Positive and Negative Regulation of Angiogenesis by Soluble Vascular Endothelial Growth Factor Receptor-1.

Vascular endothelial growth factor receptor (VEGFR)-1 exists in different forms, derived from alternative splicing of the same gene. In addition to the transmembrane form, endothelial cells produce a soluble VEGFR-1 (sVEGFR-1) isoform, whereas non-endothelial cells produce both sVEGFR-1 and a different soluble molecule, known as soluble fms-like tyrosine kinase (sFlt)1-14. By binding members of the vascular endothelial growth factor (VEGF) family, the soluble forms reduce the amounts of VEGFs available for the interaction with their transmembrane receptors, thereby negatively regulating VEGFR-mediated signaling. In agreement with this activity, high levels of circulating sVEGFR-1 or sFlt1-14 are associated with different pathological conditions involving vascular dysfunction. Moreover, sVEGFR-1 and sFlt1-14 have an additional role in angiogenesis: they are deposited in the endothelial cell and pericyte extracellular matrix, and interact with cell membrane components. Interaction of sVEGFR-1 with α5β1 integrin on endothelial cell membranes regulates vessel growth, triggering a dynamic, pro-angiogenic phenotype. Interaction of sVEGFR-1/sFlt1-14 with cell membrane glycosphingolipids in lipid rafts controls kidney cell morphology and glomerular barrier functions. These cell⁻matrix contacts represent attractive novel targets for pharmacological intervention in addition to those addressing interactions between VEGFs and their receptors.

Feasibility of a selective targeted strategy of HIV testing in emergency departments: a before-after study.

BACKGROUND AND IMPORTANCE: The rates of hidden infection and late diagnosis of HIV still remain high in Western countries. Missed diagnostic opportunities represent the key point in changing the course of the epidemic. OBJECTIVE: To evaluate the feasibility and results of implementation of a selective strategy to test for HIV in the emergency department (ED) in patients with six pre-defined medical situations: sexually transmitted infections, herpes zoster, community-acquired pneumonia, mononucleosis syndrome, practice of chemsex (CS) or request of post-exposure prophylaxis. DESIGN: This quasi-experimental longitudinal study evaluated the pre- and post-implementation results of HIV testing in the six aforementioned clinical scenarios. SETTINGS AND PARTICIPANTS: Patients attended 34 Spanish EDs. INTERVENTION OR EXPOSURE: The intervention was an intensive educational program and pathways to facilitate and track orders and results were designed. We collected and compared pre- and post-implementation ED census and diagnoses, and HIV tests requested and results. OUTCOME MEASURES AND ANALYSIS: The main outcome was adherence to the recommendations. Secondary outcomes were to evaluate the effectiveness of the program by the rate of positive test and the new HIV diagnoses. Differences between first and second periods were assessed. The magnitude of changes (absolute and relative) was expressed with the 95% confidence interval (CI). MAIN RESULTS: HIV tests increasing from 7080 (0.42% of ED visits) to 13 436 (relative increase of 75%, 95% CI from 70 to 80%). The six conditions were diagnosed in 15 879 and 16 618 patients, and HIV testing was ordered in 3393 (21%) and 7002 (42%) patients (increase: 97%; 95% CI: 90-104%). HIV testing significantly increased for all conditions except for CS. The positive HIV test rates increased from 0.92 to 1.67%. Detection of persons with undiagnosed HIV increased from 65 to 224, which implied a 220% (95% CI: 143-322%) increase of HIV diagnosis among all ED comers and a 71% (95% CI: 30-125%) increase of positive HIV tests. CONCLUSION: Implementation of a strategy to test for HIV in selective clinical situations in the ED is feasible and may lead to a substantial increase in HIV testing and diagnoses.

Analysis of the reasons for requesting HIV serology in the emergency department other than those defined in the targeted screening strategy of the "Urgències VIHgila" program and its potential inclusion in a future consensus document.

OBJECTIVE: To describe other reasons for requesting HIV serology in emergency departments (ED) other than the 6 defined in the SEMES-GESIDA consensus document (DC-SEMES-GESIDA) and to analyze whether it would be efficient to include any of them in the future. METHODS: Review of all HIV serologies performed during 2 years in 20 Catalan EDs. Serologies requested for reasons not defined by the DC-SEMES-GESIDA were grouped by common conditions, the prevalence (IC95%) of seropositivity for each condition was calculated, and those whose 95% confidence lower limit was >0.1% were considered efficient. Sensitivity analysis considered that serology would have been performed on 20% of cases attended and the remaining 80% would have been seronegative. RESULTS: There were 8044 serologies performed for 248 conditions not recommended by DC-SEMES-GESIDA, in 17 there were seropositive, and in 12 the performance of HIV serology would be efficient. The highest prevalence of detection corresponded to patients from endemic countries (7.41%, 0.91-24.3), lymphopenia (4.76%, 0.12-23.8), plateletopenia (4.37%, 1.20-10.9), adenopathy (3.45%, 0.42-11.9), meningoencephalitis (3.12%, 0.38-10.8) and drug use (2.50%, 0.68-6.28). Sensitivity analysis confirmed efficiency in 6 of them: endemic country origin, plateletopenia, drug abuse, toxic syndrome, behavioral-confusional disorder-agitation and fever of unknown origin. CONCLUSION: The DC-SEMES-GESIDA targeted HIV screening strategy in the ED could efficiently include other circumstances not previously considered; the most cost-effective would be origin from an endemic country, plateletopenia, drug abuse, toxic syndrome, behavioral-confusional-agitation disorder and fever of unknown origin.

Mortality risk model validation in a prospective cohort of patients from the sixth wave of the COVID-19 pandemic in a hospital emergency department. / Validación del modelo de riesgo de mortalidad en una cohorte prospectiva de pacientes de la sexta ola epidémica de la COVID-19 en un servicio de urgencias hospitalario.

OBJECTIVES: To validate risk factors for mortality in patients treated for COVID-19 in a hospital emergency department during the sixth wave of the pandemic. MATERIAL AND METHODS: Prospective observational noninterventional study. We included patients over the age of 18 years with a confirmed diagnosis of COVID-19 between December 1, 2021, and February 28, 2022. For each patient we calculated a risk score based on age 50 years or older (2 points) plus 1 point each for the presence of the following predictors: Barthel index less than 90 points, altered level of consciousness, ratio of arterial oxygen saturation to fraction of inspired oxygen less than 400, abnormal breath sounds, platelet concentration less than 100 × 109/L, C-reactive protein level of 5 mg/dL or more, and glomerular filtration rate less than 45 mL/min. The model was assessed with the area under the receiver operating characteristic curve (AUC). RESULTS: Of the 1156 patients included, 790 (68%) had received at least 2 vaccine doses. The probability of 30-day survival was 96%. A risk score was calculated for 609 patients. Four hundred seventeen patients were at low risk of death, 180 were at intermediate risk, and 10 were at high risk. The probability of death within 30 days was 1%, 13%, and 50% for patients in the 3 risk groups, respectively. The sensitivity, specificity, and positive and negative predictive values of a risk score of 3 points or less were 88%, 72%, 19%, 99%, respectively.The AUC for the model was 0.87. CONCLUSION: The risk model identified low risk of mortality and allowed us to safely discharge patients treated for COVID-19 in our tertiary-care hospital emergency department.

