29 research outputs found

    Efficacy of short-course colchicine treatment in hospitalized patients with moderate to severe COVID-19 pneumonia and hyperinflammation: a randomized clinical trial

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    Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si lo hubiere, y los autores pertenecientes a la UAMSome patients with COVID-19 pneumonia develop an associated cytokine storm syndrome that aggravates the pulmonary disease. These patients may benefit of anti-inflammatory treatment. The role of colchicine in hospitalized patients with COVID-19 pneumonia and established hyperinflammation remains unexplored. In a prospective, randomized controlled, observer-blinded endpoint, investigator-initiated trial, 240 hospitalized patients with COVID-19 pneumonia and established hyperinflammation were randomly allocated to receive oral colchicine or not. The primary efficacy outcome measure was a composite of non-invasive mechanical ventilation (CPAP or BiPAP), admission to the intensive care unit, invasive mechanical ventilation requirement or death. The composite primary outcome occurred in 19.3% of the total study population. The composite primary outcome was similar in the two arms (17% in colchicine group vs. 20.8% in the control group; p = 0.533) and the same applied to each of its individual components. Most patients received steroids (98%) and heparin (99%), with similar doses in both groups. In this trial, including adult patients with COVID-19 pneumonia and associated hyperinflammation, no clinical benefit was observed with short-course colchicine treatment beyond standard care regarding the combined outcome measurement of CPAP/BiPAP use, ICU admission, invasive mechanical ventilation or deat

    Low-count monoclonal B-cell lymphocytosis persists after seven years of follow up and is associated with a poorer outcome

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    [EN]Low-count monoclonal B-cell lymphocytosis is defined by the presence of very low numbers of circulating clonal B cells, usually phenotypically similar to chronic lymphocytic leukemia cells, whose biological and clinical significance remains elusive. Herein, we re-evaluated 65/91 low-count monoclonal B-cell lymphocytosis cases (54 chronic lymphocytic leukemia-like and 11 non-chronic lymphocytic leukemialike) followed-up for a median of seven years, using high-sensitivity flow cytometry and interphase fluorescence in situ hybridization. Overall, the clone size significantly increased in 69% of low-count monoclonal B-cell lymphocytosis cases, but only one subject progressed to high-count monoclonal B-cell lymphocytosis. In parallel, the frequency of cytogenetic alterations increased over time (32% vs. 61% of cases, respectively). The absolute number of the major T-cell and natural killer cell populations also increased, but only among chronic lymphocytic leukemia-like cases with increased clone size vs. age- and sex-matched controls. Although progression to chronic lymphocytic leukemia was not observed, the overall survival of low-count monoclonal B-cell lymphocytosis individuals was significantly reduced vs. non-monoclonal Bcell lymphocytosis controls (P=0.03) plus the general population from the same region (P≤0.001), particularly among females (P=0.01); infection and cancer were the main causes of death in low-count monoclonal B-cell lymphocytosis. In summary, despite the fact that mid-term progression from low-count monoclonal B-cell lymphocytosis to high-count monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia appears to be unlikely, these clones persist at increased numbers, usually carrying more genetic alterations, and might thus be a marker of an impaired immune system indirectly associated with a poorer outcome, particularly among females

    Peripheral T-cell lymphoma: Molecular profiling recognizes subclasses and identifies prognostic markers

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    Peripheral T-cell lymphoma (PTCL) is a clinically aggressive disease, with a poor response to therapy and a low overall survival rate of approximately 30% after 5 years. We have analyzed a series of 105 cases with a diagnosis of PTCL using a customized NanoString platform (NanoString Technologies, Seattle, WA) that includes 208 genes associated with T-cell differentiation, oncogenes and tumor suppressor genes, deregulated pathways, and stromal cell subpopulations. A comparative analysis of the various histological types of PTCL (angioimmunoblastic T-cell lymphoma [AITL]; PTCL with T follicular helper [TFH] phenotype; PTCL not otherwise specified [NOS]) showed that specific sets of genes were associated with each of the diagnoses. These included TFH markers, cytotoxic markers, and genes whose expression was a surrogate for specific cellular subpopulations, including follicular dendritic cells, mast cells, and genes belonging to precise survival (NF-κB) and other pathways. Furthermore, the mutational profile was analyzed using a custom panel that targeted 62 genes in 76 cases distributed in AITL, PTCL-TFH, and PTCL-NOS. The main differences among the 3 nodal PTCL classes involved the RHOAG17V mutations (P < .0001), which were approximately twice as frequent in AITL (34.09%) as in PTCL-TFH (16.66%) cases but were not detected in PTCL-NOS. A multivariate analysis identified gene sets that allowed the series of cases to be stratified into different risk groups. This study supports and validates the current division of PTCL into these 3 categories, identifies sets of markers that can be used for a more precise diagnosis, and recognizes the expression of B-cell genes as an IPI-independent prognostic factor for AITL

