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Introducción. La permisividad ante la hiperglucemia es nociva para los pacientes ingresados. DIAGETHER es una aplicación que ayuda al médico en el tratamiento del paciente diabético. Objetivos. Determinar grado de usabilidad, nivel de confianza y valoración global de DIAGETHER empleada por médicos residentes en distintos escenarios clínicos. Método. Estudio descriptivo multicéntrico, basado en una encuesta de valoración sobre DIAGETHER, a 42 residentes de dos hospitales, valorando la toma de decisiones con respecto a la terapéutica de pacientes con alteraciones glucémicas en distintos escenarios clínicos. Resultados. DIAGETHER fue valorado positivamente respecto a usabilidad, confianza en resolución de casos, y tiempo empleado. La valoración global de la herramienta fue del 87,5. En el lado negativo, es necesario realizar estudios en terreno real para saber la adaptación real de la herramienta al trabajo médico. Conclusiones. La aplicación DIAGETHER® es una herramienta fácil de usar, rápida en la toma de decisiones y le da al médico seguridad en el tratamiento de pacientes con hiperglucemia, lo que hace que su valoración global sea alta. En el lado negativo, el estudio fue realizado en condiciones “no reales”, sería interesante desarrollar futuros estudio en varios servicios de urgencias.

ObjectivesTo present a model that enhances the accuracy of clinicians when presented with a possibly critical Covid-19 patient.MethodsA retrospective study was performed with information of 5,745 SARS-CoV2 infected patients admitted to the Emergency room of 4 public Hospitals in Madrid belonging to Quirón Salud Health Group (QS) from March 2020 to February 2021. Demographics, clinical variables on admission, laboratory markers and therapeutic interventions were extracted from Electronic Clinical Records. Traits related to mortality were found through difference in means testing and through feature selection by learning multiple classification trees with random initialization and selecting the ones that were used the most. We validated the model through cross-validation and tested generalization with an external dataset from 4 hospitals belonging to Sanitas Hospitals Health Group. The usefulness of two different models in real cases was tested by measuring the effect of exposure to the model decision on the accuracy of medical professionals.ResultsOf the 5,745 admitted patients, 1,173 died. Of the 110 variables in the dataset, 34 were found to be related with our definition of criticality (death in

This work has been supported by Ministerio de Ciencia, Innovación y Universidades, Plan Estatal 2017-2020 Retos - Proyectos I + D + i (PID2019-104767RB-I00). MRGL also thanks Ministerio de Economía y Competitividad, Instituto de Salud Carlos III (grants PI19/00589, PI19/01404, PI16/01842, PI17/00535 and GLD19/00100) for financial support. This work was supported by funds from MIUR Ministero dell’Istruzione, dell’Università della Ricerca Italiano, project PRIN 2017, ORIGINALE CHEMIAE in Antiviral Strategy—Origin and Modernization of Multi-Component Chemistry as a Source of Innovative Broad-Spectrum Antiviral Strategy (cod. 2017BMK8JR) and from Tuscany region, project Tuscany Antiviral Research Network -TUSCAVIR.NET (Bando Ricerca Salute 2018). We would like to thank Giulietta Venturi for making the ZIKV H/PF/2013 strain available for this study. This work has also been funded by the Fundación Séneca de la Región de Murcia under Project 20988/PI/18. This research was partially supported by the computer resources and the technical support provided by the supercomputing infrastructure of the NLHPC (ECM-02), Powered@NLHPC and the Extremadura Research Centre for Advanced Technologies (CETA − CIEMAT), funded by the European Regional Development Fund (ERDF). CETA − CIEMAT is part of CIEMAT and the Government of Spain. Authors thank CITIUS (Centro de Investigación, Tecnología e Innovación de la Universidad de Sevilla) for its important contribution in recording NMR and Mass spectra and in elemental analysis determination., Supplementary data to this article can be found online at https://doi.org/10.1016/j.bioorg.2023.106408, Since 2011 Direct Acting antivirals (DAAs) drugs targeting different non-structural (NS) viral proteins (NS3, NS5A or NS5B inhibitors) have been approved for clinical use in HCV therapies. However, currently there are not licensed therapeutics to treat Flavivirus infections and the only licensed DENV vaccine, Dengvaxia, is restricted to patients with preexisting DENV immunity. Similarly to NS5 polymerase, the NS3 catalytic region is evolutionarily conserved among the Flaviviridae family sharing strong structural similarity with other proteases belonging to this family and therefore is an attractive target for the development of pan-flavivirus therapeutics. In this work we present a library of 34 piperazine-derived small molecules as potential Flaviviridae NS3 protease inhibitors. The library was developed through a privileged structures-based design and then biologically screened using a live virus phenotypic assay to determine the half-maximal inhibitor concentration (IC50) of each compound against ZIKV and DENV. Two lead compounds, 42 and 44, with promising broad-spectrum activity against ZIKV (IC50 6.6 µM and 1.9 µM respectively) and DENV (IC50 6.7 µM and 1.4 µM respectively) and a good security profile were identified. Besides, molecular docking calculations were performed to provide insights about key interactions with residues in NS3 proteases’ active sites., Ministerio de Ciencia, Innovacion y Universidades, Plan Estatal 2017-2020 Retos-Proyectos I + D + i (PID2019-104767RB-I00), Spanish Government PI19/00589 PI19/01404 PI16/01842 PI17/00535 GLD19/00100, MIUR Ministero dell'Istruzione, dell'Universita della Ricerca Italiano, project PRIN 2017, ORIGINALE CHEMIAE in Antiviral Strategy-Origin and Modernization of Multi-Component Chemistry as a Source of Innovative Broad-Spectrum Antiviral Strategy 2017BMK8JR, Tuscany region, project Tuscany Antiviral Research Network-TUSCAVIR.NET (Bando Ricerca Salute 2018), Fundación Séneca 20988/PI/18, NLHPC ECM-02, European Commission

