Análisis de mediadores moleculares implicados en angiogénesis en pacientes con cáncer de pulmón no microcítico: determinación de su valor como biomarcadores

El cáncer de pulmón constituye un importante problema de salud pública, siendo el cáncer con los índices de mortalidad más elevados. Su diagnóstico se ve dificultado por la ausencia de síntomas en pacientes con tumores en estado precoz, diagnosticándose la mayoría de casos en fases ya avanzadas. Además la importancia del cáncer de pulmón radica en su mal pronóstico, ya que a pesar de los avances en el diagnóstico y en la terapéutica, el índice de supervivencia media tras 5 años es aproximadamente del 15%. La neovascularización tumoral, por medio de los procesos de angiogénesis, vasculogénesis y linfangiogénesis, resulta clave para el crecimiento y diseminación del tumor y se inicia ya en etapas tempranas de la enfermedad. La familia de ligandos y receptores del factor de crecimiento del endotelio vascular (VEGF) son los principales reguladores de estos procesos. Por ello, debido a su importancia, la angiogénesis ha sido foco de intensos estudios en los últimos años, incluyendo también el desarrollo de agentes farmacológicos que inhiben VEGF como una atractiva diana antitumoral. Sin embargo, a pesar de disponer de terapias biológicas específicas, siguen existiendo cifras considerables de pacientes que recidivan, incluso en estadios tempranos. Así pues, la identificación de nuevos biomarcadores y una visión más completa de las interacciones de los distintos elementos que componen la familia de VEGF, serían necesarios para poder detectar a aquellos pacientes que presentarán un peor curso clínico y para ayudar a plantear nuevas estrategias de tratamiento multimodal que mejoren los resultados en términos de supervivencia. Por todo ello, la finalidad de este trabajo es abordar el estudio de marcadores relacionados con los procesos de angiogénesis y linfangiogénesis en pacientes con cáncer de pulmón no microcítico (CPNM), integrando la información obtenida mediante distintas técnicas moleculares, y asociarlos con características clínico-patológicas, con el fin de establecer perfiles o patrones moleculares, que pudieran tener valor como biomarcadores para el diagnóstico y/o pronóstico en esta patología. Para ello se llevaron a cabo dos estudios en paralelo: el estudio de marcadores solubles y el estudio de marcadores tisulares. Los resultados en el estudio de marcadores solubles demostraron que los pacientes con CPNM presentan niveles plasmáticos de VEGF-A y sVEGFR-2 superiores a los sujetos sanos, y dado el adecuado nivel de especificidad y sensibilidad de la determinación de VEGF-A, su determinación en plasma podría ser una herramienta más de apoyo al diagnóstico del CPNM. Además, los análisis del valor pronóstico de estos biomarcadores plasmáticos revelaron que un perfil formado por la combinación de niveles altos de VEGF-A y niveles bajos de sVEGFR-2 permite identificar a un subgrupo de pacientes con CPNM avanzado que presentan un curso clínico más desfavorable. El estudio de expresión a nivel de ARNm a partir de muestras tisulares de pacientes con CPNM resecable mostró que el gen PlGF se encuentra sobreexpresado y los genes VEGFR-2, VEGFR-3 y VEGF-D se encuentran infraexpresados en tejido tumoral respecto al tejido pulmonar normal. Los análisis de supervivencia para los marcadores tisulares revelaron que los niveles más altos de ARNm de VEGF-A o PlGF, así como los niveles bajos de VEGF-B o VEGF-D se relacionan con un peor pronóstico de los pacientes con CPNM resecable, y además, que las combinaciones de estos cuatro marcadores se correlacionan con el pronóstico de los pacientes aún con mayor significación estadística que las variables de forma individual. Estos hallazgos nos permitieron generar una firma genética en función de los niveles de PlGF, VEGF-A y VEGF-B que mostró ser una apropiada herramienta para la clasificación de los pacientes con CPNM resecable en grupos de riesgo, que proporcionaría información valiosa para el manejo terapéutico de estos pacientes. En conclusión, tanto los análisis de marcadores solubles como tisulares, indicaron que la mejor vía para abordar el estudio de factores angiogénicos y/o linfangiogénicos sería el estudio de los perfiles de expresión de marcadores combinados o firmas genéticas, ya que aportan más información acerca de la compleja interacción de estos factores en la regulación de dichos mecanismos. Esta aproximación podría representar un complemento a la labor clínica habitual que permitiría una mejor caracterización de aquellos pacientes con un perfil molecular más angiogénico y que podrían ser candidatos a terapias dirigidas

