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https://www.readbyqxmd.com/read/28873970/immunosuppressive-agents-in-adult-kidney-transplantation-in-the-national-health-service-a-model-based-economic-evaluation
#1
Tristan M Snowsill, Jason Moore, Ruben E Mujica Mota, Jaime L Peters, Tracey L Jones-Hughes, Nicola J Huxley, Helen F Coelho, Marcela Haasova, Chris Cooper, Jenny A Lowe, Jo L Varley-Campbell, Louise Crathorne, Matt J Allwood, Rob Anderson
Background: Immunosuppression is required in kidney transplantation to prevent rejection and prolong graft survival. We conducted an economic evaluation to support England's National Institute for Health and Care Excellence in developing updated guidance on the use of immunosuppression, incorporating new immunosuppressive agents, and addressing changes in pricing and the evidence base. Methods: A discrete-time state transition model was developed to simulate adult kidney transplant patients over their lifetime...
July 1, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28869461/effects-of-tacrolimus-or-sirolimus-on-the-adhesion-of-vascular-wall-cells-controlled-in-vitro-comparison-study
#2
A Krüger-Genge, B Hiebl, R P Franke, A Lendlein, F Jung
In drug eluting stents the cytostatic drugs Sirolimus or Tacrolimus are used to inhibit blood vessel restenosis by limiting the proliferation of smooth muscle cells. However, the cytostatic activity of both drugs was shown to be not cell specific and could also affect the stent endothelialisation, respectively. Currently, only limited in vitro data are available about the impact of Sirolimus and Tacrolimus on endothelial cell proliferation over a broad concentration range. To answer this question the following study was performed...
August 28, 2017: Clinical Hemorheology and Microcirculation
https://www.readbyqxmd.com/read/28860611/impact-of-immunosuppression-on-the-metagenomic-composition-of-the-intestinal-microbiome-a-systems-biology-approach-to-post-transplant-diabetes
#3
M Bhat, E Pasini, J Copeland, M Angeli, S Husain, D Kumar, E Renner, A Teterina, J Allard, D S Guttman, A Humar
Solid organ transplantation (SOT) outcomes have continued to improve, although long-term use of immunosuppressants can lead to complications such as diabetes, compromising post-transplant outcomes. In this study, we have characterized the intestinal microbiome (IM) composition at the metagenomic level in the context of hyperglycemia induced by immunosuppressants. Sprague-Dawley rats were subjected to doses of tacrolimus and sirolimus that reliably induce hyperglycemia and an insulin-resistant state. Subsequent exposure to probiotics resulted in reversal of hyperglycemia...
August 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28836934/sirolimus-associated-with-tacrolimus-at-low-doses-in-elderly-kidney-transplant-patients-a-prospective-randomized-controlled-trial
#4
Cristiane Akemi Kojima, Hong Si Nga, Henrique Mochida Takase, Ariane Moyses Bravin, Márcia de Fátima Faraldo Martinez Garcia, Paula Dalsoglio Garcia, Mariana Moraes Contti, Luis Gustavo Modelli de Andrade
OBJECTIVES: There is no consensus on the best immunosuppressive regimen for elderly renal transplant recipients. The objective of this study was to assess cytomegalovirus infection incidence and kidney transplant outcomes in elderly recipients treated with mammalian target of rapamycin inhibitors sirolimus/ tacrolimus at low doses compared with those receiving tacrolimus/mycophenolate sodium. MATERIALS AND METHODS: In this single-center prospective randomized study (Trial Registration No...
August 28, 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/28836275/impact-of-treatment-and-outcomes-for-patients-with-posttransplant-drug-associated-thrombotic-microangiopathy
#5
Narendranath Epperla, Kathleen Hemauer, Mehdi Hamadani, Kenneth D Friedman, Lisa Baumann Kreuziger
BACKGROUND: Drug-induced transplant-associated thrombotic microangiopathy (DTA-TMA) is a rare but serious complication that can occur after hematopoietic cell transplantation (HCT) or solid organ transplantation (SOT) without guidelines for optimal management of this condition. STUDY DESIGN AND METHODS: Given the ambiguity surrounding the treatment for DTA-TMA, we conducted a retrospective review to evaluate the impact of different treatment strategies in DTA-TMA patients...
