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INTRODUCTION: United States stroke systems are increasingly transitioning from alteplase (TPA) to tenecteplase (TNK). Real-world data on the safety and effectiveness of replacing TPA with TNK before large vessel occlusion (LVO) stroke endovascular treatment (EVT) are lacking. METHODS: Four Pennsylvania stroke systems transitioned from TPA to TNK during the study period 01/2020-06/2023. LVO stroke patients who received intravenous thrombolysis with TPA or TNK before EVT were reviewed. Multivariate logistic analysis was conducted adjusting for age, sex, National Institute of Health Stroke Scale (NIHSS), occlusion site, last-known-well-to-intravenous thrombolysis time, interhospital-transfer and stroke system. RESULTS: Of 635 patients, 309 (48.7%) received TNK and 326 (51.3%) TPA prior to EVT. The site of occlusion was the M1 middle cerebral artery (MCA) (47.7%), M2 MCA (25.4%), internal carotid artery (14.0%), tandem carotid with M1 or M2 MCA (9.8%) and basilar artery (3.1%). A favorable functional outcome (90-day mRS ≤ 2) was observed in 47.6% of TNK and 49.7% of TPA patients (p = 0.132). TNK versus TPA groups had similar rates of early recanalization (11.9% vs. 8.4%, p = 0.259), successful endovascular reperfusion (93.5% vs. 89.3%, p = 0.627), symptomatic intracranial hemorrhage (3.2% vs. 3.4%, p = 0.218) and 90-day all-cause mortality (23.1% vs. 21.5%, p = 0.491). CONCLUSIONS: This U.S. multicenter real-world clinical experience demonstrated that switching from TPA to TNK before EVT for LVO stroke resulted in similar endovascular reperfusion, safety, and functional outcomes.
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Diffuse gliomas are epigenetically dysregulated, immunologically cold, and fatal tumors characterized by mutations in isocitrate dehydrogenase (IDH). Although IDH mutations yield a uniquely immunosuppressive tumor microenvironment, the regulatory mechanisms that drive the immune landscape of IDH mutant (IDHm) gliomas remain unknown. Here, we reveal that transcriptional repression of retinoic acid (RA) pathway signaling impairs both innate and adaptive immune surveillance in IDHm glioma through epigenetic silencing of retinol binding protein 1 (RBP1) and induces a profound anti-inflammatory landscape marked by loss of inflammatory cell states and infiltration of suppressive myeloid phenotypes. Restorative retinoic acid therapy in murine glioma models promotes clonal CD4 + T cell expansion and induces tumor regression in IDHm, but not IDH wildtype (IDHwt), gliomas. Our findings provide a mechanistic rationale for RA immunotherapy in IDHm glioma and is the basis for an ongoing investigator-initiated, single-center clinical trial investigating all-trans retinoic acid (ATRA) in recurrent IDHm human subjects.