***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: See related article , p 2509  Intra-arterial therapy ( IAT ) for acute ischemic stroke ( AIS ) has dramatically evolved during the past decade to include aspiration and stent-retriever devices . Recent r and omized controlled trials have demonstrated the superior revascularization efficacy of stent-retrievers compared with the first-generation Merci device.1,2 Additionally , the Diffusion and Perfusion Imaging Evaluation for Underst and ing Stroke Evolution ( DEFUSE ) 2 , the Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy ( MR RESCUE ) , and the Interventional Management of Stroke ( IMS ) III trials have confirmed the importance of early revascularization for achieving better clinical outcome .3–5 Despite these data , the current heterogeneity in cerebral angiographic revascularization grading ( CARG ) poses a major obstacle to further advances in stroke therapy . To date , several CARG scales have been used to measure the success of IAT.6–14 Even when the same scale is used in different studies , it is applied using varying operational criteria , which further confounds the interpretation of this key metric.10 The lack of a uniform grading approach limits comparison of revascularization rates across clinical trials and hinders the translation of promising , early phase angiographic results into proven , clinical ly effective treatments.6–14 For these reasons , it is critical that CARG scales be st and ardized and end points for successful revascularization be refined.6 This will lead to a greater underst and ing of the aspects of revascularization that are strongly predictive of clinical response . The optimal grading scale must demonstrate ( 1 ) a strong correlation with clinical outcome , ( 2 ) simplicity and feasibility of scale interpretation while ensuring characterization of relevant angiographic findings , and ( 3 ) high inter-rater reproducibility . To address these issues , a multidisciplinary panel of neurointerventionalists , neuroradiologists , and stroke neurologists with extensive experience in neuroimaging and IAT , convened at the “ Consensus Meeting on Revascularization Grading Following Endovascular Therapy ” with the goal Background and Purpose — The only Food and Drug Administration ( FDA ) -approved treatment for acute ischemic stroke is tissue plasminogen activator ( tPA ) given intravenously within 3 hours of symptom onset . An alternative strategy for opening intracranial vessels during stroke is mechanical embolectomy , especially for patients ineligible for intravenous tPA .  Methods — We investigated the safety and efficacy of a novel embolectomy device ( Merci Retriever ) to open occluded intracranial large vessels within 8 hours of the onset of stroke symptoms in a prospect i ve , nonr and omized , multicenter trial . All patients were ineligible for intravenous tPA .  Primary outcomes were recanalization and safety , and secondary outcomes were neurological outcome at 90 days in recanalized versus nonrecanalized patients . Results — Recanalization was achieved in 46 % ( 69/151 ) of patients on intention to treat analysis , and in 48 % ( 68/141 ) of patients in whom the device was deployed . This rate is significantly higher than that expected using an historical control of 18 % ( P<0.0001 ) . Clinical ly significant procedural complications occurred in 10 of 141 ( 7.1 % ) patients . Symptomatic intracranial hemorrhages was observed in 11 of 141 ( 7.8 % ) patients . Good neurological outcomes ( modified Rankin score ≤2 ) were more frequent at 90 days in patients with successful recanalization compared with patients with unsuccessful recanalization ( 46 % versus 10 % ; relative risk [ RR ] , 4.4 ; 95 % CI , 2.1 to 9.3 ; P<0.0001 ) , and mortality was less ( 32 % versus 54 % ; RR , 0.59 ; 95 % CI , 0.39 to 0.89 ; P=0.01 ) . Conclusions — A novel endovascular embolectomy device can significantly restore vascular patency during acute ischemic stroke within 8 hours of stroke symptom onset and provides an alternative intervention for patients who are otherwise ineligible for thrombolytics Background and Purpose — Desmoteplase is a novel plasminogen activator with favorable features in vitro compared with available agents . This study evaluated safety and efficacy of intravenous ( IV ) desmoteplase in patients with perfusion/diffusion