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everolimus and transplantation

Amelia G Mociornita, Mitchell B Adamson, Laura C Tumiati, Heather J Ross, Vivek Rao, Diego H Delgado
Human Leukocyte Antigen-G (HLA-G) expression is modulated by immunosuppressant use and is associated with lower incidence of graft rejection and cardiac allograft vasculopathy (CAV). We examined if everolimus induces HLA-G expression and inhibits human coronary artery smooth muscle cell (HCASMC) proliferation, a critical event in CAV. Also, we examined if TNFα-stimulated neutrophil adhesion is inhibited by HLA-G on human coronary artery endothelial cells (HCAECs). HLA-G expression in HCASMCs following everolimus treatment was determined by Western-blot densitometric analysis...
July 9, 2018: American Journal of Transplantation
Tainá Veras de Sandes-Freitas, Petrucia Maria Antero Pinheiro, Maria Luíza de Mattos Brito Oliveira Sales, Celi Melo Girão, Érika Fernandes Campos, Ronaldo de Matos Esmeraldo
There is no evidence of whether everolimus(EVR) reduces cytomegalovirus(CMV) events in patients receiving steroid-free regimens.Besides, studies evaluating a tacrolimus(TAC) and EVR regimen are limited to 1-year follow-up. In this single-center prospective randomized trial, the incidence of CMV and 3-year efficacy and safety outcomes of EVR were compared to those of mycophenolate sodium(MPS) in a steroid-free regimen based on low-exposure TAC.Both groups received rabbit anti-thymocyte globulin(r-ATG) induction(6mg/kg) and the steroids were withdrawn at day 7...
July 3, 2018: Transplant International: Official Journal of the European Society for Organ Transplantation
Ute Eisenberger, Klemens Budde, Frank Lehner, Claudia Sommerer, Petra Reinke, Oliver Witzke, Rudolf P Wüthrich, Rolf Stahl, Katharina Heller, Barbara Suwelack, Anja Mühlfeld, Ingeborg A Hauser, Silvio Nadalin, Martina Porstner, Wolfgang Arns
BACKGROUND: Conversion from calcineurin inhibitor (CNI) therapy to everolimus within 6 months after kidney transplantation improves long-term graft function but can increase the risk of mild biopsy-proven acute cellular rejection (BPAR). We performed a post-hoc analysis of histological data from a randomized trial in order to further analyze histologic information obtained from indication and protocol biopsies up to 5 years after transplantation. METHODS: Biopsy samples obtained up to 5 years post-transplant were analyzed from the randomized ZEUS study, in which kidney transplant patients were randomized at month 4...
June 28, 2018: BMC Nephrology
T Simundic, L Zibar, K Sego
We describe the case of a transplanted patient with high-risk HPV infection that manifested as multiple genital condylomas and abnormal Papanicolaou (Pap) smear. Her immunosuppressants were corticosteroids, cyclosporine, and azathioprine. Since gynecologic treatments to eradicate condylomas were completely unsuccessful, cyclosporine was replaced by everolimus. Soon after, condylomas disappeared, HPV status became negative, and Pap smear returned to normal and has remained normal since.
August 2018: Gynecologic Oncology Reports
Koji Nanmoku, Akira Kurosawa, Taro Kubo, Takahiro Shinzato, Toshihiro Shimizu, Takaaki Kimura, Takashi Yagisawa
OBJECTIVES: Although steroid withdrawal has been attempted to ameliorate various complications in kidney transplant recipients, a steroid-sparing strategy has more frequently led to acute rejection. We investigated the use of everolimus to safely overcome steroid withdrawal in kidney transplant recipients with posttransplant diabetes mellitus under maintenance immunosuppressive therapy. MATERIALS AND METHODS: A total of 75 de novo consecutive kidney transplant recipients received conventional immunosuppressive therapy comprising tacrolimus (trough level of 5 ng/mL), mycophenolate mofetil (1000 mg), and methylprednisolone (4 mg)...