OBJETIVO: Validación de un indicador de mortalidad derivado durante los primeros meses de la pandemia de la COVID-19 en pacientes con COVID-19 atendidos durante la sexta ola epidémica en un servicio de urgencias hospitalario (SUH). METODO: Estudio observacional prospectivo no intervencionista. Se incluyeron pacientes > 18 años diagnosticados de casos confirmados de COVID-19 (1 diciembre 2021-28 febrero 2022). Se calculó el indicador para cada paciente: edad $ 50 años (2 puntos), índice de Barthel 90 puntos (1 punto), alteración de consciencia (1 punto), índice de SaO2/FIO2 400 (1 punto), auscultación respiratoria patológica (1 punto), plaquetas 100 x 109/L (1 punto), proteína C reactiva $ 5 mg/dL (1 punto) y filtrado glomerular 45 mL/min (1 punto). El rendimiento del indicador se valoró con el análisis del área bajo la curva de la característica operativa del receptor (ABC-COR). RESULTADOS: De los 1.156 pacientes incluidos en el estudio, 790 (68%) habían recibido como mínimo una dosis de vacuna. La probabilidad de supervivencia a los 30 días de la serie fue del 96%. El indicador de riesgo se pudo calcular en 609 pacientes. Cuatrocientos diecisiete pacientes se clasificaron como de riesgo bajo, 182 de riesgo intermedio y 10 de riesgo alto. La probabilidad de mortalidad a los 30 días fue de 1%, 13% y 50%, respectivamente. La sensibilidad, especificidad y valores predictivos positivo y negativo para un punto de corte menor o igual a 3 puntos fue 88%, 72%, 19%, 99%, respectivamente. El ABC-COR para el indicador fue de 0,87. CONCLUSIONES: Un valor del indicador de bajo riesgo permite dar de alta con seguridad a los pacientes con COVID-19 que se atienden en un SUH de un centro de tercer nivel.

Factors associated with erroneous emergency department noncardiac chest pain classifications in men and women. / Análisis individualizado por sexo de los factores asociados a la clasificación inicial errónea en urgencias del dolor torácico como no coronario.

OBJECTIVES: To analyze the frequency and clinical characteristics associated with erroneous initial classifications of noncardiac chest pain (NCP) in men and women. MATERIAL AND METHODS: We analyzed all case records in which chest pain was initially classified as noncardiac in origin according to clinical signs and electrocardiograms evaluated in our emergency department between 2008 and 2017. We considered the initial evaluation of NCP to be in error if the final diagnosis was acute coronary syndrome. A risk model for an erroneous initial classification of NCP was developed based on multivariable analysis of our patient data. We also used multivariable analysis to explore associations between 10 clinical signs of chest pain and an erroneous initial NCP classification. The data for men and women were analyzed separately. RESULTS: NCP was the initial classification for 8093 women; their median (interquartile range) age was 54 (38-73) years. The classification was in error for 72 women (0.9%). Odds ratios (ORs) showed that patient risk factors associated with an erroneous NCP classification in the women in our series were obesity (OR, 0.40; 95% CI, 0.17- 0.97) and cocaine consumption (OR, 5.18; 95% CI, 1.16-23.2). Clinical risk factors associated with erroneous NCP classification in women were recent physical exertion (OR, 2.01; 95% CI, 1.21-3.33), radiation exposure (OR, 2.05; 95% CI, 1.23-3.41), and vegetative symptoms (OR, 1.86; 95% CI, 1.02-3.41). For 9979 men with a median age of 47 (33-64) years, NCP was the initial classification; in 83 of the men (0.8%) the classification was erroneous. Patient factors associated with erroneous NCP classification in men were age over 40 years (OR, 1.74; 95% CI, 1.04-2.91) and hypertension (OR, 0.45; 95% CI, 0.24-0.84). No clinical signs of chest pain in men were associated with error. CONCLUSION: More clinical characteristics are associated with an erroneous classification of NCP in women. Our findings underline the need to assess the possibility of acute coronary syndrome differently in women, in whom the signs have usually been considered to be atypical.

OBJETIVO: Analizar de forma independiente en mujeres y hombres la frecuencia y las características clínicas asociadas a una clasificación inicial errónea (CIE) en urgencias del dolor torácico (DT) como no coronario. METODO: Se analizan todas las consultas por DT atendidas en urgencias entre 2008 y 2017 clasificadas inicialmente (historia clínica y ECG) como DT no coronario. Se consideró como CIE si el diagnóstico final fue síndrome coronario agudo (SCA). Se crearon dos modelos multivariable, uno con 10 factores de riesgo, y otro con 10 características clínicas del DT, en los que se investigó la asociación de estas variables con una CIE. Se analizaron independientemente mujeres y hombres. RESULTADOS: Se analizaron 8.093 mujeres con DT clasificado inicialmente como no coronario (edad mediana: 54 años, RIC: 38-73), 72 con CIE (0,9%). Los factores de riesgo asociados independientemente a CIE fueron obesidad (OR = 0,40; IC 95% = 0,17-0,97) y consumo de cocaína (5,18; 1,16-23,2), y las características clínicas fueron relación con el esfuerzo (2,01; 1,21-3,33), existencia de irradiación (2,05; 1,23-3,41) y síntomas vegetativos acompañantes (1,86; 1,02-3,41). Se analizaron 9.979 hombres (edad mediana: 47 años, RIC: 33-64), 83 con CIE (0,8%). Los factores de riesgo asociados a CIE fueron edad > 40 años (1,74; 1,04-2,91) e hipertensión (0,45; 0,24-0,84). No hubo características clínicas del DT asociadas a CIE. CONCLUSIONES: En las mujeres con dolor torácico, se idenfitican más características asociadas al error de clasificación que en los hombres. Este estudio remarca la necesidad de análisis independiente por sexo en el SCA, en el que clásicamente se ha considerado la clínica en las mujeres como atípica.

Risk score for mortality due to COVID-19: a prospective temporal validation cohort study in the emergency department of a tertiary care hospital. / Validación temporal de un modelo de riesgo de mortalidad por COVID-19 en una cohorte prospectiva en un servicio de urgencias de un hospital de tercer nivel.

OBJECTIVES: To validate a previously described hospital emergency department risk model to predict mortality in patients with COVID-19. MATERIAL AND METHODS: Prospective observational noninterventional study. Patients aged over 18 years diagnosed with COVID-19 were included between December 1, 2020, and February 28, 2021. We calculated a risk score for each patient based on age 50 years (2 points) plus 1 point each for the presence of the following predictors: Barthel index 90 points, altered level of consciousness, ratio of arterial oxygen saturation to fraction of inspired oxygen 400, abnormal breath sounds, platelet concentration 100 × 109/L, C reactive protein level 5 mg/dL, and glomerular filtration rate 45 mL/min. The dependent variable was 30-day mortality. We assessed the score's performance with the area under the receiver operating characteristic curve (AUC). RESULTS: The validation cohort included 1223 patients. After a median follow-up of 80 days, 143 patients had died; 901 patients were classified as having low risk (score, 4 points), 270 as intermediate risk (5-6 points), and 52 as high risk ( 7 points). Thirty-day mortality rates at each risk level were 2.8%, 22.5%, and 65.4%, respectively. The AUC for the score was 0.883; for risk categorization, the AUC was 0.818. CONCLUSION: The risk score described is useful for stratifying risk for mortality in patients with COVID-19 who come to a tertiary-care hospital emergency department.

