Assessing the Impact of the COVID-19 Pandemic on Stroke and Emergency Department Volumes

Background and Objectives: The initial wave of the COVID pandemic in spring of 2020 caused a well-documented and dramatic reduction in nationwide stroke volumes as well as total emergency department (ED) visits. The recovery of these volumes has not been well described across subsequent waves of the pandemic. We quantified the impact of three pandemic waves on both stroke and ED volume trends from a community and free-standing ED perspective. Methods: We performed a 15-month retrospective multi-center analysis of COVID cases, total ED visits, and stroke data from an academic community hospital designated as a primary stroke center (PSC) as well as a nearby free-standing ED (FSED) across three waves of the pandemic and the intervening recovery periods. Monthly ED volume and COVID data were collected from health system dashboards. Monthly stroke volume and stroke quality of care metrics were obtained from stroke manager’s database of stroke alerts and stroke metrics. Variables are presented as count and frequency and compared between groups using a chi square test. Results: ED volumes decreased from 83,785 combined ED visits in 2019, to 62,481 combined ED visits in 2020 for a 25.4% reduction in visits. In 2021, both EDs saw partial volume recovery and finished the year at 71,065 combined ED visits which was 84.8% of 2019’s pre-COVID volume. There was a total of 160,033 ED visits and 1,059 stroke cases included in the analysis (105,631 from PSC and 54,402 from FSED). There was a significant change in both stroke diagnosis (p=.03) and stroke alerts (p \u3c.001) between the different COVID waves and recovery periods. Stroke diagnosis peaked during the first COVID wave and second recovery period and then began to decline towards pre-COVID rates. Stroke alerts were lowest pre-COVID and highest in the second recovery period. There was not a significant association between COVID waves and tissue plasminogen activator (tPA) use at the PSC, but at the FSED, there was a significant association between COVID waves and tPA use (p=0.024) with tPA use peaking during the first recovery wave and third COVID wave. Conclusion: The COVID 19 pandemic caused significant ED volume decreases during 2020. This study of two EDs may suggest a generalizable trend toward increased ED visits in 2021. There was significant fluctuation in stroke volumes and stroke alerts over the course of three COVID waves and recovery periods which has not been previously reported

Ontogeny and Vulnerabilities of Drug-Tolerant Persisters in HER2+ Breast Cancer.

Resistance to targeted therapies is an important clinical problem in HER2-positive (HER2+) breast cancer. "Drug-tolerant persisters" (DTP), a subpopulation of cancer cells that survive via reversible, nongenetic mechanisms, are implicated in resistance to tyrosine kinase inhibitors (TKI) in other malignancies, but DTPs following HER2 TKI exposure have not been well characterized. We found that HER2 TKIs evoke DTPs with a luminal-like or a mesenchymal-like transcriptome. Lentiviral barcoding/single-cell RNA sequencing reveals that HER2+ breast cancer cells cycle stochastically through a "pre-DTP" state, characterized by a G0-like expression signature and enriched for diapause and/or senescence genes. Trajectory analysis/cell sorting shows that pre-DTPs preferentially yield DTPs upon HER2 TKI exposure. Cells with similar transcriptomes are present in HER2+ breast tumors and are associated with poor TKI response. Finally, biochemical experiments indicate that luminal-like DTPs survive via estrogen receptor-dependent induction of SGK3, leading to rewiring of the PI3K/AKT/mTORC1 pathway to enable AKT-independent mTORC1 activation.info:eu-repo/semantics/publishe