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https://www.readbyqxmd.com/read/29111569/the-influence-of-immunosuppressants-on-direct-acting-antiviral-therapy-is-dependent-on-hepatitis-c-virus-genotype
#1
Alexandra Frey, Katja Piras-Straub, Andreas Walker, Jörg Timm, Guido Gerken, Kerstin Herzer
BACKGROUND: Direct-acting antivirals (DAA) have substantially increased sustained virological response rates after liver transplantation, with improved tolerance compared to interferon-based therapy. The influence of immunosuppressive agents on the efficacy of DAAs has not been clarified. METHODS: Subgenomic HCV replicons for genotype (GT) 1b, 2b, 3a and 4a were treated with the mammalian target of rapamycin (mTOR) inhibitors everolimus and sirolimus or with the calcineurin inhibitors (CNI) cyclosporine or tacrolimus, either alone or in combination with selected DAAs...
November 7, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/29057561/pre-clinical-results-in-pig-to-non-human-primate-islet-xenotransplantation-using-anti-cd40-antibody-2c10r4-based-immunosuppression
#2
Jun-Seop Shin, Jong-Min Kim, Byoung-Hoon Min, Il Hee Yoon, Hyun Je Kim, Jung-Sik Kim, Yong-Hee Kim, Seong-Jun Kang, Jiyeon Kim, Hee-Jung Kang, Dong-Gyun Lim, Eung-Soo Hwang, Jongwon Ha, Sang-Joon Kim, Wan Beom Park, Chung-Gyu Park
BACKGROUND: Islet transplantation is an effective therapy for selected patients with type 1 diabetes with labile glycemic control and hypoglycemic unawareness, but donor organs are limited. Islet xenotransplantation using porcine islets will potentially solve this problem. Although successful proof of concept studies using clinically inapplicable anti-CD154 monoclonal antibody (mAb) in pig-to-non-human primate (NHP) islet xenotransplantation has been demonstrated by several groups worldwide, potentially clinically applicable anti-CD40 (2C10R4) mAb-based studies have not been reported...
October 22, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/29057176/the-effect-of-conversion-from-a-calcineurin-inhibitor-to-sirolimus-on-skin-cancer-reduction-in-post-renal-transplantation-patients
#3
REVIEW
Aaron Smith, Wei Niu, Anand Desai
In kidney transplant patients, skin cancer is the most commonly involved neoplasm. More than 90% of post-transplantation skin cancers are nonmelanoma skin cancers (NMSCs). The majority of them are squamous cell carcinomas and basal cell carcinomas. Calcineurin inhibitors (CNIs) such as cyclosporine and tacrolimus are immunosuppressive agents given after solid organ transplantation, but they can also promote tumor growth. Sirolimus is a novel class of immunosuppressants and has been proven to have antineoplastic properties...
August 13, 2017: Curēus
https://www.readbyqxmd.com/read/29045704/new-onset-diabetes-after-kidney-transplantation-can-the-risk-be-modified-by-choosing-immunosuppression-regimen-based-on-pretransplant-viral-serology
#4
Alfonso H Santos, Chao Chen, Michael J Casey, Karl L Womer, Xuerong Wen
Background: This study aimed to analyze adult kidney transplant recipients (KTRs) for the risk of new-onset diabetes after transplantation (NODAT) associated with viral serologies and immunosuppression regimens [tacrolimus (Tac) + mycophenolate (MPA), cyclosporine (CSA) + MPA, sirolimus (SRL) + MPA, SRL + CSA or SRL +Tac]. Methods: Cox regression models were used to examine the risk of NODAT in the first posttransplant year associated with: (i) CSA + MPA, SRL + MPA, SRL + MPA or SRL + Tac versus reference, Tac + MPA; (ii) pretransplant viral serology [+ or -; hepatitis B core (HBc), hepatitis C (HCV), cytomegalovirus (CMV) or Epstein Barr Virus (EBV)]; and (iii) interactions between immunosuppression regimens and the viral serology found significant in the main analysis...
