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immunosuppression minimization

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https://www.readbyqxmd.com/read/28319600/early-and-late-factors-impacting-patient-and-graft-outcome-in-pediatric-liver-transplantation-summary-of-an-espghan-monothematic-conference
#1
Valérie A McLin, Upton Allen, Olivia Boyer, John Bucuvalas, Michele Colledan, Maria-Cristina Cuturi, Lorenzo d'Antiga, Dominique Debray, Antal Dezsofi, Jean de Ville de Goyet, Anil Dhawan, Ozlem Durmaz, Christine Falk, Sandy Feng, Björn Fischler, Stéphanie Franchi-Abella, Esteban Frauca, Rainer Ganschow, Stephen Gottschalk, Nedim Hadzic, Loreto Hierro, Simon Horslen, Stefan Hubscher, Vincent Karam, Deirdre Kelly, Britta Maecker-Kolhoff, George Mazariegos, Patrick McKiernan, Anette Melk, Valerio Nobili, Funda Ozgenç, Raymond Reding, Marco Sciveres, Khalid Sharif, Piotr Socha, Christian Toso, Pietro Vajro, Anita Verma, Barbara E Wildhaber, Ulrich Baumann
As pediatric liver transplantation comes of age, experts gathered to discuss current paradigms and define gaps in knowledge warranting research to further improve patient and graft outcomes. Identified areas ripe for collaborative research include understanding the molecular and cellular mechanisms of tolerance and the role of donor-specific antibodies, considering ways to expand donor pool, minimizing long term side effects of immunosuppression, and fine-tuning surgical techniques to minimize biliary and vascular complications...
March 17, 2017: Journal of Pediatric Gastroenterology and Nutrition
https://www.readbyqxmd.com/read/28298471/bk-polyomavirus-clinical-aspects-immune-regulation-and-emerging-therapies
#2
REVIEW
George R Ambalathingal, Ross S Francis, Mark J Smyth, Corey Smith, Rajiv Khanna
BK polyomavirus (BKV) causes frequent infections during childhood and establishes persistent infections within renal tubular cells and the uroepithelium, with minimal clinical implications. However, reactivation of BKV in immunocompromised individuals following renal or hematopoietic stem cell transplantation may cause serious complications, including BKV-associated nephropathy (BKVAN), ureteric stenosis, or hemorrhagic cystitis. Implementation of more potent immunosuppression and increased posttransplant surveillance has resulted in a higher incidence of BKVAN...
April 2017: Clinical Microbiology Reviews
https://www.readbyqxmd.com/read/28289723/setting-the-target-for-pemphigus-vulgaris-therapy
#3
REVIEW
Christoph T Ellebrecht, Aimee S Payne
Despite the rising incidence of autoimmunity, therapeutic options for patients with autoimmune disease still rely on decades-old immunosuppressive strategies that risk severe and potentially fatal complications. Thus, novel therapeutic approaches for autoimmune diseases are greatly needed in order to minimize treatment-related toxicity. Such strategies would ideally target only the autoreactive immune components to preserve beneficial immunity. Here, we review how several decades of basic, translational, and clinical research on the immunology of pemphigus vulgaris (PV), an autoantibody-mediated skin disease, have enabled the development of targeted immunotherapeutic strategies...
March 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28280037/local-activation-of-p53-in-the-tumor-microenvironment-overcomes-immune-suppression-and-enhances-antitumor-immunity
#4
Gang Guo, Miao Yu, Wei Xiao, Esteban Celis, Yan Cui
Mutations in tumor suppressor p53 remain a vital mechanism of tumor escape from apoptosis and senescence. Emerging evidence suggests that p53 dysfunction also fuels inflammation and supports tumor immune evasion, thereby serving as an immunological driver of tumorigenesis. Therefore, targeting p53 in the tumor microenvironment (TME) also represents an immunologically desirable strategy for reversing immunosuppression and enhancing antitumor immunity. Using a pharmacological p53 activator nutlin-3a, we show that local p53 activation in TME comprising overt tumor infiltrating leukocytes (TILeus) induces systemic antitumor immunity and tumor regression, but not in TME with scarce TILeus, such as B16 melanoma...
