Suitability of the use of low-molecular-weight heparins in the prevention of venous thromboembolism

Objetivo: Conocer la prevalencia de prescripción de heparinas de bajo peso molecular (HBPM) en la profilaxis de la enfermedad tromboembólica venosa en un hospital general, así como la adecuación a las recomendaciones de las guías de práctica clínica. Método: Estudio observacional, descriptivo, de corte transversal, tipo indicación-prescripción, con pacientes ingresados en servicios médicos y quirúrgicos. Resultados: Se incluyeron 345 pacientes. La prevalencia de prescripción de HBPM fue del 44,6% (intervalo de confianza [IC] del 95%, 39,3-50,1). Según el nivel de riesgo tromboembólico se encontró adecuación en la decisión de tratar profilácticamente (o no) en 261 casos (75,7%; IC del 95%, 70,7-80,1), en el resto la pauta de actuación no fue la adecuada, destacando 55 pacientes (15,9%; IC del 95%, 12,2-20,2) con riesgo alto a los que no se había prescrito profilaxis (infrautilización), y 29 pacientes (8,4%; IC del 95%, 5,7- 11,8) con riesgo bajo que estaban con profilaxis (sobreutilización). En los pacientes médicos la prevalencia de prescripción fue de 22,6% (IC del 95%, 16,9-29,1) y sólo el 33,3% de los de riesgo tomboembólico alto-moderado recibió profilaxis. La prevalencia de prescripción en cirugía general fue del 84,2% y en traumatología del 91,3%. Conclusiones: En pacientes quirúrgicos el nivel de profilaxis alcanzado es adecuado, pero hay un porcentaje importante de pacientes médicos con riesgo tromboembólico medio-alto, que sigue sin recibir la adecuada profilaxis (infrautilización), a pesar de las recomendaciones de consenso con amplio respaldo científico y profesional.Objective: To investigate the prevalence of low-molecular-weight heparin (LMWH) prescription in venous thromboembolism prophylaxis in a general hospital and the suitability of the recommendations from the clinical practice guidelines. Method: A descriptive, observational and cross-sectional study of the indication-prescription type, carried out on patients admitted to medical departments and for surgery. Results: 345 patients were included. The prevalence of HBPM use was 44.6% (95% CI, 39.3-50.1). Depending on the risk of thromboembolism, the decision to treat prophylactically (or not) was appropriate in 261 cases (75.7%; 95% CI, 70.7-80.1), and the action guidelines were not suitable for the remainder of patients. 55 patients (15.9%; 95% CI, 12.2-20.2) presented a high risk and were not prescribed prophylactically (underuse); and 29 patients (8.4%; 95% CI, 5.7-11.8) at low risk were treated prophylactically (overuse). There was a relationship between the appropriateness of the prescription and the type of patient (p<0.01). In the group of medical patients theprevalence of prescription was 22.6% (95% CI, 16.9-29.1) and only 33.3% of patients with a high to moderate risk of thromboembolism received prophylaxis. The prevalence of prescription in general surgery was 84.2% and 91.3% in traumatology. Conclusions: The degree of prophylaxis is adequate in surgical patients, but there was a significant percentage of medical patients with a high to moderate risk who did not receive suitable prophylaxis (underuse), despite recommendations with scientific and professional backing.Consejería de Salud de la Junta de AndalucíaInstituto de Salud Carlos II

Activating Transcription Factor 4 Modulates TGFβ-Induced Aggressiveness in Triple-Negative Breast Cancer via SMAD2/3/4 and mTORC2 Signaling

