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everolimus and transplantation

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https://www.readbyqxmd.com/read/28109543/the-risk-of-cancer-in-kidney-transplant-recipients-may-be-reduced-in-those-maintained-on-everolimus-and-reduced-cyclosporine
#1
Wai H Lim, Graeme R Russ, Germaine Wong, Helen Pilmore, John Kanellis, Steven J Chadban
Kidney transplant recipients are at a high risk of developing cancers after transplantation. Switching from calcineurin inhibitors to sirolimus has been shown to prevent secondary nonmelanoma skin cancer but whether everolimus with reduced exposure to calcineurin inhibitors has similar anti-cancer effects remains unknown. Therefore, we compared the risk of incident cancer over seven years of follow-up among kidney transplant recipients randomized to everolimus plus reduced exposure cyclosporine versus mycophenolate sodium and standard exposure cyclosporine...
January 18, 2017: Kidney International
https://www.readbyqxmd.com/read/28107397/efficacy-and-safety-of-everolimus-for-maintenance-immunosuppression-of-kidney-transplantation-a-meta-analysis-of-randomized-controlled-trials
#2
Jinyu Liu, Dong Liu, Juan Li, Lan Zhu, Chengliang Zhang, Kai Lei, Qiling Xu, Ruxu You
BACKGROUND: Conversion to everolimus is often used in kidney transplantation to overcome calcineurin inhibitor (CNI) nephrotoxicity but there is conflicting evidence for this approach. OBJECTIVES: To investigate the benefits and harm from randomized clinical trials (RCTs) involving the conversion from CNI to everolimus after kidney transplantation. METHODS: Databases were searched up to March 2016. Two reviewers independently assessed trials for eligibility and quality, and extracted data...
2017: PloS One
https://www.readbyqxmd.com/read/28104155/immunosuppression-modification-by-everolimus-with-minimization-of-calcineurin-inhibitors-recovers-kidney-graft-function-even-in-patients-with-very-late-conversion-and-also-with-poor-graft-function
#3
M Nojima, Y Yamada, Y Higuchi, K Shimatani, A Kanematsu, S Yamamoto
BACKGROUND: Although kidney graft survival within 5 years after transplantation is now achieved in >95% of recipients, chronic graft deterioration remains a factor limiting long-term survival. Chronic nephrotoxicity induced by calcineurin inhibitors (CNIs) is one of the major causes of chronic graft injury; thus, minimization of CNIs by administration of everolimus (EVR) is expected to relieve their toxic effects. METHODS: Fifty-six kidney transplant recipients receiving CNI-based immunosuppression (tacrolimus, n = 34; cyclosporine, n = 22) were analyzed...
January 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28104152/experience-of-quatro-therapy-with-everolimus-to-minimize-calcineurin-inhibitor-for-kidney-transplant-recipients
#4
N Nakamura, T Miyazaki, H Matsuzaki, R Furuya, S Miyajima, S Irie, H Matsuoka, M Tanaka
BACKGROUND: This study was divided into three phases, on the occasion of the introduction of everolimus (EVR) in our hospital. METHODS: In the first phase, a study group of six maintenance patients (three living related donors, three deceased donors) who had a history of malignant disease with less than 500 mg/day of proteinuria were enrolled; a high serum creatinine and upper limit of duration after kidney transplant operation was not considered. EVR was discontinued in four of the six patients because of side effects or worsening renal function...
January 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28104132/everolimus-induced-systemic-serositis-after-simultaneous-liver-and-kidney-transplantation-a-case-report
#5
K Kim, D W Jeong, Y H Lee, Y G Kim, J-Y Moon, K-H Jeong, T W Lee, C-G Ihm, S-H Joo, H-C Park, S-H Lee
Although everolimus, a mammalian target of rapamycin inhibitor, has been used as a potent immunosuppressive agent in organ transplantation, data regarding its adverse effect profile compared with that of sirolimus in clinical circumstances are limited. A 50-year-old man who underwent simultaneous liver and kidney transplantation 14 months previously was admitted with large pleural effusion, pericardial effusion, and ascites. Laboratory findings and cultures for possible infectious causes were all negative. Pericardial window surgery with drainage of the pericardial fluid was performed on day 3...
