Clinical characteristics and outcomes of thymoma-associated myasthenia gravis

[Background and purpose] Prognosis of myasthenia gravis (MG) in patients with thymoma is not well established. Moreover, it is not clear whether thymoma recurrence or unresectable lesions entail a worse prognosis of MG.[Methods] This multicenter study was based on data from a Spanish neurologist-driven MG registry. All patients were aged >18 years at onset and had anti-acetylcholine receptor antibodies. We compared the clinical data of thymomatous and nonthymomatous patients. Prognosis of patients with recurrent or nonresectable thymomas was assessed.[Results] We included 964 patients from 15 hospitals; 148 (15.4%) had thymoma-associated MG. Median follow-up time was 4.6 years. At onset, thymoma-associated MG patients were younger (52.0 vs. 60.4 years, p < 0.001), had more generalized symptoms (odds ratio [OR]: 3.02, 95% confidence interval [CI]: 1.95–4.68, p < 0.001) and more severe clinical forms according to the Myasthenia Gravis Foundation of America (MGFA) scale (OR: 1.6, 95% CI: 1.15–2.21, p = 0.005). Disease severity based on MGFA postintervention status (MGFA-PIS) was higher in thymomatous patients at 1 year, 5 years, and the end of follow-up. Treatment refractoriness and mortality were also higher (OR: 2.28, 95% CI: 1.43–3.63, p = 0.001; hazard ratio: 2.46, 95% CI: 1.47–4.14, p = 0.001). Myasthenic symptoms worsened in 13 of 27 patients with recurrences, but differences in long-term severity were not significant. Fifteen thymomatous patients had nonresectable thymomas with worse MGFA-PIS and higher mortality at the end of follow-up.[Conclusions] Thymoma-associated MG patients had more severe myasthenic symptoms and worse prognosis. Thymoma recurrence was frequently associated with transient worsening of MG, but long-term prognosis did not differ from nonrecurrent thymoma. Patients with nonresectable thymoma tended to present severe forms of MG.This work is supported by Fondo de Investigaciones Sanitarias (FIS) grant FIS19/01774, Instituto de Salud Carlos III and cofunded by the European Union (ERDF/ESF, A Way to Make Europe/Investing in Your Future). Rodrigo Álvarez-Velasco was supported by a PhD for Medical Doctors grant from the Pla Estratègic de Recerca i Innovació en Salut (PERIS), Generalitat de Catalunya (SLT008/18/00207). Elena Cortés-Vicente was supported by a Juan Rodés grant (JR19/00037) from the Fondo de Investigación en Salud, Instituto de Salud Carlos III, Ministry of Health (Spain).Peer reviewe

COVID-19 vaccine effectiveness against hospitalization due to SARS-CoV-2: A test-negative design study based on Severe Acute Respiratory Infection (SARI) sentinel surveillance in Spain

Background: With the emergence of SARS-CoV-2, influenza surveillance systems in Spain were transformed into a new syndromic sentinel surveillance system. The Acute Respiratory Infection Surveillance System (SiVIRA in Spanish) is based on a sentinel network for acute respiratory infection (ARI) surveillance in primary care and a network of sentinel hospitals for severe ARI (SARI) surveillance in hospitals. Methods: Using a test-negative design and data from SARI admissions notified to SiVIRA between January 1 and October 3, 2021, we estimated COVID-19 vaccine effectiveness (VE) against hospitalization, by age group, vaccine type, time since vaccination, and SARS-CoV-2 variant. Results: VE was 89% (95% CI: 83-93) against COVID-19 hospitalization overall in persons aged 20 years and older. VE was higher for mRNA vaccines, and lower for those aged 80 years and older, with a decrease in protection beyond 3 months of completing vaccination, and a further decrease after 5 months. We found no differences between periods with circulation of Alpha or Delta SARS-CoV-2 variants, although variant-specific VE was slightly higher against Alpha. Conclusions: The SiVIRA sentinel hospital surveillance network in Spain was able to describe clinical and epidemiological characteristics of SARI hospitalizations and provide estimates of COVID-19 VE in the population under surveillance. Our estimates add to evidence of high effectiveness of mRNA vaccines against severe COVID-19 and waning of protection with time since vaccination in those aged 80 or older. No substantial differences were observed between SARS-CoV-2 variants (Alpha vs. Delta).The data of the study was originally collectedas part of the following projects run by the European Centre for Disease Prevention and Control:“Establishing Severe Acute Respiratory Infections (SARI) surveillance and performing hospital-based COVID-19 transmission studies”, “Developing an infrastructure and performing vaccine effectiveness studies for COVID-19 vaccines in the EU/EEA”, and the “Vaccine Effectiveness, Burden and Impact Studies(VEBIS) of COVID-19 and Influenza".S

