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  • 1
    In: The Lancet, Elsevier BV, Vol. 394, No. 10193 ( 2019-07), p. 139-147
    Type of Medium: Online Resource
    ISSN: 0140-6736
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2019
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    SSG: 5,21
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  • 2
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 42, No. 6 ( 2011-06), p. 1596-1601
    Abstract: The ischemic penumbra may be classical, with complete annular configuration around the infarct core, or nonclassical with a more fragmented pattern. We tested the hypotheses that these penumbral patterns may: be associated with specific predictive factors, influence infarct growth and clinical outcome, and influence the effect of tissue plasminogen activator (t-PA). Methods— Using the EPITHET/DEFUSE data set, in which patients received alteplase or placebo 3 to 6 hours poststroke, perfusion-weighted imaging and diffusion-weighted imaging images were analyzed. These mismatch patterns were defined as “classical” or “nonclassical.” Multivariate analysis was used to identify variables associated with mismatch patterns, the effect of t-PA, as well as the relationship between mismatch patterns, infarct growth, and clinical outcomes. Results— We included 158 patients (median age, 74 years; median National Institute of Health Stroke Scale score, 12). Multivariate analysis indicated that the factors associated with classical mismatch pattern type were large mismatch volume ( P 〈 0.001) and cortical infarct location ( P =0.036). Infarct growth, clinical outcome, and the efficacy of t-PA were not statistically different between patterns. Conclusions— Coregistered mismatch volume and cortical location of infarction were the important factors associated with presence of the classical mismatch pattern. The lack of effect of the type of mismatch patterns on infarct growth, clinical outcomes, or the benefit of t-PA would suggest that mismatch topography is less important during the hyperacute phase of ischemic stroke than during subacute phase.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2011
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  • 3
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 44, No. 1 ( 2013-01), p. 87-93
    Abstract: Two phase 2 studies of alteplase in acute ischemic stroke 3 to 6 hours after onset, Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET; a randomized, controlled, double-blinded trial), and Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study (DEFUSE; open-label, treatment only) using MR imaging-based outcomes have been conducted. We have pooled individual patient data from these to assess the response to alteplase. The primary hypothesis was that alteplase would significantly attenuate infarct growth compared with placebo in mismatch-selected patients using coregistration techniques. Methods— The EPITHET–DEFUSE study datasets were pooled while retaining the original inclusion and exclusion criteria. Significant hypoperfusion was defined as a Tmax delay 〉 6 seconds), and coregistration techniques were used to define MR diffusion-weighted imaging/perfusion-weighted imaging mismatch. Neuroimaging, parameters including reperfusion, recanalization, symptomatic intracerebral hemorrhage, and clinical outcomes were assessed. Alteplase and placebo groups were compared for the primary outcome of infarct growth as well for secondary outcome measures. Results— From 165 patients with adequate MR scans in the EPITHET–DEFUSE pooled data, 121 patients (73.3%) were found to have mismatch. For the primary outcome analysis, 60 patients received alteplase and 41 placebo. Mismatch patients receiving alteplase had significantly attenuated infarct growth compared with placebo ( P =0.025). The reperfusion rate was also increased (62.7% vs 31.7%; P =0.003). Mortality and clinical outcomes were not different between groups. Conclusions— The data provide further evidence that alteplase significantly attenuates infarct growth and increases reperfusion compared with placebo in the 3- to 6- hour time window in patients selected based on MR penumbral imaging. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00238537
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2013
    detail.hit.zdb_id: 1467823-8
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  • 4
