***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Objective The Pragmatic Ischaemic Thrombectomy Evaluation ( PISTE ) trial was a multicentre , r and omised , controlled clinical trial comparing intravenous thrombolysis ( IVT ) alone with IVT and adjunctive intra-arterial mechanical thrombectomy ( MT ) in patients who had acute ischaemic stroke with large artery occlusive anterior circulation stroke confirmed on CT angiography ( CTA ) . Design Eligible patients had IVT started within 4.5 hours of stroke symptom onset . Those r and omised to additional MT underwent thrombectomy using any Conformité Européene (CE)-marked device , with target interval times for IVT start to arterial puncture of < 90 min . The primary outcome was the proportion of patients achieving independence defined by a modified Rankin Scale ( mRS ) score of 0–2 at day 90 . Results Ten UK centres enrolled 65 patients between April 2013 and April 2015 . Median National Institutes of Health Stroke Scale score was 16 ( IQR 13–21 ) . Median stroke onset to IVT start was 120 min . In the intention-to-treat analysis , there was no significant difference in disability-free survival at day 90 with MT ( absolute difference 11 % , adjusted OR 2.12 , 95 % CI 0.65 to 6.94 , p=0.20 ) . Secondary analyses showed significantly greater likelihood of full neurological recovery ( mRS 0–1 ) at day 90 ( OR 7.6 , 95 % CI 1.6 to 37.2 , p=0.010 ) . In the per- protocol population ( n=58 ) , the primary and most secondary clinical outcomes significantly favoured MT ( absolute difference in mRS 0–2 of 22 % and adjusted OR 4.9 , 95 % CI 1.2 to 19.7 , p=0.021 ) . Conclusions The trial did not find a significant difference between treatment groups for the primary end point . However , the effect size was consistent with published data and across primary and secondary end points . Proceeding as fast as possible to MT after CTA confirmation of large artery occlusion on a background of intravenous alteplase is safe , improves excellent clinical outcomes and , in the per- protocol population , improves disability-free survival . Trial registration number NCT01745692 ; Results Background and Purpose — The National Institutes of Health ( NIH ) estimates that stroke costs now exceed $ 45 billion per year . Stroke is the third leading cause of death and one of the leading causes of adult disability in North America , Europe , and Asia . A number of well- design ed r and omized stroke trials and case series have now been reported in the literature to evaluate the safety and efficacy of thrombolytic therapy for the treatment of acute ischemic stroke . These stroke trials have included intravenous studies , intra-arterial studies , and combinations of both , as well as use of mechanical devices for removal of thromboemboli and of neuroprotectant drugs , alone or in combination with thrombolytic therapy . At this time , the only therapy demonstrated to improve outcomes from an acute stroke is thrombolysis of the clot responsible for the ischemic event . There is room for improvement in stroke lysis studies . Divergent criteria , with disparate reporting st and ards and definitions , have made direct comparisons between stroke trials difficult to compare and contrast in terms of overall patient outcomes and efficacy of treatment . There is a need for more uniform definitions of multiple variables such as collateral flow , degree of recanalization , assessment of perfusion , and infa rct size . In addition , there are multiple unanswered questions that require further investigation , in particular , questions as to which patients are best treated with thrombolysis . One of the most important predictors of clinical success is time to treatment , with early treatment of <3 hours for intravenous tissue plasminogen activator and < 6 hours for intra-arterial thrombolysis demonstrating significant improvement in terms of 90-day clinical outcome and reduced cerebral hemorrhage . It is possible that improved imaging that identifies the ischemic penumbra and distinguishes it from irreversibly infa rct ed tissue will more accurately select patients for therapy than duration of symptoms . There are additional problems in the assessment of patients eligible for thrombolysis . These include being able to predict whether a particular site of occlusion can be successfully revascularized , predict an individual patient ’s prognosis and outcome after revascularization , and in particular , to predict the development of intracerebral hemorrhage , with and without clinical deterioration . It is not clear to assume that achieving immediate flow restoration due to thrombolytic therapy implies clinical success and improved outcome . There is no simple correlation between recanalization and observed clinical benefit in all ischemic stroke patients , because other interactive variables , such as collateral circulation , the ischemic penumbra , lesion location and extent , time to treatment , and hemorrhagic conversion , are all interrelated to outcome . Methods — This article was written under the auspices of the Technology Assessment Committees for both the American Society of Interventional and Therapeutic Neuroradiology and the Society of Interventional Radiology . The purpose of this document is to provide guidance for the ongoing study design of trials of intra-arterial cerebral thrombolysis in acute ischemic stroke . It serves as a background for the intra-arterial thrombolytic trials in North America and Europe , discusses limitations of thrombolytic therapy , defines predictors for success , and offers the rationale for the different considerations that might be important during the design of a clinical trial for intra-arterial thrombolysis in acute stroke . Included in this guidance document are suggestions for uniform reporting st and ards for such trials . These definitions and st and ards are mainly intended for research trials ; however , they should also be helpful in clinical practice and applicable to all publications . This article serves to st and ardize reporting terminology and includes pretreatment assessment , neurologic evaluation with the NIH Stroke Scale score , imaging evaluation , occlusion sites , perfusion grade s , follow-up imaging studies , and neurologic assessment s. Moreover , previously used and established definitions for patient selection , outcome assessment , and data analysis are provided , with some possible variations on specific end points . This document is therefore targeted to help an investigator to critically review the scales and scores used previously in stroke trials . This article also seeks to st and ardize patient selection for treatment based on neurologic condition at presentation , baseline imaging studies , and utilization of st and ardized inclusion /exclusion criteria . It defines outcomes from therapy in phase I , II , and III studies . Statistical approaches are presented for analyzing outcomes from prospect i ve , r and omized trials with both primary and secondary variable analysis . A discussion on techniques for angiography , intra-arterial thrombolysis , anticoagulation , adjuvant therapy , and patient management after therapy is given , as well as recommendations for posttreatment evaluation , duration of follow-up , and reporting of disability outcomes .  Imaging assessment before and after treatment is given . In the past , noncontrast CT brain scans were used as the initial screening examination of choice to exclude cerebral hemorrhage . However , it is now possible to quantify the volume of early infa rct by using contiguous , discrete ( nonhelical ) images of 5 mm . In addition , CT angiography by helical scanning and 100 mL of intravenous contrast agent can be used expeditiously to obtain excellent vascular anatomy , define the occlusion site , obtain 2D and 3D reformatted vascular images , grade collateral blood flow , and perform tissue-perfusion studies to define transit times of a contrast bolus through specific tissue beds and regions of interest in the brain . Dynamic CT perfusion scans to assess the whole dynamics of a contrast agent transit curve can now be routinely obtained at many hospitals involved in these studies . The rationale , current status of this technology , and potential use in future clinical trials are given . Many hospitals are also performing MR brain studies at baseline in addition to , or instead of , CT scans . MRI has a high sensitivity and specificity for the diagnosis of ischemic stroke in the first several hours from symptom onset , identifies arterial occlusions , and characterizes ischemic pathology noninvasively . Case series have demonstrated and characterized the early detection of intraparenchymal hemorrhage and subarachnoid hemorrhage by MRI . Echo planar images , used for diffusion MRI and , in particular , perfusion MRI are inherently sensitive for the susceptibility changes caused by intraparenchymal blood products . Consequently , MRI has replaced CT to rule out acute hemorrhage in some centers . The rationale and the potential uses of MR scanning are provided . In addition to established criteria , technology is continuously evolving , and imaging techniques have been introduced that offer new insights into the pathophysiology of acute ischemic stroke . For example , a better patient stratification might be possible if CT and /or MRI brain scans are used not only as exclusion criteria but also to provide individual inclusion and exclusion criteria based on tissue physiology . Imaging techniques might also be used as a surrogate outcome measure in future thrombolytic trials . The context of a controlled study is the best environment to vali date emerging imaging and treatment techniques . The final section details reporting st