Mortalidad a corto plazo en los pacientes con insuficiencia cardiaca en estadios finales

Objectives: This study is aimed at analyzing the impact of the main factors contributing to short and long-term mortality in patients at final stages of heart failure (HF). Setting: Patients attended at any of the 279 primary health care centers belonging to the Institut Català de la Salut, in Catalonia (Spain). Participants: Patients with Advanced HF. Design: Multicenter cohort study including 1148 HF patients followed for one-year after reaching New York Heart Association (NYHA) IV. Main measurements: The primary outcome was all-cause mortality. Multivariate logistic regression models were performed to assess the outcomes at 1, 3, 6, and 12 months. Results: Mean age of patients was 82 (SD 9) years and women represented 61.7%. A total of 135 (11.8%) and 397 (34.6%) patients died three months and one year after inclusion, respectively. Male gender, age, and decreased body mass index were associated with higher mortality at three, six and twelve months. In addition, low systolic blood pressure levels, severe reduction in glomerular filtration, malignancy, and higher doses of loop diuretics were related to higher mortality from 6 to 12 months. The most important risk factor over the whole period was presenting a body mass index lower than 20 kg/m2 (three months OR 3.06, 95% CI: 1.58–5.92; six months OR 4.42, 95% CI: 2.08–9.38; and 12 months OR 3.68, 95% CI: 1.76–7.69). Conclusions: We may conclude that male, age, and decreased body mass index determined higher short-term mortality in NYHA IV. In addition, low systolic blood pressure, reduced glomerular filtration, malignancy, and higher doses of loop diuretics contribute to increasing the risk of mortality at medium and long-term. Such variables are easily measurable and can help to decide the best way to face the most advances stages of the disease.Objetivos: Analizar los factores que contribuyen a la mortalidad de pacientes en las etapas finales de la insuficiencia cardiaca (IC). Ámbito: Centros de atención primaria del Institut Català de la Salut, Cataluña, España. Participantes: Pacientes con IC avanzada. Diseño: Estudio de cohortes multicéntrico. Incluyó 1.148 pacientes de IC seguidos durante un año tras el registro de estadio funcional NYHA IV. Mediciones principales: El resultado principal fue la mortalidad por todas las causas. Se realizaron modelos de regresión logística multivariada (1, 3, 6 y 12 meses). Resultados: Edad media 82 años (DE 9), las mujeres representaron el 61,7%. Un total de 135 (11,8%) y 397 (34,6%) pacientes murieron 3 meses y un año después de su inclusión. El sexo masculino, la edad y el índice de masa corporal (IMC) < 20 kg/m2 se asociaron con una mayor mortalidad a los 3, 6 y 12 meses. Bajos niveles de presión arterial sistólica, reducción severa en el filtrado glomerular, malignidad y dosis altas de diuréticos fueron relacionadas con una mortalidad más alta de 6 a 12 meses. El factor de riesgo más importante fue un IMC < 20 kg/m2 (3 meses OR: 3,06; IC 95%: 1,58-5,92; 6 meses OR: 4,42; IC 95%: 2,08-9,38 y 12 meses OR: 3,68; IC 95%: 1,76-7,69). Conclusiones: Los varones, la edad avanzada y un IMC disminuido determinaron una mortalidad a corto plazo más alta en pacientes NYHA IV. La baja presión arterial sistólica, la reducción del filtrado glomerular, la malignidad y las dosis altas de diuréticos aumentan el riesgo de mortalidad a medio y largo plazo. Estas variables son fáciles de obtener, y pueden ayudar a decidir las mejores estrategias para afrontar los estadios más avanzados de la enfermedad

