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tacrolimus and sirolimus

Kai-Fan Tsai, Lung-Chih Li, Chien-Ning Hsu, Chih-Che Lin, Yu-Hung Lin, Yu-Fan Cheng, Chih-Chi Wang, Chao-Long Chen
Mammalian targets of rapamycin inhibitors (mTORIs), including sirolimus and everolimus, are used for minimizing calcineurin inhibitors after liver transplantation. However, head-to-head randomized comparisons of these 2 mTORIs are lacking. We assessed the differences in renoprotection and possible mechanisms between sirolimus and everolimus in liver transplant recipients. For this prospective cohort study, we recruited liver transplant recipients whose regimens were switched from tacrolimus to sirolimus or everolimus at a Taiwan medical center...
November 2, 2018: Journal of Clinical Pharmacology
Noruel Gerard A Salvador, Sin-Yong Wee, Chih-Che Lin, Chao-Chien Wu, Hung-I Lu, Ting-Lung Lin, Wei-Feng Lee, Yi-Chia Chan, Li-Man Lin, Chao-Long Chen
BACKGROUND This study aimed to determine clinical outcomes using various drugs during tuberculosis (TB) treatment among living donor liver transplant (LDLT) recipients with TB and to assess the impact of performing LDLT in patients with active TB at the time of LDLT. MATERIAL AND METHODS Out of 1313 LDLT performed from June 1994 to May 2016, 26 (2%) adult patients diagnosed with active TB were included in this study. Active TB was diagnosed using either TB culture, PCR, and/or tissue biopsy. RESULTS The median age was 56 years and the male/female ratio was 1...
October 19, 2018: Annals of Transplantation: Quarterly of the Polish Transplantation Society
Shuhui Si, Zijie Wang, Haiwei Yang, Zhijian Han, Jun Tao, Hao Chen, Ke Wang, Miao Guo, Ruoyun Tan, Ji-Fu Wei, Min Gu
The P450 oxidoreductase (POR) and peroxisome proliferator-activated receptor alpha (PPARA) genes are associated with the activity of cytochrome P450 enzymes in vivo. We aimed to investigate the impact of single nucleotide polymorphisms (SNPs) in the POR and PPARA genes on the pharmacokinetics of tacrolimus (TAC) in renal transplant recipients. A total of 220 recipients were assessed and 105 recipients were included for final quantitative analysis. Blood samples were collected and DNA was extracted. Targeting sequencing based on next-generation sequencing was applied to detect the SNPs in the POR and PPARA genes...
October 15, 2018: Pharmacogenomics Journal
Van Kieu, Kristi Jhangiani, Sanjeet Dadwal, Ryotaro Nakamura, Doreen Pon
INTRODUCTION: Isavuconazole, a triazole antifungal, is an inhibitor of cytochrome P450 3A4, which also metabolizes tacrolimus and sirolimus. In previous studies, isavuconazole administration increased tacrolimus and sirolimus area under the curve values by 2.3-fold and 1.8-fold, respectively, in healthy adults and tacrolimus concentration/dose (C/D) ratio by 1.3-fold in solid organ transplant patients. We aimed to determine the magnitude of effect of isavuconazole administration on tacrolimus and sirolimus C/D ratios in allogeneic hematopoietic stem cell transplant (alloHSCT) patients...
October 8, 2018: Transplant Infectious Disease: An Official Journal of the Transplantation Society
Raül Rigo-Bonnin, Francesca Canalias
BACKGROUND: Due to the high inter-variability in immunosuppressants pharmacokinetics, therapeutic drug monitoring of these drugs is essential in order to minimize the risk of rejection after organ transplantation. Thus, results facilitated to clinicians by clinical laboratories for these drugs should be as reliable as possible. The knowledge of metrological traceability and performing compatibility studies can allow ensuring reliability of these results, mainly, when laboratories introduce substantial changes in their measurement procedures, e...
October 3, 2018: Clinical Biochemistry
Nicolas Pallet, Ana A Fernández-Ramos, Marie-Anne Loriot
Energetic metabolism supports rapid cell growth and proliferation, differentiation, polarization, and effector functions of T cells. T lymphocytes have the remarkable plasticity that allows them to shape their metabolism to adapt to extracellular and intracellular cues, a process that involves molecular modules referred to as "metabolic checkpoints" that sense metabolic signals and transduce effector messages. These metabolic checkpoints may represent a novel therapeutic strategy for immune modulation...
