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Immunosuppression withdrawal

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https://www.readbyqxmd.com/read/28432716/deciphering-tacrolimus-induced-toxicity-in-pancreatic-%C3%AE-cells
#1
J Triñanes, A E Rodriguez-Rodriguez, Y Brito, A Wagner, A P J De Vries, G Cuesto, A Acebes, E Salido, A Torres, E Porrini
β-cell transcription factors like: FoxO1, MafA, PDX-1, NeuroD, are dysfunctional in type 2 diabetes (T2DM). PTDM resembles T2DM and reflects interaction between pre-transplant insulin resistance and immunosuppressants, mainly calcineurin inhibitors. We evaluated the effect of tacrolimus, cyclosporine-A and metabolic stressors (glucose+palmitate) on insulinoma β-cells (INS-1) in vitro and in pancreata of obese and lean Zucker rats. Cells were cultured for five days with 100μM palmitate and 22mM glucose; cyclosporin-A (250ng/mL) or tacrolimus (15ng/mL) were added the last 48h...
April 22, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28384413/comparative-effectiveness-of-tacrolimus-based-steroid-sparing-versus-steroid-maintenance-regimens-in-kidney-transplantation-results-from-discrete-event-simulation
#2
Vibha C A Desai, Yann Ferrand, Teresa M Cavanaugh, Christina M L Kelton, J Jaime Caro, Jens Goebel, Pamela C Heaton
BACKGROUND: Corticosteroids used as immunosuppressants to prevent acute rejection (AR) and graft loss (GL) following kidney transplantation are associated with serious cardiovascular and other adverse events. Evidence from short-term randomized controlled trials suggests that many patients on a tacrolimus-based immunosuppressant regimen can withdraw from steroids without increased AR or GL risk. OBJECTIVES: To measure the long-term tradeoff between GL and adverse events for a heterogeneous-risk population and determine the optimal timing of steroid withdrawal...
April 1, 2017: Medical Decision Making: An International Journal of the Society for Medical Decision Making
https://www.readbyqxmd.com/read/28375828/autologous-peripheral-blood-haematopoietic-stem-cell-transplantation-for-systemic-lupus-erythematosus-the-observation-of-long-term-outcomes-in-a-chinese-centre
#3
Can Cao, Menglei Wang, Jing Sun, Xuebiao Peng, Qifa Liu, Liang Huang, Yanyan Chai, Kuan Lai, Pingjiao Chen, Qingxiu Liu, Qian Li, Yusheng Peng, Hao Xiong, Jing Zhang, Minghua Chen, Kang Zeng
OBJECTIVES: We aimed to evaluate the safety and long-term efficacy of autologous peripheral blood haematopoietic stem cell transplantation (APHSCT). METHODS: We did not want to evaluate the efficacy of antibodies but rather the clinical response by investigating progression-free survival and serologic response by assessing autoantibody titres and complement levels. RESULTS: Overall, 22 patients with SLE (17 females; median age, 23 years) undergoing APHSCT were included...
March 31, 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28366698/steroid-free-immunosuppression-is-associated-with-enhanced-th1-transcripts-in-kidney-transplantation
#4
Petra Hruba, Irena Tycova, Eva Krepsova, Eva Girmanova, Alena Sekerkova, Janka Slatinska, Ilja Striz, Eva Honsova, Ondrej Viklicky
BACKGROUND: Steroid avoidance in immunosuppression in kidney transplantation offers several metabolic advantages, however it is associated with higher early acute rejection rate. Cellular and molecular mechanisms of this phenomenon remain poorly understood. METHODS: In this single center observational study, low-risk kidney transplant recipients randomized into large multicenter prospective ADVANCE trial with steroid avoidance/early withdrawal and center standard of care treated patients were monitored for 12months...
March 30, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28361117/the-privilege-of-induction-avoidance-and-calcineurin-inhibitors-withdrawal-in-2-haplotype-hla-matched-white-kidney-transplantation
#5
Zaid Brifkani, Daniel C Brennan, Krista L Lentine, Timothy A Horwedel, Andrew F Malone, Rowena Delos Santos, Thin Thin Maw, Tarek Alhamad
BACKGROUND: White recipients of 2-haplotype HLA-matched living kidney transplants are perceived to be of low immunologic risk. Little is known about the safety of induction avoidance and calcineurin inhibitor withdrawal in these patients. METHODS: We reviewed our experience at a single center and compared it to Organ Procurement and Transplantation Network (OPTN) registry data and only included 2-haplotype HLA-matched white living kidney transplants recipients between 2000 and 2013...
