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Transplantation induction therapies

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https://www.readbyqxmd.com/read/29786549/pluripotent-stem-cells-induction-and-self-renewal
#1
REVIEW
R Abu-Dawud, N Graffmann, S Ferber, W Wruck, J Adjaye
Pluripotent stem cells (PSCs) lie at the heart of modern regenerative medicine due to their properties of unlimited self-renewal in vitro and their ability to differentiate into cell types representative of the three embryonic germ layers-mesoderm, ectoderm and endoderm. The derivation of induced PSCs bypasses ethical concerns associated with the use of human embryonic stem cells and also enables personalized cell-based therapies. To exploit their regenerative potential, it is essential to have a firm understanding of the molecular processes associated with their induction from somatic cells...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29785311/acute-lymphoblastic-leukemia-following-lenalidomide-maintenance-for-multiple-myeloma-two-cases-with-unexpected-presentation-and-good-prognostic-features
#2
Abdullah M Khan, Jameel Muzaffar, Hermant Murthy, John R Wingard, Jan S Moreb
Lenalidomide maintenance following autologous stem cell transplant (ASCT) is considered the standard of care for eligible patients with multiple myeloma (MM). A recent meta-analysis has provided additional evidence that lenalidomide maintenance is associated with a higher incidence of second primary malignancies, including both hematologic and solid malignancies. Acute lymphoblastic leukemia (ALL) as a second primary malignancy is rarely described in the literature. Herein, we describe two patients with MM treated with induction therapy, ASCT, and lenalidomide maintenance that experienced cytopenias while on maintenance...
2018: Case Reports in Hematology
https://www.readbyqxmd.com/read/29784741/management-of-multiple-myeloma
#3
Shaji K Kumar
The most recent NCCN Guidelines for Multiple Myeloma include a ranking of the many treatment options for various settings as "preferred," "other," and "useful in certain circumstances." For patients eligible for autologous stem cell transplant (ASCT), the preferred regimen remains bortezomib/lenalidomide/dexamethasone (category 1) or bortezomib/cyclophosphamide/dexamethasone. Upfront ASCT also remains a preferred strategy for patients who are transplant-eligible, despite highly effective newer agents such as induction therapy...
May 2018: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/29780592/preleukemic-and-second-hit-mutational-events-in-an-acute-myeloid-leukemia-patient-with-a-novel-germline-runx1-mutation
#4
Isaac Ks Ng, Joanne Lee, Christopher Ng, Bustamin Kosmo, Lily Chiu, Elaine Seah, Michelle Meng Huang Mok, Karen Tan, Motomi Osato, Wee-Joo Chng, Benedict Yan, Lip Kun Tan
Background: Germline mutations in the RUNX1 transcription factor give rise to a rare autosomal dominant genetic condition classified under the entity: Familial Platelet Disorders with predisposition to Acute Myeloid Leukaemia (FPD/AML). While several studies have identified a myriad of germline RUNX1 mutations implicated in this disorder, second-hit mutational events are necessary for patients with hereditary thrombocytopenia to develop full-blown AML. The molecular picture behind this process remains unclear...
2018: Biomarker Research
https://www.readbyqxmd.com/read/29778558/successful-kidney-transplant-with-eculizumab-thymoglobulin-and-belatacept-therapy-in-a-highly-sensitised-patient-with-atypical-haemolytic-uraemic-syndrome-due-to-factor-h-mutation
#5
John Fredy Nieto-Ríos, Mónica Zuluaga-Quintero, Diana Carolina Bello-Márquez, Arbey Aristizabal-Alzate, Catalina Ocampo-Kohn, Lina María Serna-Higuita, Lina Arias, Gustavo Zuluaga-Valencia
Atypical haemolytic uremic syndrome is a disease caused by complement regulation abnormalities that generally progresses to chronic end-stage renal disease with a high rate of recurrence in kidney transplantation and a high risk of graft loss. Anti-complement therapy has improved the prognosis of these patients, achieving disease remission in most cases, increasing the likelihood of a successful kidney transplant and increasing patient and graft survival. Drugs with low risk of induction of thrombotic microangiopathies such as belatacept and mycophenolate have also been used with satisfactory results...
May 16, 2018: Nefrología: Publicación Oficial de la Sociedad Española Nefrologia
https://www.readbyqxmd.com/read/29777547/tacrolimus-induced-asymptomatic-thrombotic-microangiopathy-diagnosed-by-laboratory-tests-in-pig-to-rhesus-corneal-xenotransplantation-a-case-report
#6
Jong-Min Kim, Jaeyoung Kim, Se-Hyun Choi, Jun-Seop Shin, Byoung-Hoon Min, Won Young Jeong, Ga-Eul Lee, Min-Sun Kim, Seeun Kwon, Mee Kum Kim, Chung-Gyu Park
Tacrolimus-associated thrombotic microangiopathy (TA-TMA) is a rare complication. TA-TMA is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and organ damage due to thrombus. We report asymptomatic TA-TMA diagnosed by laboratory tests in pig-to-rhesus corneal xenotransplantation. Corneal transplantation had been conducted from a wild-type SNU miniature pig to a rhesus macaque. The veterinary records were retrospectively reviewed in this case. The immunosuppressive regimen consisted of rituximab, basiliximab, and IVIg as inductive therapies, and steroids with tacrolimus (0...
