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Everolimus transplantation

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https://www.readbyqxmd.com/read/29779413/tailoring-tacrolimus-therapy-in-kidney-transplantation
#1
Thomas Jouve, Johan Noble, Lionel Rostaing, Paolo Malvezzi
BACKGROUND: 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, 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, tacrolimus-based therapy can be tailored to medical needs: to achieve this, we searched for suitable articles in PubMed...
May 19, 2018: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/29774169/phase-2-study-of-everolimus-for-relapsed-or-refractory-classical-hodgkin-lymphoma
#2
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
https://www.readbyqxmd.com/read/29771270/effect-of-conversion-from-calcineurin-inhibitors-to-everolimus-on-hepatitis-c-viremia-in-adult-kidney-transplant-recipients
#3
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
https://www.readbyqxmd.com/read/29769264/rhoa-g17v-is-sufficient-to-induce-autoimmunity-and-promotes-t-cell-lymphomagenesis-in-mice
#4
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
https://www.readbyqxmd.com/read/29757893/impact-of-early-initiated-everolimus-on-the-recurrence-of-hepatocellular-carcinoma-after-liver-transplantation
#5
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
https://www.readbyqxmd.com/read/29757021/advagraf%C3%A2-with-or-without-an-induction-therapy-for-de-novo-kidney-transplant-recipients
#6
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...
May 14, 2018: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/29752413/everolimus-with-reduced-calcineurin-inhibitor-exposure-in-renal-transplantation
#7
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
https://www.readbyqxmd.com/read/29722128/five-year-outcomes-in-kidney-transplant-patients-randomized-to-everolimus-with-cyclosporine-withdrawal-or-low-exposure-cyclosporine-versus-standard-therapy
#8
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 one-year randomized, multicenter trial. Patients were randomized at three 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, 417/497 (83.9%) patients from the core study entered a four-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
https://www.readbyqxmd.com/read/29713487/everolimus-induced-pneumonitis-in-a-lung-transplant-recipient
#9
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
https://www.readbyqxmd.com/read/29710388/antitumor-effect-of-sorafenib-and-mtor-inhibitor-in-liver-transplantation-recipients-with-hepatocellular-carcinoma-recurrence
#10
Dong-Hwan Jung, Eunyoung Tak, Shin Hwang, Gi-Won Song, Chul-Soo Ahn, Ki-Hun Kim, Deok-Bog Moon, Tae-Yong Ha, Gil-Chun Park, Baek-Yeol Ryoo, Kyoung-Jin Lee, Nayoung Kim, Jae-Hyeon Kwon, Eun-Kyoung Jwa, Sung-Gyu Lee
Both sorafenib and mTOR inhibitor (mTORi) have antitumor effects. This study aimed to evaluate their antitumor effects in liver transplantation (LT) recipients with hepatocellular carcinoma (HCC) recurrence. We performed a laboratory study using sorafenib and mTORi and subsequently validated their survival benefit at clinical LT setting. In the laboratory study, HepG2.2.15 liver tumor cell line and five patient-derived graft HCC cell lines were used for in vitro cytotoxic studies. After treatment with everolimus and sorafenib, cell viability and apoptosis assays revealed noticeable cytotoxic effects with individual agents and augmented effects by combination therapy...
April 30, 2018: Liver Transplantation
https://www.readbyqxmd.com/read/29705974/extreme-hypercalcemia-in-a-kidney-transplant-recipient
#11
Erol Demir, Cagla Karaoglan, Gulcin Yegen, Betul Sair, Halil Yazici, Aydin Turkmen, Mehmet Sukru Sever
Post-transplant hypercalcemia is a major problem in renal transplant recipients, which may negatively affect both graft and patient survival. In this paper, we present a 66-year-old male kidney transplant recipient, who was admitted to our clinic with symptoms of fever, nausea, vomiting and lethargy. Laboratory data showed good renal function; however, a serum calcium level of 22.1 mg/dL. The patient was treated by isotonic saline together with furosemide and methylprednisolone. Because of treatment resistance, subcutaneous calcitonin and ibandronate were added to the treatment protocol as well...