OBJETIVO: Validación de un indicador de mortalidad previamente descrito en pacientes con COVID-19 en un servicio de urgencias hospitalario (SUH). METODO: Estudio observacional prospectivo no intervencionista. Se incluyeron pacientes 18 años diagnosticados de COVID-19 (1 de diciembre de 2020 hasta 28 de febrero de 2021). Se calculó el indicador para cada paciente: edad 50 años (2 puntos), índice de Barthel 90 puntos (1 punto), alteración de consciencia (1 punto), índice de SaO2/ FIO2 400 (1 punto), auscultación respiratoria patológica (1 punto), plaquetas 100 x 109/L (1 punto), proteína C reactiva 5 mg/dL (1 punto) y filtrado glomerular 45 mL/min (1 punto). La variable dependiente fue la mortalidad observada a 30 días. El rendimiento del indicador se valoró con el análisis del área bajo la curva de la característica operativa del receptor (ABC-COR). RESULTADOS: La validación del indicador se realizó sobre una cohorte de 1.223 pacientes. Tras una mediana de seguimiento de 80 días, 143 pacientes habían fallecido. Un total de 901 pacientes fueron catalogados como riesgo bajo (indicador 4 puntos), 270 lo fueron como riesgo intermedio (5-6 puntos) y 52 como riesgo alto ( 7 puntos). La mortalidad a 30 días observada en cada categoría fue de 2,8%, 22,5% y 65,4%, respectivamente. El ABC-COR fue de 0,883 para el indicador utilizado cuantitativamente y de 0,818 cuando se usó cualitativamente en forma de categorías de riesgo. CONCLUSIONES: El indicador descrito es una herramienta útil para estratificar el riesgo de mortalidad de los pacientes con COVID-19 que consultan a un SUH de un centro de tercer nivel.

Undertriage of patients requiring direct admission to intensive care from the emergency department for medical conditions: impact on prognosis and associated factors. / Infratriaje en urgencias de pacientes que precisan ingreso directo en cuidados intensivos por enfermedades médicas: impacto en el pronóstico y factores asociados.

OBJECTIVES: To determine whether undertriage affects the outcome for patients requiring direct admission to the intensive care unit (ICU) from the emergency department due to a medical condition. To identify factors associated with undertriage. MATERIAL AND METHODS: Retrospective review of patients treated in 2018 for medical emergencies requiring direct admission to the ICU from the emergency department. The cases were classified in 2 groups according to the assigned triage level. Underestimation was defined as a triage level of III or more. Independent variables were demographic and epidemiologic data and indicators of severity recorded in the emergency department. The main outcome was 30-day mortality. Secondary outcomes were in-hospital mortality, prolonged ICU stay, and prolonged hospital stay. RESULTS: We included 470 patients with a median age of 68 years (first-third quartile range, 57-78 years); 61.1% were men, and 151 (32.1%) were undertriaged. Factors directly related to undertriage according to odds ratios (ORs) were age (OR = 1.017; 95% CI, 1.003-1.032), Quick Sequential Organ Failure Assessment score of 0 or 1 (OR = 1.761; 95% CI, 1.038-2.988), ratio of oxygen saturation to fraction of inspired oxygen greater than 300 (OR = 2.447; 95% CI, 1.418-4.223), a diagnosis of infection (OR = 5.003, 95% CI 2.727-9.188) whether respiratory (OR = 3.993, 95% CI 1.919-8.310) or other (OR = 1.980, 95% CI, 1.036-3.785) versus a diagnosis of cardiovascular disease. Factors inversely related to undertriage were admission during the afternoon (OR = 0.512, 95% CI, 0.306-0.856) and ambulance transfer (OR = 0.373; 95% CI, 0.232-0.600). Ninety patients (19.1%) died within 30 days. Undertriage was not related to 30-day mortality or the other outcomes analyzed. CONCLUSION: Undertriage was not associated with a worse outcome in patients requiring direct admission to the ICU for a medical emergency. The factors we found to be associated with undertriage, such as patient age and time of day admitted, merit special attention given that these factors should not be affecting the triage process.

OBJETIVO: Determinar si el infratriaje tiene impacto pronóstico en pacientes que requieren ingreso desde urgencias en cuidados intensivos por enfermedad médica e identificar factores asociados. METODO: Revisión retrospectiva de pacientes atendidos durante 2018 por enfermedades médicas con ingreso directo en cuidados intensivos desde urgencias. Se clasificaron en dos grupos en función del nivel de triaje asignado y se consideró infratriaje un nivel de triaje III. Las variables independientes incluyeron datos demográficos, epidemiológicos e indicadores de gravedad en urgencias. Se registró la mortalidad a los 30 días (objetivo primario), así como la mortalidad hospitalaria, el ingreso prolongado en cuidados intensivos o el ingreso prolongado hospitalario (objetivos secundarios). RESULTADOS: Se incluyeron 470 pacientes [edad 68 años (rango 57-78), 61,1% hombres] de los que 151 (32,1%) formaban el grupo con infratriaje. Los factores relacionados con el infratriaje fueron la edad (OR = 1,017; IC 95% 1,003- 1,032), indicador qSOFA 0-1 (OR = 1,761; IC 95% 1,038-2,988), índice SpO2/FiO2 > 300 (OR = 2,447; IC 95% 1,418- 4,223) y el diagnóstico de infección (OR = 5,003; IC 95% 2,727-9,188), respiratorio (OR = 3,993; IC 95% 1,919-8,310) u otro (OR = 1,980; IC 95% 1,036-3,785) respecto al diagnóstico cardiovascular, mientras que la admisión en horario de tarde (OR = 0,512; IC 95% 0,306-0,856) o el traslado en ambulancia (OR = 0,373; IC 95% 0,232- 0,600) se relacionaron de forma inversa con el infratriaje. El evento mortalidad a 30 días tuvo lugar en 90 pacientes (19,1%). El infratriaje no se relacionó con la mortalidad a 30 días ni con el resto de los objetivos analizados. CONCLUSIONES: El infratriaje no se relacionó con un peor pronóstico en pacientes con ingreso directo en intensivos por enfermedad médica. Se han identificado factores relacionados con el infratriaje, como la edad o el horario de admisión que merecen una atención especial, ya que no deberían afectar el proceso de triaje.

Mortality in patients treated for COVID-19 in the emergency department of a tertiary care hospital during the first phase of the pandemic: Derivation of a risk model for emergency departments. / Análisis de mortalidad de los pacientes atendidos por COVID-19 en el servicio de urgencias de un hospital de tercer nivel en la fase incial de la pandemia. Derivación de un modelo de riesgo para urgencias.

OBJECTIVES: To develop a risk model to predict 30-day mortality after emergency department treatment for COVID-19. MATERIAL AND METHODS: Observational retrospective cohort study including 2511 patients with COVID-19 who came to our emergency department between March 1 and April 30, 2020. We analyzed variables with Kaplan Meier survival and Cox regression analyses. RESULTS: All-cause mortality was 8% at 30 days. Independent variables associated with higher risk of mortality were age over 50 years, a Barthel index score less than 90, altered mental status, the ratio of arterial oxygen saturation to the fraction of inspired oxygen (SaO2/FIO2), abnormal lung sounds, platelet concentration less than 100 000/mm3, a C-reactive protein concentration of 5 mg/dL or higher, and a glomerular filtration rate less than 45 mL/min. Each independent predictor was assigned 1 point in the score except age, which was assigned 2 points. Risk was distributed in 3 levels: low risk (score of 4 points or less), intermediate risk (5 to 6 points), and high risk (7 points or above). Thirty-day risk of mortality was 1.7% for patients who scored in the low-risk category, 28.2% for patients with an intermediate risk score, and 67.3% for those with a high risk score. CONCLUSION: This mortality risk stratification tool for patients with COVID-19 could be useful for managing the course of disease and assigning health care resources in the emergency department.

