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tolerance in transplantation

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https://www.readbyqxmd.com/read/28344057/ruxolitinib-as-salvage-therapy-in-steroid-refractory-acute-graft-versus-host-disease-in-pediatric-hematopoietic-stem-cell-transplant-patients
#1
Pooja Khandelwal, Ashley Teusink-Cross, Adam S Nelson, Christopher E Dandoy, Javier El-Bietar, Rebecca A Marsh, Ashish R Kumar, Michael S Grimley, Stella M Davies, Sonata Jodele, Kasiani C Myers
We describe our retrospective clinical experience with ruxolitinib for steroid-refractory acute graft versus host disease (GVHD) in pediatric allogeneic hematopoietic stem cell transplant (HSCT) patients. Ruxolitinib was administered orally at 5 mg twice daily for children ≥ 25 kg or 2.5 mg twice daily if < 25 kg. We excluded patients who received new immune suppressive agents within two weeks before initiation of ruxolitinib from response analysis. Patients were called a treatment failure if ruxolitinib was stopped before completion of 4 weeks of therapy due to adverse effects and not because of progression of acute GVHD...
March 23, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28340818/use-of-atg-fresenius-as-an-induction-agent-in-deceased-donor-kidney-transplantation
#2
M Yilmaz, T Ö Sezer, O Kir, A Öztürk, C Hoşcoşkun, H Töz
BACKGROUND: Anti-T-lymphocyte globulins (ATG) are most commonly used as induction agents in kidney transplantation (KT). In this study, we investigated the use of ATG as induction therapy in deceased-donor KT. METHODS: Among 152 deceased-donor KT recipients transplanted between January 2009 and December 2003, 147 with exact data were enrolled in this study. Delayed graft function was defined as dialysis requirement after KT. Greater than 10% panel-reactive antibody (PRA) was considered as positive...
April 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28340673/the-advent-of-vascularized-composite-allotransplantation
#3
REVIEW
Curtis L Cetrulo, Zhi Yang Ng, Jonathan M Winograd, Kyle R Eberlin
Modern microsurgical techniques have made possible a broad spectrum of novel means for the reconstruction of complex bone and soft tissue defects. These techniques, in combination with developments in transplant immunology, have led to successful hand and facial allotransplantation and achievement of the highest rung in the reconstructive ladder - truly replacing like with like. The utilization of contemporary microsurgical technique in the context of vascularized composite allotransplantation (VCA) (1) permits successful technical execution and feasibility of VCA, (2) facilitates the study of immunologic tolerance in VCA preclinical models, and (3) optimizes functional VCA outcomes...
April 2017: Clinics in Plastic Surgery
https://www.readbyqxmd.com/read/28337883/evaluation-of-tolerance-and-safety-of-conversion-from-mycophenolate-mofetil-to-enteric-coated-mycophenolic-acid-in-renal-transplant-recipients
#4
L W Qiao, Q S Qu, X Jiang
This study was designed to evaluate the curative effect of conversion from mycophenolate mofetil (MMF) to enteric-coated mycophenolate sodium tablets (EC-MPS) and its safety. One hundred and twenty renal transplant recipients who developed MMF-associated chronic diarrhea were selected as research subjects and treated with EC-MPS. The patients were followed up for 12 months to compare the improvement of gastrointestinal symptoms and the indexes such as carbon dioxide combining power (CO2CP), serum sodium, serum potassium, serum creatinine (Scr) and 24-h urine protein before and after conversion treatment...
January 2017: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/28335642/voriconazole-for-prophylaxis-of-invasive-fungal-infections-after-allogeneic-hematopoietic-stem-cell-transplantation
#5
David I Marks, Qifa Liu, Monica Slavin
Invasive fungal infections (IFIs) following allogeneic hematopoietic stem cell transplantation (alloHSCT) are associated with a high mortality, and accordingly most alloHSCT recipients receive prophylaxis with antifungal agents. Despite some improvement in outcomes of IFIs over time, they continue to represent substantial clinical risk, mortality, and financial burden. Areas covered: We review the main pathogens responsible for IFIs in recipients of alloHSCT, current treatment recommendations, and discuss clinical and economic considerations associated with voriconazole prophylaxis of IFIs in these patients...
