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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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    detail.hit.zdb_id: 3306-6
    detail.hit.zdb_id: 1476593-7
    SSG: 5,21
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  • 2
    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
    detail.hit.zdb_id: 1467823-8
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  • 3
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 44, No. 11 ( 2013-11), p. 3039-3043
    Abstract: Intracerebral hemorrhage is a serious potential complication of stroke thrombolysis. We investigated the optimal computed tomography perfusion (CTP) parameter to predict cerebral parenchymal hematoma (PH) in acute ischemic stroke. Methods— Patients with hyperacute ischemic stroke had whole-brain CTP and follow-up computed tomography/MRI to identify hemorrhagic transformation. The association of the 3 parameters relative cerebral blood flow, relative cerebral blood volume, and time to maximum ( T max ) with PH was examined using receiver operating characteristic analysis and multivariate logistic regression. Results— Of 132 patients, 70 were treated with thrombolysis, and 14 (10.6%) developed PH on follow-up imaging. Baseline National Institutes of Health Stroke Scale score ( P =0.033) and thrombolysis ( P =0.003) were both predictive of PH. Receiver operating characteristic analysis revealed that T max 〉 14 s (area under the curve=0.748; P =0.002) and relative cerebral blood flow 〈 30% of contralateral mean (area under the curve=0.689, P =0.021) were the optimal thresholds, and the Bayesian information criterion (+2.6) indicated that T max was more strongly associated with PH than relative cerebral blood flow. T max 〉 14 s volumes of 〉 5 mL allowed prediction of PH with sensitivity of 79%, specificity of 68%, and negative likelihood ratio of 3.16. T max 〉 14 s volume and thrombolysis were both independently predictive of PH in a multivariate logistic regression model ( P 〈 0.05). Conclusions— T max 〉 14 s was the CTP parameter most strongly associated with PH. This outperformed relative cerebral blood flow 〈 30%, which closely equates to CTP estimates of ischemic core volume. Although ischemic core volume on CTP is useful in the pretreatment prediction of PH, severe hypoperfusion on T max is more strongly associated and may allow better prediction of the likely anatomic location of hemorrhage.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2013
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  • 4
    In: JAMA, American Medical Association (AMA), Vol. 323, No. 13 ( 2020-04-07), p. 1257-
    Type of Medium: Online Resource
    ISSN: 0098-7484
    RVK:
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2020
    detail.hit.zdb_id: 2958-0
    detail.hit.zdb_id: 2018410-4
    SSG: 5,21
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  • 5
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 50, No. Suppl_1 ( 2019-02)
    Abstract: Introduction: Even when accounting for lesion topography, radiological Final Infarct Volume (FIV) after acute ischemic stroke (AIS) correlates only moderately with clinical outcome. Pathology in normal-appearing “salvaged” peri-infarct tissue and partial preservation within radiologically infarcted tissue may contribute to the variance between FIV and clinical outcome. We sought to evaluate the degree of neuronal dysfunction within infarcted, peri-infarct and remote regions on follow-up MRI after AIS. Methods: In a single-centre prospective study, twenty AIS patients underwent resting state functional MRI at 1 month. Asymmetry compared to the contralateral hemisphere in connectivity values (CV) was