La reforma del aborto en España : perspectivas de un debate (re)emergente

Pertenece a la colección Religión, Género y Sexualidad / dirigida por Juan M. Vaggione ; v.8De manera creciente, desde finales del 2013 el escenario español visibiliza no sólo las marchas y contramarchas en relación a derechos sexuales y reproductivos sino cómo las disputas se renuevan poniendo de relieve la necesidad de reflexionar sobre las dimensiones que se ponen en juego en un debate sociopolítico contemporáneo. Los trabajos que integran este libro, surgen al calor del debate público abierto en España en torno a la reforma de los marcos regulatorios vigentes sobre salud reproductiva e interrupción voluntaria del embarazo. Discusiones que demandan marcos analíticos que permitan pensar estos procesos considerando tanto sus particularidades coyunturales como sus dimensiones comunes. Los análisis que integran este libro abordan desde diferentes perspectivas, diferentes dimensiones de un debate que no sólo involucra la norma explícita formal (la ley) sino lo que ese mismo debate promueve como sancionable, cuestionable. El contexto español sirve, de esta manera, como disparador de reflexiones que abren el panorama privilegiando miradas múltiples. La participación de personas provenientes de distintas disciplinas enriquece la conexión entre los trabajos poniendo de relieve la necesidad de reflexiones críticas constantes y alertando sobre la necesaria recreación de la praxis política, en particular cuando visiones más restrictivas buscan impactar sobre los marcos legales vigentes, opacando las relaciones de poder y subordinación en las que el derecho a decidir de las mujeres se actualiza como operación de control

BRCA1 and BRCA2 mutations in males with familial breast and ovarian cancer syndrome. Results of a Spanish multicenter study

Producción CientíficaMale breast cancer (MBC) is a rare disease that represents <1 % of all breast cancers (BCs). We analyze the results of a multicenter study performed in Spanish familial MBC including family history of hereditary breast and ovarian cancer syndrome (HBOCS) and clinicopathological features. We also study the relationship between BRCA1/BRCA2 mutational status in male relatives affected with cancer (MAC) and, family history and tumor types. The study included 312 men index cases with family history of HBOCS and 61 MAC BRCA1/2 mutation-carriers. Family history, histological grade (HG), clinicopathological and immunohistochemistry data were collected. BRCA1/2 mutation analyses were performed by direct sequencing or screening methods and the large rearrangements by multiplex ligation dependent probe amplification. We found 49 mutation-carriers (15.7 %), 95.9 % with BRCA2 mutations. BRCA2 mutation-carriers were associated with families with at least one MBC and one BC in female (type II; p = 0.05). Strong association were found between the presence of pathogenic mutations in MBCs and the advanced HG (p = 0.003). c.658_659delTG, c.2808_2811delACAA, c.6275_6276delTT and c.9026_9030delATCAT were the most prevalent mutations. In 61 MAC we found 20 mutations in BRCA1 and 41 in BRCA2. For MAC we show that mutational status was differentially associated with family history (p = 0.018) and tumor type, being BRCA2 mutations linked with BC and prostatic cancer (p = 0.018). MBC caused by BRCA1/2 mutations define two types of MBCs. The most frequent caused by BRCA2 mutation linked to type II families and the rarest one attributed to BRCA1 mutation. Tumor associated with MAC suggest that only BRCA2 mutations have to do with a specific type of cancer (BC and prostatic cancer); but the linkage to tumors is questionable for BRCA1 mutations

The Mutational Landscape of Acute Myeloid Leukaemia Predicts Responses and Outcomes in Elderly Patients from the PETHEMA-FLUGAZA Phase 3 Clinical Trial

