BMQ

BMQ: Boston Medical Quarterly was published from 1950-1966 by the Boston University School of Medicine and the Massachusetts Memorial Hospitals

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

TOI-1759 b: a transiting sub-Neptune around a low mass star characterized with SPIRou and TESS

We report the detection and characterization of the transiting sub-Neptune TOI-1759 b, using photometric time-series from TESS and near infrared spectropolarimetric data from SPIRou on the CFHT. TOI-1759 b orbits a moderately active M0V star with an orbital period of $18.849975\pm0.000006$ d, and we measure a planetary radius and mass of $3.06\pm0.22$ R$_\oplus$ and $6.8\pm2.0$ M$_\oplus$. Radial velocities were extracted from the SPIRou spectra using both the CCF and the LBL methods, optimizing the velocity measurements in the near infrared domain. We analyzed the broadband SED of the star and the high-resolution SPIRou spectra to constrain the stellar parameters and thus improve the accuracy of the derived planet parameters. A LSD analysis of the SPIRou Stokes $V$ polarized spectra detects Zeeman signatures in TOI-1759. We model the rotational modulation of the magnetic stellar activity using a GP regression with a quasi-periodic covariance function, and find a rotation period of $35.65^{+0.17}_{-0.15}$ d. We reconstruct the large-scale surface magnetic field of the star using ZDI, which gives a predominantly poloidal field with a mean strength of $18\pm4$ G. Finally, we perform a joint Bayesian MCMC analysis of the TESS photometry and SPIRou RVs to optimally constrain the system parameters. At $0.1176\pm0.0013$ au from the star, the planet receives $6.4$ times the bolometric flux incident on Earth, and its equilibrium temperature is estimated at $433\pm14$ K. TOI-1759 b is a likely gas-dominated sub-Neptune with an expected high rate of photoevaporation. Therefore, it is an interesting target to search for neutral hydrogen escape, which may provide important constraints on the planetary formation mechanisms responsible for the observed sub-Neptune radius desert.Comment: Accepted for publication in the 10. Planets and planetary systems section of Astronomy & Astrophysic