Micro-ARNs en el diagnóstico del asma: Estabilidad y cambios tras tratamiento biológico

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Medicina. Fecha de lectura: 14-04-2021Existe actualmente evidencia suficiente para pensar que los biomarcadores tienen un papel en diversos puntos clave del asma: incluyendo el diagnóstico, la gravedad de la enfermedad y en la respuesta al tratamiento. Las células liberan al espacio extracelular diferentes tipos de vesículas de doble membrana lipídica, entra las que se encuentran los exosomas, que funcionan como elementos muy importantes en la comunicación intercelular, puesto que son capaces de distribuir material genético, ARNm, ADN mitocondrial y microARNs (miARNs). Los miARNs son una familia de pequeñas moléculas de ARN no codificantes, de aproximadamente 22 nucleótidos de longitud. Actúan como reguladores de la expresión génica, lo que resulta en la inhibición de la traducción de proteínas o degradación de ARNm. Una de las características únicas de los miARNs es que se secretan al medio extracelular (plasma, BAL, esputo etc) y que son resistentes a la degradación por nucleasas, a la temperatura y a otras condiciones extremas, haciendo de ellos unos biomarcadores muy prometedores y estables. En este trabajo se estudia por primera vez la estabilidad de los microARNs en el paciente asmático a lo largo de todo un año, demostrándose que no hay cambios importantes en la medición de los microARNs en el tiempo cuando la enfermedad permanece estable y no se modifica el tratamiento. Además, se demuestra que existen diferencias en la expresión de ciertos miARNs tras la introducción de un tratamiento biológico en asma grave no controlada. La expresión de miR-338-3p cambia después del tratamiento, lo que podría ser un biomarcador de respuesta temprana a un fármaco biológico anti-IL-5, este cambio de expresión no se corrrelaciona con la mejoría obtenida en la función pulmona

Adding TQ-BOT into a Third-party Learning Management System

Intelligent Tutoring Systems are computer programs that aim at providing personalized instruction to students. In recent years, artificial intelligence conversational robots, usually known as chatterbots, have become very popular in the Internet. In this paper we show how chatterbots can be integrated in e-Learning Systems. To perform such an integration the Service Oriented Architecture paradigm is adopted and e-learning standardization initiatives are considered. A middleware is provided to enable the integration and reuse of chatterbots by e-Learning systems enabling a tight control of their operation. Such middleware takes to account several issues such as authorising users, creating instances, transferring data to and from the chatterbot, assigning permissions to users, and subscribing to events. Our approach is applied to the specific case of TQ-Bot, which is use to track and supervise the student progress and to provide answers orienting the student to the more appropriate course contents

How reliably can algorithms identify eosinophilic asthma phenotypes using non-invasive biomarkers?

Asthma is a heterogeneous respiratory disease that encompasses different inflammatory and functional endophenotypes. Many non-invasive biomarkers has been investigated to its pathobiology. Heany et al proposed a clinical algorithm that classifies severe asthmatic patients into likely-eosinophilic phenotypes, based on accessible biomarkers: PBE, current treatment, FeNO, presence of nasal polyps (NP) and age of onset.We assessed the concordance between the algorithm proposed by Heany et al. with sputum examination, the gold standard, in 145 asthmatic patients of the MEGA cohort with varying grades of severity.No correlation was found between both classifications 0.025 (CI = 0.013-0.037). Moreover, no relationship was found between sputum eosinophilia and peripheral blood eosinophilia count in the total studied population.In conclusion, our results suggest that grouping the biomarkers proposed by Heany et al. are insufficient to diagnose eosinophilic phenotypes in asthmatic patients. Sputum analysis remains the gold standard to assess airway inflammation.© 2022 The Authors. Clinical and Translational Allergy published by John Wiley & Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology

Ethics Committee experience during COVID-19 emergency. A brief report

La crisis sanitaria motivada por el COVID-19 hace necesaria la puesta en marcha, con celeridad, de investigaciones encaminadas a generar evidencias científicas que incidan en el control de sus devastadores efectos. Por ello, fue necesario realizar ajustes en la dinámica de trabajo de los Comités de Ética de la Investigación así como priorizar y agilizar la evaluación de los proyectos relacionados con dicha enfermedad. Este trabajo pretende analizar la actividad la actividad evaluadora del Comité de Ética de la Investigación con Medicamentos de Galicia (CEIm-G) durante dicho período de emergencia sanitaria. Se evaluaron 81 proyectos de investigación, 73 de ellos de ámbito autonómico (62 unicéntricos), 4 nacionales y 4 internacionales. En 57 proyectos el dictamen fue favorable, 4 fueron retirados por los promotores, en 6 no procedía dictamen y 14 no respondieron a las aclaraciones solicitadas hasta la fecha del cierre del estudio. La causas más frecuentes de solicitud de aclaraciones estaban relacionadas con la metodología y a continuación con la hoja de información al paciente y el consentimiento informado. También es imprescindible abordar los aspectos relacionados con la intimidad de los datos personales y las muestras y tener en cuenta la carga de trabajo de los investigadores. Como propuesta de mejora, consideramos que se debe incidir en una mayor coordinación entre los diferentes equipos de investigación para tratar de obtener resultados más robustos

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

The Influence of Peripheral Blood Eosinophil Counts in Asthma Comorbidities in Adults: A Real Life Study

Asthma and eosinophilia are two closely related pathologies whose interaction is key in the era of precision medicine. However, this relationship is rarely taken into account without the influence of therapeutic prescriptions. In this study involving 1296 subjects, the relationship between eosinophilia and asthma was analyzed without taking into account other biases. We observed that rhinitis only appears in non-asthmatic patients with elevated blood eosinophil levels, while atopy was elevated in parallel to eosinophilia regardless of whether the patients were asthmatic or not. In terms of lung function, a decrease was observed for higher blood eosinophil levels, which is especially relevant in the FEV1/FVC ratio. FENO is elevated in relation to higher eosinophilia, but total IgE is only elevated in patients with high peripheral blood eosinophil levels and asthma. Finally, the only feature of asthma that is altered by increased peripheral eosinophilia is persistent asthma, with all other features remaining unchanged

Síndrome coronario agudo por hipersensibilidad: Síndrome de Kounis

El síndrome de Kounis, angina alérgica o infarto de miocardio alérgico, fue descrito en 1991 por Kounis y Zavras como la aparición de manera simultánea, de eventos coronarios agudos y síntomas alérgicos anafilácticos/anafilactoides. Actualmente hay descritos en la literatura tres subtipos, el tipo I sin enfermedad coronaria, el tipo II con enfermedad coronaria y el tipo III en pacientes que sufren trombosis de un stent farmacoactivo. En la actualidad continúa siendo poco conocido con cerca de unas 100 entradas en Pubmed que reúnen casos, series de casos y revisiones. La epidemiología es desconocida y no existen guías de práctica clínica que establezcan el tratamiento de elección. Presentamos dos casos clínicos de este síndrome diagnosticados en nuestro centro