A randomised phase II study of osimertinib and bevacizumab versus osimertinib alone as second-line targeted treatment in advanced NSCLC with confirmed EGFR and acquired T790M mutations: the European Thoracic Oncology Platform (ETOP 10-16) BOOSTER trial.

BACKGROUND: While osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is the standard treatment in patients with advanced non-small-cell lung cancer (NSCLC) with sensitising EGFR and acquired T790M mutations, progression inevitably occurs. The angiogenic pathway is implicated in EGFR TKI resistance. PATIENTS AND METHODS: BOOSTER is an open-label randomised phase II trial investigating the efficacy and safety of combined osimertinib 80 mg daily and bevacizumab 15 mg/kg every 3 weeks, versus osimertinib alone, in patients with EGFR-mutant advanced NSCLC and acquired T790M mutations after failure on previous EGFR TKI therapy. Primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR) and adverse events (AEs). RESULTS: Between May 2017 and February 2019, 155 patients were randomised (combination: 78; osimertinib: 77). At data cut-off of 22 February 2021, median follow-up was 33.8 months [interquartile range (IQR): 26.5-37.6 months] and 129 (83.2%) PFS events were reported in the intention-to-treat population. There was no difference in median PFS between the combination [15.4 months; 95% confidence interval (CI) 9.2-18.0 months] and osimertinib arm (12.3 months; 95% CI 6.2-17.2 months; stratified log-rank P = 0.83), [hazard ratio (HR) = 0.96; 95% CI 0.68-1.37]. Median OS was 24.0 months (95% CI 17.8-32.1 months) in the combination arm and 24.3 months (95% CI 16.9-37.0 months) in the osimertinib arm (stratified log-rank P = 0.91), (HR = 1.03; 95% CI 0.67-1.56). Exploratory analysis revealed a significant interaction of smoking history with treatment for PFS (adjusted P = 0.0052) with a HR of 0.52 (95% CI 0.30-0.90) for smokers, and 1.47 (95% CI 0.92-2.33) for never smokers. ORR was 55% in both arms and the median time to treatment failure was significantly shorter in the combination than in the osimertinib arm, 8.2 months versus 10.8 months, respectively (P = 0.0074). Safety of osimertinib and bevacizumab was consistent with previous reports with grade ≥3 treatment-related AEs (TRAEs) reported in 47% and 18% of patients on combination and osimertinib alone, respectively. CONCLUSIONS: No difference in PFS was observed between osimertinib plus bevacizumab and osimertinib alone. Grade ≥3 TRAEs were more common in patients on combination.

Documento de consenso de la Sociedad Española de Médicos de Atención Primaria y Capítulo Español de Flebología y Linfología de la Sociedad Española de Angiología y Cirugía Vascular: trombosis venosa superficial de miembros inferiores en Atención Primaria / Consensus document of the Spanish Society of Primary Care Physicians and the Spanish Chapter of Phlebology and Lymphology of the Spanish Society of Angiology and Vascular Surgery: Superficial vein thrombosis of the lower limbs in Primary Care

La trombosis venosa superficial de miembros inferiores se venía considerando como una patología de naturaleza benigna con un curso clínico autolimitado, actualmente se conoce que sus potenciales complicaciones pueden ser graves o incluso mortales como pueden ser la trombosis venosa profunda o el tromboembolismo pulmonar. Existen diferentes formas de presentación clínica, factores de riesgo y diferentes tratamientos para su abordaje principalmente en Atención Primaria. Nuestro grupo de trabajo de vasculopatías de la Sociedad Española de Médicos de Atención Primaria (SEMERGEN) ha elaborado esta actualización con la evidencia científica actual de forma conjunta con el Capítulo Español de Flebología y Linfología de la Sociedad Española de Angiología y Cirugía Vascular

Superficial vein thrombosis of the lower limbs used to be considered a benign condition with a self-limiting clinical course. It is now known that its potential complications can be serious or even fatal, such as deep vein thrombosis or pulmonary thromboembolism. There are different forms of clinical presentation, risk factors and different treatments for its approach, mainly in Primary Care. The Vascular Diseases Working Group of the Spanish Society of Primary Care Physicians (SEMERGEN) has developed this update using current scientific evidence and jointly with the Spanish Chapter of Phlebology and Lymphology of the Spanish Society of Angiology and Vascular Surgery

