Background and Purpose: Endovascular thrombectomy (EVT) is effective for acute ischemic stroke with large vessel occlusion (LVO) and NIHSS ≥6. However, EVT benefit for mild deficits LVOs (NIHSS<6) is uncertain. We evaluated EVT efficacy and safety in mild strokes with LVO. Methods: A retrospective cohort of patients with anterior circulation LVO and NIHSS<6 presenting within 24hours from last-seen-normal were pooled. Patients were divided into 2 groups: EVT or medical management. 90day mRS=0–1 was the primary outcome; mRS=0–2 was the secondary. Symptomatic intracerebral hemorrhage (sICH) was the safety outcome. Clinical outcomes were compared through a multivariable logistic regression after adjusting for age, presentation NIHSS, time-last-seen-normal-to-presentation, center, IV-alteplase, ASPECTS, and thrombus location. We then performed propensity score matching as a sensitivity analysis. Results were also stratified by thrombus location. Results: 214 patients (EVT-124, medical management-90) were included from 8 US and Spain centers between January/2012 and March/2017. The groups were similar in age, ASPECTS, IV-alteplase rate and time-last-seen-normal-to-presentation. There was no difference in mRS=0–1 between EVT and medical management (55.7% versus 54.4%, respectively, aOR=1.3, 95%CI=0.64–2.64, p=0.47). Similar results were seen for mRS=0–2 (63.3% EVT versus 67.8% medical management, aOR=0.9, 95%CI=0.43–1.88, p=0.77). In a propensity matching analysis, there was no treatment effect in 62 matched pairs (53.5%EVT, 48.4% medical management; OR=1.17, 95%CI=0.54–2.52, p=0.69). There was no statistically significant difference when stratified by any thrombus location; M1 approached significance (p=0.07). sICH rates were higher with thrombectomy (5.8% EVT versus 0% medical management, p=0.02). Conclusions: Our retrospective multicenter cohort study showed no improvement in excellent and independent functional outcomes in mild strokes (NIHSS<6) receiving thrombectomy irrespective of thrombus location, with increased sICH rates, consistent with the guidelines recommending the treatment for NIHSS≥6. There was a signal towards benefit with EVT only in M1 occlusions; however this needs to be further evaluated in future RCTs.

Background and Purpose Intra-arterial therapy (IAT) promotes recanalization of large artery occlusions (LAO) in acute ischemic stroke (AIS). Despite high recanalization rates, poor clinical outcomes are common. We attempted to optimize a score that combines clinical and imaging variables to more accurately predict poor outcome after IAT in anterior circulation occlusions. Methods AIS patients undergoing IAT at UT-Houston for LAO (MCA or ICA) were reviewed. Independent predictors of poor outcome (modified Rankin Scale 4-6) were studied. External validation was conducted on IAT-treated patients at Emory University. Results 163 patients were identified at UT Houston. Independent predictors of poor outcome (p values ≤0.2) were identified as score variables using sensitivity analysis and logistic regression. Houston Intra-arterial Therapy 2 (HIAT2) score ranges 0-10: age (≤59=0, 60-79=2, ≥80 years=4), glucose (<150=0, ≥150=1), NIHSS (≤10=0), 11-20=1, ≥21=2), ASPECTS (8-10=0, ≤7=3). Patients with HIAT2 ≥5 were more likely to have poor outcomes at discharge (OR:6.43, 95%CI:2.75-15.02, p<.001). After adjusting for reperfusion (TICI≥2b) and time from symptom onset to recanalization, HIAT2 ≥5 remained an independent predictor of poor outcome (OR:5.88, 95%CI 1.96-17.64, p=0.02). Results from Emory's cohort (198 patients) were consistent; patients with HIAT 2 score ≥5 had 6 times greater odds of poor outcome at discharge and at 90 days. HIAT2 outperformed other previously published predictive scores. Conclusion The HIAT2 score, which combines clinical and imaging variables, performed better than all previous scores in predicting poor outcome after IAT for anterior circulation LAO.

Background The use of bone marrow-derived mesenchymal stromal cells (MSCs) as a cellular therapy for various diseases, such as graft-versus-host-disease, diabetes, ischemic cardiomyopathy, and Crohn's disease has produced promising results in early-phase clinical trials. However, for widespread application and use in later phase studies, manufacture of these cells needs to be cost effective, safe, and reproducible. Current methods of manufacturing in flasks or cell factories are labor-intensive, involve a large number of open procedures, and require prolonged culture times. Methods We evaluated the Quantum Cell Expansion system for the expansion of large numbers of MSCs from unprocessed bone marrow in a functionally closed system and compared the results to a flask-based method currently in clinical trials. Results After only two passages, we were able to expand a mean of 6.6×108 MSCs from 25 mL of bone marrow reproducibly. The mean expansion time was 21 days, and cells obtained were able to differentiate into all three lineages: chondrocytes, osteoblasts, and adipocytes. The Quantum was able to generate the target cell number of 2.0×108 cells in an average of 9-fewer days and in half the number of passages required during flask-based expansion. We estimated the Quantum would involve 133 open procedures versus 54,400 in flasks when manufacturing for a clinical trial. Quantum-expanded MSCs infused into an ischemic stroke rat model were therapeutically active. Discussion The Quantum is a novel method of generating high numbers of MSCs in less time and at lower passages when compared to flasks. In the Quantum, the risk of contamination is substantially reduced due to the substantial decrease in open procedures.

IMPORTANCEA direct to angiography (DTA) treatment paradigm without repeated imaging for transferred patients with large vessel occlusion (LVO) may reduce time to endovascular thrombectomy (EVT). Whether DTA is safe and associated with better outcomes in the late (>6 hours) window is unknown. Also, DTA feasibility and effectiveness in reducing time to EVT during on-call vs regular-work hours and the association of interfacility transfer times with DTA outcomes have not been established. OBJECTIVE To evaluate the functional and safety outcomes of DTA vs repeated imaging in the different treatment windows and on-call hours vs regular hours. DESIGN, SETTING, AND PARTICIPANTSThis pooled retrospective cohort study at 6 US and European comprehensive stroke centers enrolled adults (aged Ն18 years) with anterior circulation LVO (internal cerebral artery or middle cerebral artery subdivisions M1/M2) and transferred for EVT within 24 hours of the last-known-well time from January 1, 2014, to February 29, 2020.EXPOSURES Repeated imaging (computed tomography with or without computed tomographic angiography or computed tomography perfusion) before EVT vs DTA.MAIN OUTCOMES AND MEASURES Functional independence (90-day modified Rankin Scale score, 0-2) was the primary outcome. Symptomatic intracerebral hemorrhage, mortality, and time metrics were also compared between the DTA and repeated imaging groups.