Hepatitis C virus (HCV) is the main agent responsible for chronic liver disease. Recent advances in anti-HCV treatment strategies have significantly increased the viral clearance rate (>90%). However, sustained antiviral responses vary in different cohorts, and high costs limit the broad use of direct-acting antivirals (DAAs). The goal of this study is to evaluate the inhibitory ability of well characterized (LC-QTOF-MS/MS) aqueous extracts obtained from edible mushrooms (Agaricus bisporus) to diminish HCV viral replication. Our data have demonstrated an in vitro inhibitory effect of A. bisporus extracts on NS3/4A protease and HCV replication. Fractionation by ultra-filtration and sequential liquid–liquid extraction showed that the compounds responsible for the inhibition are water-soluble with low molecular weights (

Inflammation and tumorigenesis are tightly linked pathways impacting cancer development. Inflammasomes are key signalling platforms that detect pathogenic microorganisms, including hepatitis C virus (HCV) infection, and sterile stressors (oxidative stress, insulin resistance, lipotoxicity) able to activate pro-inflammatory cytokines interleukin-1β and IL-18. Most of the inflammasome complexes that have been described to date contain a NOD-like receptor sensor molecule. Redox state and autophagy can regulate inflammasome complex and, depending on the conditions, can be either pro- or anti-apoptotic. Acute and chronic liver diseases are cytokine-driven diseases as several proinflammatory cytokines (IL-1α, IL-1β, tumor necrosis factor-alpha, and IL-6) are critically involved in inflammation, steatosis, fibrosis, and cancer development. NLRP3 inflammasome gain of function aggravates liver disease, resulting in severe liver fibrosis and highlighting this pathway in the pathogenesis of non-alcoholic fatty liver disease. On the other hand, HCV infection is the primary catalyst for progressive liver disease and development of liver cancer. It is well established that HCV-induced IL-1β production by hepatic macrophages plays a critical and central process that promotes liver inflammation and disease. In this review, we aim to clarify the role of the inflammasome in the aggravation of liver disease, and how selective blockade of this main pathway may be a useful strategy to delay fibrosis progression in liver diseases.