April 28, 2018: CEN Case Reports
https://www.readbyqxmd.com/read/29684618/everolimus-is-a-new-anti-cancer-molecule-metabolic-side-effects-as-lipid-disorders-and-hyperglycemia
#12
REVIEW
L Morviducci, F Rota, L Rizza, P Di Giacinto, S Ramponi, M R Nardone, C Tubili, A Lenzi, P Zuppi, R Baldelli
In the last few years, molecular targeted therapies have replaced traditional cytotoxic chemotherapy in the fight against many cancers to the extent that our understanding of tumor biology has become more sophisticated. This shift has markedly changed adverse event profiles, compared to cytotoxic chemotherapy, affecting a diverse range of organ systems. Everolimus was approved by the FDA in 2011 for the treatment of progressive pancreatic NE tumors (Yao, 2011; Jensenn, 2012). It is an inhibitor of mammalian target of rapamycin (mTOR) and exhibits antitumor activity via disruption of various signaling pathways and it's used in the treatment of advanced renal cell cancer, breast cancer and neuroendocrine tumors (NET); it's used also as anti-rejection agent for transplantation but with lower doses for anti-rejection (1...
April 20, 2018: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/29679515/the-influence-of-mtor-inhibitors-on-the-incidence-of-cmv-infection-in-high-risk-donor-positive-recipient-negative-d-r-kidney-transplant-recipients
#13
M P Cristelli, R M Esmeraldo, C Motta Pinto, T V Sandes-Freitas, C Felipe, C F Lobo, L Viana, J Mansur, S Stopa, D W C Santos, P C Grenzi, W F Aguiar, H Tedesco-Silva, J O Medina-Pestana
Several studies and meta-analysis suggest the mTOR inhibitors are associated with reduced incidence of CMV infection after kidney transplantation, although their effects on the high-risk population have not been investigated thoroughly. This retrospective cohort study investigates the association between immunosuppression and CMV infection in D+/R- kidney transplant recipients receiving preemptive therapy. All patients received rabbit anti-thymocyte globulin, tacrolimus, prednisone and azathioprine (AZA), mycophenolate (MPA) or everolimus (EVR)...
April 21, 2018: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/29679392/comparison-of-electrochemiluminescence-immunoassay-and-latex-agglutination-turbidimetric-immunoassay-for-evaluation-of-everolimus-blood-concentrations-in-renal-transplant-patients
#14
Y Akamine, S Sato, H Kagaya, T Ohkubo, S Satoh, M Miura
WHAT IS KNOWN AND OBJECTIVE: For analysis of blood concentrations of everolimus, many hospital laboratories use either latex agglutination turbidimetric immunoassay (LTIA) or electrochemiluminescence immunoassay (ECLIA). However, no studies have compared both immunoassay methods under the same conditions. Accordingly, in this study, we compared everolimus blood concentrations obtained by LTIA and ECLIA in renal transplant patients. METHODS: Blood samples (n = 230) from 60 renal transplant patients (19 female and 41 male) were evaluated using both immunoassays...
April 20, 2018: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/29677166/in-vitro-identification-of-new-transcriptomic-and-mirnomic-profiles-associated-with-pulmonary-fibrosis-induced-by-high-doses-everolimus-looking-for-new-pathogenetic-markers-and-therapeutic-targets
#15
Simona Granata, Gloria Santoro, Valentina Masola, Paola Tomei, Fabio Sallustio, Paola Pontrelli, Matteo Accetturo, Nadia Antonucci, Pierluigi Carratù, Antonio Lupo, Gianluigi Zaza
The administration of Everolimus (EVE), a mTOR inhibitor used in transplantation and cancer, is often associated with adverse effects including pulmonary fibrosis. Although the underlying mechanism is not fully clarified, this condition could be in part caused by epithelial to mesenchymal transition (EMT) of airway cells. To improve our knowledge, primary bronchial epithelial cells (BE63/3) were treated with EVE (5 and 100 nM) for 24 h. EMT markers (α-SMA, vimentin, fibronectin) were measured by RT-PCR. Transepithelial resistance was measured by Millicell-ERS ohmmeter...