    Basophil-lineage commitment in acute promyelocytic leukemia predicts for severe bleeding after starting therapy

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    Severe hemorrhagic events occur in a significant fraction of acute promyelocytic leukemia patients, either at presentation and/or early after starting therapy, leading to treatment failure and early deaths. However, identification of independent predictors for high-risk of severe bleeding at diagnosis, remains a challenge. Here, we investigated the immunophenotype of bone marrow leukemic cells from 109 newly diagnosed acute promyelocytic leukemia patients, particularly focusing on the identification of basophil-related features, and their potential association with severe bleeding episodes and patient overall survival. From all phenotypes investigated on leukemic cells, expression of the CD203c and/or CD22 basophil-associated markers showed the strongest association with the occurrence and severity of bleeding (p ≤ 0.007); moreover, aberrant expression of CD7, coexpression of CD34+/CD7+ and lack of CD71 was also more frequently found among patients with (mild and severe) bleeding at baseline and/or after starting treatment (p ≤ 0.009). Multivariate analysis showed that CD203c expression (hazard ratio: 26.4; p = 0.003) and older age (hazard ratio: 5.4; p = 0.03) were the best independent predictors for cumulative incidence of severe bleeding after starting therapy. In addition, CD203c expression on leukemic cells (hazard ratio: 4.4; p = 0.01), low fibrinogen levels (hazard ratio: 8.8; p = 0.001), older age (hazard ratio: 9.0; p = 0.002), and high leukocyte count (hazard ratio: 5.6; p = 0.02) were the most informative independent predictors for overall survival. In summary, our results show that the presence of basophil-associated phenotypic characteristics on leukemic cells from acute promyelocytic leukemia patients at diagnosis is a powerful independent predictor for severe bleeding and overall survival, which might contribute in the future to (early) risk-adapted therapy decisions.This work was supported by the Fundación Científica de la Asociación Española Contra el Cáncer (AECC, Madrid, Spain) and the Fundación Rafael del Pino (Madrid, Spain) and both CIBERONC (CB16/12/00400, CB16/12/00233, CB16/12/00480) and grant PI16/00787 from Instituto de Salud Carlos III (Ministerio de Economía y Competitividad, Madrid, Spain)

    Marco activo de recursos de innovación docente: Madrid

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    Una guía de espacios e instituciones para actividades educativas complementarias en enseñanza secundaria y Formación Profesional

    Optimizando el abordaje del asma bronquial

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    196 páginas.El asma bronquial es una enfermedad crónica que afecta a millones de personas en todo el mundo, siendo la primera enfermedad crónica en la edad pediátrica. Se caracteriza por una inflamación de las vías respiratorias que conduce a la obstrucción del flujo de aire y a la dificultad para respirar. El asma es una enfermedad que afecta a la calidad de vida de las personas que la padece y puede ser una condición potencialmente mortal si no se trata adecuadamente. A pesar de los avances significativos en el tratamiento del asma en las últimas décadas, todavía hay muchas personas que no logran controlar adecuadamente su enfermedad. Muchos pacientes continúan experimentando síntomas a pesar de tomar medicamentos y seguir las recomendaciones médicas. Esto puede deberse a multitud de factores, como una mala adherencia al tratamiento, una falta de comprensión de la enfermedad o una falta de seguimiento por parte de los profesionales sanitarios. Una formación adecuada de los profesionales sanitarios implicados en la atención al paciente asmático (Médicos de Familia, Médicos de urgencias, Pediatras, Neumólogos, Alergólogos, etc) ayudará a establecer una estrategia de tratamiento eficaz y eficiente que pueda traducirse en una mejora del control y por tanto de la calidad de vida de nuestros pacientes. En este libro, se abordan las últimas recomendaciones basadas en la evidencia para el diagnóstico, la evaluación y el tratamiento del asma, con un enfoque multidisciplinar. A lo largo de sus diez capítulos, se describe como llegar a establecer un diagnostico correcto del asma (interpretación de pruebas alérgicas, espirometria y técnicas de imagen), uso adecuado de los distintos dispositivos de inhalación, las peculiaridades del tratamiento en el embarazo y en la edad pediátrica, el importante papel de la inmunoterapia en el tratamiento del asma alérgica, así de como debemos actuar ante una crisis de asma o cuales son los avances actuales y futuros en el asma grave o de difícil control
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