BackgroundIn patients suffering from acute ischemic stroke from large vessel occlusion (LVO), mechanical thrombectomy (MT) often leads to successful reperfusion. Only approximately half of these patients have a favorable clinical outcome. Our aim was to determine the prognostic factors associated with poor clinical outcome following complete reperfusion.MethodsPatients treated with MT for LVO from a prospective single-center stroke registry between July 2015 and April 2019 were screened. Complete reperfusion was defined as Thrombolysis in Cerebral Infarction (TICI) grade 3. A modified Rankin scale at 90 days (mRS90) of 3–6 was defined as ‘poor outcome’. A logistic regression analysis was performed with poor outcome as a dependent variable, and baseline clinical data, comorbidities, stroke severity, collateral status, and treatment information as independent variables.Results123 patients with complete reperfusion (TICI 3) were included in this study. Poor clinical outcome was observed in 67 (54.5%) of these patients. Multivariable logistic regression analysis identified greater age (adjusted OR 1.10, 95% CI 1.04 to 1.17; p=0.001), higher admission National Institutes of Health Stroke Scale (NIHSS) (OR 1.14, 95% CI 1.02 to 1.28; p=0.024), and lower Alberta Stroke Program Early CT Score (ASPECTS) (OR 0.6, 95% CI 0.4 to 0.84; p=0.007) as independent predictors of poor outcome. Poor outcome was independent of collateral score.ConclusionPoor clinical outcome is observed in a large proportion of acute ischemic stroke patients treated with MT, despite complete reperfusion. In this study, futile recanalization was shown to occur independently of collateral status, but was associated with increasing age and stroke severity.

The tyrosine kinase c-Src is activated in a large proportion of breast cancers, in which it is thought to play a key role in promoting the malignant phenotype. c-Src activity is also elevated in transgenic mouse models of breast cancer, including the widely used polyomavirus middle-T antigen (PyVmT) model, which provides an opportunity to study the importance of c-Src in mammary tumorigenesis. However, germline c-Src deletion in mammary epithelial and stromal compartments complicates the interpretation of in vivo tumorigenesis studies as a result of severe defects in mammary gland development. We have therefore engineered a mouse strain in which deletion of c-Src can be targeted to the mammary epithelium. We demonstrate that mammary epithelial disruption of c-Src impairs proliferation and tumor progression driven by PyVmT in vivo. Whereas related kinases substitute for c-Src in PyVmT signaling, c-Src ablation impairs cell cycle progression with decreased cyclin expression and elevated expression of cyclin-dependent kinase inhibitors. Our data indicate that c-Src has essential and unique functions in proliferation and tumor progression in this mouse model that may also be important in certain contexts in some human breast cancers.

Background and Purpose: Endovascular therapy is the standard of care in the treatment of acute ischemic stroke due to large-vessel occlusion. Often, more than one retrieval attempt is needed to achieve reperfusion. We aimed to quantify the influence of endovascular therapy on clinical outcome depending on the number of retrievals needed for successful reperfusion in a large multi-center cohort. Methods: For this observational cohort study, 2611 patients from the prospective German Stroke Registry included between June 2015 and April 2018 were analyzed. Patients who received endovascular therapy for acute anterior circulation stroke with known admission National Institutes of Health Stroke Scale score and Alberta Stroke Program Early CT Score, final Thrombolysis in Cerebral Infarction score, and number of retrievals were included. Successful reperfusion was defined as a Thrombolysis in Cerebral Infarction score of 2b or 3. The primary outcome was defined as functional independence (modified Rankin Scale score of 0–2) at day 90. Multivariate mixed-effects models were used to adjust for cluster effects of the participating centers and confounders. Results: The inclusion criteria were met by 1225 patients. The odds of good clinical outcome decreased with every retrieval attempt required for successful reperfusion: the first retrieval had the highest odds of good clinical outcome (adjusted odds ratio, 6.45 [95% CI, 4.0–10.4]), followed by the second attempt (adjusted odds ratio, 4.56 [95% CI, 2.7–7.7]), and finally the third (adjusted odds ratio, 3.16 [95% CI, 1.8–5.6]). Conclusions: Successful reperfusion within the first 3 retrieval attempts is associated with improved clinical outcome compared with patients without reperfusion. We conclude that at least 3 retrieval attempts should be performed in endovascular therapy of anterior circulation strokes. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03356392.