compared between 4 Regions of Interest (ROIs) defined on admission CT perfusion and 1-month MRI: (1) Early Ischemic Core with severe oligemia at presentation ( 〉 10s Tmax on admission CTP and FLAIR positivity); (2) Evolved Infarct with mild-moderate oligemia at presentation (4-8s Tmax on CTP and FLAIR positivity); (3) Peri-infarct “salvaged penumbral” tissue ( 〉 6s Tmax on CTP and FLAIR negativity); (4) remote non-ischemic tissue (normal CTP and FLAIR). Results: Asymmetry in CV were significantly different between all ROIs (p=0.018) in a preliminary analysis (n=9). Early Infarct and Evolved Infarct both showed dysfunction when compared to the contralateral hemisphere (CV = 0.384 & 0.247 respectively, p=0.717). Peri-Infarct Tissue had more dysfunction than remote tissue (CV = 0.427 vs 0.838, p=0.03) despite both being normally-appearing. Overall, Asymmetry in CV was greatest in Infarcted tissue followed by Peri-infarct Tissue and Remote Tissue. Conclusion: Peri-infarct tissue demonstrates dysfunction despite being radiologically normal. Our data suggest a gradient of neuronal injury extending beyond conventionally-delineated infarct boundaries is present in the chronic post-stroke phase.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2019
    detail.hit.zdb_id: 1467823-8
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  • 6
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 53, No. Suppl_1 ( 2022-02)
    Abstract: Introduction: The efficacy of tenecteplase (TNK) in patients with tandem lesions (TL) in the anterior circulation is unknown. The longer half-life of TNK could potentially lead to increased hemorrhage, especially in patients who require stenting of the extracranial internal carotid artery (eICA) and subsequent antiplatelet therapy. We assessed the efficacy and safety of TNK in a pooled analysis of the EXTEND-IA TNK trials. Methods: We compared the treatment effect of TNK (pooled analysis of 0.25 and 0.40mg/kg dosing) with alteplase (tPA), stratifying for TL presence. A TL was defined as a combination of eICA pathology (ipsilateral stenosis 〉 70% or occlusion) and intracranial LVO. Outcomes evaluated include 90-day mRS, intracranial reperfusion at initial angiographic assessment, mortality, ICH (symptomatic [sICH] and parenchymal hematoma [PH] ). Treatment effect was adjusted for baseline NIHSS, age, and time from symptom onset to puncture via mixed effects proportional odds and logistic regression models. Results: Of 483 patients with an anterior circulation occlusion, 71/483 (15%) patients had a TL and 43/71 (61%) patients required eICA stenting. In TL patients, reperfusion at initial angiographic assessment was observed in 11/56 (20%) of patients treated with TNK vs. 1/15 (7%) patients treated with tPA (aOR:3.71; 95% CI:0.42-32.75). sICH was observed in 4/71(6%) TL vs 7/412 (2%) nonTL patients (p=0.04). Among TL patients, sICH occurred in 4/56 (7%) patients treated with TNK vs 0/15 (0%) tPA treated patients (p=0.57); sICH occurred in 2/40 (5%) of the 0.25mg/kg TNK group and 2/16 (12.5%) of the 0.40mg/kg TNK group. PH was observed in 6/56 (11%) patients treated with TNK vs 0/15 (0%) tPA treated patients (p=0.33). 90-day mRS (TNK median 2 vs. tPA median 4, acOR:1.21; 95% CI:0.42-3.48), mortality (TNK: 5 [9%] vs. tPA: 3 [20%] , aOR:0.45; 95% CI:0.08-2.50), and eICA stenting (TNK: 35 [64%] vs. tPA: 8 [57%] , p=0.65) rates did not differ between the two treatment groups. Conclusions: Although patients with TL in the anterior circulation were at higher risk of hemorrhagic complications, these did not significantly differ between the TNK and tPA groups. A numeric increase in bleeding with TNK was not accompanied by an increase in mortality or worse functional outcome.