March 2017: Transplantation Direct
https://www.readbyqxmd.com/read/28348031/spine-trabecular-bone-score-as-an-indicator-of-bone-microarchitecture-at-the-peripheral-skeleton-in-kidney-transplant-recipients
#6
Matthew Luckman, Didier Hans, Natalia Cortez, Kyle K Nishiyama, Sanchita Agarawal, Chengchen Zhang, Lucas Nikkel, Sapna Iyer, Maria Fusaro, Edward X Guo, Donald J McMahon, Elizabeth Shane, Thomas L Nickolas
BACKGROUND AND OBJECTIVES: Studies using high-resolution peripheral quantitative computed tomography showed progressive abnormalities in cortical and trabecular microarchitecture and biomechanical competence over the first year after kidney transplantation. However, high-resolution peripheral computed tomography is a research tool lacking wide availability. In contrast, the trabecular bone score is a novel and widely available tool that uses gray-scale variograms of the spine image from dual-energy x-ray absorptiometry to assess trabecular quality...
April 3, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28330741/intermediate-steroid-withdrawal-after-renal-transplantation-and-anti-hla-antibodies-hla-abs-development
#7
Elena Monfá, David San Segundo, Juan Carlos Ruiz San Millán, Judith Sanabria, Zoila Albines, Emilio Rodrigo, Iñigo Romón, Esther Asensio, Manuel Arias, Marcos López-Hoyos
INTRODUCTION: Steroid withdrawal in renal transplantation is desirable to avoid their adverse effects. However, by decreasing the immunosuppression, could lead to an increased risk for the development of HLA-Abs. OBJECTIVE: Evaluate the relationship between steroid withdrawal and development of HLA-Abs in renal transplantation. METHODS: We analyzed sera by Luminex from 182 kidney transplants performed from 1998 to 2011, before and two years after transplantation...
March 19, 2017: Nefrología: Publicación Oficial de la Sociedad Española Nefrologia
https://www.readbyqxmd.com/read/28316834/the-cecari-study-everolimus-certican%C3%A2-initiation-and-calcineurin-inhibitor-withdrawal-in-maintenance-heart-transplant-recipients-with-renal-insufficiency-a-multicenter-randomized-trial
#8
Jan Van Keer, David Derthoo, Olivier Van Caenegem, Michel De Pauw, Eric Nellessen, Nathalie Duerinckx, Walter Droogne, Gábor Vörös, Bart Meyns, Ann Belmans, Stefan Janssens, Johan Van Cleemput, Johan Vanhaecke
In this 3-year, open-label, multicenter study, 57 maintenance heart transplant recipients (>1 year after transplant) with renal insufficiency (eGFR 30-60 mL/min/1.73 m(2)) were randomized to start everolimus with CNI withdrawal (N = 29) or continue their current CNI-based immunosuppression (N = 28). The primary endpoint, change in measured glomerular filtration rate (mGFR) from baseline to year 3, did not differ significantly between both groups (+7.0 mL/min in the everolimus group versus +1.9 mL/min in the CNI group, p = 0...
2017: Journal of Transplantation
https://www.readbyqxmd.com/read/28295181/long-term-follow-up-of-patients-receiving-allogeneic-stem-cell-transplant-for-chronic-lymphocytic-leukaemia-mixed-t-cell-chimerism-is-associated-with-high-relapse-risk-and-inferior-survival
#9
Philip A Thompson, Francesco Stingo, Michael J Keating, William G Wierda, Susan M O'Brien, Zeev Estrov, Celina Ledesma, Katayoun Rezvani, Muzaffar Qazilbash, Nina Shah, Simrit Parmar, Uday Popat, Paolo Anderlini, Nieto Yago, Stefan O Ciurea, Partow Kebriaei, Richard Champlin, Elizabeth J Shpall, Chitra M Hosing
There is limited information regarding the immunological predictors of post-allogeneic stem cell transplant (alloSCT) outcome in chronic lymphocytic leukaemia (CLL), such as mixed T-cell chimerism. We analysed 143 consecutive patients with relapsed/refractory CLL, transplanted between 2000 and 2012, to determine the prognostic relevance of mixed chimerism post-alloSCT and the ability of post-transplant immunomodulation to treat relapse. Mixed T-cell chimerism occurred in 50% of patients at 3 months and 43% at 6 months post-alloSCT; upon 3- and 6-month landmark analysis, this was associated with inferior progression-free survival (PFS) [Hazard ratio (HR) 1·93, P = 0·003 and HR 2·58, P < 0·001] and survival (HR 1·66, P = 0·05 and HR 2·17, P < 0·001), independent of baseline patient characteristics, and a lower rate of grade II-IV acute graft-versus-host disease (GHVD) (16% vs...
