Population-based multicase-control study in common tumors in Spain (MCC-Spain): rationale and study design

Introduction: We present the protocol of a large population-based case-control study of 5 common tumors in Spain (MCC-Spain) that evaluates environmental exposures and genetic factors. Methods: Between 2008-2013, 10,183 persons aged 20-85 years were enrolled in 23 hospitals and primary care centres in 12 Spanish provinces including 1,115 cases of a new diagnosis of prostate cancer, 1,750 of breast cancer, 2,171 of colorectal cancer, 492 of gastro-oesophageal cancer, 554 cases of chronic lymphocytic leukaemia (CLL) and 4,101 population-based controls matched by frequency to cases by age, sex and region of residence. Participation rates ranged from 57% (stomach cancer) to 87% (CLL cases) and from 30% to 77% in controls. Participants completed a face-to-face computerized interview on sociodemographic factors, environmental exposures, occupation, medication, lifestyle, and personal and family medical history. In addition, participants completed a self-administered food-frequency questionnaire and telephone interviews. Blood samples were collected from 76% of participants while saliva samples were collected in CLL cases and participants refusing blood extractions. Clinical information was recorded for cases and paraffin blocks and/or fresh tumor samples are available in most collaborating hospitals. Genotyping was done through an exome array enriched with genetic markers in specific pathways. Multiple analyses are planned to assess the association of environmental, personal and genetic risk factors for each tumor and to identify pleiotropic effects. Discussion: This study, conducted within the Spanish Consortium for Biomedical Research in Epidemiology & Public Health (CIBERESP), is a unique initiative to evaluate etiological factors for common cancers and will promote cancer research and prevention in Spain.The study was partially funded by the “Accion Transversal del Cancer”, approved on the Spanish Ministry Council on the 11th October 2007, by the Instituto de Salud Carlos III-FEDER (PI08/1770, PI08/0533, PI08/1359, PS09/00773, PS09/01286, PS09/01903, PS09/02078, PS09/01662, PI11/01403, PI11/01889, PI11/00226, PI11/01810, PI11/02213, PI12/00488, PI12/00265, PI12/01270, PI12/00715, PI12/00150), by the Fundación Marqués de Valdecilla (API 10/09), by the ICGC International Cancer Genome Consortium CLL, by the Junta de Castilla y León (LE22A10-2), by the Consejería de Salud of the Junta de Andalucía (PI-0571), by the Conselleria de Sanitat of the Generalitat Valenciana (AP 061/10), by the Recercaixa (2010ACUP 00310), by the Regional Government of the Basque Country by European Commission grants FOOD-CT- 2006-036224-HIWATE, by the Spanish Association Against Cancer (AECC) Scientific Foundation, by the The Catalan Government DURSI grant 2009SGR1489

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

The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients

Background: Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. Methods: Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. Results: Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0-171.2] to 180.0 [135.4-227.9] mmHg and the ventilatory ratio from 1.73 [1.33-2.25] to 1.96 [1.61-2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01-1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01-1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93-1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). Conclusions: Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation

Demandas de responsabilidad patrimonial en contra del Estado en Mezcala, Jalisco; La Lancha, Punta de Mita, Nayarit; Río Santiago, Jalisco y demanda de amprado relleno sanitario en Atemajac de Brizuela, Jalisco

El presente documento se elaboró dentro de la Clínica de Derecho y Gestión Ambiental en colaboración con la Asociación Civil denominada “Natura Viviente”, el cual consiste en dar continuidad a los procesos de investigación y asesoría iniciados por el Proyecto de Aplicación Profesional del semestre pasado, para analizar y cuestionar los resultados en el cumplimiento de las atribuciones de las autoridades gubernamentales en relación a la materia ambiental; con la finalidad de llegar a redacción de cuatro teorías de caso y los avances respectivos a las demandas de cada una de las mismas. Nuestros cuatro casos se enfocaron en demandas enfocadas a la responsabilidad patrimonial del Estado por omisión de responsabilidades que causaron perjuicio a derechos fundamentales de los ciudadanos, respecto del Río Santiago, Jalisco; el poblado de Mezcala, Jalisco; la playa La Lancha, Punta Mita y; Atemajac de Brizuela, Jalisco. Por una parte nos encontramos con la problemática del Río Santiago, de la que se derivaron dos estudios de caso, en los que los principales afectados son los poblados cercanos a la zona como por ejemplo Mezcala y Poncitlán; los pobladores están siendo afectados en la salud por la alta contaminación en el agua del río, contaminación que es el resultado de las descargas de residuos que varias empresas realizan de manera ordinaria. Estas empresas se fueron asentando en la zona alrededor de 1970, y es claro que las mismas sí cuentan con concesiones emitidas por la autoridad correspondiente, pero de igual manera es obligación de dichas autoridades la regulación de éstas descargas, ya que se está produciendo un daño ambiental además del daño a la salud pública. Como segunda problemática tenemos a la playa La Lancha que se encuentra en el Estado de Nayarit, esta playa está siendo privatizada, negándosele el acceso a turistas así como también a los mismos pobladores de la zona, se alega que está clausurada por afectaciones al ecosistema costero, mientras que al mismo tiempo existe una concesión otorgada a una empresa, la cual tiene cercado con una malla ciclónica el acceso a la playa, señalando que la misma es propiedad privada. La última problemática fue el relleno sanitario de Atemajac de Brizuela, en donde en el año 2003 se le impuso y construyó a la población de Atemajac de Brizuela un basurero o también llamado relleno sanitario, el cual no cumplía con las normas aplicables en materia de medio ambiente.ITESO, A.C