Mutational profiling using a custom 43-gene next-generation sequencing panel revealed that patients with mutated DNMT3A or EZH2, or an increase in TET2 VAF and lower TP53 VAF showed a higher overall response. NRAS and TP53 variants were associated with shorter overall survival (OS), whereas only mutated BCOR was associated with a shorter relapse-free survival (RFS). Subgroup analyses of OS according to biological and genomic characteristics showed that patients with low-intermediate cytogenetic risk and mutated NRAS benefited from azacytidine therapy and patients with mutated TP53 showed a better RFS in the azacytidine arm. In conclusion, differential mutational profiling might anticipate the outcomes of first-line treatment choices (AZA or FLUGA) in older patients with AML. We sought to predict treatment responses and outcomes in older patients with newly diagnosed acute myeloid leukemia (AML) from our FLUGAZA phase III clinical trial (PETHEMA group) based on mutational status, comparing azacytidine (AZA) with fludarabine plus low-dose cytarabine (FLUGA). Mutational profiling using a custom 43-gene next-generation sequencing panel revealed differences in profiles between older and younger patients, and several prognostic markers that were useful in young patients were ineffective in older patients. We examined the associations between variables and overall responses at the end of the third cycle. Patients with mutated DNMT3A or EZH2 were shown to benefit from azacytidine in the treatment-adjusted subgroup analysis. An analysis of the associations with tumor burden using variant allele frequency (VAF) quantification showed that a higher overall response was associated with an increase in TET2 VAF (odds ratio (OR), 1.014; p = 0.030) and lower TP53 VAF (OR, 0.981; p = 0.003). In the treatment-adjusted multivariate survival analyses, only the NRAS (hazard ratio (HR), 1.9, p = 0.005) and TP53 (HR, 2.6, p = 9.8 × 10 −7) variants were associated with shorter overall survival (OS), whereas only mutated BCOR (HR, 3.6, p = 0.0003) was associated with a shorter relapse-free survival (RFS). Subgroup analyses of OS according to biological and genomic characteristics showed that patients with low-intermediate cytogenetic risk (HR, 1.51, p = 0.045) and mutated NRAS (HR, 3.66, p = 0.047) benefited from azacytidine therapy. In the subgroup analyses, patients with mutated TP53 (HR, 4.71, p = 0.009) showed a better RFS in the azacytidine arm. In conclusion, differential mutational profiling might anticipate the outcomes of first-line treatment choices (AZA or FLUGA) in older patients with AML. The study is registered at ClinicalTrials.gov as NCT0231913

Genetic manipulation of LKB1 elicits lethal metastatic prostate cancer

Gene dosage is a key defining factor to understand cancer pathogenesis and progression, which requires the development of experimental models that aid better deconstruction of the disease. Here, we model an aggressive form of prostate cancer and show the unconventional association of LKB1 dosage to prostate tumorigenesis. Whereas loss of Lkbl alone in the murine prostate epithelium was inconsequential for tumorigenesis, its combination with an oncogenic insult, illustrated by Pten heterozygosity, elicited lethal metastatic prostate cancer. Despite the low frequency of LKB1 deletion in patients, this event was significantly enriched in lung metastasis. Modeling the role of LKB1 in cellular systems revealed that the residual activity retained in a reported kinase-dead form, LKB1(K781), was sufficient to hamper tumor aggressiveness and metastatic dissemination. Our data suggest that prostate cells can function normally with low activity of LKB1, whereas its complete absence influences prostate cancer pathogenesis and dissemination

Ludificación de la Historia de Veterinaria: Fase II

En esta convocatoria se ha aprovechado la experiencia del anterior proyecto y se ha continuado con la metodología de la ludificación o gamificación como herramienta de aprendizaje mejorando y adaptando más aun la metodología a los fines de docencia del grado. Se ha logrado incrementar la motivación entre el alumnado y se ha añadido un nuevo componente: el efecto integrador o identitario del alumnado, profesorado y PAS con la profesión y el centro. Los productos obtenidos como material audiovisual y textos y las representaciones se han expuesto en actos conmemorativos o celebraciones del centro. Por otro lado se ha incrementado el repositorio de material didáctico que con cada proyecto se elabora. En este nuevo proyecto se han realizado interpretaciones histórico-teatrales de personajes relevantes en la historia de la veterinaria, realizadas por los propios alumnos matriculados y profesores, abordando distintas problemáticas de profesionales o en diferentes períodos históricos. Entre los productos elaborados están los textos con los guiones elaborados, 9 videos con escenificaciones y 20 breves presentaciones de personajes. Otro de los productos finales en formato de video de 6,19 minutos de duración se ha presentado ante la comunidad universitaria en la Gala atrévete de la Facultad de Veterinaria de 2019, ante más de doscientos alumnos y profesores. Los productos y el proyecto han sido presentados dentro de una comunicación oral en el XXIV Congreso Nacional y XV Iberoamericano de Historia de la Veterinaria que tuvo lugar en Almería del 26 al 28 de octubre de 2018. El impacto del proyecto se ha podido verificar a lo largo de los meses de escenificación por el nivel de actividad de las redes sociales entre los alumnos y la asistencia de más profesores y alumnos incluso no involucrados, con deseo de aprender y ver esta nueva herramienta docente

