Background: and Purpose In patients with ischemic stroke and isolated cervical internal carotid artery occlusion (c-ICA-O), endovascular therapy (EVT) can improve cerebral perfusion. To maintain vessel patency, EVT is frequently combined with carotid artery stenting (CAS). We assessed the efficacy and safety of emergent CAS during EVT for isolated c-ICA-O. Methods: This retrospective multinational cohort study (42 centers) included consecutive patients who underwent EVT for isolated c-ICA-O within 24 hours from the time last seen well. Patients who underwent emergent CAS were compared with those who did not. Co-primary outcomes were c-ICA vessel patency and symptomatic intracerebral hemorrhage (sICH) 24 hours post-EVT. Secondary outcomes included any intracerebral hemorrhage (ICH) at 24 hours and disability at 3 months (modified Rankin Scale [mRS] shift). Outcomes were adjusted using inverse probability of treatment weighting. Results: Of 317 patients (mean age, 68.6 years [standard deviation, 12.9]; median National Institutes of Health Stroke Scale 11 [interquartile range, 6–17]; 26.8% female), 219 (69.1%) underwent CAS, whereas 98 (30.9%) did not. At 24 hours, vessel patency was more common after CAS (83.5% vs. 40.7%; adjusted odds ratio [aOR], 9.45; 95% confidence interval [CI], 4.91–18.17); sICH rates did not differ (2.3% vs. 3.1%; aOR, 0.92; 95% CI, 0.18–4.73). Any ICH was more common after CAS (19.3% vs. 9.3%; aOR, 2.50; 95% CI, 1.12–5.60). CAS was not associated with mRS at 3 months (adjusted common odds ratio, 0.98; 95% CI, 0.62–1.56). Conclusions In patients undergoing EVT for isolated c-ICA-O, emergent CAS was technically effective and reasonably safe. More frequent vessel patency in patients who underwent CAS did not translate into improved functional outcome at 3 months.

BACKGROUND AND OBJECTIVES: Mesenchymal stem cells (MSCs) become hypertrophic in long term despite chondrogenic differentiation following the pathway of growth plate chondrocytes. This terminal differentiation leads to phenotypically unstable cartilage and was mirrored in vitro by addition of hypertrophy inducing medium. We investigated how intrinsic TGF-β signaling is altered in pro-hypertrophic conditions. METHODS AND RESULTS: Human bone marrow derived MSC were chondrogenically differentiated in 3D culture. At day 14 medium conditions were changed to 1. pro-hypertrophic by addition of T3 and withdrawal of TGF-β and dexamethasone 2. pro-hypertrophic by addition of BMP 4 and withdrawal of TGF-β and dexamethasone and 3. kept in prochondrogenic medium conditions. All groups were treated with and without TGFβ-type-1-receptor inhibitor SB431542 from day 14 on. Aggregates were harvested for histo- and immunohistological analysis at d14 and d28, for gene expression analysis (rt-PCR) on d1, d3, d7, d14, d17, d21 and d28 and for Western blot analysis on d21 and d28. Induction of hypertrophy was achieved in the pro-hypertrophic groups while expression of TGFβ-type-1- and 2-receptor and Sox 9 were significantly downregulated compared to pro-chondrogenic conditions. Western blotting showed reduced phosphorylation of Smad 2 and 3 in hypertrophic samples, reduced TGF-β-1 receptor proteins and reduced SOX 9. Addition of SB431542 did not initiate hypertrophy under pro-chondrogenic conditions, but was capable of enhancing hypertrophy when applied simultaneously with BMP-4. CONCLUSIONS: Our results suggest that the enhancement of hypertrophy in this model is a result of both activation of pro-hypertrophic BMP signaling and reduction of anti-hypertrophic TGFβ signaling.
Blotting, Western ; Bone Marrow ; Cartilage ; Chondrocytes ; Chondrogenesis ; Dexamethasone ; Down-Regulation ; Gene Expression ; Growth Plate ; Humans ; Hypertrophy ; In Vitro Techniques ; Mesenchymal Stromal Cells ; Phosphorylation