Long-term survival in advanced non-squamous NSCLC patients treated with first-line bevacizumab-based therapy

Background/Aim. First-line bevacizumab-based therapies have been shown to improve clinical outcomes in patients with non-squamous non-small-cell lung cancer (NSCLC). We aimed to descriptively analyse patients with non-squamous NSCLC who received a long-term period of maintenance bevacizumab. Patients and methods. This retrospective study included 104 patients who had already reached a progression-free survival (PFS) of at least 9 months. Results. Median overall survival and PFS were 30.7 and 15.1 months, respectively. The overall response rate was 83 %. Weight loss ≤5 %, ECOG PS = 0, or low number of metastatic sites seem to be predictive factors of good evolution. The incidence of bevacizumab-related adverse events appeared to be similar as the previous studies. Conclusion. Our findings show that there is a long-term survivor group whom the administration of bevacizumab resulted in a relevant prolongation of response without new safety signals. Due to the population heterogeneity, it was not possible to identify the standardised predictive factors (AU)

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¿Influye la promoción de la salud escolar en los hábitos de los alumnos? / Influence of school health promotion on the life habits of schoolchildren

INTRODUCCIÓN: En las últimas décadas, han cobrado importancia las teorías globales que tratan de prevenir la obesidad mediante ambientes favorecedores de opciones saludables. El objetivo de este estudio fue analizar la influencia de los entornos promotores de la salud de las escuelas de Logroño (La Rioja, España) sobre los hábitos de sus escolares. MÉTODOS: La promoción de la salud de las 31 escuelas de la ciudad fue valorada mediante un cuestionario que completaron los directivos de cada centro. Por otro lado, se valoraron variables individuales de una muestra representativa de 329 escolares de sexto curso de Educación Primaria (11-12 años) de las citadas escuelas: medidas antropométricas, adhesión a la dieta mediterránea y hábitos sedentarios y de práctica física. RESULTADOS: La mayoría de los centros desarrollaba programas de nutrición y/o actividad física (el 77,4 y el 61,3%, respectivamente), aunque, en general, su profesorado no recibía formación al respecto. Las directrices para favorecer hábitos saludables no solían recogerse en el Proyecto Educativo de Centro y la actividad física, cuyo nivel fue mayor en los chicos (p < 0,001), era promovida principalmente tras el horario escolar. A pesar de ello, la formación del profesorado, la concreción de directrices y el acceso a las pistas polideportivas influyeron positivamente sobre los hábitos de práctica física y alimentación de los escolares (p < 0,05). CONCLUSIONES: Aunque más investigación es necesaria, nuestro estudio demostró que aspectos como la formación y la coordinación de los maestros o la presencia de pistas deportivas podrían conllevar beneficios sobre los hábitos de los alumnos en una etapa fundamental para la consolidación de los mismos

INTRODUCTION: In recent decades, attention has been directed at global theories that attempt to prevent childhood obesity by exposing them to healthy environments. The aim of this study was to analyze the influence of health-promoting environments in primary schools in Logroño (La Rioja, Spain) on the habits of school children. METHODS: The directors of the 31 primary schools in the city completed a questionnaire which examined the health promotion activities of their schools. In addition, anthropometric measurements, adherence to the Mediterranean diet, and sedentary and physical activity habits were recorded from a representative sample of 329 schoolchildren in the sixth year of primary education (11-12 year-olds). RESULTS: The majority of schools had developed nutritional and/or physical activity programs (77.4% and 61.3%, respectively); however, teachers had generally not received specific training in that area. Guidelines regarding healthy habits were not formally included in the School Educational Project. Physical activity, which was greater amongst boys (P<.001), was mostly promoted after school hours. The major influences on school children's physical activity and dietary habits of the children were training of teachers, existence of guidelines, and access to sports grounds (P<.05). CONCLUSIONS: Although further research is required, this study shows that certain modifiable aspects in the organizational or school environment can influence the habits of school children at a fundamental stage of their development

