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https://www.readbyqxmd.com/read/28465534/low-proportion-of-follicular-regulatory-t-cell-in-renal-transplant-patients-with-chronic-antibody-mediated-rejection
#1
Wen Chen, Jian Bai, Haiyan Huang, Lili Bi, Xiangrui Kong, Yu Gao, Yong Han, Li Xiao, Bingyi Shi
Follicular regulatory T (Tfr) cell can effectively regulate humoral immunity, but its function and mechanism in antibody-mediated rejection (AMR) after organ transplantation remains unclear. Here we detected follicular helper T (Tfh) cell subsets in 88 renal transplant patients with chronic renal allograft dysfunction (40 with AMR and 48 without AMR). The ratio of Tfr cells in renal graft tissues and peripheral blood of AMR patients significantly decreased, while the ratio of IL-21-producing Tfh cells (Tfh2 and Tfh17) significantly increased, compared to non-AMR patients...
May 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28452165/cutaneous-toxicities-from-transplant-related-medications
#2
M Ilyas, O R Colegio, B Kaplan, A Sharma
Despite the abundance of information on cutaneous malignancies associated with solid organ transplantation in the transplant literature, there is limited information regarding non-malignant skin changes after transplantation. There are numerous skin toxicities secondary to immunosuppressive and other transplant-related medications that can vary in presentation, severity, and prognosis. In order to limit associated morbidity and mortality, SOTR care providers should effectively identify and manage cutaneous manifestations secondary to drug toxicity...
April 27, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28439923/immunosuppressive-drugs-in-whole-blood-validation-of-a-commercially-available-lc-ms-ms-kit-and-comparison-with-immunochemical-assays
#3
Elisa Polledri, Rosa Mercadante, Chiara Ferris Fusarin, Rita Maiavacca, Silvia Fustinoni
RATIONALE: In the determination of immunosuppressive drugs cyclosporine A (CSA), tacrolimus (TARO), sirolimus (SIRO), and everolimus (EVE) in whole blood there is an open debate about which is the best assay between immunochemistry and liquid chromatography-tandem mass spectrometry (LC-MS/MS). This work is aimed to explore this topic, focusing on the use of updated assays and the analysis of a large number of samples. METHOD: A certified in vitro diagnostic kit coupled with a medical device LC-MS/MS was validated and applied to the analysis of 1192 blood samples of patients treated with immunosuppressive drugs...
April 24, 2017: Rapid Communications in Mass Spectrometry: RCM
https://www.readbyqxmd.com/read/28437284/a-retrospective-study-on-mycophenolic-acid-drug-interactions-effect-of-prednisone-sirolimus-and-tacrolimus-with-mpa
#4
Ana C Alvarez-Elías, Elisa C Yoo, Ekaterina K Todorova, Ram N Singh, Guido Filler
Mycophenolic acid (MPA), the active compound of mycophenolate mofetil (MMF), is widely used as an antirejection drug after renal transplantation. There is growing evidence supporting the notion that there is substantial variability in the intra- and interpatient exposure to MPA. Drug interactions involving MPA with tacrolimus, steroids, and sirolimus have been understudied. The objective of this study was to determine the relationship between MPA, steroids, tacrolimus, and sirolimus. MPA trough concentrations from 37 pediatric renal transplant recipients (mean age 7...
June 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28435278/genetic-factors-in-pathogenesis-of-diabetes-mellitus-after-kidney-transplantation
#5
REVIEW
Maciej Tarnowski, Sylwia Słuczanowska-Głabowska, Andrzej Pawlik, Małgorzata Mazurek-Mochol, Elżbieta Dembowska
Posttransplant diabetes mellitus (PTDM) is one of the major metabolic complications after transplantation of solid organs including the kidney. This type of diabetes mellitus affects allograft survival, cardiovascular complications and overall patient survival. The modifiable risk factors that contribute to PTDM include obesity, some viral infections (eg, hepatitis C virus, cytomegalovirus) and especially immunosuppressive drugs including corticosteroids, tacrolimus, cyclosporine and sirolimus. Currently, predisposing genetic factors have been considered important in PTDM development...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28396159/a-time-to-event-model-for-acute-kidney-injury-after-reduced-intensity-conditioning-stem-cell-transplantation-using-a-tacrolimus-and-sirolimus-based-graft-versus-host-disease-prophylaxis
#6
José Luis Piñana, Alejandro Perez-Pitarch, Irene Garcia-Cadenas, Pere Barba, Juan Carlos Hernandez-Boluda, Albert Esquirol, María Laura Fox, María José Terol, Josep M Queraltó, Jaume Vima, David Valcarcel, Rafael Ferriols-Lisart, Jorge Sierra, Carlos Solano, Rodrigo Martino
There is a paucity of data evaluating acute kidney injury (AKI) incidence and its relationship with the tacrolimus-sirolimus (Tac-Sir) concentrations in the setting of reduced-intensity conditioning (RIC) after allogeneic stem cell transplantation (allo-HSCT). This multicenter retrospective study evaluated risk factors of AKI defined by 2 classification systems, Kidney Disease Improving Global Outcome (KDIGO) score and "Grade 0-3 staging," in 186 consecutive RIC allo-HSCT recipients with Tac-Sir as graft-versus-host disease prophylaxis...
