Efficacy of oral 20-hydroxyecdysone (BIO101), a MAS receptor activator, in adults with severe COVID-19 (COVA): a randomized, placebo-controlled, phase 2/3 trial.

Background: SARS-CoV-2 binding to ACE2 is potentially associated with severe pneumonia due to COVID-19. The aim of the study was to test whether Mas-receptor activation by 20-hydroxyecdysone (BIO101) could restore the Renin-Angiotensin System equilibrium and limit the frequency of respiratory failure and mortality in adults hospitalized with severe COVID-19. Methods: Double-blind, randomized, placebo-controlled phase 2/3 trial. Randomization: 1:1 oral BIO101 (350 mg BID) or placebo, up to 28 days or until an endpoint was reached. Primary endpoint: mortality or respiratory failure requiring high-flow oxygen, mechanical ventilation, or extra-corporeal membrane oxygenation. Key secondary endpoint: hospital discharge following recovery (ClinicalTrials.gov Number, NCT04472728). Findings: Due to low recruitment the planned sample size of 310 was not reached and 238 patients were randomized between August 26, 2020 and March 8, 2022. In the modified ITT population (233 patients; 126 BIO101 and 107 placebo), respiratory failure or early death by day 28 was 11.4% lower in the BIO101 (13.5%) than in the placebo (24.3%) group, (p = 0.0426). At day 28, proportions of patients discharged following recovery were 80.1%, and 70.9% in the BIO101 and placebo group respectively, (adjusted difference 11.0%, 95% CI [-0.4%, 22.4%], p = 0.0586). Hazard Ratio for time to death over 90 days: 0.554 (95% CI [0.285, 1.077]), a 44.6% mortality reduction in the BIO101 group (not statistically significant). Treatment emergent adverse events of respiratory failure were more frequent in the placebo group. Interpretation: BIO101 significantly reduced the risk of death or respiratory failure supporting its use in adults hospitalized with severe respiratory symptoms due to COVID-19. Funding: Biophytis.

Primary mammary actinomycosis challenged with penicillin allergy.

Actinomycosis is a subacute-to-chronic bacterial infection caused by gram-positive, filamentous, non-acid-fast, facultative anaerobic bacteria. It is a normal commensal bacterium found in the oral cavity and the lower reproductive tract of women. We present a case of primary actinomycosis of the breast. A postmenopausal woman, complicated by penicillin allergy, presented with a left breast lump clinically simulating malignancy. The first line of treatment for actinomycosis is penicillin. Due to a penicillin allergy, the patient was initially treated with doxycycline. However, doxycycline was discontinued due to tremors, and was replaced by clindamycin. The patient had a good clinical response with resolution of the abscess.

The relationship between albuminuria and hormone therapy in postmenopausal women.

BACKGROUND: Elevated urinary albumin excretion and hormone therapy (HT) are associated with increased risk for cardiovascular events. We assessed the relationship between albuminuria and the use of hormonal preparations in postmenopausal women. METHODS: Data from the Insulin Resistance Atherosclerosis Study were obtained at baseline and 5-year follow-up for analysis. The generalized estimating equation procedure accounting for repeated measures was used for this analysis. HT was the main predictor variable, and log(e) urine albumin-creatinine ratio (ACR) was the main outcome variable. RESULTS: Four hundred ninety-one menopausal women were included in the analysis, 36% (n = 179) of whom received HT (either oral estrogen, progesterone, or combination therapy). At baseline, abnormal albuminuria (ACR > or = 25 mg/g) was present in 11% of women on HT and 17% not on HT (P = 0.02). After adjusting for demographics, the presence of diabetes and hypertension, and kidney function, HT was associated with a 19% reduction in ACR (P = 0.008) and an odds ratio of 0.67 (95% confidence interval, 0.43 to 1.01; P = 0.06) for the presence of abnormal albuminuria. Other predictors of abnormal albuminuria included diabetes, blood pressure, and triglyceride level. CONCLUSION: Results of this study suggest that HT is associated with a reduction in urinary albumin excretion in postmenopausal women.