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https://www.readbyqxmd.com/read/28550199/comprehensive-approach-for-identifying-the-t-cell-subset-origin-of-cd3-and-cd28-antibody-activated-chimeric-antigen-receptor-modified-t-cells
#1
Michael Schmueck-Henneresse, Bilal Omer, Thomas Shum, Haruko Tashiro, Maksim Mamonkin, Natalia Lapteva, Sandhya Sharma, Lisa Rollins, Gianpietro Dotti, Petra Reinke, Hans-Dieter Volk, Cliona M Rooney
The outcome of therapy with chimeric Ag receptor (CAR)-modified T cells is strongly influenced by the subset origin of the infused T cells. However, because polyclonally activated T cells acquire a largely CD45RO(+)CCR7(-) effector memory phenotype after expansion, regardless of subset origin, it is impossible to know which subsets contribute to the final T cell product. To determine the contribution of naive T cell, memory stem T cell, central memory T cell, effector memory T cell, and terminally differentiated effector T cell populations to the CD3 and CD28-activated CAR-modified T cells that we use for therapy, we followed the fate and function of individually sorted CAR-modified T cell subsets after activation with CD3 and CD28 Abs (CD3/28), transduction and culture alone, or after reconstitution into the relevant subset-depleted population...
May 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28544780/spinal-metastatic-disease-a-review-of-the-role-of-the-multidisciplinary-team
#2
REVIEW
Mark Curtin, Robert P Piggott, Evelyn P Murphy, Sudarshan Munigangaiah, Joseph F Baker, John P McCabe, Aiden Devitt
Historically, a simple approach centered on palliation was applicable to the majority of patients with metastatic spinal disease. With advances in diagnosis and treatment, a more complicated algorithm has devolved requiring a multidisciplinary approach with institutional commitment and support. We performed a database review including pertinent articles exploring the multidisciplinary management of spinal metastatic disease. The wide variation in clinical presentation and tumor response to treatment necessitates a multidisciplinary approach that integrates the diagnosis and treatment of the cancer, symptom management, and rehabilitation for optimal care of patients with spinal metastases...
May 24, 2017: Orthopaedic Surgery
https://www.readbyqxmd.com/read/28544595/severe-cytokine-release-syndrome-in-a-patient-receiving-pd-1-directed-therapy
#3
Seth J Rotz, Daniel Leino, Sara Szabo, Jennifer L Mangino, Brian K Turpin, Joseph G Pressey
Cytokine release syndrome (CRS) is a phenomenon of immune hyperactivation described in the setting of cellular and bispecific T-cell engaging immunotherapy. Checkpoint blockade using anti-programmed cell death 1 (anti-PD-1) inhibitors is an approach to antitumor immune system stimulation. A 29-year-old female with alveolar soft part sarcoma developed severe CRS after treatment with anti-PD-1 therapy. CRS was characterized by high fevers, encephalopathy, hypotension, hypoxia, hepatic dysfunction, and evidence of coagulopathy, and resolved after infusion of the interleukin-6 inhibitor tocilizumab and corticosteroids...
May 24, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28544545/cytoprotective-encapsulation-of-individual-jurkat-t-cells-within-durable-tio2-shells-for-t-cell-therapy
#4
Wongu Youn, Eun Hyea Ko, Mi-Hee Kim, Matthew Park, Daewha Hong, Gulaim A Seisenbaeva, Vadim G Kessler, Insung S Choi
Lymphocytes, such as T cells and natural killer (NK) cells, have therapeutic promises in adoptive cell transfer (ACT) therapy, where the cells are activated and expanded in vitro, and then infused into a patient. However, the in vitro preservation of labile lymphocytes during transfer, manipulation, and storage has been one of the bottlenecks in the development and commercialization of therapeutic lymphocytes. Herein, we suggest a "cell-in-shell" (a.k.a. artificial spore) strategy to enhance the cell viability in the practical settings, while maintaining biological activities for therapeutic efficacy...
May 25, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28543216/bridging-with-tirofiban-during-oral-antiplatelet-interruption-a-single-center-case-series-analysis-including-patients-on-hemodialysis
#5
Elizabeth A Walker, William E Dager
INTRODUCTION: Surgical patients requiring an interruption in dual-antiplatelet therapy (DAPT) within 6 months of cardiac stenting are at risk for thrombotic events. Bridging with short-acting intravenous antiplatelet agents has been proposed to minimize the risk of thrombotic and hemorrhagic complications. METHODS: This was a retrospective analysis of a tirofiban bridging strategy that did not use an initial bolus loading dose. Tirofiban infusions were initiated 24to 48 hours after the last oral antiplatelet dose at a rate of 0...