OBJETIVO: Derivar un modelo de riesgo para estimar la probabilidad de mortalidad a los 30 días de la visita a urgencias de pacientes con COVID-19. METODO: Estudio observacional de cohortes retrospectivo de 2.511 pacientes con COVID-19 atendidos en el servicio de urgencias hospitalario (SUH) del 1 de marzo al 30 de abril de 2020. Se realizó análisis de supervivencia mediante Kaplan Meier y regresión de Cox. RESULTADOS: La mortalidad por cualquier causa a los 30 días fue de un 8%. Los factores asociados de forma independiente a mayor mortalidad fueron: edad 50 años, índice de Barthel 90 puntos, alteración del nivel de consciencia, índice de SaO2/FIO2 400, auscultación respiratoria anómala, cifra de plaquetas 100.000/mm3, PCR 5 mg/dL y filtrado glomerular 45 mL/min. A estos factores se les asignó una puntuación de 1, excepto a la edad, que se le asignó un valor de 2 puntos. Se dividió el modelo de riesgo en 3 categorías: riesgo bajo (menor o igual a 4 puntos), riesgo intermedio (5-6 puntos) y riesgo alto (igual o superior a 7 puntos). Para los pacientes clasificados como de bajo riesgo la probabilidad de mortalidad a los 30 días fue del 1,7%, en los casos de riesgo intermedio fue del 28,2% y para los de alto riesgo fue del 67,3%. CONCLUSIONES: Disponer de una herramienta para estratificar el riesgo de mortalidad de los pacientes con COVID-19 que consultan a un SUH podría ser de utilidad para la gestión de los recursos sanitarios disponibles.

Predictors of mortality in emergency department patients with sepsis scored 2 or 3 on the Quick Sequential Organ Failure Assessment scale. / Factores predictivos de mortalidad en los pacientes con sepsis y un valor del indicador 'Quick Sequential Organ Failure Assessment' (qSOFA) de 2 o 3 puntos atendidos en un servicio de urgencias.

OBJECTIVES: To identify predictors of mortality after implementation of a treatment protocol in the first 3 hours for patients who come to our emergency department with sepsis scored 2 or 3 on the Quick Sequential Organ Failure Assessment (qSOFA) scale. MATERIAL AND METHODS: Our team identified adult emergency department patients with a diagnosis of sepsis on starting the morning shift between September 2018 and March 2019. We selected patients whose qSOFA score on arrival was 2 or 3. Variables were explored statistically to identify factors associated with mortality. RESULTS: A total of 90 patients with a mean (SD) age of 72 (16) years were included. Thirty-three (37%) died. Univariate analysis detected that the only qSOFA indicator that was significantly associated with mortality was altered mentation (level of consciousness), which was noted in 79% of patients who died versus 54% of survivors (P=.02). Other variables associated with higher mortality were age 70 years or older, an order to limit therapeutic interventions in emergencies, and lactic acid levels on first and second extractions. The treatment protocol was completed in 42% of the cases and compliance was associated with a lower mortality rate of 21% versus 54% when the protocol was not fully implemented (P=.003). Multivariate Cox regression analysis showed that risk for death was higher when the full protocol was not implemented within 3 hours of arrival (hazard ratio, 2.67; 95% CI, 1.15-6.21; P=.02). CONCLUSION: Full implementation of the protocol within 3 hours of hospital arrival favors survival in patients with sepsis and qSOFA scores of 2 or 3 on arrival. We recommend that emergency departments organize ways to train staff in the use of a sepsis treatment protocol and improve compliance.

OBJETIVO: Determinar los factores predictivos de mortalidad de los pacientes que acuden a urgencias con sepsis y tiene un qSOFA de 2 o 3 puntos tras la implementación de un paquete de medidas a cumplimentar en las primeras 3 horas. METODO: De septiembre de 2018 a marzo de 2019 el equipo investigador identificó a los pacientes adultos que se encontraban en urgencias en el inicio del turno de mañana con el diagnóstico de sepsis. De estos pacientes se seleccionaron los que en el momento de su llegada tenían un qSOFA de 2 o 3 puntos. Se realizó análisis estadístico para establecer los factores relacionados con mortalidad. RESULTADOS: Se incluyeron 90 pacientes con una edad media de 72 (DE 16) años. La mortalidad global fue de 33 pacientes (37%). En el análisis univariado de mortalidad, el único indicador del qSOFA con significación estadística fue el nivel de consciencia (79% vs 54%, p = 0,02). Otras variables relacionadas con mayor mortalidad fueron: edad igual o mayor de 70 años, orden de limitación del esfuerzo terapéutico en urgencias y valor de la primera y de la segunda determinación de lactato. El cumplimiento del paquete de medidas fue del 42% y se asoció a una menor mortalidad (21% vs 54%, p = 0,003). En el análisis multivariado mediante regresión de Cox, los pacientes en los que no se cumplimentó el paquete de medidas en las primeras 3 horas tuvieron mayor riesgo de mortalidad al final del episodio (HR = 2,67; IC95% = 1,15-6,21; p = 0,02). CONCLUSIONES: En los pacientes con sepsis y un qSOFA de 2-3 puntos a su llegada a urgencias el cumplimiento del paquete de medidas en las primeras 3 horas mejora la supervivencia. Es recomendable hacer los esfuerzos organizativos y docentes necesarios para mejorar el cumplimiento.

Factors associated with revisits by patients with SARS-CoV-2 infection discharged from a hospital emergency department. / Factores asociados a revisita en pacientes con diagnóstico de infección por SARS-CoV-2 dados de alta de un servicio de urgencias hospitalario.

OBJECTIVES: To analyze emergency department (ED) revisits from patients discharged with possible coronavirus disease 2019 (COVID-19). MATERIAL AND METHODS: Retrospective observational study of consecutive patients who came to the ED over a period of 2 months and were diagnosed with possible COVID-19. We analyzed clinical and epidemiologic variables, treatments given in the ED, discharge destination, need to revisit, and reasons for revisits. Patients who did or did not revisit were compared, and factors associated with revisits were explored. RESULTS: The 2378 patients included had a mean age of 57 years; 49% were women. Of the 925 patients (39%) discharged, 170 (20.5%) revisited the ED, mainly for persistence or progression of symptoms. Sixty-six (38.8%) were hospitalized. Odds ratios (ORs) for the following factors showed an association with revisits: history of rheumatologic disease (OR, 2.97; 95% CI, 1.10-7.99; P = .03), digestive symptoms (OR, 1.73; 95% CI, 1.14-2.63; P = .01), respiratory rate over 20 breaths per minute (OR, 1.03; 95% CI, 1.0-1.06; P = .05), and corticosteroid therapy given in the ED (OR, 7.78; 95% CI, 1.77-14.21, P = .01). Factors associated with hospitalization after revisits were age over 48 years (OR, 2.57; 95% CI, 1 42-4.67; P = .002) and fever (OR, 4.73; 95% CI, 1.99-11.27; P = .001). CONCLUSION: Patients under the age of 48 years without comorbidity and with normal vitals can be discharged from the ED without fear of complications. A history of rheumatologic disease, fever, digestive symptoms, and a respiratory rate over 20 breaths per minute, or a need for corticosteroid therapy were independently associated with revisits. Fever and age over 48 years were associated with a need for hospitalization.