June 18, 2018: Experimental and Clinical Transplantation
Abdulwahab A Alshahrani, Shin Hwang, Gi-Won Song, Deok-Bog Moon, Dong-Hwan Jung, Chul-Soo Ahn, Ki-Hun Kim, Tae-Yong Ha, Gil-Chun Park, Su-Min Ha, Yo-Han Park, Sung-Gyu Lee
Recurrence of hepatocellular carcinoma (HCC) 10 years after liver transplantation (LT) is very rare. Here, we present two cases of peritoneal metastasis of HCC that occurred 10 and 12 years after LT. A 77-year-old male who had undergone deceased-donor LT 10 years earlier showed slow progressive elevation of tumor marker levels over 6 months. Close observation with frequent imaging studies and monthly tumor marker analyses revealed a solitary peritoneal seeding mass. Imaging studies revealed that the mass was highly likely to be metastatic HCC...
May 2018: Annals of Hepato-Biliary-Pancreatic Surgery
Jun Li, Martina Koch, Kathrin Kramer, Katja Kloth, Abdel Rahman Abu Ganim, Silke Scheidat, Franz Rinninger, Friedrich Thaiss, Amit Gulati, Uta Herden, Eike Achilles, Lutz Fischer, Bjoern Nashan
BACKGROUND: To be an optimal immunosuppressive regimen after simultaneous pancreas kidney transplantation (SPK), low dose calcineurin inhibitor and early withdrawal of corticosteroids are desired. METHODS: Immunosuppressive regimen as such has been conducted consecutively in SPK recipients since 2009 in authors' institute. In addition to tacrolimus in low trough level and early corticosteroid withdraw, dual induction with basiliximab and low-dose thymoglobulin in combination with everolimus are the important components of the protocol...
June 6, 2018: Transplant Immunology
Ashraf Omar, Pradnya D Patil, Sami Hoshi, Jasmine Huang, Earle Collum, Tanmay S Panchabhai
A 68-year-old man presented to our ED with shortness of breath, weakness, and a 25-lb unintentional weight loss. He had undergone bilateral lung transplantation (cytomegalovirus [CMV]: donor+, recipient+; Epstein-Barr virus: donor+; recipient+) for idiopathic pulmonary fibrosis (IPF) 18 months prior. His posttransplant course was fairly unremarkable until 1 month earlier, when he was admitted for breathlessness and weakness. CT of the chest during that admission revealed mild intralobular and interlobular septal thickening...
June 2018: Chest
Stephan Ruben, Martin Kreuzer, Anja Büscher, Rainer Büscher, Julia Thumfart, Uwe Querfeld, Hagen Staude, Thurid Ahlenstiel-Grunow, Anette Melk, Dagmar-Christiane Fischer, Maren Leifheit-Nestler, Lars Pape, Dieter Haffner
BACKGROUND/AIMS: Whether the immunosuppressive regimen is associated with micro- and macro-vascular status in pediatric kidney transplant recipients (KTx) is unknown. METHODS: We performed a cross-sectional, case-control study in 44 pediatric KTx patients on either everolimus (EVR) plus calcineurin inhibitor or standard treatment, i.e. mycophenolate mofetil plus calcineurin inhibitor. Measurement of carotid intima-media thickness (cIMT) via ultrasound, central pulse wave velocity (PWV) by a cuff-based oscillometric technique, and skin microvascular blood flow during local heating via laser-Doppler-fluximetry (LDF) served as marker of subclinical vascular disease...
2018: Kidney & Blood Pressure Research
Tracey Ying, Germaine Wong, Wai Lim, John Kanellis, Helen Pilmore, Scott Campbell, Rosemary Masterson, Rowan Walker, Philip O'Connell, Graeme Russ, Steven Chadban
Choice of immunosuppression may modify the risk of cancer after kidney transplantation, however, long-term data are lacking. Using the Australian and New Zealand Dialysis and Transplant Registry, we compared the 9-year risk of incident cancer, non-melanoma skin cancer (NMSC), and death attributed to cancer among participants from Australia and New Zealand in four randomized-controlled trials which compared de novo or early switch to an everolimus-containing regimen with calcineurin-inhibitor-based triple therapy...
