Stroke; a journal of cerebral circulation
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In the Factor Seven for Acute Hemorrhagic Stroke (FAST) trial, 80 microg/kg of recombinant activated factor VII (rFVIIa) significantly reduced intracerebral hemorrhage (ICH) expansion when given within 4 hours of onset. However, in contrast to an earlier Phase 2b study, rFVIIa did not improve survival or functional outcome. In this exploratory analysis, we hypothesized that earlier treatment and exclusion of patients with a poor prognosis at baseline might enhance the benefit of rFVIIa treatment. ⋯ A prospective trial would be needed to determine whether younger patients with ICH without extensive bleeding at baseline can benefit from 80 mug/kg of rFVIIa given within 2.5 hours of symptom onset.
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Impairment of cerebrovascular autoregulation may promote secondary brain injury in acute brain insults. Until now, only limited data are available on autoregulation in patients with spontaneous intracerebral hemorrhage. In the current study, we aimed to investigate cerebrovascular reactivity and its significance for outcome in spontaneous intracerebral hemorrhage. ⋯ We found evidence for impaired cerebral vasomotor activity as measured by pressure reactivity index in patients with spontaneous intracerebral hemorrhage. We suggest that impaired cerebrovascular reactivity contributes to poor outcome in intracerebral hemorrhage patients. This effect may be mediated by fluctuations in cerebral perfusion.
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Over the past 20 years, an estimated $1 billion has been spent in research and development of stroke therapeutics; however, this huge investment has failed to produce a clinically efficacious drug with the exception of the thrombolytic agent Activase (tPA). This sobering reality has been the subject of numerous reflections by renowned leaders in stroke research with special focus on the most recent failed clinical trials. The validity of the neuroprotection strategy has been questioned and efforts to substantially modify the quality of stroke research have been examined. ⋯ In this article, we present a Translational Medicine perspective on critical issues that the pharmaceutical industry and the academic community encounter but often ignore during stroke therapeutic development. This Translational Medicine framework offers a systematic analysis of the possible deficiencies that likely underwrote the colossal failure of clinical trials with neuroprotective drugs. In addition, we offer a biomarker-based system that aims at providing "proof of concept" along the discovery and development pipeline, which if implemented along early preclinical and clinical development phases, might significantly reduce risks and enable success.
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Randomized Controlled Trial Multicenter Study
Independent associations between electrocardiographic abnormalities and outcomes in patients with aneurysmal subarachnoid hemorrhage: findings from the intraoperative hypothermia aneurysm surgery trial.
Electrocardiographic abnormalities are common after subarachnoid hemorrhage, but their significance remains uncertain. The aim of this study was to determine whether any specific electrocardiographic abnormalities are independently associated with adverse neurological outcomes. ⋯ Bradycardia, relative tachycardia, and nonspecific ST- and T-wave abnormalities are strongly and independently associated with 3-month mortality after subarachnoid hemorrhage. Further research should be performed to determine whether there is a causal relationship between cardiac dysfunction and neurological outcome after subarachnoid hemorrhage.
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Ischemia/hypoxia induces de novo expression of the sulfonylurea receptor 1-regulated NC(Ca-ATP) channel. In rodent models of ischemic stroke, early postevent administration of the sulfonylurea, glibenclamide, is highly effective in reducing edema, mortality, and lesion volume, and in patients with diabetes presenting with ischemic stroke, pre-event plus postevent use of sulfonylureas is associated with better neurological outcome. However, the therapeutic window for treatment with glibenclamide has not been studied. ⋯ Low-dose glibenclamide has a strong beneficial effect on lesion volume and has a highly favorable therapeutic window in several models of ischemic stroke.