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Wake-up stroke: Dawn of a new era.

ABSTRACT: Wake-up stroke or stroke with unclear onset of symptoms is known to occur in one-fourth of ischemic stroke patients. These patients are not considered for thrombolytic therapy based on time designation of their symptom onset as per the current guidelines. Observational studies have investigated the pathophysiology and suggested actual onset of symptoms to be approximate to the awakening time for these patients. Use of advanced imaging modalities in these patients tends to identify favorable patient profiles for thrombolysis. Results of the ongoing trials will likely beckon a seminal juncture in stroke therapy and deliver critical modifications in the current treatment guidelines for thrombolysis in this substantial, yet neglected, group of stroke patients. In this article, we have reviewed the predisposing factors, preferred imaging modalities and various ongoing thrombolytic and endovascular trials to date for patients with unclear time of symptom onset or who wake up with stroke symptoms.

SUBMITTER: Malhotra K

PROVIDER: S-EPMC6126251 | biostudies-other | 2016 Apr-Jun

REPOSITORIES: biostudies-other

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Wake-up stroke: Dawn of a new era.

Malhotra Konark K Liebeskind David S DS

Brain circulation 20160401 2

Wake-up stroke or stroke with unclear onset of symptoms is known to occur in one-fourth of ischemic stroke patients. These patients are not considered for thrombolytic therapy based on time designation of their symptom onset as per the current guidelines. Observational studies have investigated the pathophysiology and suggested actual onset of symptoms to be approximate to the awakening time for these patients. Use of advanced imaging modalities in these patients tends to identify favorable pati ...[more]

PMID: 30276276

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Project description:BackgroundAbout one in five strokes occur during sleep (wake-up stroke). People with wake-up strokes have traditionally been considered ineligible for thrombolytic treatment because the time of stroke onset is unknown. However, some studies suggest that these people may benefit from recanalisation therapies.ObjectivesTo assess the effects of intravenous thrombolysis and other recanalisation therapies versus control in people with acute ischaemic stroke presenting on awakening.Search methodsWe searched the Cochrane Stroke Group Trials Register (last search: 9 January 2018). In addition, we searched the following electronic databases in December 2017: Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 11) in the Cochrane Library, MEDLINE, Embase, US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), the ISRCTN registry, and Stroke Trials Registry. We also screened references lists of relevant trials, contacted trialists, undertook forward tracking of relevant references, and contacted manufacturers of relevant devices and equipment.Selection criteriaRandomised controlled trials of intravenous thrombolytic drugs or intra-arterial therapies in people with acute ischaemic stroke presenting upon awakening.Data collection and analysisTwo review authors applied the inclusion criteria, extracted data, and assessed trial quality and risk of bias using the GRADE approach. We obtained both published and unpublished data.Main resultsWe included one pilot trial with nine participants. The trial was a feasibility trial that included participants with an unknown onset of stroke and signs on perfusion computed tomography of ischaemic tissue at risk of infarction, who were randomised to alteplase (0.9 mg/kg) or placebo. One trial was prematurely terminated due to signs of efficacy of the intervention arm; we did not include this trial because we were not able to obtain data for the portion of the participants with wake-up stroke after requesting this information from the trial authors. We identified six ongoing trials.Authors' conclusionsThere is insufficient evidence from randomised controlled trials for recommendations concerning recanalisation therapies for wake-up stroke. Results from ongoing trials will hopefully establish the efficacy and safety of such therapies.

Project description:During their development and progression tumors acquire numerous mutations that, when translated into proteins give rise to neoantigens that can be recognized by T cells. Initially, neoantigens were not recognized as preferred targets for cancer immunotherapy due to their enormous diversity and the therefore limited options to develop "one fits all" pharmacologic solutions. In recent years, the experience obtained in clinical trials demonstrating a predictive role of neoantigens in checkpoint inhibition has changed our view on the clinical potential of neoantigens in cancer immunotherapy. Technological advances such as sequencing of whole cancer genomes, the development of reliable algorithms for epitope prediction, and an increasing number of immunotherapeutic options now facilitate the development of personalized tumor therapies directly targeting a patient's neoantigenic burden. Preclinical studies in mice that support the excellent therapeutic potential of neoantigen-directed immunotherapies have provided blueprints on how this methodology can be translated into clinical applications in humans. Consistently, very recent clinical studies on personalized vaccinations targeting in silico predicted neoepitopes shed a first light on the therapeutic potential of personalized, neoantigen-directed immunotherapies. In our review, we discuss the various subtypes of tumor antigens with a focus on neoantigens and their potential in cancer immunotherapy. We will describe the current methods and techniques of detection as well as the structural requirements for neoantigens that are needed for their recognition by T cells and for tumor destruction. To assess the clinical potential of neoantigens, we will discuss their occurrence and functional relevance in spontaneous and hereditary cancers and their prognostic and predictive value. We will present in detail the existing immunotherapeutic options that exploit the neoantigen burden of tumors encompassing both preclinical efforts that provided convincing technological proof-of-concept and the current clinical studies confirming the potential of neoantigen-directed immunotherapies.

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Wake-up stroke: Dawn of a new era.

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Wake-up stroke: Dawn of a new era.

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