May 26, 2018: American Journal of Transplantation
Geovana Basso, Claudia Rosso Felipe, Marina Pontello Cristelli, Juliana Mansur Siliano, Laila Viana, Alexandra Nicolau Ferreira Brigido, Suelen Bianca Stopa Martins, Daniel Wagner de Castro Lima Santos, Wilson Ferreira Aguiar, Helio Tedesco-Silva Junior, Jose Osmar Medina-Pestana
BACKGROUND: The use of mTOR inhibitors is associated with lower incidence of CMV infections but its effect on viral load has not been investigated. AIMS, MATERIALS AND METHODS: This post-hoc analysis included data from 273 CMV seropositive kidney transplant recipients randomized to receive anti-thymocyte globulin and everolimus (rAGT/TAC/EVR, n = 81), basiliximab and everolimus (BAS/TAC/EVR, n = 97) or basiliximab and mycophenolate (BAS/TAC/MPS, n = 95). All patients received tacrolimus (TAC) and corticosteroids...
May 24, 2018: Transplant Infectious Disease: An Official Journal of the Transplantation Society
Thomas Jouve, Johan Noble, Lionel Rostaing, Paolo Malvezzi
The prevalence of end-stage renal disease is increasing worldwide. The best treatment is kidney transplantation, although life-long immunosuppressive therapy is then mandatory. Currently, the cornerstone immunosuppressive therapy relies on tacrolimus (Tac), a calcineurin inhibitor that is nephrotoxic but whose exposition can be minimized in a delicate balance. Area covered: We addressed whether, in the setting of kidney transplantation, Tac-based therapy can be tailored to medical needs: to achieve this, we searched for suitable articles in PubMed...
June 2018: Expert Review of Clinical Pharmacology
Patrick B Johnston, Lauren C Pinter-Brown, Ghulam Warsi, Kristen White, Radhakrishnan Ramchandren
Background: The current standard of care for classical Hodgkin lymphoma (HL) is multiagent chemotherapy with or without radiation. In patients who relapse or fail to respond, additional high-dose chemotherapy with autologous hematopoietic stem cell transplantation (AHSCT) can improve progression-free survival (PFS). Novel therapies are required for patients refractory to chemotherapy and AHSCT. The mammalian target of rapamycin inhibitor everolimus has shown preliminary activity in preclinical models of HL and promising efficacy in patients with relapsed or refractory HL...
2018: Experimental Hematology & Oncology
Larissa Sgaria Pacheco, Valter Duro Garcia, Ronivan Luis Dal Prá, Bruna Doleys Cardoso, Mariana Ferras Rodrigues, Helen Kris Zanetti, Gisele Meinerz, Jorge Neumann, Diego Gnatta, Elizete Keitel
INTRODUCTION: Currently, there is no specific immunosuppressive protocol for hepatitis C (HCV)-positive renal transplants recipients. Thus, the aim of this study was to evaluate the conversion effect to everolimus (EVR) on HCV in adult kidney recipients. METHOD: This is an exploratory single-center, prospective, randomized, open label controlled trial with renal allograft recipients with HCV-positive serology. Participants were randomized for conversion to EVR or maintenance of calcineurin inhibitors...
May 14, 2018: Jornal Brasileiro de Nefrologia: ʹorgão Oficial de Sociedades Brasileira e Latino-Americana de Nefrologia
Samuel Y Ng, Leon Brown, Kristen Stevenson, Tiffany deSouza, Jon C Aster, Abner Louissaint, David M Weinstock
Patients with angioimmunoblastic T-cell lymphoma (AITL) and other peripheral T-cell lymphomas (PTCL) that harbor features of follicular helper T (TFH) cells have a very poor prognosis. These lymphomas commonly present with paraneoplastic autoimmunity and lymphopenia. RhoA G17V mutation is present in 60% of TFH-like lymphomas but its role in tumorigenesis is poorly understood. We generated transgenic mice that express RhoA G17V under the control of murine CD4 regulatory elements at levels comparable to a heterozygous mutation (tgRhoA mice)...