March 14, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28293454/can-rheumatoid-vasculitis-predate-a-diagnosis-of-rheumatoid-arthritis
#10
Sarah Sacks, Alan Steuer
We report regarding a male patient who presented with a systemic vasculitis that was consistent with a diagnosis of polyarteritis nodosa. At presentation, he had no features of inflammatory arthritis but had a high rheumatoid factor titer and low C4 level. Withdrawal of immunosuppression after 6 years resulted in the development of classical rheumatoid arthritis (RA). This case supports previous reports that revealed that vasculitis may predate the development or occur very early in the course of articular RA...
March 2017: European Journal of Rheumatology
https://www.readbyqxmd.com/read/28284916/infusion-of-mesenchymal-stromal-cells-after-deceased-liver-transplantation-a-phase-i-ii-open-label-clinical-study
#11
Olivier Detry, Morgan Vandermeulen, Marie-Hélène Delbouille, Joan Somja, Noella Bletard, Alexandra Briquet, Chantal Lechanteur, Olivier Giet, Etienne Baudoux, Muriel Hannon, Frederic Baron, Yves Beguin
BACKGROUND & AIM: Mesenchymal stromal cell (MSC) infusion could be a mean to establish tolerance in solid organ recipients. The aim of this prospective, controlled, phase-1 study was to evaluate the feasibility, safety and tolerability of a single infusion of MSCs in liver transplant recipients. METHODS: Ten liver transplant recipients under standard immunosuppression received 1.5-3x10(6)/kg third-party unrelated MSCs on post-operative day 3±2, and were prospectively compared to a control group of 10 liver transplant recipients...
March 8, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28266901/collaborative-approach-of-individual-participant-data-of-prospective-studies-of-de-escalation-in-non-immunosuppressed-critically-ill-patients-with-sepsis
#12
Antonio Gutiérrez-Pizarraya, Marc Leone, Jose Garnacho-Montero, Claude Martin, Ignacio Martin-Loeches
BACKGROUND: There is a concern to conduct de-escalation in very sick patients. AIMS: To determine if de-escalation is feasible in ICU settings. METHODS: We performed a metaanalysis of published studies conducted comparing de-escalation (defined by withdrawal of at least one antimicrobial empirically prescribed, switch to a new antimicrobial with narrower spectrum and withdrawal of at least one antimicrobial plus change of another drug to a new one with narrower spectrum) in non-immunocompromised patients with sepsis admitted to ICU...
April 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28260476/infections-after-renal-transplant-in-recipients-with-familial-mediterranean-fever-a-life-threatening-issue
#13
Erhan Tatar, Murat Karatas, Ahmet Aykas, Gokalp Okut, Giray Bozkaya, Adam Uslu
OBJECTIVES: We evaluated long-term results and infections requiring hospitalization in kidney transplant patients with Familial Mediterranean Fever (associated amyloidosis-type). MATERIALS AND METHODS: We retrospectively reviewed medical records of patients with familial Mediterranean fever with at least 1-year posttransplant follow-up. Kidney transplant recipients with primary glomerulonephritis and equivalent demography, immunity status, and follow-up comprised the control group...
February 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/28257602/the-biomarkers-of-lupus-disease-study-a-bold-approach-may-mitigate-interference-of-background-immunosuppressants-in-clinical-trials
#14
Joan T Merrill, Fred Immermann, Maryann Whitley, Tianhui Zhou, Andrew Hill, Margot O'Toole, Padmalatha Reddy, Marek Honczarenko, Aikaterini Thanou, Joe Rawdon, Joel M Guthridge, Judith A James, Sudhakar Sridharan
OBJECTIVES: Molecular medicine raised expectations for strategically targeted biologics in systemic lupus erythematosus (SLE), but clinical trials have been disappointing and difficult to interpret. Most studies add investigational agents to various, often effective, standard of care (SoC) immunosuppressants used at baseline, with unknown treatment interactions. Eliminating polypharmacy in trials of active lupus patients remains controversial. The BOLD study tested immunosuppressant withdrawal as a novel approach to interpretable SLE trials...
March 3, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28230646/effect-of-calcineurin-inhibitor-free-everolimus-based-immunosuppressive-regimen-on-albuminuria-and-glomerular-filtration-rate-after-heart-transplantation
#15
Lærke M Nelson, Arne K Andreassen, Bert Andersson, Einar Gude, Hans Eiskjær, Göran Rådegran, Göran Dellgren, Lars Gullestad, Finn Gustafsson
BACKGROUND: Albuminuria in maintenance heart transplantation (HTx) is associated with poor renal response when switching to a calcineurin inhibitor (CNI)-lowered or free immunosuppressive regimen using everolimus (EVR), but the significance of albuminuria associated with EVR treatment after early CNI withdrawal in de novo HTx is unknown. METHODS: We tested if glomerular filtration rate (mGFR, measured by CrEDTA clearance) was associated with urine albumin/creatinine ratio (UACR) post-HTx in a subgroup of patients included in the SCHEDULE trial, where de novo HTx patients (n=115) were randomized to EVR with complete CNI elimination 7-11 weeks post-HTx or standard CNI immunosuppression...