Cancer cells have unlimited replicative potential, insensitivity to growth-inhibitory signals, evasion of apoptosis, cellular stress, and sustained angiogenesis, invasiveness and metastatic potential. Cancer cells adequately adapt cell metabolism and integrate several intracellular and redox signaling to promote cell survival in an inflammatory and hypoxic microenvironment in order to maintain/expand tumor phenotype. The administration of tyrosine kinase inhibitor (TKI) constitutes the recommended therapeutic strategy in different malignancies at advanced stages. There are important interrelationships between cell stress, redox status, mitochondrial function, metabolism and cellular signaling pathways leading to cell survival/death. The induction of apoptosis and cell cycle arrest widely related to the antitumoral properties of TKIs result from tightly controlled events involving different cellular compartments and signaling pathways. The aim of the present review is to update the most relevant studies dealing with the impact of TKI treatment on cell function. The induction of endoplasmic reticulum (ER) stress and Ca2+ disturbances, leading to alteration of mitochondrial function, redox status and phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt)-mammalian target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK) signaling pathways that involve cell metabolism reprogramming in cancer cells will be covered. Emphasis will be given to studies that identify key components of the integrated molecular pattern including receptor tyrosine kinase (RTK) downstream signaling, cell death and mitochondria-related events that appear to be involved in the resistance of cancer cells to TKI treatments., This study was funded by Institute of Health Carlos III (ISCiii) (PI16/00090, PI19/00838 and PI19/01266), Spanish Ministry of Economy and Competitiveness (BFU2016-80006-P), Andalusian Ministry of Economy, Innovation, Science and Employment (BIO-216 and CTS-6264), Andalusian Ministry of Equality, Health and Social Policies (PI-0198-2016) and Valencian Ministry of Education, Culture and Sports (PROMETEO/2019/027). P de la C-O was supported by FPU predoctoral fellowship (FPU17/00026) from Spanish Ministry of Education, Culture and Sports. E N-V was supported by the the predoctoral i-PFIS IIS-enterprise contract in science and technologies in health (IFI18/00014) from ISCiii. We thank the Biomedical Research Network Center for Cardiovascular Diseases (CIBERcv), and the Biomedical Research Network Center for Liver and Digestive Diseases (CIBERehd) founded by the ISCiii and co-financed by European Regional Development Fund (ERDF) "A way to achieve Europe" for their financial support.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and the fourth most frequent cause of cancer-related death worldwide. Sorafenib is the first line recommended therapy for patients with locally advanced/metastatic HCC. The low response rate is attributed to intrinsic resistance of HCC cells to Sorafenib. The potential resistance to Sorafenib-induced cell death is multifactorial and involves all hallmarks of cancer. However, the presence of sub-therapeutic dose can negatively influence the antitumoral properties of the drug. In this sense, the present study showed that the sub-optimal Sorafenib concentration (10 nM) was associated with activation of caspase-9, AMP-activated protein kinase (AMPK), sustained autophagy, peroxisome proliferator-activated receptor-coactivator 1α (PGC-1α) and mitochondrial function in HepG2 cells. The increased mitochondrial respiration by Sorafenib (10 nM) was also observed in permeabilized HepG2 cells, but not in isolated rat mitochondria, which suggests the involvement of an upstream component in this regulatory mechanism. The basal glycolysis was dose dependently increased at early time point studied (6 h). Interestingly, Sorafenib increased nitric oxide (NO) generation that played an inhibitory role in mitochondrial respiration in sub-therapeutic dose of Sorafenib. The administration of sustained therapeutic dose of Sorafenib (10 µM, 24 h) induced mitochondrial dysfunction and dropped basal glycolysis derived acidification, as well as increased oxidative stress and apoptosis in HepG2. In conclusion, the accurate control of the administered dose of Sorafenib is relevant for the potential prosurvival or proapoptotic properties induced by the drug in liver cancer cells., We thank Dr. María Monsalve (Biomedical Research Institute "Alberto Sols", IIBM, Spain) for supplying the PGC-1α constructs. We also thank the Institute of Health Carlos III (ISCIII) (Spain) (PI13/00021 and PI16/00090), the Andalusian Government (Consejería de Igualdad, Salud y Políticas Sociales) (Spain) (PI-00025-2013 and PI-0198-2016), and Charles University research program PROGRES Q40/02 (Czech Republic) for their financial support. We thank the Biomedical Research Network Center for Liver and Digestive Diseases (CIBERehd) founded by the ISCIII (Spain) and co-financed by European Development Regional Fund ”A way to achieve Europe“ ERDF (Belgium) for their financial support.

