Evolution du facteur XI au cours de la grossesse

BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

Hyperplaquettoses et protéase du facteur Von Willebrand

BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

A novel cholesteryl ester transfer protein promoter polymorphism (−971G/A) associated with plasma high-density lipoprotein cholesterol levels

International audienc

Macropinocytosis requires Gal-3 in a subset of patient-derived glioblastoma stem cells

Recently, we involved the carbohydrate-binding protein Galectin-3 (Gal-3) as a druggable target for KRAS-mutant-addicted lung and pancreatic cancers. Here, using glioblastoma patient-derived stem cells (GSCs), we identify and characterize a subset of Gal-3high glioblastoma (GBM) tumors mainly within the mesenchymal subtype that are addicted to Gal-3-mediated macropinocytosis. Using both genetic and pharmacologic inhibition of Gal-3, we showed a significant decrease of GSC macropinocytosis activity, cell survival and invasion, in vitro and in vivo. Mechanistically, we demonstrate that Gal-3 binds to RAB10, a member of the RAS superfamily of small GTPases, and β1 integrin, which are both required for macropinocytosis activity and cell survival. Finally, by defining a Gal-3/macropinocytosis molecular signature, we could predict sensitivity to this dependency pathway and provide proof-of-principle for innovative therapeutic strategies to exploit this Achilles’ heel for a significant and unique subset of GBM patients

Contaminação bacteriana em concentrados plaquetários: identificação, perfil de sensibilidade aos antimicrobianos e sepse associada à transfusão Bacterial contamination on platelet concentrates: identification, antimicrobial susceptibility profile and transfusion-related sepsis

INTRODUÇÃO: Devido à sepse bacteriana associada à transfusão de concentrados plaquetários (CPs) ter sérias consequências clínicas para os pacientes, alguns procedimentos têm sido incorporados na preparação e no controle de qualidade dos componentes sanguíneos para reduzir o risco da contaminação bacteriana. Este artigo descreve a prevalência da contaminação bacteriana dos CPs que foram transfundidos, o espectro bacteriano detectado com seu perfil de sensibilidade aos antimicrobianos e as reações transfusionais nos receptores. MÉTODOS: Um total de 292 CPs (278 randômicos e 14 por aférese), proveniente do Hemocentro do Estado do Rio Grande do Sul (HEMORGS) de Santa Maria foi testado. As quantidades de 100&#956;L e 200&#956;L foram coletadas da porção tubular da bolsa de plaquetas e semeadas utilizando dois tipos de metodologias. RESULTADOS: Em cinco unidades(1,7%; 5/292) foram isoladas bactérias pela metodologia qualitativa e apenas uma pela quantitativa. Staphylococcus epidermidis foi o microrganismo identificado em todas as amostras. Dois pacientes apresentaram sepse associada à transfusão com desfecho fatal. CONCLUSÕES: A contaminação bacteriana pelas transfusões de CPs constitui-se num importante problema de saúde pública devido a sua associação com altas taxas de morbidade e mortalidade. Neste estudo, somente microrganismos gram-positivos foram isolados sendo que nenhuma amostra obtida por aférese apresentou contaminação.<br>INTRODUCTION: Bacterial sepsis associated with the transfusion of platelet concentrates (PCs) results in serious clinical implications for patients. Given these implications, certain procedures have been integrated into the preparation and quality control of blood components to reduce the risk of bacterial contamination. This article describes the prevalence of bacterial contamination on transfused PCs, the bacterial spectrum detected and their antimicrobial susceptibility profile and transfusion reactions in receptors. METHODS: A total of 292 PCs (278 random and 14 per apheresis) from the Blood Center of the State of Rio Grande do Sul (HEMORGS), located in the city of Santa Maria, were tested. Quantities of 100&#956;L and 200&#956;L were collected from platelet bag tubing and seeded using two methodologies. RESULTS: Using the qualitative methodology, bacteria were isolated in five units (1.7%; 5/292), while only one was isolated using the quantitative methodology. Staphylococcus epidermidis was the microorganism identified in all samples. Two patients died of transfusion-related sepsis. CONCLUSIONS: Bacterial contamination due to PC transfusion is considered a major public health problem due to its association with high rates of morbidity and mortality. In this study only gram-positive microorganisms were isolated and none of the samples obtained by apheresis presented contamination

Immunosuppression for acquired hemophilia A: results from the European Acquired Haemophilia Registry (EACH2)

Acquired hemophilia A (AHA) is an autoimmune disease caused by an autoantibody to factor VIII. Patients are at risk of severe and fatal hemorrhage until the inhibitor is eradicated, and guidelines recommend immunosuppression as soon as the diagnosis has been made. The optimal immunosuppressive regimen is unclear; therefore, data from 331 patients entered into the prospective EACH2 registry were analyzed. Steroids combined with cyclophosphamide resulted in more stable complete remission (70%), defined as inhibitor undetectable, factor VIII more than 70 IU/dL and immunosuppression stopped, than steroids alone (48%) or rituximab-based regimens (59%). Propensity score-matched analysis controlling for age, sex, factor VIII level, inhibitor titer, and underlying etiology confirmed that stable remission was more likely with steroids and cyclophosphamide than steroids alone (odds ratio = 3.25; 95% CI, 1.51-6.96; P <.003). The median time to complete remission was approximately 5 weeks for steroids with or without cyclo-phosphamide; rituximab-based regimens required approximately twice as long. Immunoglobulin administration did not improve outcome. Second-line therapy was successful in approximately 60% of cases that failed first- line therapy. Outcome was not affected by the choice of first-line therapy. The likelihood of achieving stable remission was not affected by underlying etiology but was influenced by the presenting inhibitor titer and FVIII level. (Blood. 2012;120(1):47-55