May 16, 2018: Blood
Manuel Rodríguez-Perálvarez, Marta Guerrero, Lydia Barrera, Gustavo Ferrín, Jose M Álamo, María D Ayllón, Gonzalo Suarez Artacho, José L Montero, Javier Briceño, Carmen Bernal, Javier Padillo, Luis M Marín-Gómez, Juan M Pascasio, Antonio Poyato, Miguel A Gómez-Bravo, Manuel De la Mata
BACKGROUND: Many centers implement everolimus-based immunosuppression in liver transplant patients with hepatocellular carcinoma. We aimed to explore the potential impact of early initiated everolimus on tumor recurrence after liver transplantation. METHODS: This study included 192 patients with hepatocellular carcinoma undergoing liver transplantation among who 64 individuals were prospectively enrolled (2012-2015) and received early initiated everolimus (ie, started between postoperative day 15 to 21), while the remaining 128 patients acted as historical controls without everolimus...
May 11, 2018: Transplantation
Johan Noble, Thomas Jouve, Lionel Rostaing, Paolo Malvezzi
Cornerstone immunosuppressive therapy currently relies on immediate-release tacrolimus, a calcineurin inhibitor (CNI) that is potentially nephrotoxic and is more diabetogenic than cyclosporine A. Two new formulations of tacrolimus have been launched: an extended-release formulation (Advagraf®/Astagraf XL®, Astellas company) and a long-lasting formulation (Envarsus®, Veloxis company). Area covered: Herein, we assess the efficacy of an extended-release formulation of tacrolimus (Advagraf®/Astagraf XL®) used in conjunction with or without an induction therapy (i...
June 2018: Expert Review of Clinical Immunology
Julio Pascual, Stefan P Berger, Oliver Witzke, Helio Tedesco, Shamkant Mulgaonkar, Yasir Qazi, Steven Chadban, Federico Oppenheimer, Claudia Sommerer, Rainer Oberbauer, Yoshihiko Watarai, Christophe Legendre, Franco Citterio, Mitchell Henry, Titte R Srinivas, Wen-Lin Luo, AnaMaria Marti, Peter Bernhardt, Flavio Vincenti
Background Everolimus permits reduced calcineurin inhibitor (CNI) exposure, but the efficacy and safety outcomes of this treatment after kidney transplant require confirmation. Methods In a multicenter noninferiority trial, we randomized 2037 de novo kidney transplant recipients to receive, in combination with induction therapy and corticosteroids, everolimus with reduced-exposure CNI (everolimus arm) or mycophenolic acid (MPA) with standard-exposure CNI (MPA arm). The primary end point was treated biopsy-proven acute rejection or eGFR<50 ml/min per 1...
May 11, 2018: Journal of the American Society of Nephrology: JASN
Claudia Sommerer, Michael Duerr, Oliver Witzke, Frank Lehner, Wolfgang Arns, Volker Kliem, Daniel Ackermann, Markus Guba, Johannes Jacobi, Ingeborg A Hauser, Rolf Stahl, Petra Reinke, Thomas Rath, Justyna Veit, Arianeb Mehrabi, Martina Porstner, Klemens Budde
HERAKLES was a 1-year randomized, multicenter trial. Patients were randomized at 3 months after kidney transplantation to remain on cyclosporine-based therapy, switch to everolimus without a calcineurin inhibitor (CNI), or switch to everolimus with low-exposure cyclosporine. Overall, 417 of 497 (83.9%) patients from the core study entered a 4-year extension study. The randomized regimen was continued to year 5 in 75.9%, 41.9% and 24.6% of patients in the standard-CNI, CNI-free and low-CNI groups, respectively...
May 2, 2018: American Journal of Transplantation
Ambalavanan Arunachalam, Syed Rizwan Ali, Brett J Wakefield, Charles R Lane, Atul C Mehta
Everolimus is a mechanistic target of rapamycin inhibitor used for the treatment of various cancers and prevention of allograft rejection in solid organ transplantation. We present a case of a lung transplant recipient on everolimus who was admitted with generalized weakness, hypoxia and new onset bilateral pulmonary infiltrates on imaging. Extensive workup revealed no infectious etiology and high levels of serum everolimus levels. Her condition deteriorated over the hospital course with symptoms and signs of systemic everolimus toxicity...
April 2018: Oxford Medical Case Reports
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