Consensus guidelines for the use and interpretation of angiogenesis assays

The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference

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

Percolation of a CO2-enriched fluid in a limestone’s core: Evolutions of the hydraulic, electrical, chemical and structural properties

Percolation of CO2-rich fluids in limestones causes the dissolution (and eventual reprecipitation) of calcium carbonate minerals, which affect the rock microstructure and change the rock petrophysical properties (i.e., hydraulic, electrical, and elastic properties). In addition, microstructural changes further feed back to affect the chemical reactions. To better understand this coupled problem and to assess the possibility of geophysical monitoring, we performed reactive percolation laboratory experiments on a well-characterized carbonate sample 35 cm in length and 10 cm in diameter. In a comprehensive study, we present integrated measurements of aqueous chemistry (pH, calcium concentration, and total alkalinity), petrophysical properties (permeability, electrical formation factor, and acoustic velocities), and X-ray tomography imaging. The measured chemical and electrical parameters allowed rapid detection of the dissolution of calcite in the downstream fluid. After circulating fluids of various salinities at 5mL min 1 for 32 days (about 290 pore sample volumes) at a pCO2 of 1 atm (pH = 4), porosity increased by 7% (from 0.29 to 0.31), permeability increased by 1 order of magnitude (from 0.12 D to 0.97 D), and the electrical formation factor decreased by 15% (from 15.7 to 13.3). X-ray microtomography revealed the creation of wormholes; these, along with the convex curvature of the permeability-porosity relationship, are consistent with a transport-controlled dissolution regime for which advection processes are greater than diffusion processes, confirming results from previous numerical studies. This study shows that nonseismic geophysical techniques (i.e., electrical measurements) are promising for monitoring geochemical changes within the subsurface due to fluid-rock interactions