April 20, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29661455/management-of-juvenile-idiopathic-arthritis-in-abo-incompatible-kidney-transplantation-a-case-report
#16
S Ishikawa, M Tasaki, T Kuroda, D Kobayashi, K Saito, Y Nakagawa, M Ikeda, K Takahashi, Y Tomita
Biologic agents are a beneficial therapy for juvenile idiopathic arthritis (JIA). However, there is a lack of evidence with regard to management of these agents for JIA patients who undergo kidney transplantation (KTx). A 36-year-old woman with JIA who was treated with tocilizumab targeting interleukin-6 (IL-6) receptor underwent ABO-incompatible kidney transplantation (ABOi KTx). To prevent over-immunosuppression, tocilizumab was discontinued before ABOi KTx. Rituximab, tacrolimus, mycophenolate mofetil, everolimus, and methylprednisolone were used for immunosuppression...
April 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/29650438/hepatitis-e-virus-infection-mimicking-acute-graft-rejection-in-a-liver-transplant-recipient
#17
M Allaire, C Bazille, J Selves, E Salamé, M Altieri
INTRODUCTION: In liver transplant (LT) patients, hepatitis E virus (HEV) can lead to acute liver failure, chronic hepatitis and graft cirrhosis. Few data on graft rejection associated with HEV are available and are subject to discussion. CASE REPORT: Here we report the case of a 58-year-old male patient who underwent LT in July 2015 for cirrhosis due to NASH and chronic alcohol intake complicated by hepatocellular carcinoma. LT was performed with a deceased donor isogroup and a mismatch CMV (donor+ and recipient-)...
April 10, 2018: Clinics and Research in Hepatology and Gastroenterology
https://www.readbyqxmd.com/read/29648533/the-effect-of-fluconazole-on-the-pharmacokinetics-of-everolimus-and-tacrolimus-in-a-heart-transplant-recipient-a-case-report
#18
Kazuki Nakagita, Kyoichi Wada, Yuka Terada, Sachi Matsuda, Nobue Terakawa, Akira Oita, Mitsutaka Takada
OBJECTIVE: Everolimus is an inhibitor of the mammalian target of rapamycin (mTOR) and has been used in combination with calcineurin inhibitors (tacrolimus and cyclosporine) to prevent allograft rejection following organ transplantation. In heart transplant recipients, everolimus should be maintained at a target blood concentration of 3 - 8 ng/mL, in combination with reduced-dose calcineurin inhibitors and therefore, requires strict monitoring. Fluconazole, an azole antifungal agent, affects blood concentration of tacrolimus by inhibiting the cytochromes P450 (CYP) 3A4 and 3A5...
April 12, 2018: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29629357/living-donor-liver-transplantation-prior-to-multiple-myeloma-treatment-in-a-patient-with-hepatitis-b-associated-hepatocellular-carcinoma-and-liver-cirrhosis-a-case-report
#19
Chan Woo Cho, Nuri Lee, Gyu-Seong Choi, Jong Man Kim, Choon Hyuck David Kwon, Jae-Won Joh
Clinical outcomes of living donor liver transplantation (LDLT) for hepatocellular carcinoma (HCC) in patients with multiple myeloma (MM) have not been established in terms of HCC recurrence and MM deterioration after LDLT. A 51-year-old man with chronic hepatitis B was diagnosed with HCC and MM. Since the patient also had decompensated liver cirrhosis (LC), he underwent LDLT prior to autologous peripheral blood stem cell transplantation (PBSCT) to prevent fulminant hepatitis due to HBV reactivation. The patient received Epstein-Barr virus prophylaxis and a triple immunosuppressive regimen of tacrolimus, everolimus, and steroid after LDLT...
April 2018: Annals of Surgical Treatment and Research
https://www.readbyqxmd.com/read/29629319/liver-transplantation-for-unresectable-pancreatic-neuroendocrine-tumors-with-liver-metastases-in-an-era-of-transplant-oncology
#20
REVIEW
Keita Shimata, Yasuhiko Sugawara, Taizo Hibi
Patients with pancreatic neuroendocrine tumors (pNETs) very often present with a metastatic disease at the first diagnosis. Liver transplantation (LT) for unresectable pNET with liver metastases (pNETLM) has been described to prolong survival in highly selected patients, although outcomes were worse than those of patients who underwent LT for gastrointestinal NETLM (GI-NETLM). In this review, several proposed criteria are described with their rationale and controversies. Most of the data used to establish these criteria do not reflect the recent improvements of non-surgical treatments that has changed the landscape of treatment for pNETs, including the development of peptide receptor radionuclide therapy and molecular-targeted agents (sunitinib and everolimus)...
February 2018: Gland Surgery
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