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

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Elaboración de unidades didácticas interculturales

Se desarrollan seis unidades didácticas, seis cuadernillos interculturales para el alumnado de primaria, así como el cuaderno-guía del profesorado, enmarcadas en el Proyecto de Interculturalidad del Colegio Apóstol Santiago. Con la puesta en práctica de las unidades didácticas se cumple el objetivo marcado en el Proyecto de Interculturalidad de convertir el centro en un centro especializado en la educación intercultural. Junto con las unidades didácticas y los cuadernillos se incluye la justificación y el desarrollo de unas sesiones de Cuentacuentos para el alumnado y el profesorado por parte del africano Boniface Ofogo Nkama. Las diferentes sesiones de Cuentacuentos arrojan una experiencia enriquecedora para toda la Comunidad Educativa ya que desde el alumnado, pasando por las familias y el profesorado se puede aprender y conocer otra cultura a través de los cuentos y su transmisión oral. Con las unidades didácticas se pretende que cada alumno o alumna trabaje de forma individual y colectiva, siendo el propio protagonista de su aprendizaje, y que aprendan a convivir con alumnos de diferentes culturas con la finalidad de lograr el enriquecimiento de todo el alumnado educando en valores como la tolerancia y el respeto.Castilla y LeónConsejería de Educación. Dirección General de Universidades e Investigación; Monasterio de Nuestra Señora de Prado, Autovía Puente Colgante s. n.; 47071 Valladolid; +34983411881; +34983411939ES

Discovering HIV related information by means of association rules and machine learning

Acquired immunodeficiency syndrome (AIDS) is still one of the main health problems worldwide. It is therefore essential to keep making progress in improving the prognosis and quality of life of affected patients. One way to advance along this pathway is to uncover connections between other disorders associated with HIV/AIDS-so that they can be anticipated and possibly mitigated. We propose to achieve this by using Association Rules (ARs). They allow us to represent the dependencies between a number of diseases and other specific diseases. However, classical techniques systematically generate every AR meeting some minimal conditions on data frequency, hence generating a vast amount of uninteresting ARs, which need to be filtered out. The lack of manually annotated ARs has favored unsupervised filtering, even though they produce limited results. In this paper, we propose a semi-supervised system, able to identify relevant ARs among HIV-related diseases with a minimal amount of annotated training data. Our system has been able to extract a good number of relationships between HIV-related diseases that have been previously detected in the literature but are scattered and are often little known. Furthermore, a number of plausible new relationships have shown up which deserve further investigation by qualified medical experts

Individualised, perioperative open-lung ventilation strategy during one-lung ventilation (iPROVE-OLV): a multicentre, randomised, controlled clinical trial

