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Objective: We aimed to assess the impact of time to endovascular thrombectomy (EVT) on clinical outcomes in the DAWN trial, while also exploring the potential effect modification of mode of stroke onset on this relationship. Methods: The association between every 1‐h treatment delay with 90‐day functional independence (modified Rankin Scale [mRS] score 0–2), symptomatic intracranial hemorrhage, and 90‐day mortality was explored in the overall population and in three modes of onset subgroups (wake‐up vs. witnessed vs. unwitnessed). Results: Out of the 205 patients, 98 (47.8%) and 107 (52.2%) presented in the 6 to 12 hours and 12 to 24 hours time window, respectively. Considering all three modes of onset together, there was no statistically significant association between time last seen well to randomization with either functional independence or mortality at 90 days in either the endovascular thrombectomy (mRS 0–2 1‐hour delay OR 1.07; 95% CI 0.93–1.24; mRS 6 OR 0.84; 95% CI 0.65–1.03) or medical management (mRS 0–2 1‐hour delay OR 0.98; 95% CI 0.80–1.14; mRS 6 1‐hour delay OR 0.94; 95% CI 0.79–1.09) groups. Moreover, there was no significant interaction between treatment effect and time (p = 0.439 and p = 0.421 for mRS 0–2 and 6, respectively). However, within the thrombectomy group, the models that tested the association between time last seen well to successful reperfusion (modified Treatment in Cerebral Infarction ≥2b) and 90‐day functional independence showed a significant interaction with mode of presentation (p = 0.013). This appeared to be driven by a nominally positive slope for both witnessed and unwitnessed strokes versus a significantly (p = 0.018) negative slope in wake‐up patients. There was no association between treatment times and symptomatic intracranial hemorrhage. Interpretation: Mode of onset modifies the effect of time to reperfusion on thrombectomy outcomes, and should be considered when exploring different treatment paradigms in the extended window. ANN NEUROL 2024;96:356–364 [ABSTRACT FROM AUTHOR]

Background: The effect of time from stroke onset to thrombectomy in the extended time window remains poorly characterized. Aim: We aimed to analyze the relationship between time to treatment and clinical outcomes in the early versus extended time windows. Methods: Proximal anterior circulation occlusion patients from a multicentric prospective registry were categorized into early (≤6 h) or extended (>6–24 h) treatment window. Patients with baseline National Institutes of Health Stroke Scale (NIHSS) ≥ 10 and intracranial internal carotid artery or middle cerebral artery-M1-segment occlusion and pre-morbid modified Rankin scale (mRS) 0–1 ("DAWN-like" cohort) served as the population for the primary analysis. The relationship between time to treatment and 90-day mRS, analyzed in ordinal (mRS shift) and dichotomized (good outcome, mRS 0–2) fashion, was compared within and across the extended and early windows. Results: A total of 1603 out of 2008 patients qualified. Despite longer time to treatment (9[7–13.9] vs. 3.4[2.5–4.3] h, p < 0.001), extended-window patients (n = 257) had similar rates of symptomatic intracranial hemorrhage (sICH; 0.8% vs. 1.7%, p = 0.293) and 90-day-mortality (10.5% vs. 9.6%, p = 0.714) with only slightly lower rates of 90-day good outcomes (50.4% vs. 57.6%, p = 0.047) versus early-window patients (n = 709). Time to treatment was associated with 90-day disability in both ordinal (adjusted odd ratio (aOR), ≥ 1-point mRS shift: 0.75; 95%CI [0.66–0.86], p < 0.001) and dichotomized (aOR, mRS 0–2: 0.73; 95%CI [0.62–0.86], p < 0.001) analyses in the early- but not in the extended-window (aOR, mRS shift: 0.96; 95%CI [0.90–1.02], p = 0.15; aOR, mRS0–2: 0.97; 95%CI [0.90–1.04], p = 0.41). Early-window patients had significantly lower 90-day functional disability (aOR, mRS shift: 1.533; 95%CI [1.138–2.065], p = 0.005) and a trend towards higher rates of good outcomes (aOR, mRS 0–2: 1.391; 95%CI [0.972–1.990], p = 0.071). Conclusions: The impact of time to thrombectomy on outcomes appears to be time dependent with a steep influence in the early followed by a less significant plateau in the extended window. However, every effort should be made to shorten treatment times regardless of ischemia duration. [ABSTRACT FROM AUTHOR]