January 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28098395/first-uhplc-ms-ms-method-coupled-with-automated-on-line-spe-for-quantification-both-of-tacrolimus-and-everolimus-in-peripheral-blood-mononuclear-cells-and-its-application-on-samples-from-co-treated-pediatric-patients
#6
Debora Pensi, Amedeo De Nicolò, Michele Pinon, Clarissa Pisciotta, Pier Luigi Calvo, Antonello Nonnato, Renato Romagnoli, Francesco Tandoi, Giovanni Di Perri, Antonio D'Avolio
Tacrolimus (TAC, FK-506) and everolimus (EVE, RAD001) are immunosuppressors used to treat pediatric patients undergoing liver transplantation. Their hematic TDM by liquid chromatography became standard practice. However, it does not always reflect concentrations at their active site. Our aim was to develop and validate a new method for the simultaneous TAC and EVE quantification into target cells: Peripheral-Blood-Mononuclear-Cells (PBMCs). PBMCs were collected using Cell-Preparation-Tubes; cells number and MCV were evaluated by an automatic cell counter...
January 18, 2017: Journal of Mass Spectrometry: JMS
https://www.readbyqxmd.com/read/28094456/waldenstr%C3%A3-m-macroglobulinemia-2017-update-on-diagnosis-risk-stratification-and-management
#7
Morie A Gertz
: Disease Overview: Waldenström macroglobulinemia (WM) is a lymphoplasmacytic lymphoma with immunoglobulin M (IgM) monoclonal protein. Clinical features include anemia, thrombocytopenia, hepatosplenomegaly, lymphadenopathy, and rarely hyperviscosity. DIAGNOSIS: Presence of IgM monoclonal protein associated with ≥10% clonal lymphoplasmacytic cells in bone marrow confirms the diagnosis. The L265P mutation in MYD88 is detectable in more than 90% of patients. Risk Stratification: Age, hemoglobin level, platelet count, β2 microglobulin, and monoclonal IgM concentrations are characteristics required for prognosis...
February 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28058211/organ-transplantation-and-drug-eluting-stents-perioperative-challenges
#8
REVIEW
Aparna Dalal
Patients listed for organ transplant frequently have severe coronary artery disease (CAD), which may be treated with drug eluting stents (DES). Everolimus and zotarolimus eluting stents are commonly used. Newer generation biolimus and novolimus eluting biodegradable stents are becoming increasingly popular. Patients undergoing transplant surgery soon after the placement of DES are at increased risk of stent thrombosis (ST) in the perioperative period. Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor such as clopidogrel, prasugrel and ticagrelor is instated post stenting to decrease the incident of ST...
December 24, 2016: World Journal of Transplantation
https://www.readbyqxmd.com/read/28056114/diagnosis-and-management-of-waldenstr%C3%A3-m-macroglobulinemia-mayo-stratification-of-macroglobulinemia-and-risk-adapted-therapy-msmart-guidelines-2016
#9
Prashant Kapoor, Stephen M Ansell, Rafael Fonseca, Asher Chanan-Khan, Robert A Kyle, Shaji K Kumar, Joseph R Mikhael, Thomas E Witzig, Michelle Mauermann, Angela Dispenzieri, Sikander Ailawadhi, A Keith Stewart, Martha Q Lacy, Carrie A Thompson, Francis K Buadi, David Dingli, William G Morice, Ronald S Go, Dragan Jevremovic, Taimur Sher, Rebecca L King, Esteban Braggio, Ann Novak, Vivek Roy, Rhett P Ketterling, Patricia T Greipp, Martha Grogan, Ivana N Micallef, P Leif Bergsagel, Joseph P Colgan, Nelson Leung, Wilson I Gonsalves, Yi Lin, David J Inwards, Suzanne R Hayman, Grzegorz S Nowakowski, Patrick B Johnston, Steven J Russell, Svetomir N Markovic, Steven R Zeldenrust, Yi L Hwa, John A Lust, Luis F Porrata, Thomas M Habermann, S Vincent Rajkumar, Morie A Gertz, Craig B Reeder
Importance: Waldenström macroglobulinemia (WM), an IgM-associated lymphoplasmacytic lymphoma, has witnessed several practice-altering advances in recent years. With availability of a wider array of therapies, the management strategies have become increasingly complex. Our multidisciplinary team appraised studies published or presented up to December 2015 to provide consensus recommendations for a risk-adapted approach to WM, using a grading system. Observations: Waldenström macroglobulinemia remains a rare, incurable cancer, with a heterogeneous disease course...
January 5, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28028691/sirolimus-therapy-is-associated-with-elevation-in-circulating-pcsk9-levels-in-cardiac-transplant-patients
#10
Vinaya Simha, Sisi Qin, Pankaj Shah, Byron H Smith, Walter K Kremers, Sudhir Kushwaha, Liewei Wang, Naveen L Pereira
Sirolimus used in transplantation is often associated with hypercholesterolemia. We measured serum lipid and PCSK9 levels in 51 heart transplant recipients who had their immunosuppressive therapy switched from calcineurin inhibitors to sirolimus. The switch resulted in a 23% increase in LDL cholesterol, and 46% increase in triglycerides and PCSK9 levels increased from 316 ± 105 ng/mL to 343 ± 107 ng/mL (p = 0.04), however the change in PCSK9 levels did not correlate with an increase in lipid levels (p = 0...