Resumen Fondo: No está claro si la individualización del enfoque perioperatorio de pulmón abierto (OLA) para la ventilación reduce las complicaciones pulmonares posoperatorias en pacientes sometidos a resección pulmonar . Comparamos una estrategia de ventilación perioperatoria individualizada OLA (iOLA) con ventilación protectora pulmonar estándar en pacientes sometidos a cirugía torácica con ventilación unipulmonar. Métodos: Este ensayo controlado aleatorio multicéntrico inscribió a pacientes programados para cirugía torácica abierta o asistida por video utilizando ventilación unipulmonar en 25 hospitales participantes en España, Italia, Turquía, Egipto y Ecuador. Los pacientes adultos elegibles (edad ≥18 años) fueron asignados aleatoriamente para recibir iOLA o ventilación con protección pulmonar estándar. Los investigadores principales locales asignaron aleatoriamente en línea a los pacientes elegibles (estratificados por centro), con una proporción de asignación de 1:1. El tratamiento con iOLA incluyó una maniobra de reclutamiento alveolar a 40 cm H2O de presión al final de la inspiración seguida de presión positiva al final de la espiración (PEEP) ajustada al mejor cumplimiento del sistema respiratorio y soporte respiratorio postoperatorio individualizado con oxigenoterapia de alto flujo. Los participantes asignados a ventilación protectora pulmonar estándar recibieron 4 cm H 2 O intraoperatorios combinados de PEEP y oxigenoterapia convencional posoperatoria. El resultado primario fue una combinación de complicaciones pulmonares posoperatorias graves dentro de los primeros 7 días posoperatorios, incluidas atelectasias que requirieron broncoscopia , insuficiencia respiratoria grave, neumotórax contralateral , fracaso de la extubación temprana (rescate con presión positiva continua en las vías respiratorias, ventilación no invasiva, ventilación mecánica invasiva , o reintubación), síndrome de dificultad respiratoria aguda , infección pulmonar, fístula broncopleural y empiema pleural . Debido al ámbito del ensayo, los datos obtenidos en el quirófano y en el postoperatorio para la monitorización de rutina no fueron cegados. A las 24 h, los datos fueron adquiridos por un investigador cegado a la asignación de grupos. Todos los análisis se realizaron por intención de tratar. Recomendaciones: Entre el 11 de septiembre de 2018 y el 14 de junio de 2022, inscribimos a 1380 pacientes, de los cuales 1308 pacientes elegibles (670 [434 hombres, 233 mujeres y tres con datos faltantes] asignados a iOLA y 638 [395 hombres, 237 mujeres y seis con datos faltantes] a ventilación estándar con protección pulmonar) se incluyeron en el análisis final. La proporción de pacientes con el resultado compuesto de complicaciones pulmonares posoperatorias graves dentro de los primeros 7 días posoperatorios fue menor en el grupo de iOLA en comparación con el grupo de ventilación con protección pulmonar estándar (40 [6 %] frente a 97 [15 %], riesgo relativo 0 ·39 [IC del 95%: 0,28 a 0,56]), con una diferencia de riesgo absoluto de –9,23 (IC del 95%: –12,55 a –5,92). Se informaron eventos adversos relacionados con la maniobra de reclutamiento en cinco pacientes. Interpretación: Entre los pacientes sometidos a resección pulmonar bajo ventilación unipulmonar, iOLA se asoció con un riesgo reducido de complicaciones pulmonares posoperatorias graves en comparación con la ventilación convencional con protección pulmonar. Fondos: Instituto de Salud Carlos III y los Fondos Europeos de Desarrollo Regional.Background: It is uncertain whether individualisation of the perioperative open-lung approach (OLA) to ventilation reduces postoperative pulmonary complications in patients undergoing lung resection. We compared a perioperative individualised OLA (iOLA) ventilation strategy with standard lung-protective ventilation in patients undergoing thoracic surgery with one-lung ventilation. Methods: This multicentre, randomised controlled trial enrolled patients scheduled for open or video-assisted thoracic surgery using one-lung ventilation in 25 participating hospitals in Spain, Italy, Turkey, Egypt, and Ecuador. Eligible adult patients (age ≥18 years) were randomly assigned to receive iOLA or standard lung-protective ventilation. Eligible patients (stratified by centre) were randomly assigned online by local principal investigators, with an allocation ratio of 1:1. Treatment with iOLA included an alveolar recruitment manoeuvre to 40 cm H2O of end-inspiratory pressure followed by individualised positive end-expiratory pressure (PEEP) titrated to best respiratory system compliance, and individualised postoperative respiratory support with high-flow oxygen therapy. Participants allocated to standard lung-protective ventilation received combined intraoperative 4 cm H2O of PEEP and postoperative conventional oxygen therapy. The primary outcome was a composite of severe postoperative pulmonary complications within the first 7 postoperative days, including atelectasis requiring bronchoscopy, severe respiratory failure, contralateral pneumothorax, early extubation failure (rescue with continuous positive airway pressure, non-invasive ventilation, invasive mechanical ventilation, or reintubation), acute respiratory distress syndrome, pulmonary infection, bronchopleural fistula, and pleural empyema. Due to trial setting, data obtained in the operating and postoperative rooms for routine monitoring were not blinded. At 24 h, data were acquired by an investigator blinded to group allocation. All analyses were performed on an intention-to-treat basis. Findings: Between Sept 11, 2018, and June 14, 2022, we enrolled 1380 patients, of whom 1308 eligible patients (670 [434 male, 233 female, and three with missing data] assigned to iOLA and 638 [395 male, 237 female, and six with missing data] to standard lung-protective ventilation) were included in the final analysis. The proportion of patients with the composite outcome of severe postoperative pulmonary complications within the first 7 postoperative days was lower in the iOLA group compared with the standard lung-protective ventilation group (40 [6%] vs 97 [15%], relative risk 0·39 [95% CI 0·28 to 0·56]), with an absolute risk difference of –9·23 (95% CI –12·55 to –5·92). Recruitment manoeuvre-related adverse events were reported in five patients. Interpretation: Among patients subjected to lung resection under one-lung ventilation, iOLA was associated with a reduced risk of severe postoperative pulmonary complications when compared with conventional lung-protective ventilation. Funding: Instituto de Salud Carlos III and the European Regional Development Funds.11,12102,642Q1Q1SCIE10,