August 23, 2017: Transfusion
https://www.readbyqxmd.com/read/28810721/de-novo-low-dose-sirolimus-versus-mycophenolate-mofetil-in-combination-with-extended-release-tacrolimus-in-kidney-transplant-recipients-a-multicentre-open-label-randomized-controlled-non-inferiority-trial
#6
Kyu Ha Huh, Jae Geun Lee, Jongwon Ha, Chang-Kwon Oh, Man Ki Ju, Chan-Duck Kim, Hong Rae Cho, Cheol Woong Jung, Beom Jin Lim, Yu Seun Kim
Background: Most of the previous studies reported that tacrolimus (TAC) with sirolimus (SRL) was associated with worse post-transplant outcomes in kidney transplantation, compared with TAC with mycophenolate mofetil (MMF). These might be attributable to high-dose SRL. However, outcomes using low-dose SRL with TAC for kidney transplantation are uncertain. The aim of this study was to assess the efficacy and safety of low-dose SRL with extended-release tacrolimus (ER-TAC) versus MMF with ER-TAC...
August 1, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28776332/sirolimus-and-metformin-synergistically-inhibits-colon-cancer-in-vitro-and-in-vivo
#7
Nadiar Mussin, Seung Cheol Oh, Kwang Woong Lee, Min Young Park, Sooin Seo, Nam Joon Yi, Hyeyoung Kim, Kyung Chul Yoon, Sung Woo Ahn, Hyo Sin Kim, Suk Kyun Hong, Dong Kyu Oh, Kyung Suk Suh
We estimated the effect of various immunosuppressants (ISs) and metformin (M) to provide theoretical background of optimal therapeutic strategy for de novo colon cancer after liver transplantation (LT). Three colon cancer cell lines (HT29, SW620, and HCT116) were used in in vitro studies. HT29 was also used in BALB/c-nude mice animal models. Following groups were used in both in vitro and in vivo studies: sirolimus (S), tacrolimus (T), cyclosporin A (CsA), M, metformin/sirolimus (Met/S), metformin/tacrolimus (Met/T), and metformin/cyclosporin A (Met/CsA)...
September 2017: Journal of Korean Medical Science
https://www.readbyqxmd.com/read/28772029/ace-inhibitor-associated-intestinal-angioedema-in-orthotopic-heart-transplantation
#8
Dushyanth Srinivasan, Garth W Strohbehn, Thomas Cascino
Angiotensin-converting enzyme inhibitor induced angioedema commonly involves the head and neck area. We report a case of angiotensin-converting enzyme inhibitor induced intestinal angioedema in a heart transplant recipient on mTOR immunosuppression. A 36-year-old Caucasian woman with history of heart transplantation on sirolimus, tacrolimus and prednisone presented to the Emergency Department with abdominal pain, one day following lisinopril initiation. A computer tomography scan demonstrated diffuse bowel wall thickening consistent with pancolitis and edema...
August 2017: ESC Heart Failure
https://www.readbyqxmd.com/read/28743539/recommendations-of-everolimus-use-in-liver-transplant
#9
Angel Rubín Suárez, Itxarone Bilbao Aguirre, Javier Fernández-Castroagudin, José Antonio Pons Miñano, Magdalena Salcedo Plaza, Evaristo Varo Pérez, Martín Prieto Castillo
Mammalian target of rapamycin (mTOR) inhibitors, everolimus (EVL) and sirolimus are immunosuppressive agents with a minor nephrotoxic effect, limited to the development of proteinuria in some cases. The combination of EVL and low-dose tacrolimus has proven to be as safe and effective as standard therapy with tacrolimus for the prevention of acute cellular rejection. Early initiation of EVL-based immunosuppressive regimens with reduced exposure to calcineurin inhibitors has been shown to significantly improve renal function of LT recipients during induction and maintenance phases, with comparable efficacy and safety profiles...
July 22, 2017: Gastroenterología y Hepatología
https://www.readbyqxmd.com/read/28742936/benefits-and-limitations-of-belatacept-in-4-hand-transplanted-patients
#10
J Grahammer, A Weissenbacher, B G Zelger, B Zelger, C Boesmueller, M Ninkovic, A Mühlbacher, I Peschel, G Brandacher, D Öfner, S Schneeberger
Belatacept (CTLA4Ig) is an emerging treatment in kidney transplantation. Lack of nephrotoxicity and possibly an inhibitory effect on the development of donor specific antibodies (DSA) make it an interesting agent in hand transplantation. In order to reduce CNI immunosuppression and preserve kidney function, we have added belatacept to the therapeutic regimen of 4 hand transplanted patients at month 4, at 6, 9, and 13 years after hand/forearm transplantation. Patients received 5mg/kg belatacept every 2 weeks, the dosing interval was extended to 4 weeks after 5 applications...