OBJETIVO: Analizar las revisitas y los factores asociados a la misma en pacientes con diagnóstico de posible COVID-19 dados de alta de un servicio de urgencias hospitalario (SUH). METODO: Estudio observacional, retrospectivo que incluyó pacientes consecutivos que consultaron al SUH en un periodo de 2 meses y fueron diagnosticados de posible de COVID-19. Se analizaron variables clínico-epidemiológicas, tratamiento administrado en urgencias, destino final, revisita al SUH y motivo de esta. Se hizo un análisis comparativo entre ambos grupos (revisita sí/no) y se identificaron factores asociados a la revisita. RESULTADOS: Se incluyeron 2.378 pacientes (edad media 57 años; 49% mujeres). De los pacientes dados de alta (39% del total; n = 925), 170 (20,5%) reconsultaron al SUH, principalmente por persistencia o progresión de síntomas, y 66 (38,8%) precisaron ingreso. Los factores relacionados con la revisita fueron: antecedentes de enfermedad reumatológica [OR: 2,97 (IC 95%: 1,10-7,99, p = 0,03)], síntomas digestivos [OR: 1,73 (IC 95%: 1,14-2,63, p = 0,01)], frecuencia respiratoria $ 20 [OR: 1,03 (IC 95%: 1,0-1,06, p = 0,05)] y haber recibido tratamiento con esteroides en urgencias [OR: 7,78 (IC 95%: 1,77-14,21, p = 0,01)]. Los factores asociados al ingreso en la revisita fueron la edad $ 48 años [OR: 2,57 (IC 95%: 1,42-4,67, p = 0,002)] y presentar fiebre [OR: 4,73 (IC 95%: 1,99-11,27, p = 0,001)]. CONCLUSIONES: Los pacientes con posible COVID-19 menores de 48 años, sin comorbilidad y con signos vitales normales podrían ser dados de alta desde urgencias sin temor a sufrir complicaciones. Los antecedentes de enfermedad reumatológica, fiebre, sintomas digestivos, frecuencia respiratoria $ 20/min o necesidad de tratamiento con esteroides fueron factores independientes de revisita, y la fiebre y edad $ 48 años de necesidad de ingreso.

Bioinformatics analysis of Ras homologue enriched in the striatum, a potential target for Huntington's disease therapy.

Huntington's disease (HD) is a lethal neurodegenerative disorder for which no cure is available yet. It is caused by abnormal expansion of a CAG triplet in the gene encoding the huntingtin protein (Htt), with consequent expansion of a polyglutamine repeat in mutated Htt (mHtt). This makes mHtt highly unstable and aggregation prone. Soluble mHtt is linked to cytotoxicity and neurotoxicity, whereas mHtt aggregates are thought to be neuroprotective. While Htt and mHtt are ubiquitously expressed throughout the brain and peripheral tissues, HD is characterized by selective degradation of the corpus striatum, without notable alterations in peripheral tissues. Screening for mRNAs preferentially expressed in rodent striatum led to the discovery of a GTP binding protein homologous to Ras family members. Due to these features, the newly discovered protein was termed Ras Homolog Enriched in Striatum (RHES). The aetiological role of RHES in HD has been ascribed to its small ubiquitin­like modifier (SUMO)­E3 ligase function. RHES sumoylates mHtt with higher efficiency than wild­type Htt, thereby protecting mHtt from degradation and increasing the amounts of the soluble form. Although RHES is an attractive target for HD treatment, essential information about protein structure and function are still missing. With the aim of investigating RHES 3D structure and function, bioinformatic analyses and molecular modelling have been performed in the present study, based on which, RHES regions predicted to be involved in the interaction with mHtt or the SUMO­E2 ligase Ubc9 have been identified. These regions have been used to design peptides aimed at inhibiting RHES interactions and, therefore, mHtt sumoylation; in turn, these peptides will be used to develop small molecule inhibitors by both rational design and virtual screening of large compound libraries. Once identified, RHES sumoylation inhibitors may open the road to the development of therapeutic agents against the severe, and currently untreatable, HD.

Novel compound mutations in the mitochondrial translation elongation factor (TSFM) gene cause severe cardiomyopathy with myocardial fibro-adipose replacement.

Primary mitochondrial dysfunction is an under-appreciated cause of cardiomyopathy, especially when cardiac symptoms are the unique or prevalent manifestation of disease. Here, we report an unusual presentation of mitochondrial cardiomyopathy, with dilated phenotype and pathologic evidence of biventricular fibro-adipose replacement, in a 33-year old woman who underwent cardiac transplant. Whole exome sequencing revealed two novel compound heterozygous variants in the TSFM gene, coding for the mitochondrial translation elongation factor EF-Ts. This protein participates in the elongation step of mitochondrial translation by binding and stabilizing the translation elongation factor Tu (EF-Tu). Bioinformatics analysis predicted a destabilization of the EF-Ts variants complex with EF-Tu, in agreement with the dramatic steady-state level reduction of both proteins in the clinically affected myocardium, which demonstrated a combined respiratory chain enzyme deficiency. In patient fibroblasts, the decrease of EF-Ts was paralleled by up-regulation of EF-Tu and induction of genes involved in mitochondrial biogenesis, along with increased expression of respiratory chain subunits and normal oxygen consumption rate. Our report extends the current picture of morphologic phenotypes associated with mitochondrial cardiomyopathies and confirms the heart as a main target of TSFM dysfunction. The compensatory response detected in patient fibroblasts might explain the tissue-specific expression of TSFM-associated disease.

Detección en urgencias de infección por VIH en pacientes que consultan por condiciones potencialmente relacionadas con infección oculta: Resultados iniciales del programa “Urgències VIHgila” / Emergency detection of HIV infection in patients consulting for conditions potentially related to occult infection: Initial results of the “Urgències VIHgila” program

Objective: To estimate the prevalence of unknown HIV infection in patients who consulted in hospital emergency services (ED) for conditions defined in the SEMES-GESIDA Consensus Document (DC), evaluate the efficiency of its im-plementation and investigate the efficiency of HIV serology determination in other conditions. Methods: Results were reviewed in 10 Catalan EDs for 12 months (July-21-June-22) after implementing CD recommendations: request HIV serology in case of suspected sexually transmitted infection, chemsex, post-exposure prophylaxis (PEP), mononucleosis syndrome, community pneumonia (18-65 y-o) or herpes zoster (18-65 y-o). Other reasons for request were included. Prevalence (%) of global seropositivity and for each circumstance was calculated, with a 95% confidence interval (95%CI). The efficient strategy was considered if the lower limit of the CI95%>0.1%. Results: A total of5,107 HIV serologies were performed: 2,847(56%) in situations specified in CD, and 2,266 (44%) in other 138 circumstances. Forty-eight unknown HIV infections were detected (prevalence=0.94%;95%CI=0.69-1.24). The prevalence was somewhat higher in DC requests (30 cas-es 1.12%) than the rest (18 cases 0.71%; p=0.16). The individualized prevalence of CD reasons ranged between 7.41% (95%CI=0.91-24.3) in chemsex and 0.42% 95%CI=0.14-0.98) in PPE, always efficient except herpes zoster (0.76%; CI95%=0.02-4.18). In other reasons, cases were detected in 12 circumstances, and in four the determination could be efficient: lymphopenia (10%;CI95%=0.25-44.5), fever with polyarthralgia-polyarthritis (7.41%;CI95% =0.91-24.3), behavioral alteration-confusion-encephalopathy (3.45%;95%CI=0.42-11.9) and fever of unknown origin (2.50%;95%CI=0.82-5.74). (AU)

