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Background: Although national organizations recognize the importance of regionalized acute ischemic stroke (AIS) care, data informing expansion are sparse. We assessed real-world regional variation in emergent AIS treatment, including growth in revascularization therapies and stroke center certification. We hypothesized that we would observe overall growth in revascularization therapy utilization, but observed differences would vary greatly regionally., Methods: A retrospective cross-sectional analysis was carried out of de-identified national inpatient Medicare Fee-for-Service datasets from 2016 to 2019. We identified AIS admissions and treatment with thrombolysis and endovascular thrombectomy (ET) with International Classification of Diseases, 10th Revision, Clinical Modification codes. We grouped hospitals in Dartmouth Atlas of Healthcare Hospital Referral Regions (HRR) and calculated hospital, demographic, and acute stroke treatment characteristics for each HRR. We calculated the percent of hospitals with stroke certification and AIS cases treated with thrombolysis or ET per HRR., Results: There were 957 958 AIS admissions. Relative mean (SD) growth in percent of AIS admissions receiving revascularization therapy per HRR from 2016 to 2019 was 13.4 (31.7)% (IQR -6.1-31.7%) for thrombolysis and 28.0 (72.0)% (IQR 0-56.0%) for ET. The proportion of HRRs with decreased or no difference in ET utilization was 38.9% and the proportion of HRRs with decreased or no difference in thrombolysis utilization was 32.7%. Mean (SD) stroke center certification proportion across HRRs was 45.3 (31.5)% and this varied widely (IQR 18.3-73.4%)., Conclusions: Overall growth in AIS treatment has been modest and, within HRRs, growth in AIS treatment and the proportion of centers with stroke certification varies dramatically., Competing Interests: Competing interests: NJ receives grant funding paid to her institution for grants unrelated to this work from NINDS (NIH U24NS107201, NIH IU54NS100064, 3R01CA202911-05S1, R21NS122389, R01HL161847). She receives an honorarium for her work as an Associate Editor of Epilepsia. JM is an investor in: Cerebrotech, Imperative Care, Endostream, Viseon, BlinkCNS, Serenity, NTI, RIST, NRT, Viz.ai, Synchron, Tulavi, Sim&Cure, Songbird, Borvo, Whisper, Neurolutions. He serves, or has recently served, as a consultant for: Imperative Care, Cerebrotech, Endostream, Vastrax, RIST, Synchron, NRT, Viz.ai, Perflow, CVAid., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: We assessed risk and determinants of new-onset depression in acute ischemic stroke (AIS) patients of all ages and no known history of depression. Additionally, we assessed patterns of post-stroke depression (PSD) treatment with pharmacotherapy. Methods: Retrospective cohort study of de-identified Marketscan Commercial Claims and Encounters and Medicare Supplemental and Coordination of Benefits Datasets for adults age ≥18 years admitted with AIS from July 1, 2016-July 1, 2017. We created Kaplan-Meier curves of cumulative risk of PSD up to 1.5 years following index AIS admission. We performed Cox regression to report hazard ratios for determinants of PSD up to 1.5 years following AIS. We summarized proportions treated with pharmacotherapy and identified the most commonly prescribed medications. Results: Of 8089 AIS patients, 1059 were diagnosed with PSD. At 1 year, cumulative risk of PSD was 13.4% (standard error .4) and 15.3% (standard error .5) at 1.5 years. History of anxiety was most strongly associated with PSD and discharge home least. Among those with PSD, 68.8% were prescribed an antidepressant and 8.4% an antipsychotic. The most commonly prescribed antidepressant was sertraline (28.5%). Conclusions: Among AIS patients of all ages, there is a persistently elevated cumulative risk of new diagnosis of PSD in the 1.5 years following AIS. Of the >2/3 treated with an antidepressant, sertraline was most commonly prescribed. Screening and treatment strategies for PSD require further study., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Nathalie Jette, MD, MSc: Dr Jette receives grant funding paid to her institution for grants unrelated to this work from NINDS (NIH U24NS107201, NIH IU54NS100064). She receives an honorarium for her work as an Associate Editor of Epilepsia. The author(s) received no financial support for the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Objective: We sought to comprehensively evaluate predictors of poststroke depression (PSD) in the United States and to compare PSD to post-myocardial infarction (MI) depression to determine whether ischemic stroke uniquely elevates risk of depression., Methods: This is a retrospective cohort study of 100% deidentified inpatient, outpatient, and subacute nursing Medicare data from 2016 to 2017 for US patients ≥65 years of age from July 1, 2016, to December 31, 2017. We calculated Kaplan-Meier unadjusted cumulative risk of depression up to 1.5 years after the index admission. We performed Cox regression to report the hazard ratio for diagnosis of depression up to 1.5 years after stroke vs MI and independent predictors of PSD, and we controlled for patient demographics, comorbid conditions, length of stay, and acute stroke interventions., Results: In fully adjusted models, patients with stroke (n = 174,901) were ≈50% more likely than patients with MI (n = 193,418) to develop depression during the 1.5-year follow-up period (Kaplan-Meier cumulative risk 0.1596 ± 0.001 in patients with stroke vs 0.0973 ± 0.000778 in patients with MI, log-rank p < 0.0001). History of anxiety was the strongest predictor of PSD, while discharge home was most protective. Female patients, White patients, and patients <75 years of age were more likely to be diagnosed with depression after stroke., Conclusions: Despite the similarities between MI and stroke, patients with stroke were significantly more likely to develop depression. There were several predictors of PSD, most significantly history of anxiety. Our findings lend credibility to a stroke-specific process causing depression and highlight the need for consistent depression screening in all patients with stroke., (© 2021 American Academy of Neurology.)

We developed a screening assay in which luciferized ID8 expressing OVA was cocultured with transgenic CD8 + T cells specifically recognizing the model antigen in an H-2b-restricted manner. The assay was screened with a small-molecule library to identify compounds that inhibit or enhance T cell-mediated killing of tumor cells. Erlotinib, an EGFR inhibitor, was the top compound that enhanced T-cell killing of tumor cells. Subsequent experiments with erlotinib and additional EGFR inhibitors validated the screen results. EGFR inhibitors increased both basal and IFNγ-induced MHC class-I presentation, which enhanced recognition and lysis of tumor cell targets by CD8 + cytotoxic T lymphocytes. The ID8 cell line was also transduced to constitutively express Cas9, and a pooled CRISPR screen, utilizing the same target tumor cell/T-cell assay, identified single-guide (sg)RNAs targeting EGFR that sensitized tumor cells to T cell-mediated killing. Combination of PD-1 blockade with EGFR inhibition showed significant synergistic efficacy in a syngeneic model, further validating EGFR inhibitors as immunomodulatory agents that enhance checkpoint blockade. This assay can be screened in high-throughput with small-molecule libraries and genome-wide CRISPR/Cas9 libraries to identify both compounds and target genes, respectively, that enhance or inhibit T-cell recognition and killing of tumor cells. Retrospective analyses of squamous-cell head and neck cancer (SCCHN) patients treated with the combination of afatinib and pembrolizumab demonstrated a rate of clinical activity exceeding that of each single agent. Prospective clinical trials evaluating the combination of an EGFR inhibitor and PD-1 blockade should be conducted., (©2018 American Association for Cancer Research.)