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.
Hypothesis: Hospital presentation for acute stroke may have been delayed during COVID-19. We hypothesize that stroke patients with mild symptoms (NIHSS <= 5) were more likely to present in a delayed fashion during the early days of the pandemic. Methods: Get with The Guidelines Stroke registry was used to identify stroke patients that presented between January 1 and August 31, 2020 to the University Hospital in San Antonio, Texas. The cohort was stratified by date of presentation (before COVID: Jan 1 - Mar 15; during COVID: Mar 16 - Aug 31) and presenting NIHSS (<=5 versus >5). We then analyzed by the thrombolytic exclusion criteria delay to arrival and the time interval of stroke symptoms discovery to hospital presentation. Subgroup analysis included age, sex, and ethnicity; race was excluded due to 90% Caucasian cohort. Results: A total of 294 subjects were included of which 115 were before and 179 were during COVID. There were no significant differences in the demographics for these two time periods, although a trend for greater male presentation was seen during COVID (Table 1). After both groups were dichotomized by NIHSS <=5, stroke symptoms discovery to hospital arrival and delay to arrival (Table 2) were not significantly different across subgroups. Conclusions: Regardless of NIHSS, a significant time delay in acute stroke presentation to our hospital was not seen when comparing before and during COVID. Although our study included a large Hispanic population, the cohort was primarily Caucasian; and therefore, the results have limited application. Whether men were more likely than women to present with stroke during COVID is unclear but warrants further study with a larger sample size.
BACKGROUND As the pandemic has evolved, there has been a growing concern on the probable adverse effect of isolation and social distancing on different aspects of stroke. There is, however, limited data on the possible effects of the pandemic on maintaining stroke quality time metrics. OBJECTIVE The purpose of this study was to identify the impact of COVID-19-related “shelter in place” restrictions on critical time metrics for treatment and outcomes of stroke patients in two metropolitan Texas cities with known historical differences in stroke risk, incidence, and prevalence: Austin and San Antonio. METHODS Patient data from stroke program accreditation registries in Austin and San Antonio were 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. Timing metrics were time last known well (TLKW) to arrival ≤ 3 hours, arrival to imaging initiation ≤ 25 minutes, and arrival to administration of thrombolytic ≤ 60 minutes. Primary outcomes included dichotomized process measures: TLKW to arrival, arrival to brain imaging initiation, and arrival to administration of thrombolytic therapy. Secondary outcomes were clinical endpoints: independent ambulation at discharge, discharge to home, in-hospital mortality. RESULTS Presentation and process measure trends for Austin patients during pre- and COVID-19 restriction periods were comparable other than TLKW to arrival, which increased during COVID-19. For San Antonio patients during COVID-19, there was increased TLKW to hospital arrival and increased time between hospital arrival to imaging initiation, even though the number of hospital arrivals < 4.5 hours from symptom onset decreased. Differences in pre- and during-COVID periods were found primarily in outcome measures for both Austin and San Antonio patients. Compared to the pre-COVID period, Austin patients had decreased length of stay (LOS), a decrease in number of discharges to hospice, and increase in patients with no symptoms on final assessment. On the other hand, more post-COVID-19 San Antonio patients than pre-COVID-19 had independent ambulation at discharge and were discharged to home, with a larger proportion of patients ranging from moderate disability/able to walk unassisted to no symptoms. CONCLUSIONS Austin and San Antonio patients did not hesitate to seek treatment for stroke symptoms during the COVID-19 restriction period, and longer times between TLKW and hospital arrival did not impact arrival-to-imaging and 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. CLINICALTRIAL Not applicable
out in 46/46 (100%) cases without need for periprocedural rescue surgery. Conclusion Embolization of the middle meningeal artery with n-BCA glue is an emerging treatment strategy for cSDHs.Here we demonstrate the use of a 10:1 glue dilution for enhanced embolization of non-visible MMA branches as a treatment paradigm for thorough glue penetration and extensive embolization. Further randomized studies across embolic substances and techniques will delineate optimal cSDH treatment effects.
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