The transcription factor cAMP response element (CRE)-binding protein (CREB) plays an essential role in the induction of many forms of long-term synaptic plasticity. Levels of CREB1, the Aplysia homolog of CREB, show sustained elevations for several hours after the induction of long-term synaptic facilitation (LTF). Furthermore, CREB1 binds to the promoter of its own gene. These results suggest the existence of a CREB1-positive feedback loop that contributes to the consolidation of LTF. In the present study, we provide a detailed, quantitative characterization of the dynamics of CREB1 mRNA and protein as well as CREB1 phosphorylation after LTF induction. Injections of CRE oligonucleotides prevented the increase in CREB1 in response to 5-HT, corroborating the existence of the CREB1 feedback loop. This loop probably sustains CRE-dependent gene transcription, which remains elevated for at least 12 h after LTF induction. LTF is blocked by injection of CREB1 antibody after the induction phase, suggesting that the CREB1-positive feedback is required for consolidation of LTF.
BACKGROUND: The use of endovascular therapy (EVT) in acute ischemic stroke patients with large vessel occlusion (LVO) has rapidly increased in the US following pivotal trials demonstrating its benefit. Information about the contribution of interhospital transfer in improving access to EVT will help organize regional systems of stroke care. METHODS: We analyzed trends of transfer-in EVT from a cohort of 1,863,693 ischemic stroke patients admitted to 2,143 Get With The Guidelines-Stroke participating hospitals between January 2012 and December 2017. We further examined the association between arrival mode and in-hospital outcomes using multivariable logistic regression models. RESULTS: Of the 37,260 patients who received EVT at 639 hospitals during the study period, 42.9% (15,975) arrived to the EVT providing hospital after interhospital transfer. Transfer-in EVT cases increased from 256 in Q1 2012 to 1,422 in Q4 2017, with sharply accelerated increases following Q4 2014 (p<0.001 for change in linear trend). Transfer-in patients were younger, more likely to be of white race, arrive during off-hours and treated at comprehensive stroke centers. Transfer-in patients had significantly longer last known well to EVT initiation time (median 289 min vs 213 min, absolute standardized difference 67.33) but were more likely to have door to EVT initiation time of ≤ 90 minutes (65.6% vs 23.6%, absolute standardized difference 93.18). Inhospital outcomes were worse for transfer-in EVT patients in unadjusted and in risk-adjusted
Background and Purpose— The safety of thrombolysis for acute stroke in patients with cancer is not well established. Our aim is to study the outcomes after thrombolysis in patients with stroke with cancer. Methods— Patients with acute ischemic stroke who received thrombolysis were identified from the 2009 and 2010 Nationwide Inpatient Sample. Patients with cancer-associated strokes and noncancer strokes were compared based on demographics, comorbidities, and outcomes. Results— Of the 32 576 strokes treated with thrombolysis, cancer-associated strokes had significantly higher comorbidity indices overall, but fewer vascular risk factors than noncancer strokes. There was no difference in the rates of home discharge and in-hospital mortality, after adjusting for confounders. Subgroup analysis showed that compared with liquid cancers, patients with solid tumors had worse home discharge (odds ratio, 0.178; 95% confidence interval, 0.109–0.290; P <0.001) and higher in-hospital mortality (odds ratio, 3.018; 95% confidence interval, 1.37–6.646; P =0.006) after thrombolysis. Metastatic cancers had poorest outcomes, but intracerebral hemorrhage rates were similar. Conclusions— Thrombolytic therapy for acute stroke in patients with cancer is not associated with increased risk of intracerebral hemorrhage or in-hospital mortality. However, careful consideration of the cancer subtype may help delineate the subset of patients with poor response to thrombolysis. Prospective confirmation is warranted.
CSCs and PSCs achieved similar overall care quality for patients with acute ischemic stroke. CSCs exceeded PSCs in timely acute reperfusion therapy for emergency department admissions, whereas PSCs had lower risk-adjusted in-hospital mortality. This information may be important for acute stroke triage and targeted quality improvement.
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