April 7, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28368376/predictors-of-overall-survival-among-patients-treated-with-sirolimus-tacrolimus-vs-methotrexate-tacrolimus-for-gvhd-prevention
#7
F Khimani, J Kim, L Chen, E Dean, V Rizk, B Betts, T Nishihori, F Locke, A Mishra, L Perez, E Ayala, M Kharfan-Dabaja, M Nieder, H Fernandez, C Anasetti, J Pidala
Sirolimus (SIR)/tacrolimus (TAC) is an alternative to methotrexate (MTX)/TAC. However, rational selection among these GvHD prophylaxis approaches to optimize survival of individual patients is not possible based on current evidence. We compared SIR/TAC (n=293) to MTX/TAC (n=414). The primary objective was to identify unique predictors of overall survival (OS). Secondary objective was to compare acute and chronic GvHD, relapse, non-relapse mortality, thrombotic microangiopathy (TMA), hepatic veno-occlusive disease (VOD/SOS), and acute kidney injury...
April 3, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28362060/maintenance-immunosuppression-for-adults-undergoing-liver-transplantation-a-network-meta-analysis
#8
REVIEW
Manuel Rodríguez-Perálvarez, Marta Guerrero-Misas, Douglas Thorburn, Brian R Davidson, Emmanuel Tsochatzis, Kurinchi Selvan Gurusamy
BACKGROUND: As part of liver transplantation, immunosuppression (suppressing the host immunity) is given to prevent graft rejections resulting from the immune response of the body against transplanted organ or tissues from a different person whose tissue antigens are not compatible with those of the recipient. The optimal maintenance immunosuppressive regimen after liver transplantation remains uncertain. OBJECTIVES: To assess the comparative benefits and harms of different maintenance immunosuppressive regimens in adults undergoing liver transplantation through a network meta-analysis and to generate rankings of the different immunosuppressive regimens according to their safety and efficacy...
March 31, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28332959/de-novo-donor-specific-antibody-formation-in-tacrolimus-based-mycophenolate-versus-mammalian-target-of-rapamycin-immunosuppressive-regimens
#9
Zain Mithani, Jane Gralla, Oluwafisayo Adebiyi, Patrick Klem, James E Cooper, Alexander C Wiseman
OBJECTIVES: De novo donor-specific antibody formation posttransplant is associated with decreased graft survival. It is not known whether mammalian target of rapamycin inhibitors may be advantageous or detrimental compared with mycophenolate in the prevention of de novo donor-specific antibody formation. MATERIALS AND METHODS: We compared 66 kidney and kidney-pancreas transplant recipients who received tacrolimus, mammalian target of rapamycin inhibitor, and prednisone (group 1; 36 of whom received everolimus and 30 of whom received sirolimus) versus 132 patients who received tacrolimus, mycophenolate, and prednisone (group 2) matched for age, sex, race, and type/timing of transplant from 2007 to 2012...
March 22, 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/28300419/dried-blood-spot-validation-of-five-immunosuppressants-without-hematocrit-correction-on-two-lc-ms-ms-systems
#10
Remco A Koster, Herman Veenhof, Rixt Botma, Alle Tjipke Hoekstra, Stefan P Berger, Stephan Jl Bakker, Jan-Willem C Alffenaar, Daan J Touw
AIM: Hematocrit (Ht) effects remain a challenge in dried blood spot (DBS) sampling. The aim was to develop an immunosuppressant DBS assay on two LC-MS/MS systems covering a clinically relevant Ht range without Ht correction. RESULTS: The method was partially validated for tacrolimus, sirolimus, everolimus, cyclosporin A and fully validated for mycophenolic acid on an Agilent and Thermo LC-MS/MS system. Bias caused by Ht effects were within 15% for all immunosuppressants between Ht levels of 0...