December 27, 2016: Journal of Cardiovascular Translational Research
https://www.readbyqxmd.com/read/28027625/early-conversion-from-calcineurin-inhibitor-to-everolimus-based-therapy-following-kidney-transplantation-results-of-the-randomized-elevate-trial
#11
Johan W de Fijter, Hallvard Holdaas, Ole Øyen, Jan-Stephan Sanders, Sankaran Sundar, Frederike J Bemelman, Claudia Sommerer, Julio Pascual, Yingyos Avihingsanon, Cholatip Pongskul, Frederic Oppenheimer, Lorenzo Toselli, Graeme Russ, Zailong Wang, Patricia Lopez, Jossy Kochuparampil, Josep M Cruzado, Markus van der Giet
In a 24-month, multicenter, open-label, randomized trial, 715 de novo kidney transplant recipients were randomized at 10-14 weeks to convert to everolimus (n=359) or remain on standard calcineurin inhibitor (CNI) therapy (n=356; 231 tacrolimus; 125 cyclosporine), all with mycophenolic acid and steroids. The primary endpoint, change in estimated GFR from randomization to month 12, was similar for everolimus versus CNI: mean (SE) 0.3(1.5)mL/min/1.73(2) versus -1.5(1.5)mL/min/1.73(2) (p=0.116). At month 24, mean (SD) estimated GFR was 62...
December 27, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/27988326/everolimus-tdm-using-thermo-fisher-qms-immunoassay-on-indiko-beckman-dxc-au680-and-au5800-analyzers
#12
Steven Hy Wong, Kamisha L Johnson-Davis, Krista Garrison, Joe D Rankin, Chro S Muhammad
OBJECTIVES: Everolimus (EVR), a mTOR inhibitor immunosuppressant approved for renal, liver and cardiac transplants. This study established the appropriate TDM performances of the Thermo Scientific QMS EVR Assay by using the Beckman DxC, followed by comparison to the Thermo Scientific Indiko and a previously published LC-MS/MS assay, and Beckman AU680 and AU5800 analyzers. DESIGN AND METHODS: The study initially established acceptable linearity, precision and accuracy of the QMS EVR turbidimetric assay...
December 15, 2016: Clinical Biochemistry
https://www.readbyqxmd.com/read/27932158/everolimus-and-advagraf-ab-initio-in-combined-liver-and-kidney-transplant-with-donor-specific-antibodies-a-case-report
#13
L Tariciotti, T M Manzia, D Sforza, A Anselmo, G Tisone
Although donor-specific antibodies are regarded as a contraindication for kidney transplantation, the data available for combined liver and kidney transplantation (cLKTx) are scarce, and there is no established therapeutic approach for this category of transplant recipients. De novo use of everolimus and a reduced dose of calcineurin inhibitor reportedly provides excellent kidney function compared with a standard regimen containing a calcineurin inhibitor. This strategy, however, has been applied in only some recipient categories...
November 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27915965/systematic-review-on-role-of-mammalian-target-of-rapamycin-inhibitors-as-an-alternative-to-calcineurin-inhibitors-in-renal-transplant-challenges-and-window-to-excel
#14
Jayant Kumar, Julie M Bridson, Ajay Sharma, Ahmed Halawa
OBJECTIVES: This review focuses on the current limited evidence of graft function and graft survival in various immunosuppressive regimens involving mammalian target of rapamycin inhibitors with or without calcineurin inhibitors. MATERIALS AND METHODS: We evaluated the current literature for describing the role of mammalian target of rapamycin inhibitors as an alternative to calcineurin inhibitors by searching the PubMed, EMBASE, Cochrane, Crossref, and Scopus databases using medical subject heading terms...
December 2, 2016: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/27862865/long-term-clinical-and-angiographic-outcomes-of-percutanenous-coronary-intervention-with-everolimus-eluting-stents-for-the-treatment-of-cardiac-allograft-vasculopathy
#15
Richard Cheng, Christopher Vanichsarn, Jignesh K Patel, Jesse Currier, David H Chang, Michelle M Kittleson, Raj Makkar, Jon A Kobashigawa, Babak Azarbal
BACKGROUND: Percutaneous coronary intervention (PCI) with bare-metal and first-generation drug-eluting stents (DES) for cardiac allograft vasculopathy (CAV) is associated with unexpectedly high restenosis rates and target lesion revascularization (TLR). Long-term outcomes of stenting for CAV using second-generation everolimus-eluting stents (EES) are not established. OBJECTIVE: To evaluate clinical and angiographic outcomes of CAV stenting with EES. METHODS: Patients who underwent PCI with EES for CAV were studied...
