Resultados de investigación

Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't;Comment in: Hemophilia Therapy--Navigating Speed Bumps on the Innovation Highway. [N Engl J Med. 2016], The development of neutralizing anti-factor VIII alloantibodies (inhibitors) in patients with severe hemophilia A may depend on the concentrate used for replacement therapy. We conducted a randomized trial to assess the incidence of factor VIII inhibitors among patients treated with plasma-derived factor VIII containing von Willebrand factor or recombinant factor VIII. Patients who met the eligibility criteria (male sex, age <6 years, severe hemophilia A, and no previous treatment with any factor VIII concentrate or only minimal treatment with blood components) were included from 42 sites. Of 303 patients screened, 264 underwent randomization and 251 were analyzed. Inhibitors developed in 76 patients, 50 of whom had high-titer inhibitors (≥5 Bethesda units). Inhibitors developed in 29 of the 125 patients treated with plasma-derived factor VIII (20 patients had high-titer inhibitors) and in 47 of the 126 patients treated with recombinant factor VIII (30 patients had high-titer inhibitors). The cumulative incidence of all inhibitors was 26.8% (95% confidence interval [CI], 18.4 to 35.2) with plasma-derived factor VIII and 44.5% (95% CI, 34.7 to 54.3) with recombinant factor VIII; the cumulative incidence of high-titer inhibitors was 18.6% (95% CI, 11.2 to 26.0) and 28.4% (95% CI, 19.6 to 37.2), respectively. In Cox regression models for the primary end point of all inhibitors, recombinant factor VIII was associated with an 87% higher incidence than plasma-derived factor VIII (hazard ratio, 1.87; 95% CI, 1.17 to 2.96). This association did not change in multivariable analysis. For high-titer inhibitors, the hazard ratio was 1.69 (95% CI, 0.96 to 2.98). When the analysis was restricted to recombinant factor VIII products other than second-generation full-length recombinant factor VIII, effect estimates remained similar for all inhibitors (hazard ratio, 1.98; 95% CI, 0.99 to 3.97) and high-titer inhibitors (hazard ratio, 2.59; 95% CI, 1.11 to 6.00). Patients treated with plasma-derived factor VIII containing von Willebrand factor had a lower incidence of inhibitors than those treated with recombinant factor VIII. (Funded by the Angelo Bianchi Bonomi Foundation and others; ClinicalTrials.gov number, NCT01064284; EudraCT number, 2009-011186-88.)., Si, 2016-11-26

Phosphatidylinositol 3-kinase (PI3K) pathway activation in preclinical models of breast cancer is associated with tumor growth and resistance to anticancer therapies, including paclitaxel. Effects of the pan-Class I PI3K inhibitor buparlisib (BKM120) appear synergistic with paclitaxel in preclinical and clinical models. BELLE-4 was a 1:1 randomized, double-blind, placebo-controlled, adaptive phase II/III study investigating the combination of buparlisib or placebo with paclitaxel in women with human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer with no prior chemotherapy for advanced disease. Patients were stratified by PI3K pathway activation and hormone receptor status. The primary endpoint was progression-free survival (PFS) in the full and PI3K pathway-activated populations. An adaptive interim analysis was planned following the phase II part of the study, after ≥125 PFS events had occurred in the full population, to decide whether the study would enter phase III (in the full or PI3K pathway-activated population) or be stopped for futility. As of August 2014, 416 patients were randomized to receive buparlisib (207) or placebo (209) with paclitaxel. At adaptive interim analysis, there was no improvement in PFS with buparlisib versus placebo in the full (median PFS 8.0 versus 9.2 months, hazard ratio [HR] 1.18), or PI3K pathway-activated population (median PFS 9.1 versus 9.2 months, HR 1.17). The study met protocol-specified criteria for futility in both populations, and phase III was not initiated. Median duration of study treatment exposure was 3.5 months in the buparlisib arm versus 4.6 months in the placebo arm. The most frequent adverse events with buparlisib plus paclitaxel (≥40% of patients) were diarrhea, alopecia, rash, nausea, and hyperglycemia. Addition of buparlisib to paclitaxel did not improve PFS in the full or PI3K pathway-activated study population. Consequently, the trial was stopped for futility at the end of phase II., Si

Presentación del documental "Paciente" en el Instituto Caro y Cuervo. Plano general sentados en butacas dando la espalda a la pantalla. De izquierda a derecha, Jorge Caballero, cineasta colombiano, autor de "Paciente"; e Iván Guarnizo, editor del documental.

Presentación del documental «Paciente» en el Instituto Caro y Cuervo. Plano medio de perfil, de izquierda a derecha, Jorge Caballero, cineasta colombiano, autor de «Paciente»; e Iván Guarnizo, editor del documental.

Presentación del documental "Paciente" en el Instituto Caro y Cuervo. Plano medio de perfil, de izquierda a derecha, Jorge Caballero, cineasta colombiano, autor de "Paciente"; e Iván Guarnizo, editor del documental.

Con motivo del Día Mundial de la Poesía el Instituto Cervantes organiza «Todas con Gloria. Homenaje a Gloria Fuertes», un acto dedicado a Gloria Fuertes en el año en que se conmemora el centenario de su nacimiento, reuniendo a varias poetas españolas e hispanoamericanas. Plano medio de Espido Freire, poeta española, en la Caja de las Letras del Instituto Cervantes.

Con motivo del Día Mundial de la Poesía el Instituto Cervantes organiza «Todas con Gloria. Homenaje a Gloria Fuertes», un acto dedicado a Gloria Fuertes en el año en que se conmemora el centenario de su nacimiento, reuniendo a varias poetas españolas e hispanoamericanas. Plano medio de Vanesa Pérez Sauquillo, poeta española, en la Caja de las Letras del Instituto Cervantes.

Con motivo del Día Mundial de la Poesía el Instituto Cervantes organiza «Todas con Gloria. Homenaje a Gloria Fuertes», un acto dedicado a Gloria Fuertes en el año en que se conmemora el centenario de su nacimiento, reuniendo a varias poetas españolas e hispanoamericanas. Plano medio de María Jesús Fuentes, poeta española, en la Caja de las Letras del Instituto Cervantes.

Con motivo del Día Mundial de la Poesía el Instituto Cervantes organiza «Todas con Gloria. Homenaje a Gloria Fuertes», un acto dedicado a Gloria Fuertes en el año en que se conmemora el centenario de su nacimiento, reuniendo a varias poetas españolas e hispanoamericanas. Plano medio de María Jesús Fuentes, poeta española, en la Caja de las Letras del Instituto Cervantes.

Con motivo del Día Mundial de la Poesía el Instituto Cervantes organiza «Todas con Gloria. Homenaje a Gloria Fuertes», un acto dedicado a Gloria Fuertes en el año en que se conmemora el centenario de su nacimiento, reuniendo a varias poetas españolas e hispanoamericanas. Plano medio de María Fernanda Santiago Bolaños, poeta española, en la Caja de las Letras del Instituto Cervantes.