April 2017: Bioanalysis
https://www.readbyqxmd.com/read/28282713/treatment-of-an-early-kaposi-s-sarcoma-case-post-kidney-transplantation-by-sirolimus-a-case-report
#11
Farzaneh Najafi, Parichehr Kafaie, Hossein Neamatzadeh
Kaposi᾽s sarcoma (KS) can develop in 0.06% to 4.1% of kidney transplant recipients. Here we describe a case of 50-year-old man who developed KS a few months after kidney transplantation. After transplantation, he had delayed graft function and was managed by anti-thymocyte globulin (ATG) for five days. At the discharge, his immunosuppressive therapy was prednisolone 20 mg/day, tTacrolimus (Pprograf®) 4 mg/day, and mycophenolate mofetil (MMF) 2 gr/day, while he also took Vvalcyte and diltiazem. Once diagnosed with KS, the Prograf® (tacrolimus)  was replaced by prednisolone (5 mg/day) and sirolimus (2 mg/day)...
February 2017: Acta Medica Iranica
https://www.readbyqxmd.com/read/28258588/gastrostomy-tube-placement-for-long-term-oral-drug-administration-in-non-human-primates
#12
Jong-Min Kim, Jun-Seop Shin, Byoung-Hoon Min, Jung-Sik Kim, Il-Hee Yoon, Won-Young Jeong, Ga-Eul Lee, Min-Sun Kim, Ju-Eun Kim, Chung-Gyu Park
BACKGROUND: Non-human primates (NHPs) are often used as recipients in preclinical transplantation research that in most cases involves administration of various drugs including immunosuppressants. Long-term oral drug administration, particularly tacrolimus, is challenging in the transplant recipient NHPs. Oral drug administration method using the mixture of drug and fruit juice has been used in NHPs, but this is not always effective in all monkeys. To those monkeys who are poorly compliant, oral drug administration in restraint or administration using gastrostomy tube should be necessary...
March 3, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28205445/severe-hypertriglyceridemia-induced-by-sirolimus-treated-with-medical-management-without-plasmapheresis
#13
Kazuhiko Kido, Rickey A Evans, Anil Gopinath, Jeremy D Flynn
Hypertriglyceridemia and hyperlipidemia are the most remarkable metabolic complications seen with long-term sirolimus therapy. We report the case of a 36-year-old woman status post bilateral lung transplantation on a maintenance immunosuppression regimen of sirolimus, tacrolimus, and prednisone who presented with status migrainosus, chest pain, abdominal discomfort, and triglyceride levels greater than 4425 mg/dL. In previously reported cases of severe hypertriglyceridemia that developed on maintenance sirolimus therapy, plasmapheresis has been utilized as an early strategy to rapidly lower triglycerides in order to minimize the risk of acute complications such as pancreatitis, but our case was managed medically without plasmapheresis...
January 1, 2017: Journal of Pharmacy Practice
https://www.readbyqxmd.com/read/28182044/efficacy-and-safety-of-early-tacrolimus-conversion-to-sirolimus-after-kidney-transplantation-long-term-results-of-a-prospective-randomized-study
#14
A E El-Agroudy, S M Alarrayed, S M Al-Ghareeb, E Farid, H Alhelow, S Abdulla
We report a prospective, open-label, randomized study to evaluate the safety and efficacy of converting patients with a stable renal function from tacrolimus (Tac)-based regimen to a sirolimus (SRL)-based regimen after kidney transplantation. Fifty-eight low-risk renal allograft recipients who receiving Tac 6 months posttransplant, were randomly assigned to continue Tac (n = 29) or convert to SRL (n = 29). We evaluated the 3-year outcomes including patient and graft survival, graft function, and safety profile...
January 2017: Indian Journal of Nephrology
https://www.readbyqxmd.com/read/28121742/association-of-baseline-viral-serology-and-sirolimus-regimens-with-kidney-transplant-outcomes-a-14-year-registry-based-cohort-study-in-the-united-states
#15
Alfonso H Santos, Michael J Casey, Wen Xuerong, Karl L Womer
BACKGROUND: The risks for transplant outcomes associated with baseline viral serostatus in kidney transplant recipients (KTR) on sirolimus have not been widely studied. METHODS: We performed a cohort-study of 61 590 adult KTR in 2000 to 2013. We used Cox regression models to determine the adjusted hazard ratio (aHR) of patient death, death-censored graft loss and posttransplant malignancy associated with the baseline serostatus (+ or -: hepatitis B core [HBc], hepatitis C virus [HCV], Epstein-Barr virus [EBV], or cytomegalovirus [CMV]) in KTR on sirolimus (SRL) + mycophenolate (MPA) or SRL + tacrolimus (Tac), relative to the control-regimen: Tac + MPA...