May 23, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28542711/preventing-relapse-after-haematopoietic-stem-cell-transplantation-for-acute-leukaemia-the-role-of-post-transplantation-minimal-residual-disease-mrd-monitoring-and-mrd-directed-intervention
#6
REVIEW
Xiao-Dong Mo, Meng Lv, Xiao-Jun Huang
Relapse is the main cause of treatment failure after allogeneic haematopoietic stem cell transplantation (allo-HSCT) for acute leukaemia (AL). Post-transplantation minimal residual disease (MRD) monitoring enables risk stratification and identifies AL patients at higher risk of relapse. MRD assessment primarily involves the determination of leukaemia-associated immunophenotypic patterns using multiparameter flow cytometry, and the polymerase chain reaction (PCR)-based evaluation of expression levels of leukaemia-related genes (specific reciprocal gene rearrangements and other mutation types)...
May 23, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28542043/induction-therapy-with-biosimilar-infliximab-in-children-with-crohn-s-disease
#7
Joanna Sieczkowska-Golub, Monika Meglicka, Anna Plocek, Aleksandra Banaszkiewicz, Dorota Jarzębicka, Ewa Toporowska-Kowalska, Agnieszka Gawronska, Grzegorz Oracz, Jaroslaw Kierkus
INTRODUCTION: In most European countries, an infliximab biosimilar (CT-P13) is currently in common use. In vitro and in vivo studies have proved a high similarity between CT-P13 and the reference infliximab. CT-P13 was licensed for use in patients with Crohn's diseases (CD) based on the extrapolation of data from preclinical studies and clinical trials in rheumatology indications. The aim of this study was to assess the similarity between CT-P13 and the originator infliximab in induction therapy in CD paediatric patients...
May 24, 2017: Journal of Pediatric Gastroenterology and Nutrition
https://www.readbyqxmd.com/read/28541596/effects-of-ivabradine-and-beta-blocker-therapy-on-dobutamine-induced-ventricular-arrhythmias
#8
Kadir Uğur Mert, Gurbet Özge Mert, Bektas Morrad, Senan Tahmazov, Fezan Mutlu, Yüksel Cavusoglu
BACKGROUND: Indirect evidences suggest that the If blocker (ivabradine) may exert an antiarrhythmic effect in ventricular myocardium in heart failure patients by inhibiting spontaneous depolarizations but the clinical relevance of this mechanism is not known. Dobutamine (DOB) has been known to increase heart rate and the incidence of cardiac arrhythmias. In this study, we evaluated the effects of ivabradine on DOB-induced ventricular arrhythmias and compared it with that of β blocker therapy...
May 25, 2017: Kardiologia Polska
https://www.readbyqxmd.com/read/28541510/optimization-of-linezolid-therapy-in-the-critically-ill-the-effect-of-adjusted-infusion-regimens
#9
Max Taubert, Johannes Zander, Sebastian Frechen, Christina Scharf, Lorenz Frey, Michael Vogeser, Uwe Fuhr, Michael Zoller
Objectives: Insufficient linezolid levels, which are associated with a poorer outcome, are often observed in ICU patients who receive standard dosing. Although strategies to overcome these insufficient levels have been discussed, appropriate alternative dosing regimens remain to be identified. Methods: Various infusion regimens (1200-3600 mg/day; q6h, q8h, q12h and continuous) were simulated in 67 000 ICU patients. The probability of attaining pharmacodynamic targets ( T >MIC ≥85%, AUC/MIC ≥100, cumulative fraction of response for Staphylococcus aureus and Enterococcus spp...
May 24, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28541131/clinical-use-of-continuous-glucose-monitoring-in-adults-with-type-1-diabetes
#10
David Slattery, Pratik Choudhary
With the emphasis on intensive management of type 1 diabetes, data from studies support frequent monitoring of glucose levels to improve glycemic control and reduce glucose variability, which can be related to an increase in macro and microvascular complications. However, few perform capillary blood glucose that frequently. There are currently two available alternatives that this review will discuss, continuous glucose monitoring (CGM) and flash glucose monitoring. CGM has become an important diagnostic and therapeutic option in optimizing diabetes management...
