Cardiovascular subphenotypes in patients with COVID-19 pneumonitis whose lungs are mechanically ventilated: a single-centre retrospective observational study.

Unsupervised clustering methods of transthoracic echocardiography variables have not been used to characterise circulatory failure mechanisms in patients with COVID-19 pneumonitis. We conducted a retrospective, single-centre cohort study in ICU patients with COVID-19 pneumonitis whose lungs were mechanically ventilated and who underwent transthoracic echocardiography between March 2020 and May 2021. We performed latent class analysis of echocardiographic and haemodynamic variables. We characterised the identified subphenotypes by comparing their clinical parameters, treatment responses and 90-day mortality rates. We included 305 patients with a median (IQR [range]) age 59 (49-66 [16-83]) y. Of these, 219 (72%) were male, 199 (65%) had moderate acute respiratory distress syndrome and 113 (37%) did not survive more than 90 days. Latent class analysis identified three cardiovascular subphenotypes: class 1 (52%; normal right ventricular function); class 2 (31%; right ventricular dilation with mostly preserved systolic function); and class 3 (17%; right ventricular dilation with systolic impairment). The three subphenotypes differed in their clinical characteristics and response to prone ventilation and outcomes, with 90-day mortality rates of 22%, 42% and 73%, respectively (p < 0.001). We conclude that the identified subphenotypes aligned with right ventricular pathophysiology rather than the accepted definitions of right ventricular dysfunction, and these identified classifications were associated with clinical outcomes.

Effects of ageing and hormonal manipulations on the level of oestrogen receptors in the guinea-pig prostate.

Cytosolic oestrogen receptor levels in guinea-pig prostate tissue were found to decrease with increasing age, irrespective of whether the binding was expressed relative to cytosolic protein or cellular DNA. This decrease in oestrogen receptor levels was also observed using enriched fibromuscular stromal tissue prepared by mechanical fractionation of the prostate. The most pronounced change in cytosolic oestrogen receptor levels (from 133 to 35 fmol/mg protein) occurred at the onset of puberty. The pubertal decrease in receptor levels could not be attributed to an increase in the level of proteolytic activity in prostatic cytosol fractions derived from mature animals, a change in the affinity of the receptor for oestradiol or an increase in oestrogen receptor levels in salt-extracted nuclear fractions. Administration of tamoxifen (1 mg/day) to intact guinea-pigs throughout the transpubertal growth phase did not influence the age-related decrease in cytosolic and nuclear oestrogen receptor levels. In contrast, the decrease in oestrogen receptor levels was prevented by castration. Administration of dihydrotestosterone (DHT; 1 mg/day) to intact prepubertal animals for 4 days before study resulted in diminished cytosolic oestrogen receptor levels; this effect of DHT was blocked by the non-steroidal antiandrogen flutamide (2 mg/day). Furthermore, elimination of testicular hormones by castration during the late-pubertal growth phase resulted in a greater than twofold increase in prostatic oestrogen receptor levels. Collectively, these observations suggest an age-related decrease in oestrogen receptor levels in the guinea-pig prostate which, in part, may be due to increased testicular function at puberty.