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 54, No. 3 ( 2023-03), p. 706-714
    Abstract: Intracranial occlusion site, contrast permeability, and clot burden are thrombus characteristics that influence alteplase-associated reperfusion. In this study, we assessed the reperfusion efficacy of tenecteplase and alteplase in subgroups based on these characteristics in a pooled analysis of the EXTEND-IA TNK trial (Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke). Methods: Patients with large vessel occlusion were randomized to treatment with tenecteplase (0.25 or 0.4 mg/kg) or alteplase before thrombectomy in hospitals across Australia and New Zealand (2015–2019). The primary outcome, early reperfusion, was defined as the absence of retrievable thrombus or 〉 50% reperfusion on first-pass angiogram. We compared the effect of tenecteplase versus alteplase overall, and in subgroups, based on the following measured with computed tomography angiography: intracranial occlusion site, contrast permeability (measured via residual flow grades), and clot burden (measured via clot burden scores). We adjusted for covariates using mixed effects logistic regression models. Results: Tenecteplase was associated with higher odds of early reperfusion (75/369 [20%] versus alteplase: 9/96 [9%] , adjusted odds ratio [aOR], 2.18 [95% CI, 1.03–4.63] ). The difference between thrombolytics was notable in occlusions with low clot burden (tenecteplase: 66/261 [25%] versus alteplase: 5/67 [7%] , aOR, 3.93 [95% CI, 1.50–10.33]) when compared to high clot burden lesions (tenecteplase: 9/108 [8%] versus alteplase: 4/29 [14%], aOR, 0.58 [95% CI, 0.16–2.06] ; P interaction =0.01). We did not observe an association between contrast permeability and tenecteplase treatment effect (permeability present: aOR, 2.83 [95% CI, 1.00–8.05] versus absent: aOR, 1.98 [95% CI, 0.65–6.03] ; P interaction =0.62). Tenecteplase treatment effect was superior with distal M1 or M2 occlusions (53/176 [30%] versus alteplase: 4/42 [10%] , aOR, 3.73 [95% CI, 1.25–11.11]), but both thrombolytics had limited efficacy with internal carotid artery occlusions (tenecteplase 1/73 [1%] versus alteplase 1/19 [5%], aOR, 0.22 [95% CI, 0.01–3.83] ; P interaction =0.16). Conclusions: Tenecteplase demonstrates superior early reperfusion versus alteplase in lesions with low clot burden. Reperfusion efficacy remains limited in internal carotid artery occlusions and lesions with high clot burden. Further innovation in thrombolytic therapies are required.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
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  • 5
    In: International Journal of Stroke, SAGE Publications, Vol. 10, No. 1 ( 2015-01), p. 51-54
    Abstract: Advanced imaging may refine patient selection for ischemic stroke treatment but delays to acquire and process the imaging have limited implementation. Aims We examined the feasibility of imaging selection in clinical practice using fully automated software in the EXTEND trial program. Methods CTP and perfusion-diffusion MRI data were processed using fully-automated software to generate a yes/no ‘mismatch’ classification that determined eligibility for trial therapies. The technical failure/mismatch classification error rate and time to image and treat with CT vs. MR-based selection were examined. Results In a consecutive series of 776 patients from five sites over six-months the technical failure rate of CTP acquisition/processing (uninterpretable maps) was 3·4% (26/776, 95%CI 2·2–4·9%). Mismatch classification was overruled by expert review in an additional 9·0% (70/776, 95%CI 7·1–11·3%) due to artifactual ‘perfusion lesion’. In 154 consecutive patients at one site, median additional time to acquire CTP after noncontrast CT was 6·5 min. Subsequent RAPID processing time varied from 3–10 min across 20 trial centers (median 5 min 20 s). In the EXTEND trial, door-to-needle times in patients randomized on the basis of CTP ( n = 47) were median 78 min shorter than MRI-selected ( n = 16) patients ( P 〈 0·001). Conclusions Automated CTP-based mismatch selection is rapid, robust in clinical practice, and associated with faster treatment decisions than MRI. This technological advance has the potential to improve the standardization and reproducibility of interpretation of advanced imaging and extend use to practice settings beyond highly specialized academic centers.