February 23, 2017: Transplantation
https://www.readbyqxmd.com/read/28203157/azathioprine-hypersensitivity-syndrome-two-cases-of-febrile-neutrophilic-dermatosis-induced-by-azathioprine
#16
Majed Aleissa, Perrine Nicol, Marion Godeau, Emilie Tournier, Frederic de Bellissen, Marie-Angèle Robic, Cristina Bulai Livideanu, Juliette Mazereeuw-Hautier, Carle Paul
BACKGROUND: Azathioprine is an immunosuppressive agent used in the treatment of immune-mediated diseases. Azathioprine hypersensitivity syndrome is a rare adverse reaction occurring a few days to weeks after the administration of azathioprine. CASE 1: A 36-year-old male with ulcerative colitis presented with erythematous plaques, pustules and erosions on the lower back, buttocks and thighs associated with high fever (39°C) 2 weeks after the initiation of azathioprine 100 mg/day...
January 2017: Case Reports in Dermatology
https://www.readbyqxmd.com/read/28196776/ebv-induced-lymphoproliferative-disorders-in-rheumatic-patients-a-systematic-review-of-the-literature
#17
Alvise Berti, Mara Felicetti, Susanna Peccatori, Roberto Bortolotti, Anna Guella, Paolo Vivaldi, Luca Morelli, Mattia Barabareschi, Giuseppe Paolazzi
OBJECTIVES: Epstein-Barr virus (EBV) is involved in the pathogenesis of approximately 40% of lymphoproliferative disorders (LPDs) arising in patients receiving immunosuppressive treatment (IST) for rheumatic diseases, but data from large cohorts are still not available. We aimed to identify clinicopathological features, management and outcome of this condition. METHODS: We reviewed all published cases of EBV-encoded RNA (EBER)-positive LPDs and included in our analysis one unpublished patient diagnosed in our Hospital...
February 11, 2017: Joint, Bone, Spine: Revue du Rhumatisme
https://www.readbyqxmd.com/read/28176617/progressive-multifocal-leukoencephalopathy-in-a-kidney-transplant-recipient
#18
Federico Cicora, Javier Roberti
Progressive multifocal leukoencephalopathy (PML) is a debilitating and often fatal viral disease of the central nervous system. A 39-year-old male kidney transplant recipient presented to our hospital with weakness of the left arm and leg, his immunosuppressive regimen consisted of tacrolimus, mycophenolate sodium, and meprednisone. Magnetic resonance imaging of the brain revealed hypercellularity in neural tissue and a lesion affecting the right ventral and lateral areas of the thalamus and the posterior limb of the internal capsule...
February 7, 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/28163950/tacrolimus-toxicity-due-to-biliary-obstruction-in-a-combined-kidney-and-liver-transplant-recipient
#19
Samuel Chan, Michael T Burke, David W Johnson, Ross S Francis, David W Mudge
The immunosuppressant tacrolimus has a narrow therapeutic window, necessitating therapeutic drug monitoring to maintain efficacy and minimise toxicity. There are very few reports examining the impact of impaired biliary excretion on tacrolimus blood levels or toxicity. We report the case of a 26-year-old combined liver and kidney transplant recipient, who developed acute biliary obstruction leading to tacrolimus toxicity with very high blood tacrolimus levels. Despite a careful evaluation, no alternative cause was found for her acute kidney injury, and her kidney function returned to previous baseline within several days following treatment of the biliary obstruction and temporary withdrawal of tacrolimus...
2017: Case Reports in Transplantation
https://www.readbyqxmd.com/read/28152949/improving-screening-and-prophylaxis-of-hepatitis-b-in-immunosuppressed-patients
#20
Violeta Rabrenovich, David M Baer, Joanne E Schottinger
139 Background: Kaiser Permanente (KP) is an integrated health care delivery system that provides clinical services to over 10 million members in nine states and the District of Columbia. Since 2007, KP oncology community collaborates at the national level to systematically improve safety and quality of care. Our improvements are accelerated by rapid adoption of evidence based protocols, leveraging of EMR and integration of quality improvement methods into clinical operations. METHODS: KP created a team that included oncologists, hepatologists, rheumatologist, pharmacy, and quality improvement experts to evaluate safety of existing practice...
March 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
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