October 16, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28974433/impact-of-immunosuppressive-drugs-on-circulating-tfh-cells-in-kidney-transplant-recipients-a-pilot-study
#5
Ya Mei Li, Yi Li, Yun Ying Shi, Lin Yan, Xiao Juan Wu, Jiang Tao Tang, Yang Juan Bai, Lan Lan Wang
BACKGROUND: T follicular helper cells (Tfh) are recently revealed to be vital in antibody-mediated rejection (AMR) in kidney transplant recipients (KTRs). However, the impact of immunosuppressive drugs on Tfh cells is not fully understood. The purpose of this study was to investigate the variation of Tfh cells phenotypically and functionally in KTRs treated with different immunosuppression regimens. METHODS: We recruited 26 KTRs treated with tacrolimus (TAC) -based regimen, 13 with sirolimus (SRL) -based regimen and 10 healthy controls (HC) in this study...
September 30, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28972684/the-effects-of-topical-aqueous-sirolimus-on-tear-production-in-normal-dogs-and-dogs-with-refractory-dry-eye
#6
Ronald Spatola, Brad Nadelstein, Andrew Berdoulay, Robert V English
PURPOSE: To evaluate the effect of twice daily aqueous 0.02% sirolimus drops on tear production in normal dogs and dogs with refractory keratoconjunctivitis sicca (KCS). METHODS: Two groups of dogs were studied. Ten normal dogs with no signs of ocular disease were administered topical 0.02% sirolimus ophthalmic solution in right eye, and a vehicle control in the left eye twice daily for 4 weeks. Complete ophthalmic examinations, including Schirmer tear test were performed weekly...
October 3, 2017: Veterinary Ophthalmology
https://www.readbyqxmd.com/read/28970719/autoimmune-hepatitis-standard-treatment-and-systematic-review-of-alternative-treatments
#7
REVIEW
Benedetta Terziroli Beretta-Piccoli, Giorgina Mieli-Vergani, Diego Vergani
Autoimmune hepatitis is a rare chronic inflammatory liver disease, affecting all ages, characterised by elevated transaminase and immunoglobulin G levels, positive autoantibodies, interface hepatitis at liver histology and good response to immunosuppressive treatment. If untreated, it has a poor prognosis. The aim of this review is to summarize the evidence for standard treatment and to provide a systematic review on alternative treatments for adults and children. Standard treatment is based on steroids and azathioprine, and leads to disease remission in 80%-90% of patients...
September 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28941319/donor-derived-kaposi-s-sarcoma-in-a-liver-kidney-transplant-recipient
#8
S C Dollard, D Douglas, S V Basavaraju, D S Schmid, M Kuehnert, B Aqel
Human herpes virus 8 (HHV-8), also known as Kaposi's sarcoma associated herpesvirus (KSHV), is an oncogenic virus that can cause Kaposi's sarcoma (KS). KS can develop following organ transplantation through reactivation of the recipient's latent HHV-8 infection, or less commonly through donor-derived infection which has higher risk for severe illness and mortality. We describe a case of probable donor-derived KS in the recipient of a liver-kidney transplant. The donor had multiple risk factors for HHV-8 infection...
September 23, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28873970/immunosuppressive-agents-in-adult-kidney-transplantation-in-the-national-health-service-a-model-based-economic-evaluation
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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...
November 2017: Gastroenterología y Hepatología
https://www.readbyqxmd.com/read/28742936/benefits-and-limitations-of-belatacept-in-4-hand-transplanted-patients
#18
J Grahammer, A Weissenbacher, B G Zelger, B Zelger, C Boesmueller, M Ninkovic, A Mühlbacher, I Peschel, G Brandacher, D Öfner, S Schneeberger
Belatacept (cytotoxic T-lymphocyte-associated protein 4 Ig) is an emerging treatment in kidney transplantation. Lack of nephrotoxicity and possibly an inhibitory effect on the development of donor-specific antibodies (DSAs) make it an interesting agent in hand transplantation. To reduce calcineurin inhibitor immunosuppression and preserve kidney function, we have added belatacept to the therapeutic regimen of 4 hand-transplanted patients at month 4 and at 6, 9, and 13 years after hand-forearm transplantation...
December 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28731207/polyclonal-and-monoclonal-antibodies-for-treating-acute-rejection-episodes-in-kidney-transplant-recipients
#19
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
#20
REVIEW
Andreas H Groll, Robert Townsend, Amit Desai, Nkechi Azie, Mark Jones, Marc Engelhardt, Anne-Hortense Schmitt-Hoffman, Roger J M 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
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