    Type of Medium: Online Resource
    ISSN: 1747-4930 , 1747-4949
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2015
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  • 6
    In: Cerebrovascular Diseases, S. Karger AG, Vol. 36, No. 4 ( 2013), p. 273-280
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 CHADS 〈 sub 〉 2 〈 /sub 〉 and CHA 〈 sub 〉 2 〈 /sub 〉 DS 〈 sub 〉 2 〈 /sub 〉 -VASc scores are validated tools for assessing stroke risk in patients with atrial fibrillation (AF). We investigated whether these scores are associated with 3-month stroke outcomes and evaluated the utility of these scores in stratifying 3-month stroke outcomes in both patients with and without AF. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 We analysed 6,612 acute ischaemic stroke patients from the Virtual International Stroke Trials Archive who received either placebo or ineffective active treatments not associated with significant cardiac complications. Outcomes included 3-month mortality, good functional outcomes defined as modified Rankin Scale score ≤1 and serious cardiac adverse events (SCAEs) defined as one of acute coronary syndrome, symptomatic heart failure, cardiopulmonary arrest, life-threatening arrhythmia and cardiac death. The association between the pre-stroke CHADS 〈 sub 〉 2 〈 /sub 〉 and CHA 〈 sub 〉 2 〈 /sub 〉 DS 〈 sub 〉 2 〈 /sub 〉 -VASc scores and 3-month stroke outcomes was assessed using binary logistic regression. The utility of the two scores in estimating 3-month stroke outcomes was assessed using area under the receiver operator characteristic curves (AUC) and compared using the & #x03C7; 〈 sup 〉 2 〈 /sup 〉 test. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 In this cohort, 26.5% had AF, 35.3% received IV tissue plasminogen activator (tPA), 17.7% died, 25.1% achieved good functional outcomes and 9.5% had ≥1 SCAE at 3 months. High-risk (≥2) pre-stroke CHADS 〈 sub 〉 2 〈 /sub 〉 and CHA 〈 sub 〉 2 〈 /sub 〉 DS 〈 sub 〉 2 〈 /sub 〉 -VASc scores are both associated with 3-month mortality (CHADS 〈 sub 〉 2 〈 /sub 〉 : odds ratio, OR, 2.33, 95% confidence interval 1.81-3.00; CHA 〈 sub 〉 2 〈 /sub 〉 DS 〈 sub 〉 2 〈 /sub 〉 -VASc: OR 3.01, 2.00-4.80), good functional outcomes (CHADS 〈 sub 〉 2 〈 /sub 〉 : OR 0.47, 0.39-0.57; CHA 〈 sub 〉 2 〈 /sub 〉 DS 〈 sub 〉 2 〈 /sub 〉 -VASc: OR 0.55, 0.42-0.71) and SCAEs (CHADS 〈 sub 〉 2 〈 /sub 〉 : OR 1.76, 1.28-2.42; CHA 〈 sub 〉 2 〈 /sub 〉 DS 〈 sub 〉 2 〈 /sub 〉 -VASc: OR 2.69, 1.53-4.73) after adjusting for baseline differences in neurological impairment, tPA use and AF. The pre-stroke CHA 〈 sub 〉 2 〈 /sub 〉 DS 〈 sub 〉 2 〈 /sub 〉 -VASc score is better than the CHADS 〈 sub 〉 2 〈 /sub 〉 score in estimating 3-month stroke outcomes in both patients with and without AF (p ≤ 0.005 in all AUC comparisons). High-risk pre-stroke CHA 〈 sub 〉 2 〈 /sub 〉 DS 〈 sub 〉 2 〈 /sub 〉 -VASc score has high sensitivity for mortality (AF: 0.96, 0.94-0.98; no AF: 0.88, 0.86-0.91) and negative predictive value for SCAE (AF: 0.93, 0.87-0.96; no AF: 0.96, 0.95-0.97) within 3 months. Low risk pre-stroke CHA 〈 sub 〉 2 〈 /sub 〉 DS 〈 sub 〉 2 〈 /sub 〉 -VASc score has high specificity for good functional outcome (AF: 0.99, 0.98-0.994; no AF: 0.94, 0.93-0.95) at 3 months. 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 The pre-stroke CHA 〈 sub 〉 2 〈 /sub 〉 DS 〈 sub 〉 2 〈 /sub 〉 -VASc score appears to be a simple tool for identifying patients at lower risk of poor outcomes and serious cardiac complications within 3 months following ischaemic stroke in patients with and without AF.