Goal: to evaluate the adherence of Emergency Physicians to clinical guidelines for medical treatment in in-hospital patients, evaluated by using a specific computing tool (GLIKAL©) in patients with hyperglycemia and/or diabetes mellitus. Methodology: An observational study with descriptive cases was designed, with no intervention, including patients from an urban, tertiary university hospital. Patients pending admittance were recruited, starting at the very first hours of the day, any day of the week. Inclusion criteria were age above 18 years old, with glycaemia >150 mg/dl upon admittance to hospital (with a known diabetes or not) who were admitted to hospital from the Emergency Department. The study period included was from June to October 2012. The independent variables were age, sex, previous treatment for diabetes, type of diet prescribed upon admittance, corticosteroid treatment, serum creatinine and glycaemia upon admittance to the Emergency Department. The outcome variable was the treatment suggested by the software program, which was evaluated with 11 items gathered by the specific computing tool (GLIKAL©). Results: 125 patients were gathered, amongst which eight were discarded due to mistakes in the initial data collected. Of the remaining 117 patients, the mean age was of 78.1 years old, with 61% males. Among these 117 patients, 74 of them (63.4%) were being treated with oral antidiabetic drugs alone or in combination with insulin, of which 13 cases (17.5%) continued having it prescribed by the physician even when it was not suitable, while no mistake was detected in the treatment specified by GLIKAL© (p

Sorafenib is the unique accepted molecular targeted drug for the treatment of patients in advanced stage of hepatocellular carcinoma. The current study evaluated cell signaling regulation of endoplasmic reticulum (ER) stress, c-Jun-N-terminal kinase (JNK), Akt, and 5′AMP-activated protein kinase (AMPK) leading to autophagy and apoptosis induced by sorafenib. Sorafenib induced early (3–12 hr) ER stress characterized by an increase of Ser51P-eIF2α/eIF2α, C/EBP homologous protein (CHOP), IRE1α, and sXBP1, but a decrease of activating transcription factor 6 expression, overall temporally associated with the increase of Thr183,Tyr185P-JNK1/2/JNK1/2, Thr172P-AMPKα, Ser413P-Foxo3a, Thr308P-AKt/AKt and Thr32P-Foxo3a/Foxo3a ratios, and reduction of Ser2481P-mammalian target of rapamycin (mTOR)/mTOR and protein translation. This pattern was related to a transient increase of tBid, Bim EL, Beclin-1, Bcl-xL, Bcl-2, autophagy markers, and reduction of myeloid cell leukemia-1 (Mcl-1) expression. The progressive increase of CHOP expression, and reduction of Thr308P-AKt/AKt and Ser473P-AKt/AKt ratios were associated with the reduction of autophagic flux and an additional upregulation of Bim EL expression and caspase-3 activity (24 hr). Small interfering-RNA (si-RNA) assays showed that Bim, but not Bak and Bax, was involved in the induction of caspase-3 in sorafenib-treated HepG2 cells. Sorafenib increased autophagic and apoptotic markers in tumor-derived xenograft model. In conclusion, the early sorafenib-induced ER stress and regulation of JNK and AMPK-dependent signaling were related to the induction of survival autophagic process. The sustained drug treatment induced a progressive increase of ER stress and PERK-CHOP-dependent rise of Bim EL, which was associated with the shift from autophagy to apoptosis. The kinetic of Bim EL expression profile might also be related to the tight balance between AKt- and AMPK-related signaling leading to Foxo3a-dependent BIM EL upregulation. Ministerio de Economía y Competitividad BFU2016‐75352‐P Instituto de Salud Carlos III PI15/00034, PI13/ 00021, PI16/00090, PI14/01349 Ministerio de Educación FPU16/05127, FPU12/01433, FPU13/01237 Junta de Andalucía CTS-6264, PI-00025-2013, PI-0127-2013, PI-0198-2016

Genetics and epigenetics play a key role in the development of several diseases, including nonalcoholic fatty liver disease (NAFLD). Family studies demonstrate that first degree relatives of patients with NAFLD are at a much higher risk of the disease than the general population. The development of the Genome Wide Association Study (GWAS) technology has allowed the identification of numerous genetic polymorphisms involved in the evolution of diseases (e.g., PNPLA3, MBOAT7). On the other hand, epigenetic changes interact with inherited risk factors to determine an individual’s susceptibility to NAFLD. Modifications of the histones amino-terminal ends are key factors in the maintenance of chromatin structure and gene expression (cAMP-responsive element binding protein H (CREBH) or SIRT1). Activation of SIRT1 showed potential against the physiological mechanisms related to NAFLD. Abnormal DNA methylation represents a starting point for cancer development in NAFLD patients. Besides, the evaluation of circulating miRNA profiles represents a promising approach to assess and non-invasively monitor liver disease severity. To date, there is no approved pharmacologic therapy for NAFLD and the current treatment remains weight loss with lifestyle modification and exercise. In this review, the status of research into relevant genetic and epigenetic modifiers of NAFLD progression will be discussed.