Objetivo: Estimar la prevalencia de infección por VIH des-conocida en pacientes que consultan en servicios de urgencias hospitalarios (SUH) por las condiciones definidas en el Documento de Consenso (DC) de SEMES-GESIDA, evaluar la eficiencia de su implementación e investigar si en otras condiciones la determinación de serología VIH puede resultar eficiente.Método: Se revisaron los resultados obtenidos en 10 SUH catalanes durante los 12 meses (julio-21 a junio-22) siguientes a implementar las recomendaciones del DC de solicitar serología VIH a pacientes con sospecha de infección de transmisión sexual, práctica de chemsex, solicitud profilaxis post-exposición (PPE), síndrome mononucleósico, neumonía comunitaria (18-65 años) o herpes zóster (18-65 años). Se consignaron también otros motivos de solicitud. Se calculó la prevalencia (%) de seropositividad global y para cada circunstancia, con su intervalo de confianza del 95% (IC95%). Se consideró la estrategia eficiente si el límite inferior del IC95% era >0,1%.Resultados: Se realizaron 5.107 serologías VIH: 2.847 (56%) en situaciones especificadas en el DC, y 2.266 (44%) en otras 138 circunstancias. Se detectaron 48 infecciones por VIH desconocidas (prevalencia=0,94%; IC95%=0,69-1,24). La preva-lencia fue algo superior en las solicitudes ajustadas al DC (30 ca-sos, 1,12%) que en las que no (18 casos, 0,71%; p=0,16). La prevalencia individualizada para los motivos especificados en el DC osciló entre 7,41% IC95%=0,91-24,3) en práctica de chemsex y 0,42% (IC95%=0,14-0,98) en PPE, y siempre resultó eficiente, con excepción de herpes zóster (0,76%, IC95%=0,02-4,18). Respecto al resto de motivos de solicitud, se detectaron casos en 12 circunstancias, y en cuatro la determinación podría ser eficiente: linfopenia (10%, IC95%=0,25-44,5), fiebre con poliartralgias-poliartritis (7,41%, IC95%=0,91-24,3), alteración conductual-confusión-encefalopatía (3,45%,IC95%=0,42-11,9) y fiebre de origen desconocido(2,50%,IC95%=0,82-5,74)(AU)

Proteomic and functional analyses reveal pleiotropic action of the anti-tumoral compound NBDHEX in Giardia duodenalis.

Giardiasis, a parasitic diarrheal disease caused by Giardia duodenalis, affects one billion people worldwide. Treatment relies only on a restricted armamentarium of drugs. The disease burden and the increase in treatment failure highlight the need for novel, safe and well characterized drug options. The antitumoral compound NBDHEX is effective in vitro against Giardia trophozoites and inhibits glycerol-3-phosphate dehydrogenase. Aim of this work was to search for additional NBDHEX protein targets. The intrinsic NBDHEX fluorescence was exploited in a proteomic analysis to select and detect modified proteins in drug treated Giardia. In silico structural analysis, intracellular localization and functional assays were further performed to evaluate drug effects on the identified targets. A small subset of Giardia proteins was covalently bound to the drug at specific cysteine residues. These proteins include metabolic enzymes, e.g. thioredoxin reductase (gTrxR), as well as elongation factor 1B-γ (gEF1Bγ), and structural proteins, e.g. α-tubulin. We showed that NBDHEX in vitro binds to recombinant gEF1Bγ and gTrxR, but only the last one could nitroreduce NBDHEX leading to drug modification of gTrxR catalytic cysteines, with concomitant disulphide reductase activity inhibition and NADPH oxidase activity upsurge. Our results indicate that NBDHEX reacts with multiple targets whose roles and/or functions are specifically hampered. In addition, NBDHEX is in turn converted to reactive intermediates extending its toxicity. The described NBDHEX pleiotropic action accounts for its antigiardial activity and encourages the use of this drug as a promising alternative for the future treatment of giardiasis.

Validación temporal de un modelo de riesgo de mortalidad por COVID-19 en una cohorte prospectiva en un servicio de urgencias de un hospital de tercer nivel / Risk score for mortality due to COVID-19: a prospective temporal validation cohort study in the emergency department of a tertiary care hospital

Objetivo. Validación de un indicador de mortalidad previamente descrito en pacientes con COVID-19 en un servicio de urgencias hospitalario (SUH). Método. Estudio observacional prospectivo no intervencionista. Se incluyeron pacientes $ 18 años diagnosticados de COVID-19 (1 de diciembre de 2020 hasta 28 de febrero de 2021). Se calculó el indicador para cada paciente: edad $ 50 años (2 puntos), índice de Barthel < 90 puntos (1 punto), alteración de consciencia (1 punto), índice de SaO2/ FIO2 < 400 (1 punto), auscultación respiratoria patológica (1 punto), plaquetas < 100 x 109/L (1 punto), proteína C reactiva $ 5 mg/dL (1 punto) y filtrado glomerular < 45 mL/min (1 punto). La variable dependiente fue la mortalidad observada a 30 días. El rendimiento del indicador se valoró con el análisis del área bajo la curva de la característica operativa del receptor (ABC-COR). Resultados. La validación del indicador se realizó sobre una cohorte de 1.223 pacientes. Tras una mediana de seguimiento de 80 días, 143 pacientes habían fallecido. Un total de 901 pacientes fueron catalogados como riesgo bajo (indicador # 4 puntos), 270 lo fueron como riesgo intermedio (5-6 puntos) y 52 como riesgo alto ($ 7 puntos). La mortalidad a 30 días observada en cada categoría fue de 2,8%, 22,5% y 65,4%, respectivamente. El ABC-COR fue de 0,883 para el indicador utilizado cuantitativamente y de 0,818 cuando se usó cualitativamente en forma de categorías de riesgo. Conclusión. El indicador descrito es una herramienta útil para estratificar el riesgo de mortalidad de los pacientes con COVID-19 que consultan a un SUH de un centro de tercer nivel.

Objective. To validate a previously described hospital emergency department risk model to predict mortality in patients with COVID-19. Methods. Prospective observational noninterventional study. Patients aged over 18 years diagnosed with COVID-19 were included between December 1, 2020, and February 28, 2021. We calculated a risk score for each patient based on age $50 years (2 points) plus 1 point each for the presence of the following predictors: Barthel index <90 points, altered level of consciousness, ratio of arterial oxygen saturation to fraction of inspired oxygen <400, abnormal breath sounds, platelet concentration <100 × 109/L, C reactive protein level $5 mg/dL, and glomerular filtration rate <45 mL/min. The dependent variable was 30-day mortality. We assessed the score’s performance with the area under the receiver operating characteristic curve (AUC). Results. The validation cohort included 1223 patients. After a median follow-up of 80 days, 143 patients had died; 901 patients were classified as having low risk (score, #4 points), 270 as intermediate risk (5-6 points), and 52 as high risk ($7 points). Thirty-day mortality rates at each risk level were 2.8%, 22.5%, and 65.4%, respectively. The AUC for the score was 0.883; for risk categorization, the AUC was 0.818. Conclusion. The risk score described is useful for stratifying risk for mortality in patients with COVID-19 who come to a tertiary-care hospital emergency department.

Análisis individualizado por sexo de los factores asociados a la clasificación inicial errónea en urgencias del dolor torácico como no coronario / Factors associated with erroneous emergency department noncardiac chest pain classifications in men and women

Introducción. Analizar de forma independiente en mujeres y hombres la frecuencia y las características clínicas asociadas a una clasificación inicial errónea (CIE) en urgencias del dolor torácico (DT) como no coronario. Método. Se analizan todas las consultas por DT atendidas en urgencias entre 2008 y 2017 clasificadas inicialmente (historia clínica y ECG) como DT no coronario. Se consideró como CIE si el diagnóstico final fue síndrome coronario agudo (SCA). Se crearon dos modelos multivariable, uno con 10 factores de riesgo, y otro con 10 características clínicas del DT, en los que se investigó la asociación de estas variables con una CIE. Se analizaron independientemente mujeres y hombres. Resultados. Se analizaron 8.093 mujeres con DT clasificado inicialmente como no coronario (edad mediana: 54 años, RIC: 38-73), 72 con CIE (0,9%). Los factores de riesgo asociados independientemente a CIE fueron obesidad (OR = 0,40; IC 95% = 0,17-0,97) y consumo de cocaína (5,18; 1,16-23,2), y las características clínicas fueron relación con el esfuerzo (2,01; 1,21-3,33), existencia de irradiación (2,05; 1,23-3,41) y síntomas vegetativos acompañantes (1,86; 1,02-3,41). Se analizaron 9.979 hombres (edad mediana: 47 años, RIC: 33-64), 83 con CIE (0,8%). Los factores de riesgo asociados a CIE fueron edad > 40 años (1,74; 1,04-2,91) e hipertensión (0,45; 0,24-0,84). No hubo características clínicas del DT asociadas a CIE. Conclusión. En las mujeres con dolor torácico, se identifican más características asociadas al error de clasificación que en los hombres. Este estudio remarca la necesidad de análisis independiente por sexo en el SCA, en el que clásica- mente se ha considerado la clínica en las mujeres como atípica. (AU)