May 2017: Diabetes Technology & Therapeutics
https://www.readbyqxmd.com/read/28540910/rituximab-induced-urticarial-dermatitis-during-the-treatment-of-membranous-nephropathy
#11
Radhika Chemmangattu Radhakrishnan, Gopal Basu, Renu E George, Harshad Parmar, Veerasami Tamilarasi
Rituximab is a monoclonal antibody directed against B cells and is being increasingly used for various renal indications. Acute dermatologic manifestations such as urticaria are well known to occur during rituximab infusion. Here, we report the case of a 53- year-old female who was treated with rituximab for membranous nephropathy and developed an exanthematous rash, which progressed with a further dose of rituximab and was diagnosed as urticarial dermatitis. A review of literature showed that urticarial dermatitis following rituximab therapy has been seldom reported and identification of this complication is very important to avoid giving further doses and thus, increasing the severity of lesions...
May 2017: Saudi Journal of Kidney Diseases and Transplantation
https://www.readbyqxmd.com/read/28540187/case-report-of-treatment-experience-with-idursulfase-beta-hunterase-in-an-adolescent-patient-with-mps-ii
#12
Lock-Hock Ngu, Winnie Ong Peitee, Huey Yin Leong, Hui Bein Chew
Mucopolysaccharidosis (MPS) II or Hunter syndrome is a chronic, progressive, multi-systemic illness associated with significant morbidity and early mortality. Available evidence in Asian populations shows that Hunter syndrome has a mean age of onset of 2 to 5 years and a life expectancy of 13 years in more severely affected individuals, with respiratory failure reported as the leading cause of death. Enzyme replacement therapy (ERT) with idursulfase (Elaprase, Shire Pharmaceuticals) and idursulfase beta (Hunterase, Green Cross Corp) are the only approved treatment for patients with MPS II...
September 2017: Molecular Genetics and Metabolism Reports
https://www.readbyqxmd.com/read/28540033/use-of-repeated-intravenous-ketamine-therapy-in-treatment-resistant-bipolar-depression-with-suicidal-behaviour-a-case-report-from-spain
#13
REVIEW
Álvaro López-Díaz, José Luis Fernández-González, José Evaristo Luján-Jiménez, Sara Galiano-Rus, Luis Gutiérrez-Rojas
The rapidly-acting antidepressant properties of ketamine are a trend topic in psychiatry. Despite its robust effects, these are ephemeral and can lead to certain adverse events. For this reason, there is still a general concern around the off-label use of ketamine in clinical practice settings. Nonetheless, for refractory depression, it should be an indication to consider. We report the case of a female patient admitted for several months due to a treatment-resistant depressive bipolar episode with chronic suicidal behaviour...
April 2017: Therapeutic Advances in Psychopharmacology
https://www.readbyqxmd.com/read/28539536/remission-induction-therapy-with-rituximab-for-microscopic-polyangiitis-a-feasibility-study
#14
Ayako Saito, Yoichi Takeuchi, Saeko Kagaya, Yoshie Ojima, Hirotaka Fukami, Hiroyuki Sato, Ken Matsuda, Tasuku Nagasawa
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is systemic vascular inflammation. Microscopic polyangiitis (MPA) is a major type of AAV in Japan. MPA often affects the kidneys and lungs, leading to death if untreated. Induction therapy (i.e., initial treatment) for MPA has not been optimized, although methylprednisolone and cyclophosphamide are commonly used. Recently, rituximab (RTX) (a monoclonal antibody against the protein CD20) has also been used to treat refractory AAV. RTX at 375 mg/m(2)/week for 4 weeks (i...
2017: Tohoku Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28537788/the-precision-of-hepatic-arterial-infusion-scintigraphy-as-a-quantitative-biomarker-of-tumor-microvasculature
#15
Mark Dunphy, Neeta Pandit-Taskar, Josef J Fox, Nancy Kemeny
OBJECTIVE: Optimal clinical development of new cancer therapies targeting tumor vasculature requires new target-specific response assays. This clinical study examined the test-retest repeatability of SPECT as an in vivo assay of angiogenic hepatic tumor microvasculature using an intraarterial infusion of (99m)Tc-macroaggregated albumin (MAA) delivered via a hepatic artery infusion (HAI) pump. MATERIALS AND METHODS: Patients with primary or secondary cancerous liver tumors with HAI pump-catheter implants placed for HAI chemotherapy underwent hepatic SPECT after separate arterial infusions of 37 and 185 MBq of (99m)Tc-MAA via an HAI pump...