Diccionario Multilingüe de Turismo

Este recurso lexicográfico ha sido elaborado por el Grupo de investigación COMETVAL (Corpus Multilingüe de Turismo de la Universitat de València) http://www.uv.es/cometval/wikibase/cas/index.wiki). COMETVAL se crea en 2009 y desde entonces ha contado con ayudas de diversos organismos (Universitat de València, la Agencia Valenciana de Turismo y, en la actualidad, el Ministerio de Economía y Competitividad). Pertenecen a dicho grupo un importante número de investigadores de diferentes departamentos y universidades españolas (Universitat de València, Universitat Politècnica de València, Universidad Católica de Valencia San Vicente Mártir, Universitat Jaume I de Castellón y Universidad de Almería). Entre las tareas realizadas por COMETVAL destaca la creación de una amplia base de datos de discurso turístico procedente básicamente de sitios web en español, francés e inglés. Entre sus cometidos se encuentra el análisis del discurso turístico desde vertientes teóricas y aplicadas. La faceta aplicada se materializa en la elaboración del presente diccionario multilingüe en línea, cuyas características se exponen a continuación.Diccionario elaborado en el marco del Proyecto de investigación concedido por el Ministerio de Economía y Competitividad. Referencia FFI2011-24712, Análisis léxico y discursivo de corpus paralelos y comparables (español, inglés y francés) de páginas electrónicas de promoción turística. 2011-2014.Humanidade

Model of teleconsultation pharmaceutical integrated in the electronic clinical history of the patient

OBJECTIVE: Describe the phases of implementation, scaling and integration of a pharmacy teleconsultation model in electronic history, to coordinate the care transition of patients. METHOD: Descriptive and retrospective study in a health area of 500,000 inhabitants (3 years). In the first phase, a working group was created, a communication platform was designed and a continuity program was piloted between a hospital pharmacist and the 13 primary care pharmacists. The objective was to solve problems related to medications (especially those of sanitary approval) in polymedicated patients hospitalized in the Short Stay Unit- Emergency. In a second phase, the program included all the patients in any unit and all the pharmacists in the hospital. In the third phase, the program was extended to the teleconsultation format within the corporate information systems of the Health Service. Quantitative descriptive variables were recorded (number, motives and resolution of the teleconsultations). RESULTS: In total, more than 470 consultations were registered (118 in the first phase, 158 in the second and 194 in the third), which were resolved in 90% of the cases. The main reasons were discrepancies in type approval drugs, prescribed in the care transition and nutritional assessment. CONCLUSIONS: Teleconsultation allows the coordination of pharmaceutical care between levels, quickly and easily. Increase the visibility and access of professionals. Problems are resolved without displacements or time delays for patients

Serovigilancia de enfermedades prevenibles por vacunación: una mirada desde la experiencia con la tosferina

Introduction: Serological surveillance (serosurveillance) provides the most direct measure of herd immunity of vaccine-preventable diseases. Little is known about the opportunities and challenges of serosurveillance experiences, particularly pertussis.Objective: To describe the process of serosurveillance for vaccine-preventable diseases with an emphasis on the experience of pertussis in the metropolitan area of Antioquia (Valle de Aburrá) in 2015 and 2016 and analyze the contributions and challenges for its sustainability.Materials and methods: We described the planning and conduction of serosurveillance of pertussis antibodies of mothers and in the umbilical cord at the time of delivery in eight hospitals based on random sampling and their capacity to advance the serosurveillance periodically. We compared the contributions and the challenges of this experience with other probabilistic and non-probabilistic programs.Results: We achieved the participation of hospitals and mothers respecting the delivery care process. We established a serum bank following ethical and technical guidelines. This program based on the random selection of hospitals and mothers has enabled the estimation of antibodies prevalence in mothers and in the umbilical cord, which has been possible given the high coverage of hospital care during childbirth at a lower cost and fewer risks than a population-based survey in conflictive areas. The main challenges for the sustainability of this program are the creation of stable jobs and access to funding and legal and methodological long-term frameworks.Conclusions: Hospital serosurveillance as described is an option to monitor the impact of vaccination on the population. Our experience could be reproduced in other regions under similar conditions if the above-mentioned challenges are solved.Introducción. La vigilancia serológica es la forma más directa de medir la inmunidad de rebaño frente a las enfermedades prevenibles por vacunación. Poco se sabe acerca de las oportunidades y los desafíos de las experiencias de serovigilancia, en general y, específicamente, la de la tosferina.Objetivo. Describir el proceso de serovigilancia de enfermedades prevenibles por vacunación con énfasis en la experiencia en el caso de la tosferina en el área metropolitana de Antioquia (Valle de Aburrá) en el 2015 y el 2016 y analizar lo que dicha experiencia ha aportado y los desafíos que persisten para su sostenibilidad.Materiales y métodos. Se describió el proceso de planeación y el desarrollo de la serovigilancia de tosferina en el momento del parto en ocho hospitales seleccionados al azar, así como la capacidad para adelantar el programa de manera periódica. Se compararon los aportes y los desafíos en el curso de esta experiencia con los de otros programas poblacionales probabilistas e institucionales no probabilistas.Resultados. Se logró la participación de los hospitales y de las madres con pleno respeto del proceso de atención del parto, y se conformó un banco de sueros siguiendo lineamientos éticos y técnicos. El programa permitió estimar la prevalencia de anticuerpos en la madre y en el cordón umbilical, lo que se facilitó por la alta cobertura de atención hospitalaria del parto, a un menor costo y menos riesgos que los programas poblacionales en zonas conflictivas. Los principales desafíos para la sostenibilidad del programa son la estabilidad laboral del personal de salud, así como normas y una financiación de largo plazo.Conclusiones. La serovigilancia hospitalaria es una opción para monitorizar el impacto poblacional de la vacunación. Esta experiencia se podría extender a otras regiones en condiciones similares si se resuelven los retos mencionados