and ards for complications and adverse outcomes ; defines serious adverse events , adverse events , and unanticipated adverse events ; and describes severity of complications and their relation to treatment groups . Recommendations are made regarding comparing treatment groups , r and omization and blinding , intention-to-treat analysis , quality -of-life analysis , and efficacy analysis . This document concludes with an analysis of general costs associated with therapy , a discussion regarding entry criteria , outcome measures , and the variability of assessment of the different stroke scales currently used in the literature is also featured . Conclusion — In summary , this article serves to provide a more uniform set of criteria for clinical trials and reporting outcomes used in design ing stroke trials involving intra-arterial thrombolytic agents , either alone or in combination with other therapies . It is anticipated that by having a more uniform set of reporting st and ards , more meaningful analysis of the data and the literature will be able to be achieved Background and Purpose — Thrombectomy , primarily with stent retrievers with or without adjunctive aspiration , provided clinical benefit across multiple prospect i ve r and omized trials . Whether this benefit is exclusive to stent retrievers is unclear . Methods — THERAPY ( The R and omized , Concurrent Controlled Trial to Assess the Penumbra System ’s Safety and Effectiveness in the Treatment of Acute Stroke ; NCT01429350 ) was an international , multicenter , prospect i ve , r and omized ( 1:1 ) , open label , blinded end point evaluation , concurrent controlled clinical trial of aspiration thrombectomy after intravenous alteplase ( IAT ) administration compared with intravenous-alteplase alone  in patients with large vessel ischemic stroke because of a thrombus length of ≥8 mm . The primary efficacy end point was the percent of patients achieving independence at 90 days ( modified Rankin Scale score , 0–2 ; intention-to-treat analysis ) . The primary safety end point was the rate of severe adverse events ( SAEs ) by 90 days ( as treated analysis ) . Patients were r and omized 1:1 across 36 centers in 2 countries ( United States and Germany ) . Results — Enrollment was halted after 108 ( 55 IAT and 53 intravenous ) patients ( of 692 planned ) because of external evidence of the added benefit of endovascular therapy to intravenous-alteplase alone . Functional independence was achieved in 38 % IAT and 30 % intravenous intention-to-treat groups ( P=0.52 ) . Intention-to-treat ordinal modified Rankin Scale odds ratio was 1.76 ( 95 % confidence interval , 0.86–3.59 ; P=0.12 ) in favor of IAT . Secondary efficacy analyses all demonstrated a consistent direction of effect toward benefit of IAT . No differences in symptomatic intracranial hemorrhage rates ( 9.3 % IAT versus 9.7 % intravenous , P=1.0 ) or 90-day mortality ( IAT : 12 % versus intravenous : 23.9 % , P=0.18 ) were observed . Conclusions — THERAPY did not achieve its primary end point in this underpowered sample . Directions of effect for all prespecified outcomes were both internally and externally consistent toward benefit . It is possible that an alternate method of thrombectomy , primary aspiration , will benefit selected patients harboring large vessel occlusions . Further study on this topic is indicated . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01429350 Background and Purpose — Clinical trials have demonstrated improved 90-day outcomes for patients with acute ischemic stroke treated with stent retriever thrombectomy plus tissue-type plasminogen activator ( SST+tPA )  compared with tPA . Previous studies suggested that this strategy may be cost-effective , but models were derived from pooled data and older assumptions . Methods — In this prospect i ve economic sub study conducted alongside the SWIFT-PRIME trial ( Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke ) , in-trial costs were measured for patients using detailed medical re source utilization and hospital billing data . Utility weights were assessed at 30 and 90 days using the EuroQol-5 dimension question naire . Post-trial costs and life-expectancy were estimated for each surviving patient using a model based on trial data and inputs derived from a contemporary cohort of ischemic stroke survivors . Results — Index hospitalization costs were $ 17 183 per patient higher for SST+tPA than for tPA ( $ 45 761 versus $ 28  
    Output:
    
Trial sequential analysis indicated that the information size requirement was fulfilled to conclude the evidence for mechanical thrombectomy is robust .
Trial sequential analysis demonstrated sufficient evidence for effectiveness and safety of mechanical thrombectomy .
Uncertainty remains as to whether mechanical thrombectomy reduces mortality or increases risk of symptomatic intracranial haemorrhage