A tale of two cities: A retrospective observational cohort study of the impact of COVID-19 on acute stroke presentation, timing, and outcomes.

OBJECTIVES: The purpose of this study was to identify the impact of COVID-19-related "shelter in place" restrictions on stroke metrics in two metropolitan Texas cities, Austin and San Antonio. MATERIALS AND METHODS: Data was derived from stroke quality metric registries and compared between two treatment periods: (1) during the state's COVID-19 "shelter in place" restriction period, and (2) the corresponding period during the previous year for Austin and San Antonio, Texas. Primary outcomes include the dichotomized process measures of time last known well (TLKW) to arrival, arrival to brain imaging initiation, and arrival to administration of thrombolytic therapy. Secondary outcomes are clinical endpoints: independent ambulation at discharge, discharge to home, and in-hospital mortality. RESULTS: Austin patients were older and presented with less-severe strokes. San Antonio patients were more likely to be Hispanic, suffer from a large vessel occlusion, and have independent ambulation at discharge (adjusted odds ratio, 2.04; 95% confidence intervals, (1.25-3.37). Within-city analyses revealed a trend toward increased TLKW to arrival in Austin and San Antonio during COVID-19. During COVID, Austin patients had decreased length of stay (LOS) while a higher proportion of San Antonio patients had a favorable outcome (discharged home & independent ambulation). CONCLUSIONS: Longer TLKW to hospital arrival during COVID did not impact arrival-to-imaging, arrival-to-treatment times nor patient outcomes, even in patients at higher risk for stroke. Future studies should continue to assess the impact of COVID-19 on stroke care and outcomes pre- and post-introduction of the COVID-19 vaccine, and as infectivity rates spike or recede.

CDDO-Me protects normal lung and breast epithelial cells but not cancer cells from radiation.

Although radiation therapy is commonly used for treatment for many human diseases including cancer, ionizing radiation produces reactive oxygen species that can damage both cancer and healthy cells. Synthetic triterpenoids, including CDDO-Me, act as anti-inflammatory and antioxidant modulators primarily by inducing the transcription factor Nrf2 to activate downstream genes containing antioxidant response elements (AREs). In the present series of experiments, we determined if CDDO-Me can be used as a radioprotector in normal non-cancerous human lung and breast epithelial cells, in comparison to lung and breast cancer cell lines. A panel of normal non-cancerous, partially cancer progressed, and cancer cell lines from both lung and breast tissue was exposed to gamma radiation with and without pre-treatment with CDDO-Me. CDDO-Me was an effective radioprotector when given ∼18 hours before radiation in epithelial cells (average dose modifying factor (DMF) = 1.3), and Nrf2 function was necessary for CDDO-Me to exert these radioprotective effects. CDDO-Me did not protect cancer lines tested from radiation-induced cytotoxicity, nor did it protect experimentally transformed human bronchial epithelial cells (HBECs) with progressive oncogenic manipulations. CDDO-Me also protected human lymphocytes against radiation-induced DNA damage. A therapeutic window exists in which CDDO-Me protects normal cells from radiation by activating the Nrf2 pathway, but does not protect experimentally transformed or cancer cell lines. This suggests that use of this oral available, non-toxic class of drug can protect non-cancerous healthy cells during radiotherapy, resulting in better outcomes and less toxicity for patients.