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

NATURAL AND MAGNETIC-INDUCED POLARIZATION OF ELECTRIC QUADRUPOLE TRANSITIONS IN ELECTRONIC SPECTRA OF MOLECULES

Author Institution: Department of Chemistry, University of MissouriHigh resolution polarization studies of electronic absorption and emission spectra of molecular systems may be used to determine the Multi-pole nature of particular transitions. In this presentation we will discuss the polarization properties expected for ``pure"" electric-quadrupole transitions in ordinary absorption and emission spectroscopy, as well as the induced polarization (circular and linear) introduced through the application of an external magnetic field. Results will he presented for randomly oriented molecules, and calculations based on selected model systems will be discussed

Chiroptical spectroscopy, emission theory

© 2017 Elsevier Ltd. unless otherwise stated. All rights reserved. Circularly polarised emission spectroscopy, otherwise known as circularly polarised luminescence, detects the partial circular polarisation of light emitted from excited chiral molecules and is therefore complementary to circular dichroism spectroscopy. It provides a means of probing both the structure and behaviour of excited states of chiral molecules and of their processes of excitation. Moreover, in certain cases, even racemic mixtures of enantiomeric molecules can be studied by preferentially exciting a particular enatiomer with incident circularly polarised light

Solution and solid state spectroscopy of tetrakis complexes of 2,2′-bipyridine-1,1′-dioxide with europium(III)

Previous studies on the crystal structure of a complex formed with 2,2′-bipyridine-1,1′-dioxide (bpyO2) and La(III) ions have shown the existence of an tetrakis eight coordinate complex in which the metal ion sits in a site of approximate D4 symmetry. In this paper we describe high-resolution luminescence and circularly polarized luminescence results on Eu(bpyO2)43+. The appearance of several crystal-field transitions in the emission for the Eu(III) complex are interpreted in terms of distortions from the D4 symmetry seen for the La(III) analog. Extraordinarily large absorption and emission intensities for the hypersensitive transitions of Nd(bpyO2)43+ and Eu(bpyO2)43+ are observed and discussed. Large circularly polarized luminescence is observed from Eu(bpyO2)43+ dissolved in acetonitrile following circularly polarized laser excitation. This result suggests that the complex occurs in solution as a racemic complex that does not racemize on the emission time scale

Perturbation of the Racemic Equilibrium between D \u3c inf\u3e 3 Lanthanide Complexes through the Addition of Sugars

The perturbation of the racemic equilibrium of the D3 complexes of lanthanide (III) ions with 2, 6-pyridinedicarboxylate by a number of sugars is studied by circularly polarized luminescence spectroscopy. Various spectroscopic probes show that the addition of the chiral sugar has no observable effect on the structure of the lanthanide complex. The dependence of the enantiomeric excess on the concentration of added sugar is shown to be linear for all of the sugars studied. This dependence is in agreement with an equilibrium model in which the optically-active lanthanide complex forms weakly bound diastereomeric outer-sphere associated species with the various sugars. No structural correlation is found between the configuration and conformation of the sugars studied and the sign of the enantiomeric excess. © 1995, American Chemical Society. All rights reserved