Titanium dioxide nanoparticles induce the expression of early and late receptors for adhesion molecules on monocytes

BACKGROUND: There is growing evidence that exposure to titanium dioxide nanoparticles (TiO(2) NPs) could be harmful. Previously, we have shown that TiO(2) NPs induces endothelial cell dysfunction and damage in glial cells. Considering that inhaled particles can induce systemic effects and the evidence that nanoparticles may translocate out of the lungs, we evaluated whether different types of TiO(2) NPs can induce the expression of receptors for adhesion molecules on monocytes (U937 cell line). We evaluated the role of reactive oxygen spices (ROS) on these effects. METHODS: The expression of receptors for early (sLe(x) and PSGL-1) and late (LFA-1, VLA-4 and αVβ3) adhesion molecules was evaluated in U937 cells on a time course (3–24 h) using a wide range of concentrations (0.001-100 μg/mL) of three types of TiO(2) NPs (<25 nm anatase, 50 nm anatase-rutile or < 100 nm anatase). Cells exposed to TNFα were considered positive controls, and unexposed cells, negative controls. In some experiments we added 10 μmolar of N-acetylcysteine (NAC) to evaluate the role of ROS. RESULTS: All tested particles, starting at a concentration of 0.03 μg/mL, induced the expression of receptors for early and late adhesion molecules. The largest increases were induced by the different molecules after 3 h of exposure for sLe(x) and PSGL-1 (up to 3-fold of the positive controls) and after 18 h of exposure for LFA-1, VLA-4 and αVβ3 (up to 2.5-fold of the positive controls). Oxidative stress was observed as early as 10 min after exposure, but the maximum peak was found after 4 h of exposure. Adhesion of exposed or unexposed monocytes to unexposed or exposed endothelial cells was tested, and we observed that monocytes cells adhere in similar amounts to endothelial cells if one of the two cell types, or both were exposed. When NAC was added, the expression of the receptors was inhibited. CONCLUSIONS: These results show that small concentrations of particles may activate monocytes that attach to endothelial cells. These results suggest that distal effects can be induced by small amounts of particles that may translocate from the lungs. ROS play a central role in the induction of the expression of these receptors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12989-016-0147-3) contains supplementary material, which is available to authorized users

Childhood asthma outcomes during the COVID-19 pandemic: Findings from the PeARL multi-national cohort

International audienc

Childhood asthma outcomes during the COVID-19 pandemic: findings from the PeARL multinational cohort

Background: The interplay between COVID-19 pandemic and asthma in children is still unclear. We evaluated the impact of COVID-19 pandemic on childhood asthma outcomes. Methods: The PeARL multinational cohort included 1,054 children with asthma and 505 non-asthmatic children aged between 4 and 18 years from 25 pediatric departments, from 15 countries globally. We compared the frequency of acute respiratory and febrile presentations during the first wave of the COVID-19 pandemic between groups and with data available from the previous year. In children with asthma, we also compared current and historical disease control. Results: During the pandemic, children with asthma experienced fewer upper respiratory tract infections, episodes of pyrexia, emergency visits, hospital admissions, asthma attacks, and hospitalizations due to asthma, in comparison with the preceding year. Sixty-six percent of asthmatic children had improved asthma control while in 33% the improvement exceeded the minimal clinically important difference. Pre-bronchodilatation FEV1 and peak expiratory flow rate were improved during the pandemic. When compared to non-asthmatic controls, children with asthma were not at increased risk of LRTIs, episodes of pyrexia, emergency visits, or hospitalizations during the pandemic. However, an increased risk of URTIs emerged. Conclusion: Childhood asthma outcomes, including control, were improved during the first wave of the COVID-19 pandemic, probably because of reduced exposure to asthma triggers and increased treatment adherence. The decreased frequency of acute episodes does not support the notion that childhood asthma may be a risk factor for COVID-19. Furthermore, the potential for improving childhood asthma outcomes through environmental control becomes apparent.</p