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  • 1
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 55, No. Suppl_1 ( 2024-02)
    Abstract: Background: Endovascular thrombectomy (EVT) improves long-term outcome in patients presenting with large ischemic core but is associated with early neurological worsening (ENW), potentially related to cerebral edema post-reperfusion. We investigated whether EVT increases edema development, and the relationship between edema and ENW in a secondary analysis of the SELECT2 trial. Methods: SELECT 2 tested the efficacy and safety of EVT versus medical therapy in patients with large ischemic core (ASPECTS 3-5 or core volume ≥50ml on CT Perfusion[CTP]/MR diffusion). Core volume was defined as the larger of the CTP-CBF relative cerebral blood flow 〈 30% or the visible hypodensity on non-contrast CT. Cerebral edema was measured as the maximum midline shift (MLS) on 24h follow-up MRI or CT. ENW was defined as 〉 =4 point worsening in NIHSS at 24h compared to baseline. Probabilistic index model was used in multivariable analyses to assess ≥1 point improvement on modified Rankin Scale at 90-days. Results: After exclusion of 10 patients with hemicraniectomy, the median MLS in 327 patients was 2.75mm (IQR 0-5.85) in EVT and 0mm (IQR 0-4.02) in control patients (p=0.005). EVT was independently associated with greater MLS (adjusted odds ratio, aOR 1.50, 95%CI 1.17-1.92, p=0.0012) after adjusting for age and core volume. There was no interaction between EVT and core volume on the association with MLS (p 〉 0.79). Patient with ENW had greater MLS (5.05mm [IQR2.06-10.2] vs 0mm [IQR0-3.94, p 〈 0.001]) MLS was associated with development of ENW (aOR 1.22, 95%CI 1.13-1.32, p 〈 0.001), and lower likelihood of long-term functional improvement (adjusted generalized OR 0.96, 95%CI 0.92-0.97, p 〈 0.001, adjusted for core volume, EVT, age and baseline NIHSS). Sensitivity analysis testing alternative definitions of core volume (CTP core volume only and Hypodensity on non-contrast only) showed concordant results. Conclusion: In patients presenting with large ischemic core, EVT was associated with increased cerebral edema at 24h which, in turn, was associated with ENW. Despite overall benefit of EVT, EVT-related edema is independently associated with neurological deterioration and long-term disability and is therefore a potential treatment target to improve EVT outcomes.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2024
    detail.hit.zdb_id: 1467823-8
    Location Call Number Limitation Availability
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  • 2
    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
    Location Call Number Limitation Availability
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  • 3
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 55, No. Suppl_1 ( 2024-02)
    Abstract: Introduction: Endovascular thrombectomy (EVT) reduces disability in patients with large ischemic core stroke. Increasing core volume is prognostic but does not modify treatment effect. CT hypodensity can vary within an area of core. We assessed the relationship between the severity of CT core hypodensity and clinical outcome in the SELECT2 trial. Methods: Non-contrast CT ischemic core was drawn manually by two blinded investigators with consensus review by a third investigator. An absolute Hounsfield unit (HU) threshold for severe hypodensity was set at the lower 99% confidence interval [CI] for normal contralateral thalamic grey matter. Outcomes assessed included ordinal mRS, functional independence (mRS 0-2), independent ambulation (mRS 0-3), and mortality at 90 days. The association between the volume of severe hypodensity and outcome was adjusted for age, baseline NIHSS, and total baseline core volume, via logistic and proportional odds models with treatment*hypodensity interaction. Results: Of 317 assessable patients, the median hypodensity of ischemic core was 31HU (IQR 28-33). Median density of normal thalamus was 38HU. The severe hypodensity threshold (lower 99% CI) was 26HU with median volume affected 14mL (IQR 5.6-29.2) or median 19% (IQR 9-35%) of the total hypodensity volume. The volume of core ≤26HU (per 1 mL increase) was associated with a 90-day mRS shift towards worse outcomes in EVT patients (n=161, adjusted common odds ratio, acOR 1.03, 95%CI 1.01-1.05) but not medical management ([MM], n=156, acOR 1.00, 95%CI 0.98-1.02, p-interaction 0.005); lower functional independence in EVT (aOR 0.96 95%CI 0.93-0.99) but not MM (aOR 1.02, 95%CI 0.99-1.06, p-interaction 0.004); lower independent ambulation in EVT (aOR 0.97, 95%CI 0.94-0.99) but not MM (aOR 1.01, 95%CI 0.98-1.04, p-interaction 0.002) and higher mortality in EVT (aOR 1.03, 95%CI 1.01-1.05) but not MM (aOR 1.00, 95%CI 0.98-1.02, p-interaction 0.02). Conclusion: In patients with large ischemic core, areas of significant CT hypodensity are associated with worse clinical outcomes after EVT but not MM. This is independent of total core volume and modifies the treatment effect of EVT. This may improve prognostic decision-making and drive developments in automated image processing.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2024
    detail.hit.zdb_id: 1467823-8
    Location Call Number Limitation Availability
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