There is limited information on hemorrhagic complications during invasive dental procedures in patients treated with double antiplatelet therapy. The objective of this study is to assess the frequency of hemorrhagic complications of patients taking dual antiplatelet medication undergoing dental extractions.An observational, multicenter, prospective, cohort study was performed in 11 oral and dental care units of primary care. The study sample was derived from the population of patients aged 18 years or older who were undergoing double antiplatelet therapy and presented to the oral and dental care units requiring dental extraction. Double antiplatelet therapy is the combination of 100 mg per day of acetylsalicylic acid and a second antiplatelet agent. The predictor variables were type of extraction performed, number of extracted teeth, number of extracted roots, and presence of inflammation. The primary outcome variable was intraoperative hemorrhage, and the secondary outcome variables were hemorrhage at 24 hours and hemorrhage at 10 days. First, a univariate analysis that considered all studied variables was performed. All variables with P.25 in the univariate analysis were included in a multivariate analysis. The association between hemorrhage severity and its relevant factors was evaluated using logistic regression analysis.The study included 181 patients. Light hemorrhage (30 minutes) was observed in 165 patients (91.2%). Intraoperative hemorrhage lasted more than 30 minutes in 15 patients (8.3%) and more than 60 minutes in only 1 patient, whose hemorrhage was controlled by local hemostatic measures. The presence of inflammation and 3-root extractions increased the probability of hemorrhage persisting for more than 30 minutes by factors of 10 and 7.3, respectively.In 8.3% of patients treated with dual antiplatelet therapy, dental extractions cause hemorrhagic complications lasting more than 30 minutes are resolved using local hemostatic measures. The results of this study support the safety of dental extraction without withdrawal double antiplatelet therapy.

Hepatitis C virus (HCV) infection has been related to increased risk of development of hepatocellular carcinoma (HCC) while metformin (M) and statins treatment seemed to protect against HCC development. In this work, we aim to identify the mechanisms by which metformin and simvastatin (S) could protect from liver cancer. Huh7.5 cells were infected with HCV particles and treated with M+S. Human primary hepatocytes were treated with M+S. Treatment with both drugs inhibited Huh7.5 cell growth and HCV infection. In non-infected cells S increased translational controlled tumor protein (TCTP) and phosphatase and tensin homolog (PTEN) proteins while M inhibited mammalian target of rapamycin (mTOR) and TCTP. Simvastatin and metformin co-administered down-regulated mTOR and TCTP, while PTEN was increased. In cells infected by HCV, mTOR, TCTP, p62 and light chain 3B II (LC3BII) were increased and PTEN was decreased. S+M treatment increased PTEN, p62 and LC3BII in Huh7.5 cells. In human primary hepatocytes, metformin treatment inhibited mTOR and PTEN, but up-regulated p62, LC3BII and Caspase 3. In conclusion, simvastatin and metformin inhibited cell growth and HCV infection in vitro. In human hepatocytes, metformin increased cell-death markers. These findings suggest that M+S treatment could be useful in therapeutic prevention of HCV-related hepatocellular carcinoma., This work was supported by the Spanish Ministry of Economy, Innovation and Competitivity, Instituto de Salud Carlos III, grant numbers PI13/01192, PI14/01349, co-funded by European Union (ERDF/ESF, “Investing in your future”) and Consejería de Salud de la Junta de Andalucía (PI-0892-2012). JA Del Campo was supported by Nicolás Monardes Program from Servicio Andaluz de Salud (SAS).