mismatch on MRI 3 to 9 hours after onset of acute ischemic stroke . Methods — DEDAS was a placebo-controlled , double-blind , r and omized , dose-escalation study investigating doses of 90 & mgr;g/kg and 125 & mgr;g/kg desmoteplase . Eligibility criteria included baseline National Institute of Health Stroke Scale ( NIHSS ) scores of 4 to 20 and MRI evidence of perfusion/diffusion mismatch . The safety end point was the rate of symptomatic intracranial hemorrhage . Primary efficacy co-end points were MRI reperfusion 4 to 8 hours after treatment and good clinical outcome at 90 days . The primary analyses were intent-to-treat . Before unblinding , a target population , excluding patients violating specific MRI criteria , was defined . Results — Thirty-seven patients were r and omized and received treatment ( intent-to-treat ; placebo : n=8 ; 90 & mgr;g/kg : n=14 ; 125 & mgr;g/kg : n=15 ) . No symptomatic intracranial hemorrhage occurred . Reperfusion was achieved in 37.5 % ( 95 % CI [ 8.5 ; 75.5 ] ) of placebo patients , 18.2 % ( 2.3 ; 51.8 ) of patients treated with 90 & mgr;g/kg desmoteplase , and 53.3 % ( 26.6 ; 78.7 ) of patients treated with 125 & mgr;g/kg desmoteplase .  Good clinical outcome at 90 days occurred in 25.0 % ( 3.2 ; 65.1 ) treated with placebo , 28.6 % ( 8.4 ; 58.1 ) treated with 90 & mgr;g/kg desmoteplase and 60.0 % ( 32.3 ; 83.7 ) treated with 125 & mgr;g/kg desmoteplase . In the target population ( n=25 ) , the difference compared with placebo increased and was statistically significant for good clinical outcome with 125 & mgr;g/kg desmoteplase ( P=0.022 ) . Conclusions — Treatment with IV desmoteplase 3 to 9 hours after ischemic stroke onset appears safe . At a dose of 125 & mgr;g/kg desmoteplase appeared to improve clinical outcome , especially in patients fulfilling all MRI criteria . The results of DEDAS generally support the results of its predecessor study , Desmoteplase in Acute Ischemic Stroke ( DIAS ) Background and Purpose — The Penumbra Pivotal Stroke Trial reported a 25 % good outcome ( modified Rankin scale score ≤2 ) despite an 81 % recanalization rate . We evaluated the association of a favorable initial noncontrast CT and a short time to recanalization in predicting good outcome . Methods — Data were from the Penumbra Pivotal Stroke Trial . Baseline scans were evaluated by 2 experienced readers blinded to outcomes using ASPECTS . ASPECTS scores were dichotomized into > 7 and ≤7 for primary analysis . Data on degree of recanalization based on thrombolysis in myocardial infa rct ion scores , stroke onset to recanalization , and CT to recanalization times were obtained . Primary outcome was modified Rankin scale score ≤2 at 3 months . Results —  Median baseline NIHSS was 18 ( range , 8–34 ) and median baseline ASPECTS score was 6 ( range , 0–10 ) ; 81.2 % achieved recanalization ( thrombolysis in myocardial infa rct ion , 2–3 ) and ( 27.7 % ) achieved good outcome . Good outcome was significantly higher in the  ASPECTS  score > 7 group when compared to the ASPECTS score ≤7 group ( 50 % vs 15 % ; RR , 3.3 ; 95 % CI , 1.6–6.8 ; P=0.0001 ) . No patient with an ASPECTS score ≤4 ( n=28 ) or without recanalization ( n=16 ) had a good outcome . There was an interaction between baseline ASPECTS score ( > 7 and ≤7 ) and onset to recanalization time ( ≤300 minutes and > 300 minutes ) in predicting good outcome ( P=0.06 ) . Conclusion — Patients with baseline CT ASPECTS score ≤4 do not benefit from recanalization . Fast recanalization may benefit patients with evident damage on the CT scan ( ASPECTS score > 4 ) . Overall , patients benefit the most with early recanalization and a favorable baseline CT scan ( ASPECTS score > 7 ) Background and Purpose — The Middle Cerebral Artery Embolism Local Fibrinolytic Intervention Trial ( MELT ) Japan was organized to determine the safety and clinical efficacy of intraarterial infusion of urokinase ( UK ) in patients with stroke within 6 hours of onset . Methods — Patients with ischemic stroke presenting within 6 hours of onset and displaying occlusions of the M1 or M2 portion of the middle cerebral artery on carotid angiography were r and omized to the UK or control groups . Clinical outcome was assessed by the modified Rankin Scale , National Institutes of Health Stroke Scale , and Barthel Index . Results — The Independent Monitoring Committee