    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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  • 7
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 54, No. Suppl_1 ( 2023-02)
    Abstract: Background: 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 trials. Methods: Patients with large vessel occlusion (LVO) were randomized to treatment with tenecteplase (0.25mg/kg or 0.4mg/kg) or alteplase (0.9mg/kg) prior to thrombectomy. The primary outcome, early reperfusion, was defined as the absence of retrievable thrombus or 〉 50% reperfusion on initial angiographic assessment. We compared the treatment effect of tenecteplase versus alteplase overall, and in subgroups based on intracranial occlusion site, the presence of contrast permeability (measured via residual flow grades), and clot burden (measured via clot burden scores), whilst adjusting for relevant covariates using mixed effects logistic regression models. Results: Among the 465 patients in the primary analysis, early reperfusion occurred in 18% (84/465). Tenecteplase was associated with a higher odds of early reperfusion (tenecteplase: 75/369 [20%] vs. alteplase: 9/96 [9%] , aOR: 2.18 [95%CI: 1.03-4.63]). The difference between thrombolytics was most notable in distal M1 or M2 occlusions (tenecteplase: 53/176 [30%] vs. alteplase: 4/42 [10%], aOR: 3.73 [95%CI: 1.25-11.11] ), thrombi with contrast permeability (tenecteplase: 38/160 [24%] vs. alteplase: 5/48 [10%] , aOR: 2.83 [95%CI: 1.00-8.05]), and in low clot burden occlusions (tenecteplase: 66/261 [25%] vs. alteplase: 5/67 [7%], aOR: 3.93 [95%CI: 1.50-10.33] ). Both thrombolytics had limited early reperfusion efficacy in proximal occlusions (ICA: tenecteplase 1/73 [1%] vs. alteplase 1/19 [5%] ) and in high clot burden occlusions (tenecteplase: 9/108 [8%] vs. alteplase: 4/29 [14%] , aOR: 0.58 [95%CI: 0.16-2.06]). Conclusions: Tenecteplase demonstrates superior early reperfusion versus alteplase in distal LVO, in contrast-permeable thrombi, and in lesions with low clot burden. Reperfusion efficacy remains limited in ICA occlusions and lesions with high clot burden. Further improvements in intravenous thrombolytics are required.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 1467823-8
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  • 8
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 51, No. Suppl_1 ( 2020-02)
    Abstract: Background: Tenecteplase (TNK) is a genetically modified variant of alteplase with greater fibrin specificity and longer half-life than alteplase. The recent Tenecteplase versus Alteplase before Endovascular Therapy for Ischemic Stroke (EXTEND-IA TNK) trial demonstrated that increased reperfusion with TNK compared to alteplase prior to endovascular thrombectomy (EVT) in large vessel occlusion ischaemic strokes. However, only 6 patients with basilar artery occlusion (BAO) were included. We aimed to investigate the efficacy of TNK versus alteplase before EVT in patients with basilar artery occlusion (BAO). Methods: Clinical and procedural data of consecutive BAO diagnosed on CT Angiography or MR Angiography from the multisite international Basilar Artery Treatment and MANagement (BATMAN) collaboration were retrospectively analysed. The primary outcome was reperfusion of greater than 50% of the involved ischemic territory or absence of retrievable thrombus at the time of the initial angiographic assessment. Results: We included 119 BAO patients treated with intravenous thrombolysis prior to EVT; mean age 68 (SD 14), median NIHSS 16 (IQR 7-32). Eleven patients were treated with TNK (0.25mg/kg or 0.4mg/kg) and 108 with alteplase (0.9mg/kg). Overall, 113 patients had catheter angiography or early repeat imaging after thrombolysis. Reperfusion of greater than 50% of the ischemic territory or absence of retrievable thrombus occurred in 4/11 (36%) of patients treated with TNK vs 8/102 (8%) treated with alteplase (p=0.02). Onset-to-needle time did not differ between the two groups (p=0.4). Needle-to-groin-puncture time was 61 (IQR 33-100) mins in patients reperfused with TNK vs 111 (IQR 86-198) mins in patients reperfused with alteplase (p=0.048). Overall, the rate of symptomatic haemorrhage was 3/119 (2.5%). No differences were found in the rate of symptomatic intracranial haemorrhage (p=0.3) between the two thrombolytic agents. Conclusions: Despite shorter needle-to-groin-puncture times, tenecteplase was associated with an increased rate of reperfusion in comparison with alteplase before EVT in BAO. Randomized controlled trials to compare tenecteplase with alteplase in BAO patients before endovascular thrombectomy are warranted.