Purpose: On the basis of the identified stress-independent cellular functions of activating transcription factor 4 (ATF4), we reported enhanced ATF4 levels in MCF10A cells treated with TGFβ1. ATF4 is overexpressed in patients with triple-negative breast cancer (TNBC), but its impact on patient survival and the underlying mechanisms remain unknown. We aimed to determine ATF4 effects on patients with breast cancer survival and TNBC aggressiveness, and the relationships between TGFβ and ATF4. Defining the signaling pathways may help us identify a cell signaling-tailored gene signature.Experimental Design: Patient survival data were determined by Kaplan-Meier analysis. Relationship between TGFβ and ATF4, their effects on aggressiveness (tumor proliferation, metastasis, and stemness), and the underlying pathways were analyzed in three TNBC cell lines and in vivo using patient-derived xenografts (PDX).Results: ATF4 overexpression correlated with TNBC patient survival decrease and a SMAD-dependent crosstalk between ATF4 and TGFβ was identified. ATF4 expression inhibition reduced migration, invasiveness, mammosphere-forming efficiency, proliferation, epithelial-mesenchymal transition, and antiapoptotic and stemness marker levels. In PDX models, ATF4 silencing decreased metastases, tumor growth, and relapse after chemotherapy. ATF4 was shown to be active downstream of SMAD2/3/4 and mTORC2, regulating TGFβ/SMAD and mTOR/RAC1-RHOA pathways independently of stress. We defined an eight-gene signature with prognostic potential, altered in 45% of 2,509 patients with breast cancer.Conclusions: ATF4 may represent a valuable prognostic biomarker and therapeutic target in patients with TNBC, and we identified a cell signaling pathway-based gene signature that may contribute to the development of combinatorial targeted therapies for breast cancer

CMS physics technical design report : Addendum on high density QCD with heavy ions

Peer reviewe

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

De epitelio a epitelio, estableciendo un vínculo materno-filial

Resumen del trabajo presentado al XXVII Congreso de Neonatología y Medicina Perinatal, celebrado en Madrid del 2 al 4 de octubre de 2019.[Introducción: La lactancia materna conjuga funciones y acciones de carácter nutritivo y no-nutritivo que contribuyen al desarrollo adecuado del recién nacido. Resulta relevante el hecho de que la maquinaria biológica de la gládula mamaria haya evolucionado para proporcionar al neonato con un alimento estructurado que contiene porciones de las membranas celulares del epitelio mamario de la madre, la membrana del glóbulo graso lácteo (MFGM). Así, el reto para el aparato digestivo del recién nacido es 'desmontar' de forma eficiente la MFGM, de forma que las secreciones pancreáticas alcancen el corazón del glóbulo graso lácteo rico en triacilglicéridos (TAGs). A pesar de la importancia de este proceso, todavía no se ha considerado cómo a través del contacto entre la MFGM, que procede del epitelio mamario, y las membranas de las células del epitelio intestinal del neonato se puede reconocer un nuevo vínculo materno-filial que incida en la funcionalidad del aparato digestivo, un hecho de importancia en el caso de prematuros. [Objetivo]: Determinar mediante modelos de digestión in vitro, microscopía y técnicas de etiquetado, y cultivos celulares in vitro la evolución de MFGMs obtenidas a partir de muestras de calostro y leche madura. [Población y Método]: Madres lactantes que cumplen los criterios de inclusión (mujeres sanas o con patología de embarazo menor, de edad gestacional 25-40 semanas). Se obtendrá calostro (3-7 días postparto) y leche madura (15-30 días postparto). Se aisla la fracción de glóbulos grasos de cada muestra de leche materna mediante centrifugración por densidad y los aislados se someten a un proceso estandarizado de digestión in vitro. Mediante microscopía y etiquetado por fluorescencia se marca la MFGM y se realiza el seguimiento de su evolución durante la digestión. De igual forma se aplican estas técnicas para visualizar la captación de MFGMs en el modelo celular del epitelio intestinal. [Resultados]: Durante la digestión in vitro se produce una transformación de los glóbulos grasos lácteos, tanto en tamaño como en composición debido a la transferencia desde los glóbulos grasos a las micelas mixtas del contenido lipídico hidrolizado enzimáticamente. Este proceso se puede monitorizar exitosamente mediante el análisis químico de la composición en lípidos de los digestatos y por microscopía de fluorescencia, así como por el modelo celular del epitelio intestinal. Conclusión. Las técnicas in vitro permiten establecer el grado de eficiencia en la asimilación de lípidos, TAGs y lípidos polares de membrana

