Genetic profile in patients with complicated acute aortic syndrome: the GEN-AOR study.

INTRODUCTION AND OBJECTIVES: Genetic testing is becoming increasingly important for diagnosis and personalized treatments in aortopathies. Here, we aimed to genetically diagnose a group of acute aortic syndrome (AAS) patients consecutively admitted to an intensive care unit and to explore the clinical usefulness of AAS-associated variants during treatment decision-making and family traceability. METHODS: We applied targeted next-generation sequencing, covering 42 aortic diseases genes in AAS patients with no signs consistent with syndromic conditions. Detected variants were segregated by Sanger sequencing in available family members. Demographic features, risk factors and clinical symptoms were statistically analyzed by Fisher or Fisher-Freeman-Halton Exact tests, to assess their relationship with genetic results. RESULTS: Analysis of next-generation sequencing data in 73 AAS patients led to the detection of 34 heterozygous candidate variants in 14 different genes in 32 patients. Family screening was performed in 31 relatives belonging to 9 families. We found 13 relatives harboring the family variant, of which 10 showed a genotype compatible with the occurrence of AAS. Statistical tests revealed that the factors associated with a positive genetic diagnosis were the absence of hypertension, lower age, family history of AAS and absence of pain. CONCLUSIONS: Our findings broaden the spectrum of the genetic background for AAS. In addition, both index patients and studied relatives benefited from the results obtained, establishing the most appropriate level of surveillance for each group. Finally, this strategy could be reinforced by the use of stastistically significant clinical features as a predictive tool for the hereditary character of AAS. CLINICALTRIALS: gov (Identifier: NCT04751058).

Científicos e intelectuales, una nueva cultura política: José Cuatrecasas y las colecciones de flora tropical / Scientists and intellectuals, a new political culture: José Cuatrecasas and the collections of tropical flora

Este trabajo quiere mostrar una faceta del papel desempeñado por el coleccionismo y las colecciones científicas en la formación de los naturalistas durante la Edad de Plata de la ciencia española. El objetivo es evidenciar que la Junta para Ampliación de Estudios, principal institución que impulsó ese proyecto, aspiraba a crear intelectuales con capacidad de participar en la gobernanza del país (una nueva cultura política). La JAE encarnó un proyecto científico racionalista que se oponía a las visiones más conservadoras, defensoras de una ciencia católica, en una lucha que no se restringía a la ciencia, sino que alcanzaba lo social, lo político y lo cultural. Para ello recurrimos a la biografía del botánico José Cuatrecasas partiendo del enfoque de una historia sociocultural de la ciencia y una historia de las ideas

This work aims to show a piece of the important role that collecting and scientific collections played in the training to become naturalist during the Silver Age of Spanish science (1900-1936). It attempts to show that the Junta para Ampliación de Estudios (JAE), the main institution that promoted such a modern scientific project, aspired to create an intellectual elite with the capacity to participate in the governance of the State (a new political culture). The JAE incarnated a rationalist scientific model that opposed the ultraconservative positions, which were defenders of a Catholic science. Both of them were involved in a struggle that was not only restricted to science, but it reached all social, political and cultural aspects of national living. This article takes the biography of the botanic José Cuatrecasas as starting point and its analysis will be processed from the sociocultural History of Science and the History of Ideas

Adequate antibiotic therapy prior to ICU admission in patients with severe sepsis and septic shock reduces hospital mortality.

INTRODUCTION: In patients with severe sepsis and septic shock as cause of Intensive Care Unit (ICU) admission, we analyze the impact on mortality of adequate antimicrobial therapy initiated before ICU admission. METHODS: We conducted a prospective observational study enrolling patients admitted to the ICU with severe sepsis or septic shock from January 2008 to September 2013. The primary end-point was in-hospital mortality. We considered two groups for comparisons: patients who received adequate antibiotic treatment before or after the admission to the ICU. RESULTS: A total of 926 septic patients were admitted to ICU, and 638 (68.8%) had available microbiological isolation: 444 (69.6%) received adequate empirical antimicrobial treatment prior to ICU and 194 (30.4%) after admission. Global hospital mortality in patients that received treatment before ICU admission, between 0-6h ICU, 6-12h ICU, 12-24h ICU and after 24 hours since ICU admission were 31.3, 53.2, 57.1, 50 and 50.8% (p<0.001). The multivariate analysis showed that urinary focus (odds ratio (OR) 0.20; 0.09-0.42; p<0.001) and adequate treatment prior to ICU admission (OR 0.37; 0.24-0.56; p<0.001) were protective factors whereas APACHE II score (OR 1.10; 1.07-1.14; p<0.001), septic shock (OR 2.47; 1.57-3.87; p<0.001), respiratory source (OR 1.91; 1.12-3.21; p=0.016), cirrhosis (OR 3.74; 1.60-8.76; p=0.002) and malignancy (OR 1.65; 1.02-2.70; p=0.042) were variables independently associated with in-hospital mortality. Adequate treatment prior to ICU was a protective factor for mortality in patients with severe sepsis (n=236) or in septic shock (n=402). CONCLUSIONS: The administration of adequate antimicrobial therapy before ICU admission is decisive for the survival of patients with severe sepsis and septic shock. Our efforts should be directed to assure the correct administration antibiotics before ICU admission in patients with sepsis.

Optimum treatment strategies for carbapenem-resistant Acinetobacter baumannii bacteremia.

