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

Importance of Multiple-window Assessment for the Diagnosis of Ascending Aortic Dissection Using Point-of-care Ultrasound: Report of Three Cases

Acute ascending aortic dissection has a high mortality rate and requires rapid diagnosis and treatment. Point-of-care ultrasound (POCUS) can aid in the diagnosis. The aortic root is usually evaluated in the parasternal long-axis view; however, a dissection flap is not always visible in this projection. We present three cases of acute, type A aortic dissection in which the dissection flap was only evident in the apical five-chamber and subxyphoid views. These cases suggest that POCUS may play a pivotal role in the initial diagnosis of acute ascending aortic dissection and highlight the importance of viewing multiple windows to fully evaluate this possibility

Importance of Multiple-window Assessment for the Diagnosis of Ascending Aortic Dissection Using Point-of-care Ultrasound: Report of Three Cases

Acute ascending aortic dissection has a high mortality rate and requires rapid diagnosis and treatment. Point-of-care ultrasound (POCUS) can aid in the diagnosis. The aortic root is usually evaluated in the parasternal long-axis view; however, a dissection flap is not always visible in this projection. We present three cases of acute, type A aortic dissection in which the dissection flap was only evident in the apical five-chamber and subxyphoid views. These cases suggest that POCUS may play a pivotal role in the initial diagnosis of acute ascending aortic dissection and highlight the importance of viewing multiple windows to fully evaluate this possibility

Evaluation of end-tidal carbon dioxide gradient as a predictor of volume responsiveness in spontaneously breathing healthy adults

Abstract Background Methods to guide fluid therapy in spontaneously breathing patients are scarce. No studies have reported the accuracy of end-tidal CO2 (ET-CO2) to predict volume responsiveness in these patients. We sought to evaluate the ET-CO2 gradient (ΔET-CO2) after a passive leg rise (PLR) maneuver to predict volume responsiveness in spontaneously breathing healthy adults. Methods We conducted a prospective study in healthy adult human volunteers. A PLR maneuver was performed and cardiac output (CO) was measured by transthoracic echocardiography. ET-CO2 was measured with non-invasive capnographs. Volume responsiveness was defined as an increase in cardiac output (CO) > 12% at 90 s after PLR. Results Of the 50 volunteers, 32% were classified as volume responders. In this group, the left ventricle outflow tract velocity time integral (VTILVOT) increased from 17.9 ± 3.0 to 20.4 ± 3.4 (p = 0.0004), CO increased from 4.4 ± 1.5 to 5.5 ± 1.6 (p = 0.0), and ET-CO2 rose from 32 ± 4.84 to 33 ± 5.07 (p = 0.135). Within the entire population, PLR-induced percentage ∆CO was not correlated with percentage ∆ET-CO2 (R 2 = 0.13; p = 0.36). The area under the receiver operating curve for the ability of ET-CO2 to discriminate responders from non-responders was of 0.67 ± 0.09 (95% CI 0.498–0.853). A ΔET-CO2 ≥ 2 mmHg had a sensitivity of 50%, specificity of 97.06%, positive likelihood ratio of 17.00, negative likelihood ratio of 0.51, positive predictive value of 88.9%, and negative predictive value of 80.5% for the prediction of fluid responsiveness. Conclusions ΔET-CO2 after a PLR has limited utility to discriminate responders from non-responders among healthy spontaneously breathing adults