In vitro digestion of human milk: influence of the lactation stage on the micellar carotenoids content

Human milk is a complex fluid with nutritive and non-nutritive functions specifically structured to cover the needs of the newborn. The present study started with the study of carotenoid composition during progress of lactation (colostrum, collected at 3–5 d postpartum; mature milk, collected at 30 d postpartum) with samples donated from full-term lactating mothers (women with no chronic diseases, nonsmokers on a regular diet without supplements, n = 30). Subsequently, we applied an in vitro protocol to determine the micellarization efficiency of the carotenoids, which were separated by HPLC and quantified by the external standard method. That in vitro protocol is tailored for the biochemistry of the digestive tract of a newborn. To the best of our knowledge, the present study is the first report of carotenoids micellar contents, obtained in vitro. This study reveals, from the in vitro perspective, that colostrum and mature milk produce significant micellar contents of carotenoids despite lipids in milk are within highly complex structures. Indeed, the lactation period develops some influence on the micellarization efficiency, influence that might be attributed to the dynamics of the milk fat globule membrane (MFGM) during the progress of lactation.This research was funded by the Ministerio de Ciencia, Investigación y Universidades, Agencia Estatal de Investigación, grant number AGL2017-87884-R. A.A.O.X. is a fellow of the Science without Borders Program of the Brazilian National Council for Scientific and Technological Development, fellowship 238163/2012-1.Peer reviewe

Late Holocene deposits distribution and structuration ¡n the Bay of Cádiz

Late Holocene deposits characterization in the Bay of Cádiz has been carry out by means of a high resolution seismic profiles grid. Sedimentaiy cover distribution allows to distinguish two different sectors in the external bay: a) eastern sector, with a thick sedimentary infill, composed of three major depocenters with a NNW-SSE direction; and b) western sector, with a thinner sedimentary cover which increases progressively towards the continental shelf. This Holocene sedimentary cover is composed of three seismic units: 1) unit a: sigmoida-oblique progradational configuration; 2) unit b: sigmoidal progradational configuration; and 3) unit c: aggradational superficial unit that is only present in the western sector of the Ba

Surface-enhanced Raman scattering and theoretical studies of the C-terminal peptide of the β-subunit human chorionic gonadotropin without linked carbohydrates

Raman and surface-enhanced Raman scattering (SERS) spectra of the synthetic carboxy terminal peptide of human chorionic gonadatropin β-subunit free of carbohydrate moieties (P37) are reported. The spectral analysis is performed on the basis of our reported Raman spectrum and SERS data of oligopeptides displaying selected amino acids sequences MRKDV, ADEDRDA, and LGRGISL. SERS samples of P37 were prepared by coating the solid peptide with metal colloids on a quartz slide. This treatment makes possible to obtain high spectral batch to batch reproducibility. Amino acids components of P37 display net charges and hydrophobic characteristics, which are related to particular structural aspects of the adsorbate-substrate interaction. The spectroscopic results are supported by quantum chemical calculations performed by using extended Hückel theory method for a model of P37 interacting with an Ag surface. The P37-metal interaction is drove by positively charged fragments of selected amino acids, mainly threonine 109, lysine 122, and arginine in positions 114 and 133. Data here reported intend to contribute to the knowledge about the antigen-antibody interaction and to the drugs delivery research area. © 2010 Wiley Periodicals, Inc.Contract grant sponsor: CSIC-CONICYT Contract grant number: 2007-145 Contract grant sponsors: Fondecyt Contract grant number: 1070078, 1085124, and 1090074 Contract grant sponsors: Ministerio de Educacio´n y Ciencia of Spain Contract grant number: FIS2007-63065 Contract grant sponsors: Comunidad de Madrid Contract grant number: S2009/TIC-1476 MICROSERES II Contract grant sponsors: Doctoral Fellowship CONICYT (to A.E.A.) Contract grant number: AT-24090050 (to A.E.A.)Peer Reviewe