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

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Epigenetic clues to rheumatoid arthritis

The innate immune response needs to be tightly regulated to balance elimination of microorganisms with the magnitude of inflammation. The rupture of this balance is crucial for the outcome of diseases such as rheumatoid arthritis (RA) in which an overflowed proinflammatory response is associated with self-damage. Epigenetics alludes to systems controlling gene expression and silencing independent of the germline, but stable enough to be inherited by daughter cells upon mitosis. We will show in this review how pathological processes in RA can be shaped by epigenetics, which may in turn explain differences in phenotypes between subgroups of patients and also between subsets of fibroblasts within the joint. On the whole, the concourse of epigenetic mechanisms can precipitate the aggressive behaviour of cells and the rupture of peripheral tolerance. Targeting these emerging regulatory pathways is a promising approach for RA therapeutics

¿Por qué elegir ciclosporina A como primera línea terapéutica para la neumonía causada por COVID-19?

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High-resolution MRI detects cartilage swelling at the early stages of experimental osteoarthritis

AbstractObjective The progressive early changes in cartilage and subchondral bone in an experimental model of osteoarthritis (OA) were investigated with high-resolution magnetic resonance imaging (MRI) and microradiography.Methods Partial medial meniscectomy was performed in the left knee of 16 rabbits. Four normal and four sham-operated additional rabbits were used as controls. Changes in cartilage and subchondral bone were sequentially assessed after surgery with MRI at 0, 2, 4, 6, 8 and 10 weeks, subchondral bone variations quantified postoperatively on microradiographs of sagittal sections at 6 and 10 weeks and the macroscopic alterations graded according to the severity of joint changes.Results MRI demonstrated a progressive increase in the articular cartilage thickness in the weight-bearing area of the femur at weeks 4, 6 and 8 vs basal. Tibial cartilage thickness only showed a significant increment at week 6. No significant abnormalities were detected on X-rays in subchondral bone when compared to controls. Macroscopically, 4 weeks after the operation OA rabbits had only slight cartilage discoloration. Cartilage eburnation, pitting, superficial erosions and osteophytes were detected at week 6. These abnormalities were more evident at 8 and 10 weeks after meniscectomy.Conclusion The focal increase in cartilage thickness is one of the earliest measurable changes in OA and preceeds subchondral bone remodeling. The measurement of cartilage thickness variations with MRI can be used to follow the course of OA and to evaluate the potential beneficial effect of novel therapies