2018: International Review of Cell and Molecular Biology
Y S de Boer, R Liberal, D Vergani, G Mieli-Vergani
Background and aims: Juvenile autoimmune liver disease (JAILD) includes paediatric forms of autoimmune hepatitis (AIH) and autoimmune sclerosing cholangitis (ASC). Since evidence is scarce, there are currently no evidence-based management guidelines for juvenile AIH. This survey was carried out amongst the paediatric members of the International AIH Group (IAIHG) to describe their practices in the management of JAILD. Methods: An online survey questionnaire was distributed to members of the IAIHG with active practice (https://www...
August 2018: United European Gastroenterology Journal
Amandeep Salhotra, Matthew Mei, Tracey Stiller, Sally Mokhtari, Alex F Herrera, Robert Chen, Leslie Popplewell, Jasmine Zain, Haris Ali, Karamjeet Sandhu, Elizabeth Budde, Auayporn Nademanee, Stephen J Forman, Ryotaro Nakamura
The current standard of care for patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) is high-dose conditioning followed by autologous stem cell transplantation (ASCT). For some patients (ie, those with highest-risk disease, insufficient stem cell numbers after mobilization, or bone marrow involvement) allogeneic hematopoietic cell transplantation (alloHCT) offers the potential for cure. However, the majority of patients undergoing alloHCT receive reduced-intensity conditioning as a preparative regimen, and studies assessing outcomes of patients after alloHCT with myeloablative conditioning are limited...
September 15, 2018: Biology of Blood and Marrow Transplantation
Lin Zhou, Li-Chao Pan, Yong-Gen Zheng, Guo-Sheng Du, Xiao-Qian Fu, Zhi-Dong Zhu, Ji-Yong Song, Zhi-Jia Liu, Xiang-Zheng Su, Wen Chen, De-Hua Zheng, Long-Long Suo, Shao-Zhen Yang
Although liver transplantation (LT) lengthens the survival time of patients with hepatocellular carcinoma (HCC), LT patients exhibit a high recurrence rate; particularly those that had advanced HCC associated with the tumor biological characteristics and long-term application of immunosuppressants. A consensus on optimal prophylaxis and treatment for recurrent HCC following LT does not currently exist. The present study retrospectively analyzed data from 36 non-University of California at San Francisco criteria-eligible patients with advanced HCC who underwent LT, and then treated them with sirolimus (SRL)-based therapy with thymalfasin and huaier granules (SRL+, n=18), or with tacrolimus-based therapy (controls; n=18)...
October 2018: Oncology Letters
E Karakulska-Prystupiuk, G Basak, J Dwilewicz-Trojaczek, M Paluszewska, P Boguradzki, W Jędrzejczak
BACKGROUND: There are only a few cases of pericarditis complications following allogeneic bone marrow transplantation described in the literature and there are no data available on the risk and frequency of this condition. The aim of this study was to assess the frequency of exudative pericarditis complicating chronic graft-vs-host disease in allogeneic hematopoietic cell transplant recipients. METHODS: Retrospective analysis involved a group of 105 patients of the Outpatient Transplantation Service of the Department of Hematology, Medical University of Warsaw, who received transplants in the years 2010-2016 and were evaluated for the years 2014-2016...
September 2018: Transplantation Proceedings
Hui Yang, Wei Wang, Xiaopeng Hu, Xiaodong Zhang, Lihong Liu
RATIONALE: Drug-induced angioedema has been reported as an adverse effect of many different drugs. But small bowel angioedema associated with sirolimus (SRL) used was barely understood. It must be necessary to report a case suffering from small bowel angioedema with detailed discussion and literature review. PATIENT CONCERNS: A 38-year-old Chinese woman presented with generalized gastric pain in the following day after renal transplantation. The patient began to crampy abdominal pain accompanied by nausea, vomiting, and diarrhea on postoperative day 6 (POD)...
August 2018: Medicine (Baltimore)
A Tarasewicz, A Dębska-Ślizień, B Rutkowska, E Szurowska, M Matuszewski
Mammalian target of rapamycin inhibitors (mTORI) are increasingly used in the treatment of tuberous sclerosis complex (TSC) and as immunosuppressants after organ transplantation. In TSC patients, mTORI are the treatment of choice after kidney transplantation. It is still under debate if benefits from long-term mTORI use will not be limited by side effects. MATERIALS AND METHODS: We report long-term follow-up data of the first TSC patient after kidney transplantation treated with sirolimus de novo...
July 2018: Transplantation Proceedings
Farhad Khimani, George B McDonald, Howard M Shulman, Brian Betts, Frederick Locke, Hugo Fernandez, Claudio Anasetti, Joseph Pidala
Sirolimus-based graft vs. host disease (GVHD) prophylaxis is associated with higher incidence of veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) after allogeneic hematopoietic cell transplantation (HCT). However, whether the clinical manifestations and prognosis of VOD/SOS differs when diagnosed in the setting of sirolimus-based GVHD prophylaxis is not well studied. To address this question, we examined presenting features and treatment outcome of VOD/SOS cases identified in a large retrospective cohort of consecutive HCT procedures (n = 818 total, sirolimus (SIR)/tacrolimus (TAC) n = 308, and methotrexate (MTX) or mycophenolate mofetil (MMF)/TAC n = 510)...