    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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  • 9
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 48, No. suppl_1 ( 2017-02)
    Abstract: Background and Purpose: Simultaneous multiple intracerebral hemorrhages (SMICH) are uncommon. Few single center studies have analyzed characteristics and outcome of SMICH. We analyzed clinical characteristics and outcome of SMICH patients from two comprehensive stroke centers. Methods: Baseline imaging from consecutive intracerebral hemorrhage (ICH) patients (n=1552) from Helsinki ICH study and Royal Melbourne Hospital ICH study were screened for SMICH. ICH etiology was classified according to the SMASH-U classification system. ICH due to trauma, tumor and aneurysmal rupture were excluded. Baseline clinical and radiological characteristics and 90-day mortality were compared between SMICH and single ICH patients. Association of SMICH with 90-day mortality was assessed in multivariable logistic regression models adjusted for predictors of ICH outcome. Results: 1452 patients were included in the analysis and 85 (5.9%) were classified as SMICH. SMICH were more often female (58% vs 42%;p=0.004), had lower baseline Glasgow Coma Scale (12 vs 14;p=0.008), and more frequent lobar location (59% v 34%;p 〈 0.001) compared to single ICH. The SMASH-U etiology of SMICH patients was less often hypertensive (20% vs 37%;p=0.001), more other systemic coagulopathy (12% vs 3%;p 〈 0.001) and trended towards more cerebral amyloid angiopathy (32% vs 23%;p=0.071). SMICH was not associated with 90-day mortality on univariate (37% vs 35%;p=0.635), multivariable (OR 0.783 95%CI 0.401-1.529;p=0.473), or propensity score matched analyses (OR 0.817 95% CI 0.400-1.668,p=0.578). Conclusion: SMICH occurs in approximately 1 in 20 ICH with more often lobar located hematomas, less often hypertensive and associated with more systemic coagulopathy. The mortality is similar to single ICH. Given varied etiologies, SMICH management should target the underlying pathology.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
    detail.hit.zdb_id: 1467823-8
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  • 10
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 47, No. suppl_1 ( 2016-02)
    Abstract: Background: EXTEND is an investigator-initiated, randomised, double-blind and placebo-controlled Phase III trial of intravenous alteplase vs placebo in patients with ischemic stroke 4.5-9 hours from stroke onset or wake-up-stroke (WUS). The prevalence of intra-cranial vessel occlusion in WUS patients remains to be determined and can guide the development of optimal therapy for this unique group of stroke patients. Objective: To study the prevalence and characteristics of intra-cranial vessel occlusion in this WUS cohort. Methods: Ischemic stroke patients within 4.5-9 hours from stroke onset or with WUS (time of WUS onset defined as the midpoint between time to sleep and awakening with the stroke symptoms) are eligible for enrollment. Criteria for entry into the trial include perfusion-diffusion mismatch using a perfusion threshold of Tmax 〉 6sec and a perfusion:diffusion lesion volume ratio of 〉 1.2. Diffusion lesion volume must be 〈 70mL based on assessment by automated RAPID software. Intra-cranial vessel occlusion was assessed on MR or CT angiogram performed at randomisation and 24 later. Two expert readers assessed these images independently. Results: 97 patients had images with adequate quality, including 63 (65%) in the WUS group with median age of 77.0 yrs (IQR 67.0, 81.0) and NIHSS of 14.0 (9.0, 19.0). 62 of 63 patients (98%) had vessel occlusion with 44.4% involving M1 of the middle cerebral artery, 17.5% M2, 4.8% M3, 25.4% both internal carotid artery (ICA) and M1, 4.8% ICA alone and 3.1% the posterior cerebral artery. The median ischemic core volume was 15.0 ml (6.5, 31.5), Tmax 〉 6 volume 88.5ml (58.0, 122.0), mismatch volume 65.5ml (42.8, 92.0), and ratio of 4.8 (2.5, 8.7). 19 patients (30%) demonstrated recanalization on follow-up imaging. Conclusion: In WUS patients there is a very high rate of intracranial vessel occlusion with relatively large volumes of salvageable penumbral tissue. Intravenous thrombolytic therapy followed by thrombectomy in selected cases may be an appropriate therapeutic option with safety and efficacy remaining to be established in randomized controlled trials.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2016
    detail.hit.zdb_id: 1467823-8
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