May 18, 2018: Xenotransplantation
https://www.readbyqxmd.com/read/29760728/mesenchymal-stromal-cells-cultured-in-serum-from-heart-failure-patients-are-more-resistant-to-simulated-chronic-and-acute-stress
#7
Timo Z Nazari-Shafti, Zhiyi Xu, Andreas Matthäus Bader, Georg Henke, Kristin Klose, Volkmar Falk, Christof Stamm
Despite regulatory issues surrounding the use of animal-derived cell culture supplements, most clinical cardiac cell therapy trials using mesenchymal stromal cells (MSCs) still rely on fetal bovine serum (FBS) for cell expansion before transplantation. We sought to investigate the effect of human serum from heart failure patients (HFS) on cord blood MSCs (CB-MSCs) during short-term culture under regular conditions and during simulated acute and chronic stress. Cell survival, proliferation, metabolic activity, and apoptosis were quantified, and gene expression profiles of selected apoptosis and cell cycle regulators were determined...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29760372/a-review-of-induction-with-rabbit-antithymocyte-globulin-in-pediatric-heart-transplant-recipients
#8
Martin Schweiger, Andreas Zuckermann, Andres Beiras-Fernandez, Michael Berchtolld-Herz, Udo Boeken, Jens Garbade, Stephan Hirt, Manfred Richter, Arjang Ruhpawar, Jan Dieter Schmitto, Felix Schönrath, Rene Schramm, Uwe Schulz, Markus J Wilhelm, Markus J Barten
Pediatric heart transplantation (pHTx) represents only a small proportion of cardiac transplants. Due to these low numbers, clinical data relating to induction therapy in this special population are far less extensive than for adults. Induction is used more widely in pHTx than in adults, mainly because of early steroid withdrawal or complete steroid avoidance. Antithymocyte globulin (ATG) is the most frequent choice for induction in pHTx, and rabbit antithymocyte globulin (rATG, Thymoglobulin®) (Sanofi Genzyme) is the most widely-used ATG preparation...
May 15, 2018: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/29757956/osteogenic-differentiation-modulates-the-cytokine-chemokine-and-growth-factor-profile-of-ascs-and-shed
#9
Federico Mussano, Tullio Genova, Sara Petrillo, Ilaria Roato, Riccardo Ferracini, Luca Munaron
Great efforts have been made to improve bone regeneration techniques owing to a growing variety of sources of stem cells suitable for autologous transplants. Specifically, adipose-derived stem cells (ASCs) and stems cells from human exfoliated deciduous teeth (SHED) hold great potential for bone tissue engineering and cell therapy. After a preliminary characterization of the main biomolecules ASCs and SHED released in their conditioned media, cells were kept both in normal and osteo-inducing conditions. Conventional assays were performed to prove their osteogenic potential such as quantitative real-time polymerase chain reaction (qRT-PCR) (for RUNX-2, collagen type I, osteopontin and osteonectin), alkaline phosphatase activity, osteocalcin production, and von Kossa staining...
May 14, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29757021/advagraf%C3%A2-with-or-without-an-induction-therapy-for-de-novo-kidney-transplant-recipients
#10
Johan Noble, Thomas Jouve, Lionel Rostaing, Paolo Malvezzi
Cornerstone immunosuppressive therapy currently relies on immediate-release tacrolimus, a calcineurin inhibitor (CNI) that is potentially nephrotoxic and is more diabetogenic than cyclosporine A. Two new formulations of tacrolimus have been launched: an extended-release formulation (Advagraf®/Astagraf XL®, Astellas company) and a long-lasting formulation (Envarsus®, Veloxis company). Area covered: Herein, we assess the efficacy of an extended-release formulation of tacrolimus (Advagraf®/Astagraf XL®) used in conjunction with or without an induction therapy (i...