Autonomous cortisol secretion in patients with primary aldosteronism: prevalence and implications on cardiometabolic profile and on surgical outcomes

Purpose: The aim of this study was to evaluate the prevalence of autonomous cortisol secretion (ACS) in patients with primary aldosteronism (PA) and its implications on cardiometabolic and surgical outcomes. Methods: This is a retrospective multicenter study of PA patients who underwent 1 mg dexamethasone-suppression test (DST) during diagnostic workup in 21 Spanish tertiary hospitals. ACS was defined as a cortisol post-DST >1.8 μg/dL (confirmed ACS if >5 μg/dL and possible ACS if 1.8–5 μg/dL) in the absence of spe cific clinical features of hypercortisolism. The cardiometabolic profile was compared with a control group with ACS without PA (ACS group) matched for age and DST levels. Results: The prevalence of ACS in the global cohort of patients with PA (n = 176) was 29% (ACS–PA; n = 51). Ten patients had confirmed ACS and 41 possible ACS. The cardiometabolic profile of ACS–PA and PA-only patients was simil ar, except for older age and larger tumor size of the adrenal lesion in the ACS–PA group. When comparing the ACS–PA group (n = 51) and the ACS group (n = 78), the prevalence of hypertension (OR 7.7 (2.64–22.32)) and cardiovascular events (OR 5.0 (2.29–11.07)) was higher in ACS–PA patients than in ACS patients. The coexistence of ACS in patien ts with PA did not affect the surgical outcomes, the proportion of biochemical cure and clinical cure being similar between ACS–PA and PA-only groups. Conclusion: Co-secretion of cortisol and aldosterone affects almost one-thi rd of patients with PA. Its occurrence is more frequent in patients with larger tumors and advanced age. However, the cardiometabolic and surgical outcomes of patients with ACS–PA and PA-only are similar

Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children

We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-alpha 2 in 10 patients: IFN-alpha 2 only in three, IFN-alpha 2 plus IFN-omega in five, and IFN-alpha 2, IFN-omega plus IFN-beta in two; IFN-omega only in nine patients). Seven children (3.8%) had Abs neutralizing at least 10 ng/ml of one IFN, whereas the other 12 (6.6%) had Abs neutralizing only 100 pg/ml. The auto-Abs neutralized both unglycosylated and glycosylated IFNs. We also detected auto-Abs neutralizing 100 pg/ml IFN-alpha 2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-omega in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-alpha 2 only (OR [95% CI] = 67.6 [5.7-9,196.6]) than for auto-Abs neutralizing IFN-. only (OR [95% CI] = 2.6 [1.2-5.3]). ORs were also higher for auto-Abs neutralizing high concentrations (OR [95% CI] = 12.9 [4.6-35.9]) than for those neutralizing low concentrations (OR [95% CI] = 5.5 [3.1-9.6]) of IFN-omega and/or IFN-alpha 2

Invasive Treatment Strategy in Adults With Frailty and Non-ST-Segment Elevation Myocardial Infarction