November 10, 2016: Catheterization and Cardiovascular Interventions
https://www.readbyqxmd.com/read/27862340/everolimus-with-early-withdrawal-or-reduced-dose-calcineurin-inhibitors-improves-renal-function-in-liver-transplant-recipients-a-systematic-review-and-meta-analysis
#16
Michael Lin, Sahil Mittal, Farhad Sahebjam, Abbas Rana, Gagan K Sood
Calcineurin inhibitors (CNI) are the mainstay of immunosuppression after liver transplantation (LT), but CNIs are associated with significant nephrotoxicity. Recently, mTOR inhibitors such as sirolimus and everolimus (EVR) have been used with or without CNIs in LT recipients for their renal-sparing effect. We conducted a systematic review and meta-analysis of randomized controlled trials (RCT) that examined the effect of EVR with CNI minimization or withdrawal on renal function in LT recipients. RCT of primary adult LT recipients with baseline GFR >30 mL/min who received EVR with CNI minimization or withdrawal were included...
November 16, 2016: Clinical Transplantation
https://www.readbyqxmd.com/read/27807479/everolimus-and-malignancy-after-solid-organ-transplantation-a-clinical-update
#17
REVIEW
Hallvard Holdaas, Paolo De Simone, Andreas Zuckermann
Malignancy after solid organ transplantation remains a major cause of posttransplant mortality. The mammalian target of rapamycin (mTOR) inhibitor class of immunosuppressants exerts various antioncogenic effects, and the mTOR inhibitor everolimus is licensed for the treatment of several solid cancers. In kidney transplantation, evidence from registry studies indicates a lower rate of de novo malignancy under mTOR inhibition, with some potentially supportive data from randomized trials of everolimus. Case reports and small single-center series have suggested that switch to everolimus may be beneficial following diagnosis of posttransplant malignancy, particularly for Kaposi's sarcoma and nonmelanoma skin cancer, but prospective studies are lacking...
2016: Journal of Transplantation
https://www.readbyqxmd.com/read/27798513/longitudinal-pharmacokinetics-of-everolimus-when-combined-with-low-level-of-tacrolimus-in-elderly-renal-transplant-recipients
#18
Elias David-Neto, Fabiana Agena, Fernanda Ramos, Ana Heloisa Triboni, Paschoalina Romano, Persio de Almeida Rezende Ebner, Venceslau Coelho, Nelson Zocoler Galante, Francine Carvalinho Lemos
BACKGROUND: Although the proportion of elderly patients among renal transplant recipients has increased, pharmacokinetic (PK) studies of immunosuppressants rarely include older patients. METHODS: We studied 12-hours everolimus (EVL) PK in 16 elderly renal transplant recipients (all caucasians; 10 males; mean age, 64±2 years, (61-71y), in 4 separate time-points (at 7, 30, 60 and 150 days) after EVL introduction, corresponding to a mean post renal-transplantation day: PK1 (43±4days), PK2 (65±7 days), PK3 (106±17 days) and PK4 (206±40 days)...
October 28, 2016: Transplantation
https://www.readbyqxmd.com/read/27797804/everolimus-associated-stomatitis-in-a-patient-who-had-renal-transplant
#19
Yisi D Ji, Ali Aboalela, Alessandro Villa
Everolimus is used as an immunosuppressant in renal allograft transplant rejection and in metastatic breast cancer treatment. One side effect of everolimus is stomatitis, referred to as mammalian target of rapamycin inhibitor-associated stomatitis. This side effect can affect treatment course and contribute to discontinuation of therapy or dose reduction, previously reported in the treatment of metastatic breast cancer. Here, we present a case of everolimus-associated stomatitis with a novel management method with intralesional triamcinolone that allows for continuous course of everolimus...
October 19, 2016: BMJ Case Reports
https://www.readbyqxmd.com/read/27793122/acute-pancreatitis-associated-with-everolimus-after-kidney-transplantation-a-case-report
#20
Francesco Fontana, Gianni Cappelli
BACKGROUND: Acute pancreatitis (AP) following KT is a rare and often fatal complication of the early post-transplant period. Common causative factors for AP are rare after KT; anti-rejection drugs as CyA, prednisone and MMF have been implicated, although evidence is not strong and we found no reports on possible causative role for mTOR inhibitors. CASE PRESENTATION: A 55-year-old Caucasian man with end-stage renal disease due to idiopathic membrano-prolipherative glomerulonephritis underwent single kidney transplantation (KT) from cadaveric donor...
October 28, 2016: BMC Nephrology
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