposure risks. The estimated latency is long (10-40 years) in occupational cases and very long (60 years or more) in non-occupational cases. The symptoms and CT-scan appearance of hepatic angiosarcoma (HAS) are non-specific. We present a case of a 65-year-old Caucasian male with history of cryptogenic cirrhosis, low alpha-foetoprotein levels and a single, 4-cm nodule of potential atypical hepatocellular carcinoma (no washout at MRI and CT-scan) in segment VIII...
April 14, 2017: Clinics and Research in Hepatology and Gastroenterology
https://www.readbyqxmd.com/read/28415888/bioengineered-gold-nanoparticles-targeted-to-mesenchymal-cells-from-patients-with-bronchiolitis-obliterans-syndrome-does-not-rise-the-inflammatory-response-and-can-be-safely-inhaled-by-rodents
#3
Emanuela Cova, Simona Inghilleri, Laura Pandolfi, Monica Morosini, Sara Magni, Miriam Colombo, Davide Piloni, Chiara Finetti, Gabriele Ceccarelli, Laura Benedetti, Maria Gabriella Cusella, Manuela Agozzino, Fabio Corsi, Raffaele Allevi, Simona Mrakic-Sposta, Sarah Moretti, Simona De Gregori, Davide Prosperi, Federica Meloni
The use of gold nanoparticles as drug delivery system represents a promising issue for diseases without effective pharmacological treatment due to insufficient local drug accumulation and excessive systemic toxicity. Bronchiolitis obliterans syndrome (BOS) represents about 70% of cases of chronic lung allograft dysfunction, the main challenge to long term lung transplantation. It is believed that due to repeated insults to epithelial bronchiolar cells local inflammatory response creates a milieu that favours epithelial mesenchymal transition and activation of local mesenchymal cells leading to airway fibro-obliteration...
April 18, 2017: Nanotoxicology
https://www.readbyqxmd.com/read/28405603/mtor-inhibition-by-everolimus-does-not-impair-closure-of-punch-biopsy-wounds-in-renal-transplant-patients
#4
Shelley B Dutt, Josephine Gonzales, Megan Boyett, Anne Costanzo, Peggy P Han, Steven Steinberg, Dianne B McKay, Julie M Jameson
BACKGROUND: Mammalian target of rapamycin (mTOR) inhibitors are approved to prevent allograft rejection and control malignancy. Unfortunately, they are associated with adverse effects, such as wound healing complications that detract from more extensive use. There is a lack of prospective wound healing studies to monitor patients treated with mTOR inhibitors, such as everolimus or sirolimus, especially in nondiabetics. METHODS: Patients receiving everolimus with standard immunosuppressant therapy or standard immunosuppressant therapy without everolimus were administered 3-mm skin biopsy punch wounds in the left scapular region...
April 2017: Transplantation Direct
https://www.readbyqxmd.com/read/28345271/immunosuppression-with-mtor-inhibitors-prevents-the-development-of-donor-specific-antibodies-after-liver-transplant
#5
Katharina Willuweit, Andreas Heinold, Jassin Rashidi-Alavijeh, Falko M Heinemann, Peter A Horn, Andreas Paul, Guido Gerken, Kerstin Herzer
BACKGROUND: Donor-specific antibodies (DSAs) are an important cause of complications after solid organ transplant. Risk factors and, thus, strategies for preventing DSA development are not well defined. METHODS: The DSA status of 400 patients who underwent liver transplant (LT) at the outpatient clinic of the University Hospital Essen was determined. Human leukocyte antigen (HLA) antibodies were detected by single-antigen bead technology. The strength of DSAs was reported as mean fluorescence intensity...
March 26, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28340831/pregnancy-and-delivery-in-the-sequel-of-kidney-transplantation-single-center-study-of-8-years-experience
#6
Y Yuksel, S Tekin, D Yuksel, I Duman, M Sarier, L Yucetin, E Turan, H Celep, T Ugurlu, M M Inal, Y H Asuman, A Demirbas
BACKGROUND: Depending on hyphothalamic, hyphophyseal, and gonadal axis dysfunction, anovulatory irregular cycles occur and the probability of pregnancy decreases in the patients with chronic kidney disease (CKD). Maternal mortality and morbidity rates are increased in CKD patients; the risk of premature delivery is 70% and the risk of preeclampsia is 40% more than normal among those with a creatine level of >2.5 mg/dL. METHODS: If a pregnancy is expected in the sequel of kidney transplantation (KT), a multidisciplinary team approach should be adopted and both the gynecologist and the nephrologist should follow the patient simultaneously...