Aptitudes de aprendizaje y desempeño escolar en niños y jóvenes con epilepsia ausencia / Learning skills and academic performance in children and adolescents with absence epilepsy

Introducción: Aunque se describen desórdenes cognitivos y trastornos del aprendizaje en pacientes que presentan epilepsia, son pocos los trabajos que estudian trastornos específicos como la epilepsia ausencia. El objetivo del presente trabajo fue evaluar las características escolares y las aptitudes del aprendizaje en niños y jóvenes que presentan epilepsia ausencia. Métodos: Investigación observacional analítica de casos y controles. Los casos fueron escogidos en la consulta de la Liga Central contra la Epilepsia de Bogotá. Los controles se seleccionaron de un colegio privado y fueron pareados con los casos por edad, grado escolar y sexo. Se evaluaron la historia clínica, la frecuencia de las crisis, el tratamiento farmacológico, el desempeño académico. Las aptitudes escolares se estudiaron por medio de la Batería de Aptitudes Diferenciales y Generales (BADyG). Los datos fueron analizados por medio del test T de Student. Resultados: La muestra estuvo conformada por 19 casos y 19 controles entre los 7 y 16 años. Quince pacientes se encontraban controlados, todos habían recibido medicación antiepiléptica y el 78,9% se encontraba con tratamiento activo. Aunque los casos presentaron mayores fallas académicas, más incidencia en pérdidas de grado y mayores intervenciones terapéuticas que los controles, no hubo diferencias significativas. Igualmente no hubo diferencias en la prueba de BADyG, salvo en la subprueba de memoria inmediata en la que los casos tuvieron resultados superiores (p = 0,0006). Conclusión: Los niños con epilepsia ausencia tratados farmacológicamente y controlados en lo que se refiere a crisis tienen las aptitudes y competencias académicas que corresponden normalmente a su edad

Introduction: Although cognitive and learning disorders have been described in patients with epilepsy, very few studies focus on specific disorders such as absence epilepsy. The aim of this study was to evaluate learning skills and academic performance in children and adolescents with absence epilepsy. Methods: Observational case-control study. Cases were chosen from the Central League against Epilepsy's clinic in Bogotá, Colombia. Controls were selected from a private school and matched with cases by age, school year, and sex. Medical history, seizure frequency, antiepileptic treatment, and academic performance were assessed. Academic abilities were tested with Batería de Aptitudes Diferenciales y Generales (BADyG) (a Spanish-language test of differential and general aptitudes). Data were analysed using Student t-test. Results: The sample consisted of 19 cases and 19 controls aged between 7 and 16. In 15 patients, seizures were controlled; all patients had received antiepileptic medication at some point and 78.9% were actively being treated. Although cases had higher rates of academic failure, a greater incidence of grade retention, and more therapeutic interventions than controls, these differences were not significant. Similarly, there were no significant differences on the BADyG test, except for the immediate memory subcategory on which cases scored higher than controls (P = .0006). Conclusion: Children treated pharmacologically for absence epilepsy, whose seizures are controlled, have normal academic abilities and skills for their age

Cisplatin puls oral vinorelbine as first-line treatment for advanced non-small-cell lung cancer: a prospective study confirming that the day-8 hemogram is unnecessary

INTRODUCTION: Cisplatin plus oral vinorelbine, one of the standard treatments for metastatic non-small-cell lung cancer (NSCLC), is associated with a high rate of neutropenia, and a hemogram is performed on day 8. We analyzed the oncologists' opinions and the result of the hemogram on day 8 to address the question of whether this hemogram could be avoided. MATERIALS AND METHODS: Fifty-eight chemotherapy-naive, advanced NSCLC patients were included. Each received intravenous doses of 75 mg/m(2) cisplatin on day 1 plus oral vinorelbine [60 mg/m(2) in the first cycle (80 mg/m(2) in subsequent cycles) on days 1 and 8], every 3 weeks, for a maximum of six cycles. RESULTS: Out of 257 cycles analyzed, oral vinorelbine was administered on day 8 in 214 (83.2 %) and the dose was canceled in 6 cycles (2.3 %) due to hematological toxicity. On analyzing the patients to whom chemotherapy had been administered on day 8, based on medical opinion without the doctor knowing the hemogram result, we found that the cycle had been administered with a hemogram showing fewer than 1,500 × 10(6) neutrophils in only 3 of the 185 evaluable cycles [event rate of 1.6 %, with confidence interval 95 % = (0.34-4.67 %)]. CONCLUSION: The hemogram on day 8 can be avoided and oral vinorelbine administered in relative safety in patients with good performance status, when confirmed by the clinician's perception, thereby making this regimen more comfortable for the patient. This is the first prospective study to examine this issue (AU)