Objective. To analyze the frequency and clinical characteristics associated with erroneous initial classifications of noncardiac chest pain (NCP) in men and women. Methods. We analyzed all case records in which chest pain was initially classified as noncardiac in origin according to clinical signs and electrocardiograms evaluated in our emergency department between 2008 and 2017. We considered the initial evaluation of NCP to be in error if the final diagnosis was acute coronary syndrome. A risk model for an erroneous initial classification of NCP was developed based on multivariable analysis of our patient data. We also used multivariable analysis to explore associations between 10 clinical signs of chest pain and an erroneous initial NCP classification. The data for men and women were analyzed separately. Results. NCP was the initial classification for 8093 women; their median (interquartile range) age was 54 (38-73) years. The classification was in error for 72 women (0.9%). Odds ratios (ORs) showed that patient risk factors associated with an erroneous NCP classification in the women in our series were obesity (OR, 0.40; 95% CI, 0.17- 0.97) and cocaine consumption (OR, 5.18; 95% CI, 1.16-23.2). Clinical risk factors associated with erroneous NCP classification in women were recent physical exertion (OR, 2.01; 95% CI, 1.21-3.33), radiation exposure (OR, 2.05; 95% CI, 1.23-3.41), and vegetative symptoms (OR, 1.86; 95% CI, 1.02-3.41). For 9979 men with a median age of 47 (33-64) years, NCP was the initial classification; in 83 of the men (0.8%) the classification was erroneous. Patient factors associated with erroneous NCP classification in men were age over 40 years (OR, 1.74; 95% CI, 1.04-2.91) and hypertension (OR, 0.45; 95% CI, 0.24-0.84). No clinical signs of chest pain in men were associated with error. Conclusions. More clinical characteristics are associated with an erroneous classification of NCP in women. [...] (AU)

Adecuación del uso de antibióticos de "Categoría Especial" en el Servicio de Urgencias de un hospital de tercer nivel / Adequacy of the special category antibiotics prescriptions in the Emergency Department of a third level urban Hospital

OBJETIVO: Analizar la adecuación de las prescripciones de antibióticos de categoría especial (ATB de CE) en el Servicio de Urgencias Hospitalario (SUH) de un centro urbano de tercer nivel. MATERIAL Y MÉTODOS: Se seleccionó una muestra aleatoria de 100 pacientes diferentes a los que se les inició un ATB de CE en Urgencias durante el año 2018. El equipo investigador revisó la historia clínica del episodio de urgencias y de ingreso. Se determinó mediante regresión logística los factores independientes asociados con el grado de adecuación del tratamiento. RESULTADOS: Se analizaron 97 prescripciones de las cuales 66 (68%) cumplían los criterios de prescripción adecuada. El grado de adecuación fue del 70% si la infección estaba relacionada con la asistencia sanitaria y del 75% si el paciente tenía factores de riesgo de infección por microorganismos multirresistentes (MMR). El porcentaje de adecuación fue mayor en los casos en los que se especificó el foco de la infección (72%) y la gravedad del episodio (73%). Las variables independientes que se asociaron a una prescripción adecuada fueron: la presencia de factores de riesgo de infección por MMR (OR: 2,35 IC 95%: 1,65 - 3,17 p: 0,01), el especificar el foco de la infección (OR: 3,79 IC 95%: 1,72 - 4,22 p: 0,02) y señalar la gravedad del episodio (OR: 3,09 IC 95%: 1,12 - 3,09 p: 0,03). CONCLUSIONES: La prescripción de los ATB de CE en el SUH es adecuada en la medida que se tenga en cuenta el ámbito de adquisición de la infección, los factores de riesgo de MMR, el foco de infección y la gravedad del cuadro clínico

OBJECTIVE: The aim of the study was to analyze the adequacy of the special category antibiotics prescriptions in the Emergency Department (ED) of a third level urban Hospital. MATERIAL AND METHODS: A random sample of 100 different patients who were started with a special category antibiotic along 2018 in the ED was selected. The research team reviewed the medical history of the emergency and admission episode. The independent factors associated with the degree of adequacy of the treatment were determined by logistic regression. RESULTS: A total of 97 prescriptions were analyzed of which 66 (68%) met the criteria of adequate prescription, 23 (24%) adequate prescription, but with equally recommended alternatives and 8 (8%) were inappropriate prescriptions. The degree of adequacy was 70% if the infection was related to healthcare and 75% if the patient had risk factors for multiresistant (MR) microorganisms' infection. The percentage of adequacy was higher in the cases in which the focus of the infection (72%) and the severity of the episode (73%) were specified. The independent variables that were associated with an adequate prescription were: the presence of risk factors for MR microorganisms' infection (OR: 2.35 95% CI: 1.65 - 3.17 p: 0.01), if the focus of the infection (OR: 3.79 95% CI: 1.72 - 4.22 p: 0.02) and the severity of the episode (OR: 3.09 95% CI: 1.12 - 3.09 p: 0.03) were specified. CONCLUSIONS: The prescription of special category antibiotics in ED is appropriate if the clinical guidelines are followed and if the setting of infection acquisition, the risk factors of MR microorganisms, the focus and the severity of infection are taken into account in clinical picture

Factores predictivos de mortalidad en los pacientes con sepsis y un valor del indicador 'Quick Sequential Organ Failure Assessment' (qSOFA) de 2 o 3 puntos atendidos en un servicio de urgencias / Predictors of mortality in emergency department patients with sepsisscored 2 or 3 on the Quick Sequential Organ Failure Assessment scale

OBJETIVO. Determinar los factores predictivos de mortalidad de los pacientes que acuden a urgencias con sepsis y tiene un qSOFA de 2 o 3 puntos tras la implementación de un paquete de medidas a cumplimentar en las primeras 3 horas. MÉTODO: De septiembre de 2018 a marzo de 2019 el equipo investigador identificó a los pacientes adultos que se encontraban en urgencias en el inicio del turno de mañana con el diagnóstico de sepsis. De estos pacientes se seleccionaron los que en el momento de su llegada tenían un qSOFA de 2 o 3 puntos. Se realizó análisis estadístico para establecer los factores relacionados con mortalidad. RESULTADOS: Se incluyeron 90 pacientes con una edad media de 72 (DE 16) años. La mortalidad global fue de 33 pacientes (37%). En el análisis univariado de mortalidad, el único indicador del qSOFA con significación estadística fue el nivel de consciencia (79% vs 54%, p = 0,02). Otras variables relacionadas con mayor mortalidad fueron: edad igual o mayor de 70 años, orden de limitación del esfuerzo terapéutico en urgencias y valor de la primera y de la segunda determinación de lactato. El cumplimiento del paquete de medidas fue del 42% y se asoció a una menor mortalidad (21% vs 54%, p = 0,003). En el análisis multivariado mediante regresión de Cox, los pacientes en los que no se cumplimentó el paquete de medidas en las primeras 3 horas tuvieron mayor riesgo de mortalidad al final del episodio (HR = 2,67; IC95% = 1,15-6,21; p = 0,02). CONCLUSIÓN: En los pacientes con sepsis y un qSOFA de 2-3 puntos a su llegada a urgencias el cumplimiento del paquete de medidas en las primeras 3 horas mejora la supervivencia. Es recomendable hacer los esfuerzos organizativos y docentes necesarios para mejorar el cumplimiento