Background There is a paucity of data regarding mechanical thrombectomy (MT) in distal arterial occlusions (DAO). We aim to evaluate the safety and efficacy of MT in patients with DAO and compare their outcomes with proximal arterial occlusion (PAO) strokes. Methods The Trevo Registry was a prospective openlabel MT registry including 2008 patients from 76 sites across 12 countries. Patients were categorized into: PAO: intracranial ICA, and MCA--M1; and DAO: MCA--M2, MCA--M3, ACA, and PCA. Baseline and outcome variables were compared across the PAO vs DAO patients with pre-morbid mRS 0--2. Results Among 407 DAOs including 350 (86.0%) M2, 25 (6.1%) M3, 10 (2.5%) ACA, and 22 (5.4%) PCA occlusions, there were 376 DAO with pre-morbid mRS 0--2 which were compared with 1268 PAO patients. The median baseline NIHSS score was lower in DAO (13 [8--18] vs 16 [12--20], P<0.001). There were no differences in terms of age, sex, IV-tPA use, co-morbidities, or time to treatment across DAO vs PAO. The rates of post-procedure reperfusion, symptomatic intracranial hemorrhage (sICH), and 90-mortality were comparable between both groups. DAO showed significantly higher rates of 90-day mRS 0--2 (68.3% vs 56.5%, P<0.001). After adjustment for potential confounders, the level of arterial occlusion was not associated with the chances of excellent outcome (DAO for 90-day mRS 0--1: OR; 1.18, 95% CI [0.90 to 1.54], P=0.225), successful reperfusion or SICH. However, DAO patients were more likely to be functionally independent (mRS 0--2: OR; 1.45, 95% CI [1,09 to 1.92], P=0.01) or dead (OR; 1.54, 95% CI [1.06 to 2.27], P=0.02) at 90 days. Conclusion Endovascular therapy in DAO appears to result in a comparable safety and technical success profile as in PAO. The potential benefits of DAO thrombectomy should be investigated in future randomized trials. [ABSTRACT FROM AUTHOR]

Background In light of recent positive trial data for endovascular therapy in acute ischemic stroke (AIS), stent retriever use by practitioners without prior experience with these devices may become more common. Objective To assess the safety and efficacy of thrombectomy for AIS using Solitaire for patients treated in the roll-in period of the Solitaire With the Intention For Thrombectomy (SWIFT) trial, which represented the first clinical use of the device for these interventionalists. Methods Prospectively collected demographic, clinical, and angiographic data on patients treated in the initial roll-in and subsequent randomized phases of the SWIFT study were collected and analyzed. Key statistical analyses were validated by an independent external statistician. Results Patients in the roll-in period achieved equivalently high rates of reperfusion (55%) compared with those treated with the device in the randomized phase (61 %). Rates of adverse events were comparable (13% vs 9%). Rates of good neurological outcome were equivalent between the roll-in and randomized patients treated with Solitaire (63% vs 58%). Including the roll-in patients strengthened the conclusions of the study, that reperfusion rates without symptomatic hemorrhage with Solitaire were greater than with Merci (59% vs 24%, p<0.001). Conclusions Thrombectomy in AIS using the Solitaire stent retriever device can be performed safely and effectively when used by experienced neurointerventionalists without previous experience with the device. Trial registration number The SWIFT study is registered with ClinicalTrials.gov, number NCT 01054560. [ABSTRACT FROM AUTHOR]