May 14, 2018: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/29752413/everolimus-with-reduced-calcineurin-inhibitor-exposure-in-renal-transplantation
#11
Julio Pascual, Stefan P Berger, Oliver Witzke, Helio Tedesco, Shamkant Mulgaonkar, Yasir Qazi, Steven Chadban, Federico Oppenheimer, Claudia Sommerer, Rainer Oberbauer, Yoshihiko Watarai, Christophe Legendre, Franco Citterio, Mitchell Henry, Titte R Srinivas, Wen-Lin Luo, AnaMaria Marti, Peter Bernhardt, Flavio Vincenti
Background Everolimus permits reduced calcineurin inhibitor (CNI) exposure, but the efficacy and safety outcomes of this treatment after kidney transplant require confirmation. Methods In a multicenter noninferiority trial, we randomized 2037 de novo kidney transplant recipients to receive, in combination with induction therapy and corticosteroids, everolimus with reduced-exposure CNI (everolimus arm) or mycophenolic acid (MPA) with standard-exposure CNI (MPA arm). The primary end point was treated biopsy-proven acute rejection or eGFR<50 ml/min per 1...
May 11, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29746172/pharmacological-decrease-of-liver-stiffness-is-pressure-related-and-predicts-long-term-clinical-outcome
#12
Felix Piecha, Mattias Mandorfer, Teresa Peccerella, Ann-Kathrin Ozga, Tanja Poth, Anna Vonbank, Helmut Karl Seitz, Vanessa Rausch, Thomas Reiberger, Sebastian Mueller
Liver stiffness (LS) as measured by transient elastography is increasingly used to non-invasively assess liver fibrosis. However, LS is efficiently modulated by confounders like arterial and portal pressure (PP). We here study the effect of acute hemodynamic changes on LS (measured by µFibroscan) in a rodent model of cirrhosis in response to pharmacological modulation of PP by losartan, NO-donors and propranolol. Additionally, changes of LS and the hepatic venous pressure gradient (HVPG) under propranolol therapy were assessed with regard to clinical outcomes in a human cohort of n=38 cirrhotic patients...
May 10, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29744939/heart-transplant-outcomes-in-patients-with-chagas-cardiomyopathy-in-the-united-states
#13
Rodolfo D Benatti, Sadeer G Al-Kindi, Fernando Bacal, Guilherme H Oliveira
BACKGROUND: Chagas cardiomyopathy (CC) is one of the chronic manifestations of Trypanosoma cruzi (T. cruzi) infection and is among the leading reasons for heart transplantation (HT) in Latin America. Chagas disease is also present in areas with large Hispanic communities in the United States. Our objective is to evaluate the outcomes of cardiac allograft recipients with the diagnosis of CC in the United States. METHODS AND RESULTS: We identified 25 adult patients with CC and 15,930 with idiopathic dilated cardiomyopathy (IDCMP) who underwent HT between 1987 and 2015...
May 9, 2018: Clinical Transplantation
https://www.readbyqxmd.com/read/29737242/bms-493-modulates-retinoic-acid-induced-differentiation-during-expansion-of-human-hematopoietic-progenitor-cells-for-islet-regeneration
#14
Ruth Marise Elgamal, Gillian I Bell, Sarah Krause, David A Hess
Cellular therapies are emerging as a novel treatment strategy for diabetes. Thus, the induction of endogenous islet regeneration in situ represents a feasible goal for diabetes therapy. Umbilical cord blood (UCB)-derived hematopoietic progenitor cells (HPC) isolated by high aldehyde dehydrogenase activity (ALDH<sup>hi</sup>) have previously been shown to reduce hyperglycemia after intrapancreatic (iPan) transplantation into streptozotocin (STZ)-treated non-obese diabetic (NOD) severe combined immunodeficient (SCID) mice...
May 8, 2018: Stem Cells and Development
https://www.readbyqxmd.com/read/29734149/recent-advances-in-treatment-strategies-for-lupus-nephritis
#15
Kazunori Karasawa, Keiko Uchida, Tomo Takabe, Takahito Moriyama, Kosaku Nitta
Systemic lupus erythematosus (SLE) is an autoimmune chronic inflammatory disease that affects multiple organs and tissues. Lupus nephritis (LN) is a serious complication of SLE, which occurs at a high rate. Conventional treatment strategies of LN have been widely accepted by two concepts such as induction therapy and maintenance therapy. In LN induction therapy until recently, cyclophosphamide in combination with prednisone (PSL) has been the standard method of treatment for proliferative forms of LN. In the latest review, the combination of mycophenolate mofetil (MMF) is also considered a standard treatment option...
2018: Contributions to Nephrology
https://www.readbyqxmd.com/read/29731924/the-spectrum-of-histopathological-changes-in-the-renal-allograft-a-12-months-protocol-biopsy-study
#16
Galina Severova-Andreevska, Ladislava Grcevska, Gordana Petrushevska, Koco Cakalaroski, Aleksandar Sikole, Olivera Stojceva-Taneva, Ilina Danilovska, Ninoslav Ivanovski
INTRODUCTION: Renal transplantation became a routine and successful medical treatment for Chronic Kidney Disease in the last 30 years all over the world. Introduction of Luminex based Single Antigen Beads (SAB) and recent BANFF consensus of histopathological phenotypes of different forms of rejection enables more precise diagnosis and changes the therapeutic approach. The graft biopsies, protocol or cause, indicated, remain a golden diagnostic tool for clinical follow up of kidney transplant recipients (KTR)...