OBJECTIVE: To identify predictors of mortality after implementation of a treatment protocol in the first 3 hours for patients who come to our emergency department with sepsis scored 2 or 3 on the Quick Sequential Organ Failure Assessment (qSOFA) scale. METHODS: Our team identified adult emergency department patients with a diagnosis of sepsis on starting the morning shift between September 2018 and March 2019. We selected patients whose qSOFA score on arrival was 2 or 3. Variables were explored statistically to identify factors associated with mortality. RESULTS: A total of 90 patients with a mean (SD) age of 72 (16) years were included. Thirty-three (37%) died. Univariate analysis detected that the only qSOFA indicator that was significantly associated with mortality was altered mentation (level of consciousness), which was noted in 79% of patients who died versus 54% of survivors (P=.02). Other variables associated with higher mortality were age 70 years or older, an order to limit therapeutic interventions in emergencies, and lactic acid levels on first and second extractions. The treatment protocol was completed in 42% of the cases and compliance was associated with a lower mortality rate of 21% versus 54% when the protocol was not fully implemented (P=.003). Multivariate Cox regression analysis showed that risk for death was higher when the full protocol was not implemented within 3 hours of arrival (hazard ratio, 2.67; 95% CI, 1.15-6.21; P=.02). CONCLUSIONS: Full implementation of the protocol within 3 hours of hospital arrival favors survival in patients with sepsis and qSOFA scores of 2 or 3 on arrival. We recommend that emergency departments organize ways to train staff in the use of a sepsis treatment protocol and improve compliance

In Vivo Targeting of Cutaneous Melanoma Using an Melanoma Stimulating Hormone-Engineered Human Protein Cage with Fluorophore and Magnetic Resonance Imaging Tracers.

Nanoparticle (NP)-based materials are promising agents for enhancing cancer diagnosis and treatment. Once functionalized for selective targeting of tumor-expressed molecules, they can specifically deliver drugs and diagnostic molecules inside tumor cells. In the present work, we evaluated the in vivo melanoma-targeting ability of a nanovector (HFt-MSH-PEG) based on human protein ferritin (HFt), functionalized with both melanoma-targeting melanoma stimulating hormone (α-MSH) and stabilizing poly(ethylene glycol) (PEG) molecules. Independent and complementary techniques, such as whole-specimen confocal microscopy and magnetic resonance imaging, were used to detect in vivo localization of NP constructs with suitable tracers (i.e., fluorophores or magnetic metals). Targeted HFt-MSH-PEG NPs accumulated persistently at the level of primary melanoma and with high selectivity with respect to other organs. Melanoma localization of untargeted HFt-PEG NPs, which lack the α-MSH moiety, was less pronounced. Furthermore, HFt-MSH-PEG NPs accumulated to a significantly lower extent and with a different distribution in a diverse type of tumor (TS/A adenocarcinoma), which does not express α-MSH receptors. Finally, in a spontaneous lung metastasis model, HFt-MSH-PEG NPs localized at the metastasis level as well. These results suggest that HFt-MSH-PEG NPs are suitable carriers for selective in vivo delivery of diagnostic or therapeutic agents to cutaneous melanoma.

Factores asociados a revisita en pacientes con diagnóstico de infección por SARS-CoV-2 dados de alta de un servicio de urgencias hospitalario / Factors associated with revisits by patients with SARS-CoV-2 infection discharged from a hospital emergency department

OBJETIVO: Analizar las revisitas y los factores asociados a la misma en pacientes con diagnóstico de posible COVID-19 dados de alta de un servicio de urgencias hospitalario (SUH). MÉTODO: Estudio observacional, retrospectivo que incluyó pacientes consecutivos que consultaron al SUH en un periodo de 2 meses y fueron diagnosticados de posible de COVID-19. Se analizaron variables clínico-epidemiológicas, tratamiento administrado en urgencias, destino final, revisita al SUH y motivo de esta. Se hizo un análisis comparativo entre ambos grupos (revisita sí/no) y se identificaron factores asociados a la revisita. RESULTADOS: Se incluyeron 2.378 pacientes (edad media 57 años; 49% mujeres). De los pacientes dados de alta (39% del total; n = 925), 170 (20,5%) reconsultaron al SUH, principalmente por persistencia o progresión de síntomas, y 66(38,8%) precisaron ingreso. Los factores relacionados con la revisita fueron: antecedentes de enfermedad reumatológica [OR: 2,97 (IC 95%: 1,10-7,99, p = 0,03)], síntomas digestivos [OR: 1,73 (IC 95%: 1,14-2,63, p = 0,01)], frecuencia respiratoria>=20 [OR: 1,03 (IC 95%: 1,0-1,06, p = 0,05)] y haber recibido tratamiento con esteroides en urgencias[OR: 7,78 (IC 95%: 1,77-14,21, p = 0,01)]. Los factores asociados al ingreso en la revisita fueron la edad>=48 años[OR: 2,57 (IC 95%: 1,42-4,67, p = 0,002)] y presentar fiebre [OR: 4,73 (IC 95%: 1,99-11,27, p = 0,001)]. CONCLUSIÓN: Los pacientes con posible COVID-19 menores de 48 años, sin comorbilidad y con signos vitales normales podrían ser dados de alta desde urgencias sin temor a sufrir complicaciones. Los antecedentes de enfermedad reumatológica, fiebre, sintomas digestivos, frecuencia respiratoria>=20/min o necesidad de tratamiento con esteroides fueron factores independientes de revisita, y la fiebre y edad>=48 años de necesidad de ingreso

OBJECTIVE: To analyze emergency department (ED) revisits from patients discharged with possible coronavirus disease2019 (COVID-19). METHODS: Retrospective observational study of consecutive patients who came to the ED over a period of 2 monthsand were diagnosed with possible COVID-19. We analyzed clinical and epidemiologic variables, treatments given inthe ED, discharge destination, need to revisit, and reasons for revisits. Patients who did or did not revisit werecompared, and factors associated with revisits were explored. RESULTS: The 2378 patients included had a mean age of 57 years; 49% were women. Of the 925 patients (39%) discharged, 170 (20.5%) revisited the ED, mainly for persistence or progression of symptoms. Sixty-six (38.8%) were hospitalized. Odds ratios (ORs) for the following factors showed an association with revisits: history of rheumatologic disease (OR, 2.97; 95% CI, 1.10-7.99;P= .03), digestive symptoms (OR, 1.73; 95% CI, 1.14-2.63;P= .01), respiratory rate over 20 breaths per minute (OR, 1.03; 95% CI, 1.0-1.06;P = .05), and corticosteroid therapy given in the ED (OR, 7.78; 95% CI, 1.77-14.21,P= .01). Factors associated with hospitalization after revisits were age over 48 years (OR, 2.57; 95% CI, 1 42-4.67;P= .002) and fever (OR, 4.73; 95% CI, 1.99-11.27;P= .001). CONCLUSIONS: Patients under the age of 48 years without comorbidity and with normal vitals can be discharged from the ED without fear of complications. A history of rheumatologic disease, fever, digestive symptoms, and a respiratory rate over 20 breaths per minute, or a need for corticosteroid therapy were independently associated with revisits. Fever and age over 48 years were associated with a need for hospitalization