Pathogenic prions deviate PrP(C) signaling in neuronal cells and impair A-beta clearance.

The subversion of the normal function exerted by the cellular prion protein (PrP(C)) in neurons by pathogenic prions is assumed to have a central role in the pathogenesis of transmissible spongiform encephalopathies. Using two murine models of prion infection, the 1C11 neuronal cell line and neurospheres, we document that prion infection is associated with the constitutive activation of signaling targets normally coupled with PrP(C), including the Fyn kinase, the mitogen-associated protein kinases ERK1/2 and the CREB transcription factor. PrP(C)-dependent signaling overactivation in infected cells is associated with the recruitment of p38 and JNK stress-associated kinases. Downstream from CREB, prion-infected cells exhibit reduced activity of the matrix metalloprotease (MMP)-9. As MMP-9 catalyzes the degradation of the amyloid A-beta peptide, the decrease in MMP-9 activity in prion-infected cells causes a significant impairment of the clearance of A-beta, leading to its accumulation. By exploiting two 1C11-infected clones accumulating high or moderate levels of prions, we show that the prion-induced changes are correlated with the level of infectivity. Of note, a dose-dependent increase in A-beta levels was also found in the cerebrospinal fluid of mice inoculated with these infected clones. By demonstrating that pathogenic prions trigger increases in A-beta levels through the deviation of PrP(C) signaling, our data argue that A-beta may exacerbate prion-induced toxicity.

Saco y pseudosaco. Su importancia en el diagnóstico diferencial ecográfico de la gestación ectópica / Gestational sac and pseudosac. Their importance in ultrasound diagnosis of ectopic pregnancies

En el presente trabajo los autores tratarán de revisar los aspectos prácticos más relevantes y novedosos en relación con el diagnóstico y tratamiento de la gestación ectópica. Presentamos el caso de una paciente que acudió a la consulta de urgencias por metrorragia escasa en el primer trimestre de la gestación y en el que la presencia de un pseudosaco intrauterino dificultó el diagnóstico diferencial entre una gestación eutópica anembrionada, un embarazo heterotópico y un ectópico tubárico. El cuadro cursó con rotura espontánea de este último durante el proceso diagnóstico y precisó tratamiento con legrado evacuador y salpingectomía perlaparotómica, siendo la evolución posterior de la paciente favorable (AU)

We report the case of a pregnant woman who presented to the emergency department with slight vaginal bleeding in the first trimester of pregnancy. The the differential diagnosis between eutopic, heterotopic and tubal ectopic pregnancy was hampered by the presence of an intrauterine pseudosac. The clinical course was complicated by spontaneous rupture of a tubal ectopic pregnancy, which required curettage and laparotomic salpingectomy. The postoperative outcome was favorable. The present article reviews the most important and novel practical features related to the diagnosis and treatment of ectopic pregnancies (AU)

Implicaciones pronósticas de la posibilidad de determinar con carácter urgente el péptido natriuréticotipo B en el servicio de urgencias en pacientes con insuficiencia cardiaca aguda: estudio PICASU-2 / Prognostic implications of emergency department determination of B-type natriuretic peptide in patients with acute heart failure: the PICASU-2 study