Provirus reactivation is impaired in HIV-1 infected individuals on treatment with dasatinib and antiretroviral therapy

The latent viral reservoir formed by HIV-1, mainly in CD4 + T cells, is responsible for the failure of antiretroviral therapy (ART) to achieve a complete elimination of the virus in infected individuals. We previously determined that CD4 + T cells from individuals with chronic myeloid leukemia (CML) on treatment with dasatinib are resistant to HIV-1 infection ex vivo. The main mechanism for this antiviral effect is the preservation of SAMHD1 activity. In this study, we aimed to evaluate the impact of dasatinib on the viral reservoir of HIV-infected individuals with CML who were on simultaneous treatment with ART and dasatinib. Due to the low estimated incidence of HIV-1 infection and CML (1:65,000), three male individuals were recruited in Spain and Germany. These individuals had been on treatment with standard ART and dasatinib for median 1.3 years (IQR 1.3-5.3 years). Reservoir size and composition in PBMCs from these individuals was analyzed in comparison with HIV-infected individuals on triple ART regimen and undetectable viremia. The frequency of latently infected cells was reduced more than 5-fold in these individuals. The reactivation of proviruses from these cells was reduced more than 4-fold and, upon activation, SAMHD1 phosphorylation was reduced 40-fold. Plasma levels of the homeostatic cytokine IL-7 and CD4 effector subpopulations TEM and TEMRA in peripheral blood were also reduced. Therefore, treatment of HIV-infected individuals with dasatinib as adjuvant of ART could disturb the reservoir reactivation and reseeding, which might have a beneficial impact to reduce its size

Current international projects in the Duero and Miño-Sil basins

[EN] This paper summarizes the research work that is being carried out within the framework of three international projects with a lifetime between 2022 and 2026: (1) LIFE-IP-Duero; (2) Supporting stakeholders for adaptive, resilience and sustainable water management; (3) IGCP- 730. (1) and (2) are developed in the Duero river basin and are funded by the European Commission meanwhile (3) is being developed in the Duero and Miño-Sil basins and is funded by the International Geosciences Programme (IGCP) of UNESCO.Peer reviewe

Inappropriate antibiotic use in the COVID-19 era: Factors associated with inappropriate prescribing and secondary complications. Analysis of the registry SEMI-COVID

Background: Most patients with COVID-19 receive antibiotics despite the fact that bacterial co-infections are rare. This can lead to increased complications, including antibacterial resistance. We aim to analyze risk factors for inappropriate antibiotic prescription in these patients and describe possible complications arising from their use. Methods: The SEMI-COVID-19 Registry is a multicenter, retrospective patient cohort. Patients with antibiotic were divided into two groups according to appropriate or inappropriate prescription, depending on whether the patient fulfill any criteria for its use. Comparison was made by means of multilevel logistic regression analysis. Possible complications of antibiotic use were also identified. Results: Out of 13,932 patients, 3047 (21.6%) were prescribed no antibiotics, 6116 (43.9%) were appropriately prescribed antibiotics, and 4769 (34.2%) were inappropriately prescribed antibiotics. The following were independent factors of inappropriate prescription: February-March 2020 admission (OR 1.54, 95%CI 1.18-2.00), age (OR 0.98, 95%CI 0.97-0.99), absence of comorbidity (OR 1.43, 95%CI 1.05-1.94), dry cough (OR 2.51, 95%CI 1.94-3.26), fever (OR 1.33, 95%CI 1.13-1.56), dyspnea (OR 1.31, 95%CI 1.04-1.69), flu-like symptoms (OR 2.70, 95%CI 1.75-4.17), and elevated C-reactive protein levels (OR 1.01 for each mg/L increase, 95% CI 1.00-1.01). Adverse drug reactions were more frequent in patients who received ANTIBIOTIC (4.9% vs 2.7%, p < .001). Conclusion: The inappropriate use of antibiotics was very frequent in COVID-19 patients and entailed an increased risk of adverse reactions. It is crucial to define criteria for their use in these patients. Knowledge of the factors associated with inappropriate prescribing can be helpful