March 9, 2017: Cancer Research
https://www.readbyqxmd.com/read/28272192/optic-neuropathy-associated-with-primary-sj%C3%A3-gren-s-syndrome-a-case-series
#5
Eunoo Bak, Hee Kyung Yang, Jeong-Min Hwang
PURPOSE: To determine the diverse clinical features of optic neuropathy associated with primary Sjögren's syndrome in Korean patients. METHODS: Five women with acute and/or chronic optic neuropathy who were diagnosed as primary Sjögren's syndrome were retrospectively evaluated. Primary Sjögren's syndrome was diagnosed by signs and symptoms of keratoconjunctivitis sicca, positive serum anti-Ro/SSA and/or anti-La/SSB antibodies, and/or minor salivary gland biopsy...
March 7, 2017: Optometry and Vision Science: Official Publication of the American Academy of Optometry
https://www.readbyqxmd.com/read/28270929/changing-paradigms-in-the-management-of-rejection-in-kidney-transplantation-evolving-from-protocol-based-care-to-the-era-of-p4-medicine
#6
Mirela Maier, Tomoko Takano, Ruth Sapir-Pichhadze
PURPOSE OF REVIEW: P4 medicine denotes an evolving field of medicine encompassing predictive, preventive, personalized, and participatory medicine. Using the example of kidney allograft rejection because of donor-recipient incompatibility in human leukocyte antigens, this review outlines P4 medicine's relevance to the various stages of the kidney transplant cycle. SOURCES OF INFORMATION: A search for English articles was conducted in Medline via OvidSP (up to August 18, 2016) using a combination of subject headings (MeSH) and free text in titles, abstracts, and author keywords for the concepts kidney transplantation and P4 medicine...
2017: Canadian Journal of Kidney Health and Disease
https://www.readbyqxmd.com/read/28270810/a-novel-model-on-dst-induced-transplantation-tolerance-by-the-transfer-of-self-specific-donor-ttregs-to-a-haplotype-matched-organ-recipient
#7
Angelica Maria Mohr Gregoriussen, Henrik Georg Bohr
Donor-specific blood transfusion (DST) can lead to significant prolongation of allograft survival in experimental animal models and sometimes human recipients of solid organs. The mechanisms responsible for the beneficial effect on graft survival have been a topic of research and debate for decades and are not yet fully elucidated. Once we discover how the details of the mechanisms involved are linked, we could be within reach of a procedure making it possible to establish donor-specific tolerance with minimal or no immunosuppressive medication...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28266942/personalized-treatment-in-heart-transplantation
#8
Kiran K Khush
PURPOSE OF REVIEW: We are entering the era of personalized medicine, in which pharmacogenomics and biomarker-based assays can be used to tailor diagnostic tests and drug therapies to individual patients. This new approach to patient-specific care offers the potential to maximize the efficacy of available medical treatments while reducing the incidence of adverse side effects. Here, we present approaches to personalize the care of heart transplant recipients. RECENT FINDINGS: Four strategies for personalized posttransplant care are described, including use of pharmacogenomic data to individualize the use of immunosuppressive drugs, immune monitoring to prevent acute rejection while reducing the long-term consequences of over immunosuppression, noninvasive surveillance for acute rejection, and targeted prophylaxis against opportunistic infections...
March 6, 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/28260476/infections-after-renal-transplant-in-recipients-with-familial-mediterranean-fever-a-life-threatening-issue
#9
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/28260425/optimizing-immunosuppressive-regimens-among-living-donor-renal-transplant-recipients
#10
Mohamed Adel Bakr, Ayman Maher Nagib, Osama Ashry Gheith, Ahmed Farouk Hamdy, Ayman Fathi Refaie, Ahmed Farouk Donia, Ahmed Hassan Neamatalla, Khaled Farouk Eldahshan, Ahmed Abdelfattah Denewar, Mohamed Hamed Abbas, Amany Ismail Mostafa, Mohamed Ahmed Ghoneim
OBJECTIVES: We review different immunosuppressant protocols used for living-donor kidney transplant recipients at our center. MATERIALS AND METHODS: Many prospective randomized studies from our center have been reported between March 1976 and 2016, with more than 2700 renal transplant procedures conducted. The first study was a prospective randomized trial of azathioprine versus cyclosporine. The second study compared triple therapy (prednisolone + azathioprine + cyclosporine) versus conventional therapy (prednisolone + azathioprine)...