recommended stopping the trial after approval of intravenous infusion of recombinant tissue plasminogen activator in Japan . A total of 114 patients underwent r and omization , 57 patients in each group . Background characteristics were comparable between the 2 groups . The primary end point of favorable outcome ( modified Rankin Scale 0 to 2 ) at 90 days was somewhat more frequent in the UK group than in the control group ( 49.1 % and 38.6 % , OR : 1.54 , 95 % CI : 0.73 to 3.23 ) but did not reach a significant level ( P=0.345 ) . However , excellent functional outcome ( modified Rankin Scale 0 to 1 ) at 90 days , a preplanned secondary end point , was more frequent in the UK group than in the control group ( 42.1 % and 22.8 % , P=0.045 , OR : 2.46 , 95 % CI : 1.09 to 5.54 ) . There were significantly more patients with National Institutes of Health Stroke Scale 0 or 1 at 90 days in the UK group than the control group ( P=0.017 ) . The 90-day cumulative mortality was 5.3 % in the UK group and 3.5 % in the control group ( P=1.000 ) , and intracerebral hemorrhage within 24 hours of treatment occurred in 9 % and 2 % , respectively ( P=0.206 ) . Conclusions — The trial was aborted prematurely and the primary end point did not reach statistical significance . Nevertheless , the secondary analyses suggested that intraarterial fibrinolysis has the potential to increase the likelihood of excellent functional outcome BACKGROUND Trials of endovascular therapy for ischemic stroke have produced variable results . We conducted this study to test whether more advanced imaging selection , recently developed devices , and earlier intervention improve outcomes . METHODS We r and omly assigned patients with ischemic stroke who were receiving 0.9 mg of alteplase per kilogram of body weight less than 4.5 hours after the onset of ischemic stroke either to undergo endovascular thrombectomy with the Solitaire FR ( Flow Restoration ) stent retriever or to continue receiving alteplase alone .  All the patients had occlusion of the internal carotid or middle cerebral artery and evidence of salvageable brain tissue and ischemic core of less than 70 ml on computed tomographic ( CT ) perfusion imaging . The co primary outcomes were reperfusion at 24 hours and early neurologic improvement ( ≥8-point reduction on the National Institutes of Health Stroke Scale or a score of 0 or 1 at day 3 ) . Secondary outcomes included the functional score on the modified Rankin scale at 90 days . RESULTS The trial was stopped early because of efficacy after 70 patients had undergone r and omization ( 35 patients in each group ) . The percentage of ischemic territory that had undergone reperfusion at 24 hours was greater in the endovascular-therapy group than in the alteplase-only group ( median , 100 % vs. 37 % ; P<0.001 ) . Endovascular therapy , initiated at a median of 210 minutes after the onset of stroke , increased early neurologic improvement at 3 days ( 80 % vs. 37 % , P=0.002 ) and improved the functional outcome at 90 days , with more patients achieving functional independence ( score of 0 to 2 on the modified Rankin scale , 71 % vs. 40 % ; P=0.01 ) . There were no significant differences in rates of death or symptomatic intracerebral hemorrhage . CONCLUSIONS In patients with ischemic stroke with a proximal cerebral arterial occlusion and salvageable tissue on CT perfusion imaging , early thrombectomy with the Solitaire FR stent retriever 
    Output:
    
FINDINGS Intravenous thrombolysis is the mainstay of acute ischemic stroke management for any patient with disabling deficits presenting within 4.5 hours from symptom onset .
R and omized trials have demonstrated that more patients return to having good function ( defined by being independent and having slight disability or less ) when treated within 4.5 hours after symptom onset with intravenous recombinant tissue plasminogen activator ( IV rtPA ) therapy .
Regardless of mode of reperfusion , earlier reperfusion is associated with better clinical outcomes .
AND RELEVANCE Intravenous rtPA remains the st and ard of care for patients with moderate to severe neurological deficits who present within 4.5 hours of symptom onset .
Outcomes for some patients with acute ischemic stroke and moderate to severe neurological deficits due to proximal artery occlusion are improved with endovascular reperfusion therapy .