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

Estudio para determinar la dosis óptima, la tolerancia y la eficacia de la Toxina botulínica en la fisura anal crónica

OBJETIVOS La inyección intraesfinteriana de toxina botulínica es un tratamiento alternativo de las fisuras anales crónicas no complicadas que se acompañan de hipertonía esfinteriana. Nuestra hipótesis de trabajo era probar la eficacia de dos dosis diferentes de Toxina botulínica, utilizando dosis altas, y analizar la tolerancia al tratamiento. MATERIAL Y MÉTODO Se realizó un Ensayo clínico en fase II de grupos paralelos, aleatorizado, doble ciego, de búsqueda de dosis para determinar la dosis óptima y la efectividad y tolerancia de la Neurotoxina botulínica tipo A en el tratamiento de la Fisura anal crónica idiopática en una población de pacientes de entre 18 y 70 años que acudían al Servicio de urgencias de los Hospitales Universitarios Virgen del Rocío refiriendo dolor anal y se le diagnosticaba una fisura anal crónica. A todos los pacientes se les realiza una manometría anorrectal previa y posterior a la inyección. TRATAMIENTO A: 25 unidades de Toxina botulínica tipo A más Lidocaína al 2%. TRATAMIENTO B: 50 unidades de Toxina botulínica tipo A más Lidocaína al 2%. Los pacientes eran asignados al grupo A o al grupo B de acuerdo con una tabla de permutaciones aleatorizadas. Se inyecta la dosis total en el surco interesfinteriano a ambos lados de la fisura anal. Los pacientes son citados a la semana de la inyección y a los 3 meses y a los 6 meses. Se valoraron las siguientes variables: Dolor anal defecatorio, rectorragia, estreñimiento, Presión máxima basal (PMB), Presión máxima de contracción voluntaria (PMCV), Longitud del canal anal (LCA)

Fecal Gluten Peptides Reveal Limitations of Serological Tests and Food Questionnaires for Monitoring Gluten-Free Diet in Celiac Disease Patients.

JOURNAL ARTICLE;OBJECTIVES Treatment for celiac disease (CD) is a lifelong strict gluten-free diet (GFD). Patients should be followed-up with dietary interviews and serology as CD markers to ensure adherence to the diet. However, none of these methods offer an accurate measure of dietary compliance. Our aim was to evaluate the measurement of gluten immunogenic peptides (GIP) in stools as a marker of GFD adherence in CD patients and compare it with traditional methods of GFD monitoring. METHODS We performed a prospective, nonrandomized, multicenter study including 188 CD patients on GFD and 84 healthy controls. Subjects were given a dietary questionnaire and fecal GIP quantified by enzyme-linked immunosorbent assay (ELISA). Serological anti-tissue transglutaminase (anti-tTG) IgA and anti-deamidated gliadin peptide (anti-DGP) IgA antibodies were measured simultaneously. RESULTS Of the 188 celiac patients, 56 (29.8%) had detectable GIP levels in stools. There was significant association between age and GIP in stools that revealed increasing dietary transgressions with advancing age (39.2% in subjects ≥13 years old) and with gender in certain age groups (60% in men ≥13 years old). No association was found between fecal GIP and dietary questionnaire or anti-tTG antibodies. However, association was detected between GIP and anti-DGP antibodies, although 46 of the 53 GIP stool-positive patients were negative for anti-DGP. CONCLUSIONS Detection of gluten peptides in stools reveals limitations of traditional methods for monitoring GFD in celiac patients. The GIP ELISA enables direct and quantitative assessment of gluten exposure early after ingestion and could aid in the diagnosis and clinical management of nonresponsive CD and refractory CD. Trial registration number NCT02711397.Th is work was supported by grants from Ministerio de Ciencia e Innovación and FEDER funds (DELIAC, IPT-2011-0952-900000), and Corporación Tecnológica de Andalucía (SINGLUCHECK, 1737/0118).Ye