February 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/28257650/subcutaneous-immunoglobulins-for-the-treatment-of-a-patient-with-antisynthetase-syndrome-and-secondary-chronic-immunodeficiency-after-anti-cd20-treatment-a-case-report
#11
Patrick Cherin, Christophe de Jaeger, Jean-Charles Crave, Jean-Christophe Delain, Abir Tadmouri, Zahir Amoura
BACKGROUND: Antisynthetase syndrome is a rare and debilitating multiorgan disease characterized by inflammatory myopathy, interstitial lung disease, cutaneous involvement, and frequent chronic inflammation of the joints. Standard treatments include corticosteroids and immunosuppressants. In some cases, treatment resistance may develop. Administration of immunoglobulins intravenously is recommended in patients with drug-resistant antisynthetase syndrome. CASE PRESENTATION: Here, we describe the case of a 56-year-old woman of Algerian origin...
March 4, 2017: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/28257602/the-biomarkers-of-lupus-disease-study-a-bold-approach-may-mitigate-interference-of-background-immunosuppressants-in-clinical-trials
#12
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/28256368/checkpoint-based-immunotherapy-for-autoimmune-diseases-opportunities-and-challenges
#13
EDITORIAL
Xiao-Song He, M Eric Gershwin, Aftab A Ansari
Immune checkpoint pathways modulate the T cell response to ensure their dual function in maintaining health, eradicating or controlling malignancy and infection, as well as tolerating host autoantigens. Dysregulation of the checkpoint pathways may lead to development of cancer or persistent infection, or alternately, autoimmune diseases. Currently available treatments for autoimmune diseases, such as steroid and nonsteroid immunosuppressive medicines, have limited efficacy. Checkpoint-based immunotherapy, designed to directly block the activation pathway or agitate the inhibitory pathway of autoreactive T cells, is a promising therapeutic strategy for restoring T cell tolerance in autoimmune diseases...
February 27, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28251511/herpes-simplex-encephalitis-an-update
#14
REVIEW
John W Gnann, Richard J Whitley
PURPOSE OF REVIEW: The goal of this review is to provide an update on current thinking regarding herpes simplex encephalitis (HSE), emphasizing new information about pathogenesis, diagnosis, and immune responses. Specific questions to be addressed are the following: (1) Is there a genetic predisposition to HSE? (2) What clinical approaches have the greatest impact on improving the long-term outcomes in patients with HSE? And (3) are there immune-mediated mechanisms that may account for relapsing HSE? RECENT FINDINGS: Toll-like receptor 3 (TLR 3) plays an important role in innate immune responses, including generation of interferons...
March 2017: Current Infectious Disease Reports
https://www.readbyqxmd.com/read/28247521/combination-of-leflunomide-and-everolimus-for-treatment-of-bk-virus-nephropathy
#15
Juli Jaw, Prue Hill, David Goodman
BK nephropathy (BKN) is a common cause of graft dysfunction following kidney transplantation. Minimization of immunosuppressive therapy remains the first line of therapy, but this may lead to rejection and graft loss. In some cases, despite lowering immunosuppression, BK infection can persist, leading to chronic damage and kidney failure. Currently, there is no specific anti-BK viral therapy. Recent in vitro experiments have demonstrated a reduction in BK viral replication when infected cells are treated with the combination of Leflunomide and Everolimus...