April 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28340820/role-of-everolimus-on-cardiac-functions-in-kidney-transplant-recipients
#7
U Cakir, G Alis, T Erturk, A H Karayagiz, U Karabulut, I Berber
BACKGROUND: Kidney transplantation is known to increase the survival of dialysis patients by ameloriating cardiac status, including both systolic and diastolic functions. We aimed to evaluate the role of immunosuppressive drug regimens on cardiac functions of kidney transplant recipients (KTRs). METHODS: We prospectively evaluated 120 KTRs immediately before and 1 year after the kidney transplantation, using tissue Doppler echocardiography. A triple immunosuppressive therapy including tacrolimus, mycophenoloic acid (MPA), and prednisolone was started for all patients...
April 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28340815/expression-profile-of-microrna-biogenesis-components-in-renal-transplant-patients
#8
E Celen, M G Ertosun, H Kocak, A Dinckan, B Yoldas
BACKGROUND: MicroRNAs (miRNAs) and the miRNA biogenesis components are potential biomarkers of some prevalent diseases, such as cancer and diabetes. In light of this information, we aimed to investigate the expression profiles of miRNA biogenesis components in renal transplant patients before and after transplantation and how these profiles are related to immunosuppressive treatment and clinical outcomes of these patients. METHODS: In this study, gene and protein expression profiles of Dicer, Drosha, Pasha (DGCR8), Exportin5 (XPO5), and Argonaute2 (AGO2) in peripheral blood mononuclear cells (PBMCs) of renal transplant patients were evaluated by means of real-time quantitative polymerase chain reaction and Western blot methods before and 3 months after transplantation...
April 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28333860/cardiovascular-parameters-to-2-years-after-kidney-transplantation-following-early-switch-to-everolimus-without-calcineurin-inhibitor-therapy-an-analysis-of-the-randomized-elevate-study
#9
Hallvard Holdaas, Johan W de Fijter, Josep M Cruzado, Pablo Massari, Björn Nashan, John Kanellis, Oliver Witzke, Alex Gutierrez-Dalmau, Aydin Turkmen, Zailong Wang, Patricia Lopez, Peter Bernhardt, Jossy Kochuparampil, Markus van der Giet, Klaus Murbraech
BACKGROUND: Mammalian target of rapamycin (mTOR) inhibitors may confer cardioprotective advantages but clinical data are limited. METHODS: In the open-label ELEVATE trial, kidney transplant patients were randomized at 10-14 weeks posttransplant to convert from calcineurin inhibitor (CNI) to everolimus or remain on standard CNI therapy. Prespecified endpoints included left ventricular mass index (LVMi) and, in a subpopulation of patients, arterial stiffness as measured by pulse wave velocity (PWV)...
March 22, 2017: Transplantation
https://www.readbyqxmd.com/read/28332959/de-novo-donor-specific-antibody-formation-in-tacrolimus-based-mycophenolate-versus-mammalian-target-of-rapamycin-immunosuppressive-regimens
#10
Zain Mithani, Jane Gralla, Oluwafisayo Adebiyi, Patrick Klem, James E Cooper, Alexander C Wiseman
OBJECTIVES: De novo donor-specific antibody formation posttransplant is associated with decreased graft survival. It is not known whether mammalian target of rapamycin inhibitors may be advantageous or detrimental compared with mycophenolate in the prevention of de novo donor-specific antibody formation. MATERIALS AND METHODS: We compared 66 kidney and kidney-pancreas transplant recipients who received tacrolimus, mammalian target of rapamycin inhibitor, and prednisone (group 1; 36 of whom received everolimus and 30 of whom received sirolimus) versus 132 patients who received tacrolimus, mycophenolate, and prednisone (group 2) matched for age, sex, race, and type/timing of transplant from 2007 to 2012...
March 22, 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/28316834/the-cecari-study-everolimus-certican%C3%A2-initiation-and-calcineurin-inhibitor-withdrawal-in-maintenance-heart-transplant-recipients-with-renal-insufficiency-a-multicenter-randomized-trial
#11
Jan Van Keer, David Derthoo, Olivier Van Caenegem, Michel De Pauw, Eric Nellessen, Nathalie Duerinckx, Walter Droogne, Gábor Vörös, Bart Meyns, Ann Belmans, Stefan Janssens, Johan Van Cleemput, Johan Vanhaecke
In this 3-year, open-label, multicenter study, 57 maintenance heart transplant recipients (>1 year after transplant) with renal insufficiency (eGFR 30-60 mL/min/1.73 m(2)) were randomized to start everolimus with CNI withdrawal (N = 29) or continue their current CNI-based immunosuppression (N = 28). The primary endpoint, change in measured glomerular filtration rate (mGFR) from baseline to year 3, did not differ significantly between both groups (+7.0 mL/min in the everolimus group versus +1.9 mL/min in the CNI group, p = 0...