February 2017: Transplantation
https://www.readbyqxmd.com/read/28104702/il-2-promotes-early-treg-reconstitution-after-allogeneic-hematopoietic-cell-transplantation
#16
Brian C Betts, Joseph Pidala, Jongphil Kim, Asmita Mishra, Taiga Nishihori, Lia Perez, Jose Leonel Ochoa-Bayona, Farhad Khimani, Kelly Walton, Ryan Bookout, Michael Nieder, Divis K Khaira, Marco Davila, Melissa Alsina, Teresa Field, Ernesto Ayala, Frederick L Locke, Marcie Riches, Mohamed Kharfan-Dabaja, Hugo Fernandez, Claudio Anasetti
Graft-versus-host disease (GvHD) remains a major cause of transplant-related mortality. Interleukin-2 (IL-2) plus sirolimus (SIR) synergistically reduces acute GvHD in rodents and promotes regulatory T cells. This phase II trial tested the hypothesis that IL-2 would facilitate STAT5 phosphorylation in donor T cells, expand regulatory T cells, and ameliorate GvHD. Between 16(th) April 2014 and 19(th) December 2015, 20 patients received IL-2 (200,000 IU/m(2) thrice weekly, days 0 to +90) with SIR (5-14 ng/mL) and tacrolimus (TAC) (3-7 ng/mL) after HLA-matched related or unrelated allogeneic hematopoietic cell transplantation (HCT)...
May 2017: Haematologica
https://www.readbyqxmd.com/read/28097735/autoimmune-enteropathy-and-hepatitis-in-pediatric-heart-transplant-recipient
#17
Kimberly Lewis, Ryan Butts, J Antonio Quiros, Michelle Hudspeth, Katherine Twombley, Andrew Savage, Sally Self, Ali Burnette, Shaoli Sun
AIE is a rare disorder in children that presents with severe diarrhea and malabsorption, caused by immune-mediated damage to intestinal mucosa. AIE is often associated with various syndromes of immunodeficiency including IPEX syndrome (immune dysregulation, polyendocrinopathy and enteropathy, X-linked). Dysfunctional T regulatory cells are the source of pathology in both IPEX syndrome and AIE as they are essential in maintaining tolerance to self-antigens and eliminating autoreactive B cells. This case report describes a 10-year-old cardiac transplant and total thymectomy patient on chronic immunosuppression with tacrolimus that presented with AIE and extraintestinal manifestations of cyclical hepatitis...
March 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28081041/a-systematic-literature-review-approach-to-estimate-the-therapeutic-index-of-selected-immunosuppressant-drugs-after-renal-transplantation
#18
Jessica E Ericson, Kanecia O Zimmerman, Daniel Gonzalez, Chiara Melloni, Jeffrey T Guptill, Kevin D Hill, Huali Wu, Michael Cohen-Wolkowiez
BACKGROUND: Drugs that exhibit close margins between therapeutic and toxic blood concentrations are considered to have a narrow therapeutic index (NTI). The Food and Drug Administration has proposed that NTI drugs should have more stringent bioequivalence standards for approval of generic formulations. However, many immunosuppressant drugs do not have a well-defined therapeutic index (TI). METHODS: We sought to determine whether safety, efficacy, and pharmacokinetic data obtained from the medical literature through a comprehensive literature search could be used to estimate the TI of cyclosporine, tacrolimus, and sirolimus...
February 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28070711/immune-suppression-during-preclinical-drug-development-mitigates-immunogenicity-mediated-impact-on-therapeutic-exposure
#19
Jonathan Herskovitz, Josiah Ryman, Theingi Thway, Stephanie Lee, Lei Zhou, Narendra Chirmule, Bernd Meibohm, Vibha Jawa
In the clinical setting, anti-drug antibodies (ADA) against biotherapeutics can influence patient safety and interfere with product efficacy. High immunogenicity has been addressed in clinic by concomitant immune suppression, such as co-administration of methotrexate with enzyme replacement therapy (ERT) and combination tacrolimus/sirolimus treatment for prophylaxis against organ transplant rejection. This study investigates the use of such immune suppressants in mitigating ADA responses to a fully human monoclonal antibody (mAb1) in preclinical animal studies...
March 2017: AAPS Journal
https://www.readbyqxmd.com/read/28038988/serial-in-vivo-imaging-of-transplanted-allogeneic-neural-stem-cell-survival-in-a-mouse-model-of-amyotrophic-lateral-sclerosis
#20
Amit K Srivastava, Sarah K Gross, Akshata A Almad, Camille A Bulte, Nicholas J Maragakis, Jeff W M Bulte
Neural stem cells (NSCs) are being investigated as a possible treatment for amyotrophic lateral sclerosis (ALS) through intraspinal transplantation, but no longitudinal imaging studies exist that describe the survival of engrafted cells over time. Allogeneic firefly luciferase-expressing murine NSCs (Luc(+)-NSCs) were transplanted bilaterally (100,000 cells/2μl) into the cervical spinal cord (C5) parenchyma of pre-symptomatic (63day-old) SOD1(G93A) ALS mice (n=14) and wild-type age-matched littermates (n=14)...
March 2017: Experimental Neurology
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