June 12, 2018: Bone Marrow Transplantation
Apurva D Patel, Brian Lowes, Mohammed A Chamsi-Pasha, Stanley J Radio, Marshall Hyden, Ronald Zolty
CLINICAL FEATURES: Giant cell myocarditis (GCM) is a rare and a rapidly progressive disorder with fatal outcomes such that patients often require heart transplantation. We present a case of recurrent GCM in a transplanted patient with a history of Crohn disease requiring a novel therapeutic approach. THERAPEUTIC CHALLENGE: After the orthotopic heart transplantation, GCM recurred on aggressive immunosuppression over the months, which included corticosteroids, basiliximab, tacrolimus, antithymocyte globulin, and rituximab...
May 30, 2018: American Journal of Therapeutics
S Davis, J Gralla, L Chan, A Wiseman, C L Edelstein
BACKGROUND: The mammalian target of rapamycin (mTOR) pathway has been shown to be central to cyst formation and growth in patients with autosomal dominant polycystic kidney disease (ADPKD). Drugs that suppress mTOR signaling are frequently used as antiproliferative agents for maintenance immunosuppression in patients who have undergone kidney transplantation. The aim of this study was to determine the effect of sirolimus, an mTOR inhibitor, on cyst volume regression in patients with ADPKD who have undergone renal transplantation...
June 2018: Transplantation Proceedings
Aleksandra Wilk, Dagmara Szypulska-Koziarska, Karolina Kędzierska-Kapuza, Agnieszka Kolasa-Wołosiuk, Kamila Misiakiewicz-Has, Kazimierz Ciechanowski, Barbara Wiszniewska
A negative result of therapy based on immunosuppressive drugs is its leading to pathological alterations in the organ, including liver. Use of immunosuppressive medication may also lead to organized and genetically controlled cell death - apoptosis. The aim of this study was to examine histopathological changes in the livers of rats treated with immunosuppressive drugs, and also to determine the effects of different groups of immunosuppressive drugs on apoptosis activity in the hepatocytes of rat livers. The study was conducted on archival material obtained from Department of Nephrology, Transplantology and Internal Medicine of the Independent Public Clinical Hospital No...
May 16, 2018: Transplant Immunology
R Erro, Ruggero Bacchin, F Magrinelli, P Tomei, C Geroin, G Squintani, A Lupo, G Zaza, M Tinazzi
INTRODUCTION: Tremor is the most frequent and disabling neurological side effect under Calcineurin inhibitor-induced immunosuppression, but no studies have defined its phenomenology, severity, distribution, the impact on quality of life, as well as of other neurological symptoms associated. METHODS: 126 consecutive kidney-transplanted patients, under treatment with Cyclosporin A, Tacrolimus and non-Calcineurin inhibitors, within therapeutic range, were enrolled...
July 2018: Journal of Neurology
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
Jonathan A Fridell, Richard S Mangus, Jeanne M Chen, Tim E Taber, Arianna E Cabrales, Asif A Sharfuddin, Muhammad S Yaqub, John A Powelson
Graft survival following pancreas transplant alone (PTA) is inferior to other pancreas transplants. Steroid elimination is appealing, but a two-drug maintenance strategy may be inadequate. Additionally, recipients tend to have diabetic nephropathy and do not tolerate nephrotoxic medications. A three-drug maintenance strategy permits immunosuppression through different mechanisms as well as an opportunity to use lower doses of the individual medications. Induction consisted of five doses of rabbit antithymocyte globulin (1 mg/kg/dose)...
May 8, 2018: American Journal of Transplantation
G Schmalz, L Berisha, H Wendorff, F Widmer, A Marcinkowski, H Teschler, U Sommerwerck, R Haak, O Kollmar, D Ziebolz
BACKGROUND: Aim of this study was to investigate the association of the time under immunosuppression and different immunosuppressive medication on periodontal parameters and selected periodontal pathogenic bacteria of immunosuppressed patients after solid organ transplantation (SOT). MATERIAL AND METHODS: 169 Patients after SOT (lung, liver or kidney) were included and divided into subgroups according their time under (0-1, 1-3, 3-6, 6-10 and >10 years) and form of immunosuppression (Tacrolimus, Cyclosporine, Mycophenolate, Glucocorticoids, Sirolimus and monotherapy vs...
May 1, 2018: Medicina Oral, Patología Oral y Cirugía Bucal
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