To describe an experience with the evaluation of resident physicians doing rotations in a tertiary-care hospital emergency department and to analyze the correlation between results on the various assessment tools and the resident's rank on Spain's standardized selection examination for admission to residency programs.The residents took 2 written examinations in 2013 and 2014, and rotation supervisors wrote subjective evaluations of the residents' clinical performance in the workplace. The residents also provided self-assessments of theoretical and practical knowledge and their aptitude for emergency department work. The results on these assessment tools were tabulated independently, and it was investigated if there were correlations between them.We observed an inverse correlation between the residents' rank on the standardized selection examination and their scores on the written examinations of knowledge and the supervisors' workplace assessments. The written examination scores after the rotation correlated positively with workplace assessments. Self-assessments were distributed normally, suggesting they were of scarce value, and they did not correlate with the results of the other assessment tools.Written examinations are acceptably correlated with subjective workplace assessments of practical competencies, whereas ranking on the residency program admissions examination is not acceptably correlated with emergency department workplace performance. We believe that efforts to prepare ways to evaluate residents' emergency department performance will be of interest in the future, once a specialization in emergency medicine is approved.Describir la experiencia obtenida en un servicio de urgencias (SU) de un hospital universitario de tercer nivel en términos de evaluación de residentes así como la correlación de los resultados obtenidos por las herramientas utilizadas entre si mismas y con el número de acceso a la plaza de médico interno residente (MIR).Estudio retrospectivo observacional. Se realizaron dos pruebas escritas a lo largo del periodo lectivo 2013- 2014, y evaluaciones subjetivas por los supervisores durante las jornadas de atención continuada y se solicitó una autoevaluación de conocimientos teóricos, prácticos y de disposición al trabajo en urgencias. Los resultados de estas herramientas se exponen independientemente y se investiga si existe correlación entre ellos.El número MIR se correlacionó inversamente con los resultados de las pruebas escritas de conocimientos y con los resultados de las evaluaciones durante las jornadas de atención continuada. Los resultados de las evaluaciones escritas mostraron una correlación directa con las evaluaciones durante las jornadas de atención continuada. En términos generales, la autoevaluación presentó una distribución normal reflejando una escasa utilidad y ninguna correlación con las formas de evaluación por terceros.Las pruebas escritas consiguen una correlación aceptable con la evaluación subjetiva de competencias prácticas de los MIR en el SU y viceversa. Los esfuerzos orientados a preparar estrategias de evaluación de residentes en la actividad en urgencias serán de interés en el futuro, cuando exista la especialidad la Medicina de Urgencias.

Ensayo clinico multicentrico para la validacion de la aplicacion Glikal en la ayuda al manejo de la hiperglucemia en comparacion con la practica clinica habitual

The Raman Laser Spectrometer (RLS) on board the ESA/Roscosmos ExoMars 2020 mission will provide precise identification of the mineral phases and the possibility to detect organics on the Red Planet. The RLS will work on the powdered samples prepared inside the Pasteur analytical suite and collected on the surface and subsurface by a drill system. Raman spectroscopy is a well-known analytical technique based on the inelastic scattering by matter of incident monochromatic light (the Raman effect) that has many applications in laboratory and industry, yet to be used in space applications. Raman spectrometers will be included in two Mars rovers scheduled to be launched in 2020. The Raman instrument for ExoMars 2020 consists of three main units: (1) a transmission spectrograph coupled to a CCD detector; (2) an electronics box, including the excitation laser that controls the instrument functions; and (3) an optical head with an autofocus mechanism illuminating and collecting the scattered light from the spot under investigation. The optical head is connected to the excitation laser and the spectrometer by optical fibers. The instrument also has two targets positioned inside the rover analytical laboratory for onboard Raman spectral calibration. The aim of this article was to present a detailed description of the RLS instrument, including its operation on Mars. To verify RLS operation before launch and to prepare science scenarios for the mission, a simulator of the sample analysis chain has been developed by the team. The results obtained are also discussed. Finally, the potential of the Raman instrument for use in field conditions is addressed. By using a ruggedized prototype, also developed by our team, a wide range of terrestrial analog sites across the world have been studied. These investigations allowed preparing a large collection of real, in situ spectra of samples from different geological processes and periods of Earth evolution. On this basis, we are working to develop models for interpreting analog processes on Mars during the mission. Key Words: Raman spectroscopy—ExoMars mission—Instruments and techniques—Planetary sciences—Mars mineralogy and geochemistry—Search for life on Mars. Astrobiology 17, 627–654