April 15, 2018: Open Access Macedonian Journal of Medical Sciences
https://www.readbyqxmd.com/read/29731098/efficacy-and-safety-of-induction-therapy-in-kidney-transplantation-a-network-meta-analysis
#17
S D Hwang, J H Lee, S W Lee, K-M Park, J K Kim, M-J Kim, J H Song
BACKGROUND: Rejection and infection can occur after kidney transplantation and are important factors in preserving graft kidney function. The use of immunosuppressant agents in transplantation is therefore important, and the question of which induction therapy should be used as an immunosuppressant is controversial. OBJECTIVE: The goal of this study was to assess the comparative benefits and harms of various maintenance immunosuppressive induction agents in adults undergoing kidney transplantation by using a network meta-analysis and to generate rankings of the different immunosuppressive regimens according to their safety and efficacy...
May 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/29728700/combination-therapy-with-carfilzomib-lenalidomide-and-dexamethasone-krd-results-in-an-unprecedented-purity-of-the-stem-cell-graft-in-newly-diagnosed-patients-with-myeloma
#18
Nishant Tageja, Neha Korde, Dickran Kazandjian, Sandhya Panch, Elisabet Manasanch, Manisha Bhutani, Mary Kwok, Sham Mailankody, Constance Yuan, Maryalice Stetler-Stevenson, Susan F Leitman, Claude Sportes, Ola Landgren
Still, many physicians give 4 cycles of combination therapy to multiple myeloma patients prior to collection of stem cells for autologous bone marrow transplant. This tradition originates from older doxorubicin-containing regiments which limited the number of cycles due to cumulative cardiotoxicity. Using older regiments, most patients had residual myeloma cells in their autologous stem-cell grafts during collection. Emerging data show that newly diagnosed multiple myeloma patients treated with modern carfilzomib/lenalidomide/dexamethasone (KRd) therapy, on average, take 6 cycles until reaching minimal residual disease (MRD) negativity...
May 4, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29728401/immune-regulatory-cell-infusion-for-graft-versus-host-disease-prevention-and-therapy
#19
Bruce R Blazar, Kelli P A MacDonald, Geoffrey R Hill
Current approaches to prevent and treat graft-versus-host disease (GVHD) after stem cell transplantation rely principally on pharmacological immune suppression. Such approaches are limited by drug toxicity, non-specific immune suppression and a requirement for long-term therapy. Our increased understanding of the regulatory cells and molecular pathways involved in limiting pathogenic immune responses opens the opportunity for the use of these cell subsets to prevent and/or GVHD. The theoretical advantages of this approach is permanency of effect, potential for facilitating tissue repair, and induction of tolerance that obviates a need for ongoing drug therapy...
May 4, 2018: Blood
https://www.readbyqxmd.com/read/29720486/international-cooperative-study-identifies-treatment-strategy-in-childhood-ambiguous-lineage-leukemia
#20
Ondrej Hrusak, Valerie De Haas, Jitka Stancikova, Barbora Vakrmanova, Iveta Janotova, Ester Mejstrikova, Vaclav Capek, Jan Trka, Marketa Zaliova, Ales Luks, Kirsten Bleckmann, Anja Möricke, Julie Irving, Benigna Konatkowska, Thomas B Alexander, Hiroto Inaba, Kjeld Schmiegelow, Simone Stokley, Zuzana Zemanova, Anthony V Moorman, Jorge Gabriel Rossi, Maria Sara Felice, Luciano Dalla-Pozza, Jessa Morales, Michael Dworzak, Barbara Buldini, Giuseppe Basso, Myriam Campbell, Maria Elena Cabrera, Neda Marinov, Sarah Elitzur, Shai Izraeli, Drorit Luria, Tamar Feuerstein, Alexandra Kolenova, Peter Svec, Olena Kreminska, Karen R Rabin, Sophia Polychronopoulou, Elaine da Costa, Hanne Vibeke Marquart, Antonis Kattamis, Richard Ratei, Dirk Reinhardt, John K Choi, Martin Schrappe, Jan Stary
Despite attempts to improve the definitions of ambiguous leukemia (ALAL) during the last two decades, general therapy recommendations are missing. Herein, we report a large cohort of children with ALAL and propose a treatment strategy. A retrospective multinational study iBFM-AMBI2012 on 233 cases of pediatric ALAL patients is presented. Survival statistics were used to compare the prognosis of subsets and types of treatment. Five-year event-free survival (5yEFS) of patients with acute lymphoblastic leukemia (ALL)-type primary therapy (80±4%) was superior to that of children who received acute myeloid leukemia (AML)-type or combined-type treatments (36±7...
May 2, 2018: Blood
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