March 24, 2017: Expert Review of Anti-infective Therapy
https://www.readbyqxmd.com/read/28333015/role-of-stereotactic-body-radiation-therapy-before-orthotopic-liver-transplantation-retrospective-evaluation-of-pathologic-response-and-outcomes
#6
Edward Michael Mannina, Higinia Rosa Cardenes, Foster D Lasley, Benjamin Goodman, Jennifer Zook, Sandra Althouse, John Alvin Cox, Romil Saxena, Joseph Tector, Mary Maluccio
PURPOSE: To analyze the results of stereotactic body radiation therapy (SBRT) in patients with early-stage, localized hepatocellular carcinoma who underwent definitive orthotopic liver transplantation (OLT). METHODS AND MATERIALS: The subjects of this retrospective report are 38 patients diagnosed with hepatocellular carcinoma who underwent SBRT per institutional phase 1 to 2 eligibility criteria, before definitive OLT. Pre-OLT radiographs were compared with pathologic gold standard...
April 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28332958/effect-of-prediabetes-on-allograft-survival-and-evolution-of-new-onset-diabetes-after-transplant-in-deceased-donor-kidney-transplant-recipients-during-long-term-follow-up
#7
Frank Peter Tillmann, Amira Radtke, Lars Christian Rump, Ivo Quack
OBJECTIVES: This study investigated the effect of prediabetes in long-term deceased-donor renal transplant recipients regarding graft survival, graft function, and evolution of new-onset diabetes after transplant compared with a control group of graft recipients with normal glucose tolerance test results. MATERIALS AND METHODS: This was a follow-up trial of 187 deceased-donor renal transplant recipients. Based on oral glucose tolerance test results, the cohort was divided into groups A and B, comprising individuals with normal glucose metabolism (n = 130, 69...
March 22, 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/28331319/humanized-cd7-nanobody-based-immunotoxins-exhibit-promising-anti-t-cell-acute-lymphoblastic-leukemia-potential
#8
Yuan Yu, Jialu Li, Xuejun Zhu, Xiaowen Tang, Yangyi Bao, Xiang Sun, Yuhui Huang, Fang Tian, Xiaomei Liu, Lin Yang
BACKGROUND: Nanobodies, named as VHHs (variable domain of heavy chain of HCAb [heavy-chain antibodies]), are derived from heavy-chain-only antibodies that circulate in sera of camelids. Their exceptional physicochemical properties, possibility of humanization, and unique antigen recognition properties make them excellent candidates for targeted delivery of biologically active components, including immunotoxins. In our previous efforts, we have successfully generated the monovalent and bivalent CD7 nanobody-based immunotoxins, which can effectively trigger the apoptosis of CD7-positive malignant cells...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28328655/vascularized-composite-allotransplantation-an-emerging-concept-for-burn-reconstruction
#9
Zhi Yang Ng, Alexandre G Lellouch, Tessa Drijkoningen, Irene A Chang, David H Sachs, Curtis L Cetrulo
Vascularized composite allotransplantation (VCA) has demonstrated utility in the reconstruction of extensive soft-tissue defects following severe burns. However, pre-VCA events such as multiple transfusions, previous transplantation and pregnancies, the use of skin allografts, and mechanical support devices may result in sensitization and ultimately exclude a burn patient, who may benefit most through VCA, from a hand or face transplant. The authors sought to identify the immunologic challenges involved. All reported VCA cases up to July 2016 were reviewed...
March 15, 2017: Journal of Burn Care & Research: Official Publication of the American Burn Association
https://www.readbyqxmd.com/read/28327905/phase-ii-study-of-idelalisib-a-selective-inhibitor-of-pi3k%C3%AE-for-relapsed-refractory-classical-hodgkin-lymphoma
#10
A K Gopal, M A Fanale, C H Moskowitz, A R Shustov, S Mitra, W Ye, A Younes, A J Moskowitz
Background: The phosphatidylinositol-3-kinase delta (PI3Kδ) inhibitor idelalisib has been shown to block downstream intracellular signaling, reduce the production of prosurvival chemokines and induce apoptosis in classical Hodgkin lymphoma (HL) cell lines. It has also been shown to inhibit regulatory T cells and myeloid-derived suppressor cells in other tumor models. We hypothesized that inhibiting PI3Kδ would have both direct and indirect antitumor effects by directly targeting the malignant cells as well as modulating the inflammatory microenvironment...
