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

Laplacian eigenmaps for multimodal groupwise image registration

Multimodal groupwise registration has been of growing interest to the image processing community due to developments in scanner technologies (e.g. multiparametric MRI, DCE-CT or PET-MR) that increased both the number of modalities and number of images under consideration. In this work a novel methodology is presented for multimodal groupwise registration that is based on Laplacian eigenmaps, a nonlinear dimensionality reduction technique. Compared to recently proposed dissimilarity metrics based on principal component analysis, the proposed metric should enable a better capture of the intensity relationships between different images in the group. The metric is constructed to be the second smallest eigenvalue from the eigenvector problem defined in Laplacian eigenmaps. The method was validated in three distinct experiments: a non-linear synthetic registration experiment, the registration of quantitative MRI data of the carotid artery, and the registration of multimodal data of the brain (RIRE). The results show increased accuracy and robustness compared to other state-of-the-art groupwise registration methodologies.ImPhys/Quantitative Imagin

Registration strategies for multi-modal whole-body MRI mosaicing.

PURPOSE: To test and compare different registration approaches for performing whole-body diffusion-weighted (wbDWI) image station mosaicing, and its alignment to corresponding anatomical T1 whole-body image. METHODS: Four different registration strategies aiming at mosaicing of diffusion-weighted image stations, and their alignment to the corresponding whole-body anatomical image, were proposed and evaluated. These included two-step approaches, where diffusion-weighted stations are first combined in a pairwise (Strategy 1) or groupwise (Strategy 2) manner and later non-rigidly aligned to the anatomical image; a direct pairwise mapping of DWI stations onto the anatomical image (Strategy 3); and simultaneous mosaicing of DWI and alignment to the anatomical image (Strategy 4). Additionally, different images driving the registration were investigated. Experiments were performed for 20 whole-body images of patients with bone metastases. RESULTS: Strategies 1 and 2 showed significant improvement in mosaicing accuracy with respect to the non-registered images (P < 0.006). Strategy 2 based on ADC images increased the alignment accuracy between DWI stations and the T1 whole-body image (P = 0.0009). CONCLUSIONS: A two-step registration strategy, relying on groupwise mosaicing of the ADC stations and subsequent registration to T1 , provided the best compromise between whole-body DWI image quality and multi-modal alignment. Magn Reson Med, 2017. © 2017 International Society for Magnetic Resonance in Medicine

Development and validation of an automated and marker-free CT-based spatial analysis method (CTSA) for assessment of femoral hip implant migration In vitro accuracy and precision comparable to that of radiostereometric analysis (RSA)

Background and purpose — We developed a marker-free automated CT-based spatial analysis (CTSA) method to detect stem-bone migration in consecutive CT datasets and assessed the accuracy and precision in vitro. Our aim was to demonstrate that in vitro accuracy and precision of CTSA is comparable to that of radiostereometric analysis (RSA). Material and methods — Stem and bone were segmented in 2 CT datasets and both were registered pairwise. The resulting rigid transformations were compared and transferred to an anatomically sound coordinate system, taking the stem as reference. This resulted in 3 translation parameters and 3 rotation parameters describing the relative amount of stem-bone displacement, and it allowed calculation of the point of maximal stem migration. Accuracy was evaluated in 39 comparisons by imposing known stem migration on a stem-bone model. Precision was estimated in 20 comparisons based on a zero-migration model, and in 5 patients without stem loosening. Results — Limits of the 95% tolerance intervals (TIs) for accuracy did not exceed 0.28 mm for translations and 0.20° for rotations (largest standard deviation of the signed error (SDSE): 0.081 mm and 0.057°). In vitro, limits of the 95% TI for precision in a clinically relevant setting (8 comparisons) were below 0.09 mm and 0.14° (largest SDSE: 0.012 mm and 0.020°). In patients, the precision was lower, but acceptable, and dependent on CT scan resolution. Interpretation — CTSA allows detection of stem-bone migration with an accuracy and precision comparable to that of RSA. It could be valuable for evaluation of subtle stem loosening in clinical practice