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

IMPROVED SEGMENTATION OF MULTIPLE CAVITIES OF THE HEART IN WIDE-VIEW 3-D TRANSESOPHAGEAL ECHOCARDIOGRAMS

Minimally invasive interventions in the heart such as in electrophysiology are becoming more and more important in clinical practice. Currently, preoperative computed tomography angiography (CTA) is used to provide anatomic information during electrophysiology interventions, but this does not provide real-time feedback and burdens the patient with additional radiation and side effects of the contrast agent. Three-dimensional transesophageal echocardiography (TEE) is an excellent modality for visualization of anatomic structures and instruments in real time, but some cavities, especially the left atrium, suffer from the limited coverage of the 3-D TEE volumes. This leads to difficulty in segmenting the left atrium. We propose replacing or complementing preoperative CTA imaging with wide-view TEE. We tested this proposal on 20 patients for which TEE image volumes covering the left atrium and CTA images were acquired. The TEE images were manually registered, and wide-view volumes were generated. Five heart cavities in single-view and wide-view TEE were segmented and compared with atlas based-segmentations derived from the CTA images. We found that the segmentation accuracy ( Dice coefficients) improved relative to segmentation of single-view images by 5, 15 and 9 percentage points for the left atrium, right atrium and aorta, respectively. Average anatomic coverage was improved by 2, 29, 62 and 49 percentage points for the right ventricle, left atrium, right atrium and aorta, respectively. This finding confirms that wide-view 3-D TEE can be useful in supporting electrophysiology interventions. (C) 2015 World Federation for Ultrasound in Medicine & Biology

IMPROVED SEGMENTATION OF MULTIPLE CAVITIES OF THE HEART IN WIDE-VIEW 3-D TRANSESOPHAGEAL ECHOCARDIOGRAMS

Minimally invasive interventions in the heart such as in electrophysiology are becoming more and more important in clinical practice. Currently, preoperative computed tomography angiography (CTA) is used to provide anatomic information during electrophysiology interventions, but this does not provide real-time feedback and burdens the patient with additional radiation and side effects of the contrast agent. Three-dimensional transesophageal echocardiography (TEE) is an excellent modality for visualization of anatomic structures and instruments in real time, but some cavities, especially the left atrium, suffer from the limited coverage of the 3-D TEE volumes. This leads to difficulty in segmenting the left atrium. We propose replacing or complementing preoperative CTA imaging with wide-view TEE. We tested this proposal on 20 patients for which TEE image volumes covering the left atrium and CTA images were acquired. The TEE images were manually registered, and wide-view volumes were generated. Five heart cavities in single-view and wide-view TEE were segmented and compared with atlas based-segmentations derived from the CTA images. We found that the segmentation accuracy ( Dice coefficients) improved relative to segmentation of single-view images by 5, 15 and 9 percentage points for the left atrium, right atrium and aorta, respectively. Average anatomic coverage was improved by 2, 29, 62 and 49 percentage points for the right ventricle, left atrium, right atrium and aorta, respectively. This finding confirms that wide-view 3-D TEE can be useful in supporting electrophysiology interventions. (C) 2015 World Federation for Ultrasound in Medicine & Biology

No evidence that MDMA-induced enhancement of emotional empathy is related to peripheral oxytocin levels or 5-HT1a receptor activation

The present study aimed at investigating the effect of MDMA on measures of empathy and social interaction, and the roles of oxytocin and the 5-HT1A receptor in these effects. The design was placebo-controlled within-subject with 4 treatment conditions: MDMA (75 mg), with or without pindolol (20 mg), oxytocin nasal spray (40 IU+16 IU) or placebo. Participants were 20 healthy poly-drug MDMA users, aged between 18–26 years. Cognitive and emotional empathy were assessed by means of the Reading the Mind in the Eyes Test and the Multifaceted Empathy Test. Social interaction, defined as trust and reciprocity, was assessed by means of a Trust Game and a Social Ball Tossing Game. Results showed that MDMA selectively affected emotional empathy and left cognitive empathy, trust and reciprocity unaffected. When combined with pindolol, these effects remained unchanged. Oxytocin did not affect measures of empathy and social interaction. Changes in emotional empathy were not related to oxytocin plasma levels. It was concluded that MDMA (75 mg) selectively enhances emotional empathy in humans. While the underlying neurobiological mechanism is still unknown, it is suggested that peripheral oxytocin does not seem to be the main actor in this; potential candidates are the serotonin 2A and the vasopressin 1A receptors.This work was supported by the Netherlands Organization for Scientific Research (NWO), Grant number: 400-07-2013, awarded to JR and KK