2017: Journal of Transplantation
https://www.readbyqxmd.com/read/28279567/optimizing-everolimus-exposure-when-combined-with-calcineurin-inhibitors-in-solid-organ-transplantation
#12
REVIEW
Teun van Gelder, Lutz Fischer, Fuad Shihab, Maria Shipkova
The mammalian target of rapamycin (mTOR) inhibitor everolimus is a narrow therapeutic index drug for which optimal exposure levels are essential. The consistent pharmacokinetic profile of everolimus allows trough concentration (C0) measurement to be an appropriate and reliable index for therapeutic drug monitoring (TDM). Exposure-response analyses of data from early fixed-dose trials demonstrated that rates of biopsy-proven acute rejection (BPAR) are significantly higher if everolimus C0 declines below 3 ng/mL, an observation confirmed in subsequent concentration-controlled trials...
February 27, 2017: Transplantation Reviews
https://www.readbyqxmd.com/read/28276629/improved-fetal-hemoglobin-with-mtor-inhibitor-based-immunosuppression-in-a-kidney-transplant-recipient-with-sickle-cell-disease
#13
N Gaudre, P Cougoul, P Bartolucci, G Dörr, A Bura-Riviere, N Kamar, A Del Bello
Fetal hemoglobin induction is a key point in the management of sickle cell disease (SCD). We report the case of a kidney transplant recipient with SCD who was treated with everolimus, a mammalian target of rapamycin inhibitor. At 10 months after initiating therapy, the patient's fetal hemoglobin level was dramatically increased (from 4.8% to 15%) and there was excellent tolerance to treatment.
March 9, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28263222/mtor-and-cardiovascular-diseases-diabetes-mellitus
#14
Bruno Vergès
The mammalian targets of rapamycin (mTOR) inhibitors are potent immunosuppressors used for prevention of acute rejection following transplantation and have been more recently used as anticancer drugs. mTOR inhibitors have a significant impact on glucose metabolism and induce frequently diabetes. mTOR inhibitors, when used as immunosuppressive agents (sirolimus, everolimus), can induce diabetes with an incidence which is low when used without calcineurin inhibitors (CNI) but high when used in combination with CNI (from 11...
March 4, 2017: Transplantation
https://www.readbyqxmd.com/read/28258601/incidence-and-outcome-of-bk-polyomavirus-infection-in-a-multicenter-randomized-controlled-trial-with-renal-transplant-patients-receiving-cyclosporine-mycophenolate-sodium-or-everolimus-based-low-dose-immunosuppressive-therapy
#15
Willem B van Doesum, Lilli Gard, Frederike J Bemelman, Johan W de Fijter, Jaap J Homan van der Heide, Hubert G M Niesters, Willem J van Son, Coen A Stegeman, Henk Groen, Annelies Riezebos-Brilman, Jan Stephan F Sanders
INTRODUCTION: It remains unclear whether overall degree of immunosuppression or specific effects of individual immunosuppressive agents are causal for increased occurrence of BK polyomavirus (BKPyV) infection in renal transplant recipients (RTR). METHODS: A prospective, multicenter, open-label randomized controlled trial in 361 de novo RTR was performed. A total of 224 RTR were randomized at 6 months into three treatment groups with dual therapy consisting of prednisolone (Pred) plus either cyclosporine (CsA), mycophenolate sodium (MPS), or everolimus (EVL)...
March 4, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/28258506/persistent-hepatitis-e-infection-in-a-patient-with-tuberous-sclerosis-complex-treated-with-everolimus-a-case-report
#16
Wobke E M van Dijk, Menno A M H Vergeer, Joop E Arends
INTRODUCTION: The incidence of hepatitis E (HEV) genotype 3 is rising in developed countries. HEV infections are usually self-limiting, but can become chronic in immunocompromised patients. This might lead to rapid fibrosis development even resulting in cirrhosis. Chronic HEV is mainly described in patients after solid-organ or hematological transplantations. We present the first case of HEV infection in a patient with tuberous sclerosis complex (TSC) treated with everolimus, a mammalian target of rapamycin (mTOR) inhibitor...
March 3, 2017: Infectious Diseases and Therapy
https://www.readbyqxmd.com/read/28247521/combination-of-leflunomide-and-everolimus-for-treatment-of-bk-virus-nephropathy
#17
Juli Jaw, Prue Hill, David Goodman
BK nephropathy (BKN) is a common cause of graft dysfunction following kidney transplantation. Minimization of immunosuppressive therapy remains the first line of therapy, but this may lead to rejection and graft loss. In some cases, despite lowering immunosuppression, BK infection can persist, leading to chronic damage and kidney failure. Currently, there is no specific anti-BK viral therapy. Recent in vitro experiments have demonstrated a reduction in BK viral replication when infected cells are treated with the combination of Leflunomide and Everolimus...
April 2017: Nephrology
https://www.readbyqxmd.com/read/28230646/effect-of-calcineurin-inhibitor-free-everolimus-based-immunosuppressive-regimen-on-albuminuria-and-glomerular-filtration-rate-after-heart-transplantation
#18
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/28230643/mtor-inhibition-clinical-transplantation-pancreas-islet
#19
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/28230639/mammalian-target-of-rapamycin-inhibition-clinical-transplantation-liver
#20
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
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