Introduccion y objetivos El objetivo de este estudio es evaluar el valor pronostico del electrocardiograma (ECG) en pacientes estables hemodinamicamente con diagnostico de tromboembolia pulmonar (TEP) aguda sintomatica. Metodos Se incluyo de forma prospectiva a todos los pacientes ambulatorios estables hemodinamicamente diagnosticados de TEP aguda sintomatica en un hospital universitario terciario. Las anomalias electrocardiograficas consideradas fueron: a) taquicardia sinusal (> 100 lat/min); b) alteraciones del segmento ST o de la onda T; c) bloqueo de la rama derecha del haz de His (BRDHH); d) patron S1Q3T3, y e) arritmias auriculares de reciente comienzo. Resultados Se incluyo a 644 pacientes en el estudio. Un 5% de los pacientes con ECG anormal fallecieron por TEP en los 15 dias posteriores al diagnostico, comparado con un 2% de los pacientes con ECG normal (razon de riesgo [RR] = 2,4; intervalo de confianza [IC] del 95%, 1-5,8; p = 0,05). En el analisis multivariable, la taquicardia sinusal multiplico por 2,2 el riesgo de muerte por todas las causas en el mes posterior al diagnostico de TEP. Tras ajustar por edad, antecedentes de cancer, inmovilizacion, un ECG alterado y la presencia de taquicardia sinusal, las arritmias auriculares de reciente diagnostico se asociaron de forma significativa a la muerte por TEP durante los primeros 15 dias (RR = 2,8; IC del 95%, 1–8,3; p = 0,05). Las arritmias auriculares mostraron un alto valor predictivo negativo de muerte por TEP a los 15 dias (97%), pero la razon de probabilidad negativa fue 0,79. Conclusiones En pacientes estables hemodinamicamente con TEP aguda sintomatica, la taquicardia sinusal y las arritmias auriculares son predictoras independientes de mal pronostico. Sin embargo, su utilidad en la estratificacion pronostica de estos pacientes es limitada.

Introduction and objectives The aim of this study was to determine the prognostic value of electrocardiography in hemodynamically stable patients with a diagnosis of acute symptomatic pulmonary embolism (PE). Methods This prospective study included all hemodynamically stable outpatients who were diagnosed with PE at a university hospital. The electrocardiographic abnormalities investigated were: a) sinus tachycardia (>100 beats/min); b) ST-segment or T-wave abnormalities; c) right bundle branch block; d) an S1Q3T3 pattern; and e) recent-onset atrial arrhythmia. Results The study included 644 patients. Overall, 5% of those with an ECG abnormality died due to PE in the 15 days after diagnosis compared with 2% of those with normal ECG findings (relative risk [RR]=2.4; 95% confidence interval [Cl], 1-5,8; P=.05). Multivariate analysis showed that sinus tachycardia was associated with a 2.2-fold increased risk of death due to all causes in the month after PE diagnosis. After adjusting for age, a history of cancer, immobility, ECG abnormalities, and sinus tachycardia, the presence of recent-onset atrial arrhythmia was significantly associated with death due to PE in the first 15 days (RR=2.8; 95% Cl, 1-8.3; P=.05). The negative predictive value of atrial arrhythmia for 15-day PE-related mortality was 97%, while the negative likelihood ratio was 0.79. Conclusiones In hemodynamically stable patients with acute symptomatic PE, the presence of sinus tachycardia and atrial arrhythmia were independent predictors of a poor prognosis. However, the usefulness of these factors for stratifying risk in PE patients is limited.

El objetivo del presente estudio es el determinar el efecto de la aplicaciA³n de un programa formativo para mA©dicos internos residentes sobre manejo de patologA­a atraumAitica axial en un entorno de medicina de urgencias.El programa formativo consiste en la aplicaciA³n de una jornada de charlas magistrales de 4 horas lectivas que se imparten a lo largo del aA±o a residentes que van a empezar su segundo aA±o de programa de especializaciA³n y que realizan actividad en el servicio de urgencias.El estudio consistiA³ en valorar la aplicaciA³n de los conocimientos impartidos en la labor asistencial durante las jornadas de atenciA³n continuada (guardias de puerta) en tA©rminos de necesidad de reevaluaciones por urgencias, uso de pruebas complementarias y necesidad de hospitalizaciA³n por mal control analgA©sico.La cifra de solicitud de pruebas radiolA³gicas complementarias se redujo significativamente despuA©s de la ejecuciA³n del curso optativo sin embargo en los siguientes meses la cifra retornA³ a su valor inicial. El asistir al curso no modificA³ significativamente el tiempo hasta que los pacientes volvieron a consultar por el mismo motivo aunque se evidenciA³ una tendencia a la prolongaciA³n de este en pacientes atendidos por residentes que hicieron el curso. La especialidad de procedencia de los MIRes fue la variable que mAis influyA³ en la curva de supervivencia.Concluimos que el impacto de la formaciA³n en el manejo de la patologA­a axial depende de los cursos impartidos y del interA©s que estos generen en los MIRes.