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

Predictors of outcome of percutaneous excimer laser coronary angioplasty of saphenous vein bypass graft lesions. The Percutaneous Excimer Laser Coronary Angioplasty Registry.

A total of 495 patients underwent treatment with excimer laser angioplasty for 545 saphenous vein graft stenoses. Clinical success was achieved in 455 of 495 patients (92%), as indicated by < or = 50% residual stenosis at every target lesion and no complication during hospitalization. At least 1 in-hospital complication occurred in 30 of 495 patients (6.1%): death (1.0%), bypass surgery (0.6%), and Q-wave (2.4%) or non-Q-wave (2.2%) myocardial infarction. Relative risk analysis showed that ostial lesions (n = 65) tended to have higher clinical success (success rate = 95%, adjusted odds ratio [OR] = 2.1 [95% confidence interval (CI) 0.62, 6.88]; p = 0.24) and lower complications (complication rate = 0%, OR = 0.10 [CI 0.01, 0.79]; p = 0.03) than lesions in the body of the vein graft. Lesions > 10 mm (n = 131) had lower success (success rate = 84%, OR = 0.30 [CI 0.16, 0.56]; p = 0.001) and higher complications (complication rate = 12%, OR = 3.3 [CI 1.6, 6.6]; p = 0.004) than discrete lesions. Lesions in small vein grafts < 3.0 mm (n = 76) tended to have increased success (success rate = 94%, OR = 1.55 [CI 0.70, 3.44]; p = 0.39) and lower complications (complication rate = 2.2%, OR = 0.31 [CI 0.10, 0.94]; p = 0.03). Thus, excimer laser-facilitated angioplasty has the most favorable outcome for discrete lesions located at the ostium of all grafts and in the body of smaller saphenous vein grafts.(ABSTRACT TRUNCATED AT 250 WORDS

Predictors of outcome of percutaneous excimer laser coronary angioplasty of saphenous vein bypass graft lesions. The Percutaneous Excimer Laser Coronary Angioplasty Registry.

A total of 495 patients underwent treatment with excimer laser angioplasty for 545 saphenous vein graft stenoses. Clinical success was achieved in 455 of 495 patients (92%), as indicated by < or = 50% residual stenosis at every target lesion and no complication during hospitalization. At least 1 in-hospital complication occurred in 30 of 495 patients (6.1%): death (1.0%), bypass surgery (0.6%), and Q-wave (2.4%) or non-Q-wave (2.2%) myocardial infarction. Relative risk analysis showed that ostial lesions (n = 65) tended to have higher clinical success (success rate = 95%, adjusted odds ratio [OR] = 2.1 [95% confidence interval (CI) 0.62, 6.88]; p = 0.24) and lower complications (complication rate = 0%, OR = 0.10 [CI 0.01, 0.79]; p = 0.03) than lesions in the body of the vein graft. Lesions > 10 mm (n = 131) had lower success (success rate = 84%, OR = 0.30 [CI 0.16, 0.56]; p = 0.001) and higher complications (complication rate = 12%, OR = 3.3 [CI 1.6, 6.6]; p = 0.004) than discrete lesions. Lesions in small vein grafts < 3.0 mm (n = 76) tended to have increased success (success rate = 94%, OR = 1.55 [CI 0.70, 3.44]; p = 0.39) and lower complications (complication rate = 2.2%, OR = 0.31 [CI 0.10, 0.94]; p = 0.03). Thus, excimer laser-facilitated angioplasty has the most favorable outcome for discrete lesions located at the ostium of all grafts and in the body of smaller saphenous vein grafts.(ABSTRACT TRUNCATED AT 250 WORDS

Alpha-syntrophin deficient mice are protected from adipocyte hypertrophy and ectopic triglyceride deposition in obesity

Alpha-syntrophin (SNTA) is a molecular adapter protein which is expressed in adipocytes. Knock-down of SNTA in 3T3-L1 preadipocytes increases cell proliferation, and differentiated adipocytes display small lipid droplets. These effects are both characteristics of healthy adipose tissue growth which is associated with metabolic improvements in obesity. To evaluate a role of SNTA in adipose tissue morphology and obesity associated metabolic dysfunction, SNTA deficient mice were fed a standard chow or a high fat diet. Mice deficient of SNTA had less fat mass and smaller adipocytes in obesity when compared to control animals. Accordingly, these animals did not develop liver steatosis and did not store excess triglycerides in skeletal muscle upon high fat diet feeding. SNTA-/-animals were protected from hyperinsulinemia and hepatic insulin resistance. Of note, body-weight, food uptake, and serum lipids were normal in the SNTA null mice. SNTA was induced in adipose tissues but not in the liver of diet induced obese and ob/ob mice. In human subcutaneous and visceral fat of seven patients SNTA was similarly expressed and was not associated with body mass index. Current data demonstrate beneficial effects of SNTA deficiency in obesity which is partly attributed to smaller adipocytes and reduced white adipose tissue mass. Higher SNTA protein in fat depots of obese mice may contribute to adipose tissue hypertrophy and ectopic lipid deposition which has to be confirmed in humans

A Multicenter Weighted Lottery to Equitably Allocate Scarce COVID-19 Therapeutics

Shortages of new therapeutics to treat coronavirus disease (COVID-19) have forced clinicians, public health officials, and health systems to grapple with difficult questions about how to fairly allocate potentially life-saving treatments when there are not enough for all patients in need (1). Shortages have occurred with remdesivir, tocilizumab, monoclonal antibodies, and the oral antiviral Paxlovid (2) Ensuring equitable allocation is especially important in light of the disproportionate burden experienced during the COVID-19 pandemic by disadvantaged groups, including Black, Hispanic/Latino and Indigenous communities, individuals with certain disabilities, and low-income persons. However, many health systems have resorted to first-come, first-served approaches to allocation, which tend to disadvantage individuals with barriers in access to care (3). There is mounting evidence of racial, ethnic, and socioeconomic disparities in access to medications for COVID-19 (4, 5). One potential method to promote equitable allocation is to use a weighted lottery, which is an allocation strategy that gives all eligible patients a chance to receive the scarce treatment while also allowing the assignment of higher or lower chances according to other ethical considerations (6). We sought to assess the feasibility of implementing a weighted lottery to allocate scarce COVID-19 medications in a large U.S. health system and to determine whether the weighted lottery promotes equitable allocatio