May 24, 2017: AJR. American Journal of Roentgenology
https://www.readbyqxmd.com/read/28537756/chemoembolization-adopting-polyethylene-glycol-drug-eluting-embolics-loaded-with-doxorubicin-for-the-treatment-of-hepatocellular-carcinoma
#16
Camillo Aliberti, Riccardo Carandina, Donatella Sarti, Luca Mulazzani, Enrico Pizzirani, Stefano Guadagni, Giammaria Fiorentini
OBJECTIVE: The purpose of this study is to determine the efficacy and tolerability of transarterial chemoembolization (TACE) using polyethylene glycol (PEG) drug-elutable microspheres loaded with doxorubicin for treatment of hepatocellular carcinoma (HCC). SUBJECTS AND METHODS: Forty-two patients with unresectable HCC, as determined by a tumor board, were assigned to undergo TACE and were treated with PEG drug-elutable embolics loaded with doxorubicin. Patients were prospectively enrolled and included 32 (76%) men and 10 (24%) women...
May 24, 2017: AJR. American Journal of Roentgenology
https://www.readbyqxmd.com/read/28536935/-rituximab-for-the-treatment-of-poly-and-dermatomyositis-results-from-the-graid-2-registry
#17
C Fiehn, L Unger, H Schulze-Koops, F Proft, J C Henes, A Jacobi, T Dörner
INTRODUCTION: In the treatment of poly- and dermatomyositis, only a limited number of treatment modalities are established. OBJECTIVE: The goal of the GRAID-2 registry was to study off-label use of biologic drugs for this indication in Germany. PATIENTS AND METHODS: Analysis of the data of the GRAID-2 registry for poly- and dermatomyositis. RESULTS: In 22 of the 23 patients in the GRAID-2 registry, rituximab (RIX) was administered, while 1 patient was given tocilizumab as off-label therapy...
May 23, 2017: Zeitschrift Für Rheumatologie
https://www.readbyqxmd.com/read/28536934/-off-label-biological-therapies-in-patients-with-large-vessel-vasculitis-and-or-polymyalgia-rheumatica-safety-and-efficacy-analysis-of-a-nationwide-german-registry-graid2
#18
J C Henes, H Schulze-Koops, M Witt, H P Tony, F Mueller, M Grunke, M Czihal, T Dörner, F Proft
OBJECTIVE: To evaluate the safety and clinical outcome of biological therapies in patients with large vessel vasculitis (LVV) or polymyalgia rheumatica (PMR) refractory to standard of care therapy in a real-life setting in Germany. METHODS: GRAID 2 (German Registry in Autoimmune Diseases 2) is a retrospective, noninterventional, multicenter registry collecting data from all patients with inflammatory rheumatic diseases refractory to conventional therapy treated with an initial off-label biological between August 2006 and December 2013...
May 23, 2017: Zeitschrift Für Rheumatologie
https://www.readbyqxmd.com/read/28536366/advances-in-the-use-of-regulatory-t-cells-for-the-prevention-and-therapy-of-graft-vs-host-disease
#19
REVIEW
Reshma Ramlal, Gerhard C Hildebrandt
Regulatory T (Tregs) cells play a crucial role in immunoregulation and promotion of immunological tolerance. Adoptive transfer of these cells has therefore been of interest in the field of bone marrow and solid organ transplantation, autoimmune diseases and allergy medicine. In bone marrow transplantation, Tregs play a pivotal role in the prevention of graft-verus-host disease (GvHD). This has generated interest in using adoptive Treg cellular therapy in the prevention and treatment of GvHD. There have been several barriers to the feasibility of Treg cellular therapy in the setting of hematopoietic stem cell transplantation (HSCT) which include low Treg concentration in peripheral blood, requiring expansion of the Treg population; instability of the expanded product with loss of FoxP3 expression; and issues related to the purity of the expanded product...
May 16, 2017: Biomedicines
https://www.readbyqxmd.com/read/28535791/clinical-outcomes-in-a-subpopulation-of-adults-with-morquio-a-syndrome-results-from-a-long-term-extension-study-of-elosulfase-alfa
#20
D Hughes, R Giugliani, N Guffon, S A Jones, K E Mengel, R Parini, R Matousek, S M Hawley, A Quartel
BACKGROUND: This post hoc subanalysis examined outcomes in adult patients with Morquio A (mucopolysaccharidosis IVA) who received enzyme replacement therapy (ERT) with elosulfase alfa over a 120-weeks period. Patients ≥18 years of age evaluated in an open-label, long-term extension study of elosulfase alfa (modified per protocol [MPP], n = 32; intent-to-treat [ITT], n = 37; MOR-005; NCT01415427) were compared with the ≥18-year-old untreated population with 2-years follow-up from a Morquio A natural history study (n = 10; MorCAP; NCT00787995)...
May 23, 2017: Orphanet Journal of Rare Diseases
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