July 25, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28731207/polyclonal-and-monoclonal-antibodies-for-treating-acute-rejection-episodes-in-kidney-transplant-recipients
#11
REVIEW
Angela C Webster, Sunny Wu, Krishna Tallapragada, Min Young Park, Jeremy R Chapman, Sue J Carr
BACKGROUND: Registry data shows that the incidence of acute rejection has been steadily falling. Approximately 10% to 35% of kidney recipients will undergo treatment for at least one episode of acute rejection within the first post-transplant year. Treatment options include pulsed steroid therapy, the use of an antibody preparation, the alteration of background immunosuppression, or combinations of these options. Over recent years, new treatment strategies have evolved, and in many parts of the world there has been an increase in use of tacrolimus and mycophenolate and a reduction in the use of cyclosporin and azathioprine use as baseline immunosuppression to prevent acute rejection...
July 20, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28722255/drug-drug-interactions-between-triazole-antifungal-agents-used-to-treat-invasive-aspergillosis-and-immunosuppressants-metabolized-by-cytochrome-p450-3a4
#12
REVIEW
Andreas H Groll, Robert Townsend, Amit Desai, Nkechi Azie, Mark Jones, Marc Engelhardt, Anne-Hortense Schmitt-Hoffman, Roger J Brüggemann
Patients undergoing treatment with immunosuppressant drugs following solid organ or hematopoietic stem cell transplantation are at particular risk for development of serious infections such as invasive aspergillosis. Four triazole antifungal drugs, voriconazole, posaconazole, itraconazole, and isavuconazole, are approved to treat invasive aspergillosis either as first- or second-line therapy. All of these agents are inhibitors of cytochrome P450 3A4, which plays a key role in metabolizing immunosuppressant drugs such as cyclosporine, tacrolimus, and sirolimus...
July 19, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/28708333/conversion-from-calcineurin-inhibitors-to-mtor-inhibitors-as-primary-immunosuppressive-drugs-in-pediatric-heart-transplantation
#13
Alfred Asante-Korang, Jennifer Carapellucci, Diane Krasnopero, Abigail Doyle, Brian Brown, Ernest Amankwah
There are only a few reports of successful use of mammalian target of rapamycin (mTORI) as primary immunosuppression in pediatric heart transplantation. Compared to calcineurin inhibitors, mTORI have less side effects, especially nephrotoxicity, infections, and malignancies. A retrospective study was conducted at our institution of all 170 heart transplants from 1995 to 2015. Nineteen patients were switched from tacrolimus (n=15) or cyclosporin (n=4) to everolimus (n=4) or sirolimus (n=15) due to nephrotoxicity (n=5), malignancy (n=8), EBV viremia/reactive plasmacytic changes (n=5), and immune hemolytic anemia (n=1)...
July 14, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28706981/outcomes-of-liver-transplant-recipients-with-autoimmune-liver-disease-using-long-term-dual-immunosuppression-regimen-without-corticosteroid
#14
Sanjaya K Satapathy, Ollie D Jones, Jason M Vanatta, Faisal Kamal, Satish K Kedia, Yu Jiang, Satheesh P Nair, James D Eason
BACKGROUND: Liver transplant (LT) recipients with autoimmune liver disease (primary sclerosing cholangitis, primary biliary cholangitis, autoimmune hepatitis) are at increased risk of developing acute cellular rejection (ACR), and in many cases graft failure due to recurrent disease. We describe our experience with dual immunosuppression without steroid maintenance and analyze its effect on disease recurrence; ACR; patient and graft survivals; and complications, such as sepsis and de novo malignancy...
July 2017: Transplantation Direct
https://www.readbyqxmd.com/read/28670871/clinical-practice-patterns-are-relatively-uniform-between-pediatric-heart-transplant-centers-a-survey-based-assessment
#15
Chesney Castleberry, Sonja Ziniel, Christopher Almond, Scott Auerbach, Seth A Hollander, Ashwin K Lal, Matthew Fenton, Elfriede Pahl, Joseph W Rossano, Melanie D Everitt, Kevin P Daly
Clinical practice variations are a barrier to the study of pediatric heart transplants and coordination of multicenter RCTs in this patient population. We surveyed centers to describe practice patterns, understand areas of variation, and willingness to modify protocol. Pediatric heart transplant centers were identified, and one survey was completed per center. Simple descriptive statistics were used. The response rate was 77% (40 responses from 52 contacted centers, 37 with complete responses). Median center volume of respondents was eight transplants/year (IQR 3-19)...