Objetivo: Investigar si la determinación del péptido natriurético tipo B (BNP) con carácter urgente en el servicio de urgencias hospitalario (SUH) a pacientes con insuficiencia cardiaca aguda (ICA) proporciona ventajas en cuanto a la evolución clínica a los pacientes en los que se determina o a los SUH que disponen de dicha posibilidad. Método: El estudio PICASU-2 es un estudio de carácter analítico, multicéntrico, retrospectivo y con seguimiento de cohortes que incluyó pacientes diagnosticados basales y de ICA. Para cada caso se consignaron los datos del episodio agudo. Como variables evolutivas se recogió la mortalidad intrahospitalaria y la mortalidad y la reconsulta a urgencias los 30 días siguientes. Los pacientes se dividieron entre los que se determinó BNP urgente y los que no. Los SUH se dividieron entre los que no tienen disponibilidad de determinar BNP urgente (tipo A), los que pueden hacerlo en casos seleccionados (tipoB) y los que lo hacen de forma generalizada (tipo C).Resultados: Participaron 19 SUH, que incluyeron 2.423 pacientes: en el 32,4% se determinó BNP, mientras que su distribución en SUH tipo A, B y C fue del 34,7%, 34,6%y 30,7%, respectivamente. La mortalidad intrahospitalaria fue 7,2%, la mortalidad a 30 días 8,1% y la reconsulta a 30 días 24%. Ni la determinación de BNP en un paciente concreto ni el hecho que el SUH lo tuviese a su disposición se asociaron a un mejor pronóstico, ni tampoco después de ajustar el modelo por las diferencias basales o del episodio agudo entre grupos. Estos mismos resultados se obtuvieron cuando se analizó el subgrupo de pacientes dados de alta directamente de urgencias (..) (AU)

Objective: To investigate whether hospital emergency department measurement of B-type natriuretic peptide (BNP) in patients with acute heart failure is beneficial in terms of patient outcomes and according to hospital category (availabilityor not of BNP testing in the emergency department).Methods: PICASU-2 is an analytical multicenter retrospective study of patients with acute heart failure according to the Framingham criteria, with follow-up of cohorts. Baseline Data and data pertaining to each acute heart failure episode were collected. Outcome measures were in-hospital mortality, 30-day mortality, and revisits to the emergency department within 30 days. Cases were classified as having a record of BNP measurement or not. Hospital emergency departments were classified as not having the resources for emergency BNP measurement (type A hospital), having thepossibility of testing selectively (type B), and testing for BNP more generally (>50% of patients) (type C).Results: Nineteen hospital emergency departments contributed data on 2423 patients, 32.4% of whom had BNPmeasurements; by hospital category, 34.7% of the patients were from type A facilities, 34.6% were from type B, and30.7% were from type C. In-hospital mortality was 7.2%, 30-day mortality was 8.1%, and 24% of the patients revisited (..) (AU)

Dermatitis de contacto a acrilatos en una industria de fabricación de ascensores. A propósito de 8 casos / Contact Dermatitis Caused by Acrylates Among 8 Workers in an Elevator Factory

Introducción: Los acrilatos son sustancias químicas de bajo peso molecular, con una amplia utilización en la industria (desde su introducción en los años treinta), la medicina y el medio doméstico, que destacan por sus propiedades de polimerización. Los compuestos acrílicos más utilizados son los cianoacrilatos, los metacrilatos y los acrilatos. Objetivo: Establecer el diagnóstico de sospecha de enfermedad profesional en un grupo de trabajadores de una fábrica de ascensores. Material y métodos: Se estudian un total de 8 pacientes que presentan clínica de dermatitis en las manos, así como pulpitis en los dedos, y que trabajan en contacto con acrilatos. Se realizaron pruebas epicutáneas con batería de acrilatos (BIAL-Aristegui, Bilbao, España). Resultados: El 87,5% mostró positividad frente al dimetacrilato de etilenglicol al 1%. También mostraron positividad el hidroxietilmetacrilato al 2% (62,5%), el dimetacrilato de trietilenglicol al 1% (50%), el monómero de metil metacrilato al 10% (25%) y el monómero de etil metacrilato al 10% (37,5%), el acrilato de etilo al 1% (12,5%) y el ácido acrílico al 0,1% (12,5%). Conclusiones: Destacamos el alto poder sensibilizante de los acrilatos y la importancia de extremar las medidas preventivas en las distintas industrias, así como la evitación del contacto con el producto en los casos de sensibilización demostrada (AU)