January 24, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28321921/insights-into-cell-free-therapeutic-approach-role-of-stem-cell-soup-ernatant
#11
REVIEW
Shalini Raik, Ajay Kumar, Shalmoli Bhattacharyya
Current advances in medicine have revolutionized the field of regenerative medicine dramatically with newly evolved therapies for repair or replacement of degenerating or injured tissues. Stem cells can be harvested from different sources for clinical therapeutics which include fetal tissues, umbilical cord blood, embryos and adult tissues. Stem cells can be isolated and differentiated into desired lineages for tissue regeneration and cell replacement therapy. However, several loopholes need to be addressed properly before this can be extended for large scale therapeutic application...
March 21, 2017: Biotechnology and Applied Biochemistry
https://www.readbyqxmd.com/read/28321272/future-of-liver-disease-in-the-era-of-direct-acting-antivirals-for-the-treatment-of-hepatitis-c
#12
REVIEW
Francesca Romana Ponziani, Francesca Mangiola, Cecilia Binda, Maria Assunta Zocco, Massimo Siciliano, Antonio Grieco, Gian Lodovico Rapaccini, Maurizio Pompili, Antonio Gasbarrini
Hepatitis C virus (HCV) infection has been a global health problem for decades, due to the high number of infected people and to the lack of effective and well-tolerated therapies. In the last 3 years, the approval of new direct acting antivirals characterized by high rates of virological clearance and excellent tolerability has dramatically improved HCV infection curability, especially for patients with advanced liver disease and for liver transplant recipients. Long-term data about the impact of the new direct acting antivirals on liver fibrosis and liver disease-related outcomes are not yet available, due to their recent introduction...
March 8, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28321218/the-induction-and-maintenance-of-transplant-tolerance-engages-both-regulatory-and-anergic-cd4-t-cells
#13
Alix Besançon, Marije Baas, Tania Goncalves, Fabrice Valette, Herman Waldmann, Lucienne Chatenoud, Sylvaine You
Therapeutic tolerance to self-antigens or foreign antigens is thought to depend on constant vigilance by Foxp3(+) regulatory T cells (Tregs). Previous work using a pancreatic islet allograft model and a short pulse of CD3 antibody therapy has shown that CD8(+) T cells become anergic and use TGFβ and coinhibitory signaling as their contribution to the tolerance process. Here, we examine the role of CD4(+) T cells in tolerization by CD3 antibodies. We show that both Foxp3(+) Tregs and CD4(+) T cell anergy play a role in the induction of tolerance and its maintenance...
2017: Frontiers in Immunology
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
#14
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/28319445/nonclinical-pharmacology-toxicology-study-of-aav8-tbg-mldlr-and-aav8-tbg-hldlr-in-a-mouse-model-of-homozygous-familial-hypercholesterolemia
#15
Jenny A Greig, Maria P Limberis, Peter Bell, Shu-Jen Chen, Roberto Calcedo, Daniel J Rader, James M Wilson
The homozygous form of familial hypercholesterolemia (HoFH) is an excellent model for developing in vivo gene therapy in humans. The success of orthotropic liver transplantation in correcting the metabolic abnormalities in HoFH suggests that the correction of low-density lipoprotein receptor (LDLR) expression in hepatocytes via gene therapy should be sufficient for therapeutic efficacy. Vectors based on adeno-associated virus serotype 8 (AAV8) have been previously developed for liver-targeted gene therapy of a number of genetic diseases, including HoFH...
March 2017: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/28319075/autologous-hematopoietic-stem-cell-transplantation-for-pediatric-multiple-sclerosis-a-registry-based-study-of-the-autoimmune-diseases-working-party-adwp-and-pediatric-diseases-working-party-pdwp-of-the-european-society-for-blood-and-marrow-transplantation-ebmt
#16
J Burman, K Kirgizov, K Carlson, M Badoglio, G L Mancardi, G De Luca, B Casanova, J Ouyang, R Bembeeva, J Haas, P Bader, J Snowden, D Farge
Autologous hematopoietic stem cell transplantation (aHSCT) is a promising therapy for multiple sclerosis (MS), which has mainly been used in adults. The purpose of this study was to investigate efficacy and adverse events of aHSCT in the treatment of children with MS using data from the European Society for Blood and Marrow Transplantation registry. Twenty-one patients with a median follow-up time of 2.8 years could be identified. PFS at 3 years was 100%, 16 patients improved in expanded disability status scale score and only 2 patients experienced a clinical relapse...