Background Collaterals may affect revascularization, ischemic severity, and clinical outcomes in acute stroke owing to internal carotid artery (ICA) occlusion. Objective To examine the hypothesis that morphology of occlusive thrombus and collateral flow patterns may influence the outcome of ICA occlusions after mechanical thrombectomy. Methods Pooled analyses of ICA occlusions in the MERCI and Multi-MERCI trials employed central angiography review readings to categorize lesions as I, L, or T clots and functional lesions based on collateral flow patterns. Demographic variables, procedural details, and clinical outcomes were compared across ICA lesion types. Results A total of 72 subjects (mean age 67 years (SD 16), 51% female, median National Institutes of Health Stroke Scale 20 (range 8-35)) were included, with 90-day modified Rankin score ≤2 in 28% and 51% mortality. Clots were categorized as an I lesion in 9/72 (12.5%), L lesion in 12/72 (16.7%), and T lesion in 51/72 (70.8%). Based on collateral flow patterns, cases were categorized as having a functional I lesion in 7/72 (9.7%), functional L in 38/72 (52.8%), and functional T in only 27/72 (37.5%). Multivariate analyses showed that a functional T lesion, with insufficient collateral flow to ipsilateral anterior cerebral arteries via the contralateral ICA, was a strong predictor of both revascularization success and subsequent clinical outcomes. Conclusions Collateral flow patterns distinguish the nature and impact of ICA occlusions on expected revascularization and subsequent clinical outcomes in acute ischemic stroke. The nomenclature of terminal ICA occlusions introduced here (carotid I's, L's, and T's) may enhance future endovascular trials targeting such proximal occlusions. Trial registration number NCT00318071 (http:// clinicaltrials.gov). MERCI was not registered because enrollment began before July 1, 2005. [ABSTRACT FROM AUTHOR]

Background: Ischemic stroke has no approved treatments to enhance recovery. ALD-401 is an enriched population of aldehyde dehydrogenase-bright stem cells, capable of reducing neurological deficits in animal models. The primary objective of this trial was to determine the safety of internal carotid artery, intra-arterially delivered autologous bone marrow-derived ALD-401 in patients with disabling middle cerebral artery stroke in comparison with sham harvest with sham infusion. Secondary objectives were to determine feasibility and efficacy.Methods: This was a prospective phase 2, industry-funded, randomized, sham-controlled, parallel-group, multicenter study with blinded assessments. One hundred subjects were planned, aged 30 to 83 years, with confirmed first-time middle cerebral artery ischemic stroke with modified Rankin scale ≥3. Study patients were randomly assigned 3:2 to bone marrow harvest at 11 to 17 days after stroke followed 2 days later by intracarotid infusion of ALD-401 versus sham harvest and then sham infusion in the same timeframe. The primary study outcome was safety based on the incidence of a 4-point National Institutes of Health Stroke Scale worsening and the proportion of serious adverse events. Efficacy was based on modified Rankin scale change at 90 days. Other secondary outcomes were the proportions of patients experiencing adverse events, disability by Barthel Index, quality of life using EQ-5D, rehabilitation utilization, disability at 1 year, and MRI evidence of complications.Results: There were no infusional or allergic reactions and no difference in treatment emergent adverse events. Four patients had small areas of asymptomatic restricted diffusion on MRI in the treatment group. There was no significant difference between the ALD-401 and placebo groups on the modified Rankin scale for the intent-to-treat population at day 90 (mean difference, 0.3; 95% CI, -0.3 to 0.8; P=0.330). There were no significant differences between the groups on any of the secondary efficacy measures.Conclusions: Intracarotid infusion of ALD-401 does not lead to clinical adverse events in patients with subacute ischemic stroke, although there was a higher incidence of small lesions on MRI in the treatment group. There was no difference in the primary efficacy end point between the groups. The study provides a framework for the design and conduct of future intra-arterial cell therapy trials in stroke.Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01273337. [ABSTRACT FROM AUTHOR]