Introduction: Acrylates are widely used low-molecular-weight substances, initially introduced in industry in the 1930s and subsequently applied also in medicine and the home. One of their main features is the ability to undergo polymerization. The most commonly used acrylic compounds are cyanoacrylates, methacrylates, and acrylates. Objective: To confirm suspicion of occupational disease in a group of workers in an elevator factory. Material and methods: We studied 8 patients with dermatitis of the hands and finger pads. In their work, the patients came into contact with acrylates. Patch testing was applied with an acrylate panel (BIAL-Aristegui, Bilbao, Spain). Results: Seven of the patients (87.5%) had a positive result with 1% ethylene glycol dimethacrylate. Positive results were also observed for 2% hydroxyethyl methacrylate (5 patients, 62.5%), 1% triethylene glycol dimethacrylate (4 patients, 50%), 10% ethyl methacrylate monomer (3 patients, 37.5%), 10% methyl methacrylate monomer (2 patients, 25%), 1% ethyl acrylate (1 patient, 12.5%), and 0.1% acrylic acid (1 patient, 12.5%). Conclusions: We highlight the strong sensitizing capacity of acrylates and the importance of taking all necessary preventive measures in industries where these substances are used. Such measures should include avoidance of contact with the product in cases where sensitization has been confirmed (AU)

Himen imperforado neonatal / Neonatal imperforate hymen

La imperforación de himen es la anomalía obstructiva más frecuente del tracto genital femenino. Aunque en el neonato su presencia a menudo pasa inadvertida, su diagnóstico es relativamente simple y está basado en una adecuada anamnesis y una cuidadosa exploración física, y las pruebas de imagen quedan como medio de apoyo. Entre ellas, la ecografía es de primera elección. La detección temprana previene la morbilidad consiguiente al diagnóstico tardío, motivo por el cual resulta recomendable una exploración cuidadosa y sistemática del área genital, que debería formar parte de todo examen pediátrico. Ante la existencia de una obstrucción al drenaje vaginal se debe investigar el tracto urinario. El tratamiento de elección es la himeneotomía, si bien no hay consenso en cuanto al momento idóneo para su realización (AU)

Imperforate hymen is the most common obstructive anomaly of the female genital tract. Although this abnormality often goes unnoticed in neonates, it is relatively simple to diagnose. Diagnosis is based on history taking and thorough physical examination. Imaging studies can also be used, if required, and the procedure of choice is ultrasonography. Early diagnosis prevents the morbidity associated with late diagnosis. Consequently, thorough and systematic examination of the genital area is advisable and should form part of all pediatric examinations. When vaginal outflow obstruction is found, the urinary tract should be examined. The treatment of choice is hymenotomy. However, consensus is lacking on the optimal timing of this procedure (AU)

Comportamiento de algunos indicadores de la hemodinámica vascular en pacientes hipertensos valorados mediante ecocardiografía / Behaviour of some register in the cardiovascular hemodinamic in hypertension patients, aproved by echocardiography

Se realiza un estudio descriptivo transversal y prospectivo en el HGD "Dr. Agostinho Neto" de Guantánamo durante el período comprendido dese el 1ro de junio de 1991 hasta el 1ro de junio de 1996. Se caracteriza la hemodinámica cardiovascular del paciente hipertenso. Se seleccionaron de forma aleatoria y apareados 120 individuos reagrupados según fueran normotensos, hipertensos de grado 1 o grado 2, para evalar en ellos indicadores ecocardiográficos de lla precarga, la postcarga y la contractilidad cardíaca. La ecocardiografía permite carracterizar satisfactoriamente su hemodinámica cardiovascular e identificarla disfunción del ventrículo izquierdo aún cuando éstas no son clinicamente identificables particularmente modificaciones en la precarga, la postcarga y la contractilidad cardíaca. Se validan estadísticamente los resultados mediante el análisis de varianza por una vía y la prueba de Fisher (AU)