March 20, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28318501/sorafenib-use-for-recurrent-hepatocellular-cancer-after-resection-or-transplantation-observations-from-a-us-regional-analysis-of-the-gideon-registry
#17
Robert C G Martin, Elizabeth Bruenderman, Allen Cohn, Bilal Piperdi, Rebecca Miksad, Jean-Francois Geschwind, Alec Goldenberg, Arun Sanyal, Ellen Zigmont, Svetlana Babajanyan, Pamela Foreman, Parvez Mantry, Brendan McGuire, Pierre Gholam
Treatment of unresectable recurrent hepatocellular carcinoma (HCC) in patients who recur after resection or orthotopic liver transplantation (OLT) remains a clinical challenge. One option is sorafenib, although little is known about its safety and tolerance in this unique patient population; therefore, we analyzed patients who underwent prior surgical resection and/or OLT and were treated with sorafenib in US cohort of GIDEON registry. In US, 645 patients were enrolled; 553 for intent to treat and 563 for safety...
November 18, 2016: American Journal of Surgery
https://www.readbyqxmd.com/read/28316600/methylation-of-foxp3-tsdr-underlies-the-impaired-suppressive-function-of-tregs-from-long-term-belatacept-treated-kidney-transplant-patients
#18
Evelyn Katy Alvarez Salazar, Arimelek Cortés-Hernández, Germán Rodrigo Alemán-Muench, Josefina Alberú, Jesús R Rodríguez-Aguilera, Félix Recillas-Targa, Victoria Chagoya de Sánchez, Eric Cuevas, Eduardo Mancilla-Urrea, María Pérez García, Guillermo Mondragón-Ramírez, Mario Vilatobá, Ian Bostock, Erick Hernández-Méndez, David De Rungs, Eduardo A García-Zepeda, Gloria Soldevila
Regulatory T cells (Tregs) are considered key players in the prevention of allograft rejection in transplanted patients. Belatacept (BLT) is an effective alternative to calcineurin inhibitors that appears to preserve graft survival and function; however, the impact of this drug in the homeostasis of Tregs in transplanted patients remains controversial. Here, we analyzed the phenotype, function, and the epigenetic status of the Treg-specific demethylated region (TSDR) in FOXP3 of circulating Tregs from long-term kidney transplant patients under BLT or Cyclosporine A treatment...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28314211/the-role-of-kupffer-cells-in-hepatic-diseases
#19
REVIEW
Peizhi Li, Kun He, Jinzheng Li, Zuojin Liu, Jianping Gong
Kupffer cells (KCs) constitute 80-90% of the tissue macrophages present in the body. Essential to innate and adaptive immunity, KCs are responsible for the swift containment and clearance of exogenous particulates and immunoreactive materials which are perceived as foreign and harmful to the body. Similar to other macrophages, KCs also sense endogenous molecular signals that may result from perturbed homeostasis of the host. KCs have been implicated in host defense and the pathogenesis of various hepatic diseases, including endotoxin tolerance, liver transplantation, nonalcoholic fatty liver disease, and alcoholic liver disease...
March 14, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28302753/erythropoietin-receptor-mediated-molecular-crosstalk-promotes-t-cell-immunoregulation-and-transplant-survival
#20
Carolina Purroy, Robert L Fairchild, Toshiaki Tanaka, William M Baldwin, Joaquin Manrique, Joren C Madsen, Robert B Colvin, Alessandro Alessandrini, Bruce R Blazar, Miguel Fribourg, Chiara Donadei, Umberto Maggiore, Peter S Heeger, Paolo Cravedi
Although spontaneous kidney transplant acceptance/tolerance occurs in mice and occasionally in humans, mechanisms remain unclear. Herein we test the hypothesis that EPO, a hormone predominantly produced by the adult kidney, has immunomodulating properties that are required for spontaneous kidney graft acceptance. In vitro, in a manner dependent on the EPO receptor and CD131 on antigen-presenting cells, EPO induced the secretion of active TGFβ by antigen-presenting cells, which in turn converted naïve CD4(+) T cells into functional Foxp3(+) regulatory T cells (Treg)...
March 16, 2017: Journal of the American Society of Nephrology: JASN
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