Does a routine invasive strategy improve midterm outcomes in adults with frailty and acute non-ST-segment elevation myocardial infarction (NSTEMI)? In this secondary analysis of a randomized clinical trial of 167 patients with frailty and NSTEMI, a routine invasive strategy, when compared with a conservative strategy, did not reduce the number of days alive at a median follow-up of 1113 days. Invasive treatment was associated with shorter survival within the first year but more prolonged survival after the first year. In patients with frailty and NSTEMI, an initial invasive strategy caused early harm followed by late benefit, resulting in a neutral effect on survival at 4 years. This extended follow-up of a randomized clinical trial investigates whether restricted mean survival time differs among patients with frailty who undergo intensive vs conservative treatment for acute non-ST-segment elevation myocardial infarction. The MOSCA-FRAIL randomized clinical trial compared invasive and conservative treatment strategies in patients with frailty with non-ST-segment elevation myocardial infarction (NSTEMI). It showed no differences in the number of days alive and out of the hospital at 1 year. To assess the outcomes of the MOSCA-FRAIL trial during extended follow-up. The MOSCA-FRAIL randomized clinical trial was conducted at 13 hospitals in Spain between July 7, 2017, and January 9, 2021, and included 167 adults (aged ≥70 years) with frailty (Clinical Frailty Scale score ≥4) and NSTEMI. In this preplanned secondary analysis, follow-up was extended to January 31, 2023. Data analysis was performed from April 5 to 29, 2023, using the intention-to-treat principle. Patients were randomized to a routine invasive (coronary angiography and revascularization if feasible [n = 84]) or a conservative (medical treatment with coronary angiography only if recurrent ischemia [n = 83]) strategy. The primary end point was the difference in restricted mean survival time (RMST). Secondary end points included readmissions for any cause, considering recurrent readmissions. Among the 167 patients included in the analysis, the mean (SD) age was 86 (5) years; 79 (47.3%) were men and 88 (52.7%) were women. A total of 93 deaths and 367 readmissions accrued. The RMST for all-cause death over the entire follow-up was 3.13 (95% CI, 2.72-3.60) years in the invasive and 3.06 (95% CI, 2.84-3.32) years in the conservative treatment groups. The RMST analysis showed inconclusive differences in survival time (invasive minus conservative difference, 28 [95% CI, −188 to 230] days). Patients under invasive treatment tended to have shorter survival in the first year (−28 [95% CI, −63 to 7] days), which improved after the first year (192 [95% CI, 90-230] days). Kaplan-Meier mortality curves intersected, displaying higher mortality to 1 year in the invasive group that shifted to a late benefit (landmark analysis hazard ratio, 0.58 [95% CI, 0.33-0.99]; P = .045). Early harm was more evident in the subgroup with a Clinical Frailty Scale score greater than 4. No differences were found for the secondary end points. In this extended follow-up of a randomized clinical trial of patients with frailty and NSTEMI, an invasive treatment strategy did not improve outcomes at a median follow-up of 1113 (IQR, 443-1441) days. However, a differential distribution of deaths was observed, with early harm followed by later benefit. The phenomenon of depletion of susceptible patients may be responsible for this behavior. ClinicalTrials.gov Identifier

Cardiac troponin and COVID-19 severity: Results from BIOCOVID study.

Myocardial injury is a common finding in COVID-19 strongly associated with severity. We analysed the prevalence and prognostic utility of myocardial injury, characterized by elevated cardiac troponin, in a large population of COVID-19 patients, and further evaluated separately the role of troponin T and I. This is a multicentre, retrospective observational study enrolling patients with laboratory-confirmed COVID-19 who were hospitalized in 32 Spanish hospitals. Elevated troponin levels were defined as values above the sex-specific 99th percentile upper reference limit, as recommended by international guidelines. Thirty-day mortality was defined as endpoint. A total of 1280 COVID-19 patients were included in this study, of whom 187 (14.6%) died during the hospitalization. Using a nonspecific sex cut-off, elevated troponin levels were found in 344 patients (26.9%), increasing to 384 (30.0%) when a sex-specific cut-off was used. This prevalence was significantly higher (42.9% vs 21.9%; P  In this multicentre study, myocardial injury was a common finding in COVID-19 patients. Its prevalence increased when a sex-specific cut-off and cardiac troponin T were used. Elevated troponin was an independent predictor of 30-day mortality, irrespective of cardiac troponin assay and cut-offs to detect myocardial injury. Hence, the early measurement of cardiac troponin may be useful for risk stratification in COVID-19