August 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28621877/autoimmune-hemolytic-anemia-in-solid-organ-transplantation-the-role-of-immunosuppression
#16
REVIEW
Theoni Kanellopoulou
Hemolysis after solid organ transplantation can be caused by both immune and non-immune-mediated mechanisms, and the evaluation must take into account issues distinctive to the post-transplant period. Autoimmune hemolytic anemia usually occurs within the first year and has been attributed to immunosuppressive treatment, infections, or underlying post-transplant lymphoproliferative disorder. Review of the literature revealed 59 cases with autoimmune hemolytic anemia mostly in children after liver transplantation...
June 16, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28616377/blue-after-splenectomy
#17
Taaran Cariappa Ballachanda Subbaiah, Jeremy P Feldman
INTRODUCTION: We present a 51 year old, African American, female who presented with persistent hypoxemia. She had been taking dapsone for many years for prophylaxis against Pneumocystic Jiroveci with no symptoms but eventually developed methemoglobinemia only after a splenectomy. From our literature review there are no documented cases that have demonstrated this relationship between dapsone, splenic function and methemoglobin and we hope to share our perplexing case and shed light on the interaction...
2017: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/28593920/influence-of-cyp3a4-and-cyp3a5-polymorphisms-on-tacrolimus-and-sirolimus-exposure-in-stable-kidney-transplant-recipients
#18
Erika Y Tamashiro, Claudia R Felipe, Fabiana D V Genvigir, Alice C Rodrigues, Antony B Campos, Rosario D C Hirata, Helio Tedesco-Silva, Jose O Medina-Pestana
BACKGROUND: Polymorphisms in genes encoding for drug-metabolizing enzymes and drug transporters are among multiple factors that modulate the pharmacokinetic variability of tacrolimus (TAC) and sirolimus (SRL). This study aimed to evaluate the influence of single nucleotide polymorphisms (SNPs) on TAC and SRL dose-adjusted concentrations (C0/D) in stable kidney transplant recipients. METHODS: This is an exploratory and prospective study, which includes 46 stable kidney transplant recipients...
May 24, 2017: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/28581472/low-incidence-of-severe-cgvhd-and-late-nrm-in-a-phase-ii-trial-of-thymoglobulin-tacrolimus-and-sirolimus-for-gvhd-prevention
#19
Z Al-Kadhimi, Z Gul, M Abidi, L G Lum, A Deol, W Chen, H Jang, C Ozust, A Langston, E Waller, J Uberti
Chronic GvHD (cGvHD) is the leading cause of late non-relapse mortality (NRM) and morbidity after allogeneic hematopoietic stem cell transplant (AHSCT). We analyzed the late effects of a phase II trial testing the efficacy of intermediate dose rabbit anti-thymocyte globulin (Thymoglobulin Thymo) in combination with tacrolimus and sirolimus (TTS) in 47 patients (pts) for the prevention of acute and chronic GvHD after unrelated AHSCT. The median follow-up was 45.2 months. The cumulative incidence of NIH severe cGvHD at 48 months was 6...
September 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28556421/gastrointestinal-disorders-after-immunosuppression-an-experimental-model-to-evaluate-the-influence-of-monotherapy-on-motility-parameters
#20
Denize Jussara Rupolo Dall'Agnol, Luciana Aparecida Corá, Maria do Carmo Borges Teixeira, Maysa Bruno de Lima, Loyane Almeida Gama, José Ricardo de Arruda Miranda, Madileine Francely Américo
What is the central question of this study? The aim was to propose an animal model for investigating the effects of immunosuppressive monotherapy on gastrointestinal motility using a non-invasive biomagnetic technique. What is main finding and its importance? In our experimental study, immunosuppressive drugs currently in use accelerated gastric emptying whilst increasing the frequency and amplitude of gastric contractions after treatment, except for Mycophenolate and azathioprine. Alternating current biosusceptometry is a useful tool to evaluate side-effects of drugs on the gastrointestinal tract, which will help in understanding the symptoms and improving clinical management of patients...
May 26, 2017: Experimental Physiology
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