April 2017: Nephrology
https://www.readbyqxmd.com/read/28242033/a-composite-score-associated-with-spontaneous-operational-tolerance-in-kidney-transplant-recipients
#16
Richard Danger, Mélanie Chesneau, Chloé Paul, Pierrick Guérif, Maxim Durand, Kenneth A Newell, Sai Kanaparthi, Laurence A Turka, Jean-Paul Soulillou, Rémi Houlgatte, Magali Giral, Gérard Ramstein, Sophie Brouard
New challenges in renal transplantation include using biological information to devise a useful clinical test for discerning high- and low-risk patients for individual therapy and ascertaining the best combination and appropriate dosages of drugs. Based on a 20-gene signature from a microarray meta-analysis performed on 46 operationally tolerant patients and 266 renal transplant recipients with stable function, we applied the sparse Bolasso methodology to identify a minimal and robust combination of six genes and two demographic parameters associated with operational tolerance...
February 24, 2017: Kidney International
https://www.readbyqxmd.com/read/28238223/glucose-lowering-agents-for-treating-pre-existing-and-new-onset-diabetes-in-kidney-transplant-recipients
#17
REVIEW
Clement Lo, Min Jun, Sunil V Badve, Helen Pilmore, Sarah L White, Carmel Hawley, Alan Cass, Vlado Perkovic, Sophia Zoungas
BACKGROUND: Kidney transplantation is the preferred form of kidney replacement therapy for patients with end-stage kidney disease (ESKD) and is often complicated by worsening or new-onset diabetes. Management of hyperglycaemia is important to reduce post-transplant and diabetes-related complications. The safety and efficacy of glucose-lowering agents after kidney transplantation is largely unknown. OBJECTIVES: To evaluate the efficacy and safety of pharmacological interventions for lowering glucose levels in patients who have undergone kidney transplantation and have diabetes...
February 27, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28231415/encapsulating-an-immunosuppressant-enhances-tolerance-induction-by-siglec-engaging-tolerogenic-liposomes
#18
Lijuan Pang, Matthew S Macauley, Britni M Arlian, Corwin M Nycholat, James C Paulson
Unwanted antibody responses significantly impact human health, and current options for treating deleterious antibody responses largely rely on broad immunosuppressants that can compromise overall immunity. A desirable alternative is to induce antigen-specific immune tolerance. We have shown that co-presentation of antigen and ligands of B cell Siglecs (sialic acid-binding immunoglobulin-like lectin) on a liposomal nanoparticle induces antigen-specific tolerance. Although Siglec-engaging tolerance-inducing antigenic liposomes (STALs) induce robust B cell tolerance in naïve mice, the full potential of STALs requires long-term tolerance induction and suppression of an ongoing immune response...
February 23, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28228614/current-solutions-for-long-segment-tracheal-reconstruction
#19
Ahmed A Abouarab, Hany H Elsayed, Hussein Elkhayat, Ahmed Mostafa, David C Cleveland, Ahmed El Nori
This article is a continuation of previous reviews about the appropriate method for long-segment tracheal reconstruction. We attempted to cover the most recent, successful and promising results of the different solutions for reconstruction that are rather innovative and suitable for imminent clinical application. Latest efforts to minimize the limitations associated with each method have been covered as well. In summary, autologous and allogenic tissue reconstruction of the trachea have been successful methods for reconstruction experimentally and clinically...
February 23, 2017: Annals of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28225369/long-term-outcomes-of-rituximab-therapy-in-patients-with-noninfectious-posterior-uveitis-refractory-to-conventional-immunosuppressive-therapy
#20
Andres F Lasave, Caiyun You, Lina Ma, Khawla Abusamra, Neerav Lamba, Manuel Valdes Navarro, Halea Meese, C Stephen Foster
PURPOSE: To assess long-term effectiveness of rituximab therapy for refractory noninfectious uveitis affecting the posterior segment. METHODS: Retrospective case series. Patients diagnosed with recalcitrant noninfectious posterior uveitis who were treated with rituximab intravenous infusions between 2010 and 2015 were included. Patients underwent best-corrected visual acuity testing and fluorescein angiography evidence of disk or vascular staining at 6, 12, 18, and 24 months...
February 20, 2017: Retina
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