Carbapenem-resistant Acinetobacter baumannii (CRAB) constitutes an increasing problem worldwide. CRAB bacteremia is associated with a high fatality rate and its optimal treatment has not been established. Early institution of appropriate therapy is shown to improve survival of patients with CRAB bloodstream infection. Regrettably, treatment options are limited. Little information exists about the efficacy of sulbactam for the treatment of CRAB bacteremia. Colistin and tigecycline possess good in vitro activity and represent in many cases the only therapeutic options although clinical data are scarce. The need for a loading dose of colistin has been recently demonstrated to rapidly achieve therapeutic levels. The use of combination therapy is also a matter of debate but current evidence do not support its routine use.

Una escuela, dos laboratorios: neurociencias en la Junta para Ampliación de Estudios / One School, two Laboratories: neurosciences in the Junta para Ampliación de Estudios

El Laboratorio de Histopatología del sistema nervioso y el Laboratorio de Fisiología cerebral fueron creados por la Junta para Ampliación de Estudios e Investigaciones Científicas -JAE- durante el primer tercio del siglo XX con el objeto de consolidar una medicina científica experimental que necesitaba del apoyo estatal para garantizar su desarrollo. Desde la fundación del Laboratorio de Investigaciones Biológicas de Santiago Ramón y Cajal, en 1900, los trabajos experimentales tenían un escenario privilegiado en el que formar una escuela de investigadores. El nacimiento de la JAE garantizó y ensanchó la práctica de la medicina experimental. La llegada de Nicolás Achúcarro al laboratorio de Cajal trajo un renovado interés por la anatomía patológica en la escuela histológica española, que pronto cosechó notables resultados. Esta nueva línea de investigación maduró de la mano de los dos discípulos herederos de Achúcarro, el histopatólogo Pío del Río-Hortega, cuyos descubrimientos enriquecieron y completaron el legado de Santiago Ramón y Cajal, y el psiquiatra Gonzalo Rodríguez Lafora, cuyos trabajos sobre fisiología cerebral encontraron aplicación en la psiquiatría clínica. Ambos representan un ejemplo paradigmático de la forma cómo la biología ha experimentado sus mayores progresos a lo largo del siglo XX, partiendo de un dominio técnico que permite llevar a cabo avances significativos en la investigación. Los laboratorios de Río-Hortega y Rodríguez Lafora fueron así capaces de ensanchar los trabajos de sus maestros (AU)

The Laboratory of Histopathology of the Nervous System and the Laboratory of Brain Physiology were created by the Junta para Ampliación de Estudios e Investigaciones Científicas -JAE- in the first third of the twentieth century in order to consolidate a scientific experimental Medicine which needed the State’s support to ensure its development. Since the foundation of the Santiago Ramón y Cajal’s Laboratory for Biological Research, in 1900, experimental works could be undertaken in a privileged background where a school of researchers could be formed. The birth of the JAE enhanced the practice of experimental Medicine. The arrival of Nicolás Achúcarro to Cajal’s Laboratory caused the rising of a renewed interest in Pathological Histology inside the histological Spanish school, which was able to achieve interesting results in a short time. This new line of research grew with Achúcarro’s disciples, specially the histopathologist Pío del Río- Hortega, whose findings continued Santiago Ramón y Cajal’s legacy, and the psychiatrist Gonzalo Rodríguez Lafora, whose works on brain physiology were used in clinical psychiatry. Both of them incarnate the way how biology has accomplished its greatest progress during the twentieth century, starting from technical abilities which lead to significant findings in the research. That’s how it was possible for Río-Hortega's and Rodríguez Lafora's laboratories to expand the research of their masters (AU)

Manifestación de leucemia promielocítica aguda en el embarazo / Acute promyelocytic leukemia in pregnancy

La leucemia promielocítica aguda (LMA), también conocida como M3 de la clasificación French-American-British (FAB), se presenta en el 80% de los casos como síndrome hemorrágico grave que cuando aparece en estado de gestación, pone en peligro no solo la vida de la paciente sino también la del feto. Los resultados de estudios multicéntricos sugieren que el uso concomitante con ácido transretinoico (ATRA) e idarrubicina (IDA) constituye el tratamiento más efectivo para controlar los efectos antileucémicos. Presentamos el caso de una mujer de 32 años, en la semana 33 de gestación, con trastornos graves de coagulación por LMA, que ingresó en la unidad de cuidados intensivos con insuficiencia respiratoria por lesión pulmonar aguda. Mostramos el manejo terapéutico, la evolución inicial de la enfermedad dado lo inusual del caso y las implicaciones pronósticas del tratamiento durante la gestación (AU)

Acute promyelocytic leukemia, also known as M3 in the French-American-British classification, presents as severe hemorrhagic syndrome in 80% of affected pregnant women, posing a lethal threat to both mother and fetus. The results of multicenter studies suggest that the most effective treatment consists of the concomitant use of all-trans retinoic acid plus idarubicin. We present the case of a 32-year-old woman at 33 weeks of pregnancy with severe coagulation abnormalities due to acute promyelocytic leukemia, who was admitted to the intensive care unit for respiratory insufficiency due to an acute pulmonary lesion. The interest of this case lies in its infrequency. We describe the therapeutic management and initial course of the disease, as well as the prognostic implications of treatment during pregnancy (AU)