ABSTRACT
[This corrects the article DOI: 10.1177/11795484221119316.].
ABSTRACT
BACKGROUND: Severe cases of coronavirus disease 2019 (COVID-19) are characterized by progressive respiratory failure and the development of acute respiratory distress syndrome (ARDS), with high mortality rates for patients requiring mechanical ventilation. Levels of the vascular growth factor Angiopoietin 2 (Ang2) in plasma have been strongly correlated with increased ARDS risk in patients with pneumonia or sepsis. The intent of this study was to determine whether LY3127804, an anti-Ang2 monoclonal antibody, could reduce the need for mechanical ventilation among patients admitted to the hospital with pneumonia and presumed or confirmed COVID-19. METHODS: Patients admitted to hospital with confirmed pneumonia, presumed or confirmed COVID-19, and infiltrates on chest imaging and/or oxygen saturation of ≤ 95% on room air were stratified by age group (< 65 years and ≥ 65 years), sex, and site and randomly assigned 1:1 within each stratum to receive either LY3127804 (20â mg/kg) or placebo on Day 1 and possibly on Day 15. The primary end point for this study was number of days in which a patient did not require a ventilator over the 28-day study period. RESULTS: Interim analysis assessed study futility after 95 randomized patients had 28-day data available and showed no benefit of LY3127804 in reducing the number of ventilator days over placebo. The study was subsequently terminated. CONCLUSION: LY3127804 treatment did not decrease the need for ventilator usage in patients hospitalized with pneumonia and presumed or confirmed COVID-19. ClinicalTrialsgov identifier: NCT04342897.
ABSTRACT
Radiation damage is a significant concern with both alphavoltaic and betavoltaic cells because their performance degrades, especially with high-energy - (>200keV) beta and alpha particles. Indirect excitation methods, such as the Photon Intermediate Direct Energy Conversion (PIDEC) framework, can protect the transducer from radiation. A nuclear battery using a 90Sr beta source was constructed by the author's research group, which demonstrated the radiation resistance of a PIDEC cell driven by beta particles (PIDECß cell). Use of alpha sources to drive nuclear batteries would appear to be much more attractive than beta sources due to higher potential power density. However, they are also subject to higher rates of radiation damage. This paper describes the successful incorporation of alpha particles into the PIDEC framework using the alpha emitter 210Po to form a PIDECα cell. The PIDECα cell transducer was exposed to alpha particles for over one year without experiencing adverse effects from radiation damage.
ABSTRACT
BACKGROUND: CSL112 is a new formulation of human apolipoprotein A-I (apoA-I) being developed to reduce cardiovascular events following acute coronary syndrome. This phase 2a, randomized, double-blind, multicenter, dose-ranging trial represents the first clinical investigation to assess the safety and pharmacokinetics/pharmacodynamics of a CSL112 infusion among patients with stable atherosclerotic disease. METHODS AND RESULTS: Patients were randomized to single ascending doses of CSL112 (1.7, 3.4, or 6.8 g) or placebo, administered over a 2-hour period. Primary safety assessments consisted of alanine aminotransferase or aspartate aminotransferase elevations >3× upper limits of normal and study drug-related adverse events. Pharmacokinetic/pharmacodynamic assessments included apoA-I plasma concentration and measures of the ability of serum to promote cholesterol efflux from cells ex vivo. Of 45 patients randomized, 7, 12, and 14 received 1.7-, 3.4-, and 6.8-g CSL112, respectively, and 11 received placebo. There were no clinically significant elevations (>3× upper limit of normal) in alanine aminotransferase or aspartate aminotransferase. Adverse events were nonserious and mild and occurred in 5 (71%), 5 (41%), and 6 (43%) patients in the CSL112 1.7-, 3.4-, and 6.8-g groups, respectively, compared with 3 (27%) placebo patients. The imbalance in adverse events was attributable to vessel puncture/infusion-site bruising. CSL112 resulted in rapid (T(max)≈2 hours) and dose-dependent increases in apoA-I (145% increase in the 6.8-g group) and total cholesterol efflux (up to 3.1-fold higher than placebo) (P<0.001). CONCLUSIONS: CSL112 infusion was well tolerated in patients with stable atherosclerotic disease. CSL112 immediately raised apoA-I levels and caused a rapid and marked increase in the capacity of serum to efflux cholesterol. This potential novel approach for the treatment of atherosclerosis warrants further investigation. CLINICAL TRIAL REGISTRATION: URL: http://www.ClinicalTrials.gov. Unique identifier: NCT01499420.