    Type of Medium: Online Resource
    ISSN: 1015-9770 , 1421-9786
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2013
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  • 7
    In: New England Journal of Medicine, Massachusetts Medical Society, Vol. 378, No. 17 ( 2018-04-26), p. 1573-1582
    Type of Medium: Online Resource
    ISSN: 0028-4793 , 1533-4406
    RVK:
    Language: English
    Publisher: Massachusetts Medical Society
    Publication Date: 2018
    detail.hit.zdb_id: 1468837-2
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  • 8
    In: New England Journal of Medicine, Massachusetts Medical Society, Vol. 372, No. 11 ( 2015-03-12), p. 1009-1018
    Type of Medium: Online Resource
    ISSN: 0028-4793 , 1533-4406
    RVK:
    Language: English
    Publisher: Massachusetts Medical Society
    Publication Date: 2015
    detail.hit.zdb_id: 1468837-2
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  • 9
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 51, No. 3 ( 2020-03), p. 922-930
    Abstract: Mobile stroke units (MSUs) are increasingly used worldwide to provide prehospital triage and treatment. The benefits of MSUs in giving earlier thrombolysis have been well established, but the impacts of MSUs on endovascular thrombectomy (EVT) and effect on disability avoidance are largely unknown. We aimed to determine the clinical impact and disability reduction for reperfusion therapies in the first operational year of the Melbourne MSU. Methods— Treatment time metrics for MSU patients receiving reperfusion therapy were compared with control patients presenting to metropolitan Melbourne stroke units via standard ambulance within MSU operating hours. The primary outcome was median time difference in first ambulance dispatch to treatment modeled using quantile regression analysis. Time savings were subsequently converted to disability-adjusted life years avoided using published estimates. Results— In the first 365-day operation of the Melbourne MSU, prehospital thrombolysis was administered to 100 patients (mean age, 73.8 years; 62% men). The median time savings per MSU patient, compared with the control cohort, was 26 minutes ( P 〈 0.001) for dispatch to hospital arrival and 15 minutes ( P 〈 0.001) for hospital arrival to thrombolysis. The calculated overall time saving from dispatch to thrombolysis was 42.5 minutes (95% CI, 36.0–49.0). In the same period, 41 MSU patients received EVT (mean age, 76 years; 61% men) with median dispatch-to-treatment time saving of 51 minutes ([95% CI, 30.1–71.9], P 〈 0.001). This included a median time saving of 17 minutes ([95% CI, 7.6–26.4], P =0.001) for EVT hospital arrival to arterial puncture for MSU patients. Estimated median disability-adjusted life years saved through earlier provision of reperfusion therapies were 20.9 for thrombolysis and 24.6 for EVT. Conclusions— The Melbourne MSU substantially reduced time to reperfusion therapies, with the greatest estimated disability avoidance driven by the more powerful impact of earlier EVT. These findings highlight the benefits of prehospital notification and direct triage to EVT centers with facilitated workflow on arrival by the MSU.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 1467823-8
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  • 10
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 53, No. 5 ( 2022-05), p. 1597-1605
    Abstract: Factors contributing to cerebral edema in the post-hyperacute period of ischemic stroke (first 24–72 hours) are poorly understood. Blood-brain barrier (BBB) disruption and postischemic hyperperfusion reflect microvascular dysfunction and are associated with hemorrhagic transformation. We investigated the relationships between BBB integrity, cerebral blood flow, and space-occupying cerebral edema in patients who received acute reperfusion therapy. Methods: We performed a pooled analysis of patients treated for anterior circulation large vessel occlusion in the EXTEND-IA TNK and EXTEND-IA TNK part 2 trials who had MRI with dynamic susceptibility contrast-enhanced perfusion-weighted imaging 24 hours after treatment. We investigated the associations between BBB disruption and cerebral blood flow within the infarct with cerebral edema assessed using 2 metrics: first midline shift (MLS) trichotomized as an ordinal scale of negligible ( 〈 1 mm), mild (≥1 to 〈 5 mm), or severe (≥5 mm), and second relative hemispheric volume (rHV), defined as the ratio of the 3-dimensional volume of the ischemic hemisphere relative to the contralateral hemisphere. Results: Of 238 patients analyzed, 133 (55.9%) had negligible, 93 (39.1%) mild, and 12 (5.0%) severe MLS at 24 hours. The associated median rHV was 1.01 (IQR, 1.00–1.028), 1.03 (IQR, 1.01–1.077), and 1.15 (IQR, 1.08–1.22), respectively. MLS and rHV were associated with poor functional outcome at 90 days ( P 〈 0 .002). Increased BBB permeability was independently associated with more edema after adjusting for age, occlusion location, reperfusion, parenchymal hematoma, and thrombolytic agent used (MLS cOR, 1.12 [95% CI, 1.03–1.20], P =0.005; rHV β, 0.39 [95% CI, 0.24–0.55], P 〈 0.0001), as was reduced cerebral blood flow (MLS cOR, 0.25 [95% CI, 0.10–0.58], P =0.001; rHV β, −2.95 [95% CI, −4.61 to −11.29], P =0.0006). In subgroup analysis of patients with successful reperfusion (extended Treatment in Cerebral Ischemia 2b-3, n=200), reduced cerebral blood flow remained significantly associated with edema (MLS cOR, 0.37 [95% CI, 0.14–0.98], P =0.045; rHV β, −2.59 [95% CI, −4.32 to −0.86], P =0.004). Conclusions: BBB disruption and persistent hypoperfusion in the infarct after reperfusion treatment is associated with space-occupying cerebral edema. Further studies evaluating microvascular dysfunction during the post-hyperacute period as biomarkers of poststroke edema and potential therapeutic targets are warranted.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 1467823-8
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