Neuroanatomy and Severity of Stroke in Patients with Type A Aortic Dissection

Background: Strokes are a known complication of acute type A aortic dissection (ATAAD) repair. Understanding the neuroanatomy, mechanism, and severity of stroke will facilitate efforts to improve prediction, prevention, and treatment strategies. Methods: Retrospective review of patients who sustained stroke from a consecutive series of patients undergoing ATAAD repair. Neuroimaging was interpreted by two stroke neurologists blinded to clinical results. Severity of stroke was assessed by National Institutes of Health Stroke Scale (NIHSS). Residual disability at thirty days was assessed using the modified Rankin Scale (mRS). Results: Twenty percent (38/189) of patients undergoing repair for ATAAD had stroke [unilateral 58%, bi-hemispheric 42% (p=0.33)]. All strokes were ischemic. No significant lateralization (right vs. left) was noted with unilateral strokes (26% vs 32%, p=0.67). Etiology of stroke was embolic (58%), hypoperfusion (26%), mixed (11%) and unknown (5%). There were no intraoperative variables that correlated with the neuroanatomy or mechanism of stroke. Pre-operative carotid dissection was seen in 40% (n=15), while postoperatively 10% (n=4) sustained intracranial large vessel occlusion (LVO). Strokes were moderate or severe (NIHSS ≥ 9) in 97% of cases, with 66% incidence of moderate residual disability (mRS ≥ 3) at one month postoperatively. Conclusions: Stroke associated with ATAAD is heterogeneous in etiology and location. Most strokes are severe on detection and result in significant residual disability. One in 10 strokes are due to LVO amenable to endovascular treatment. Future trials may evaluate the role for early neuroimaging and treatment of incident stroke given modern advancements in endovascular stroke therapy.</jats:p

Characterizing heterogeneity in the response of synovial mesenchymal progenitor cells to synovial macrophages in normal individuals and patients with osteoarthritis

BACKGROUND: Resident macrophages in OA synovial tissue contribute to synovitis through pro-inflammatory mediators driving cartilage loss. What remains unknown is how these macrophages interact with synovial mesenchymal progenitor cells (sMPCs) in the joint. sMPCs have the potential to undergo chondrogenesis, but for yet unknown reasons, this ability is decreased in OA patients. In this study, we sought to identify if alteration of macrophage activity regulates the chondrogenic capacity of sMPCs. METHODS: An explant model was developed using human synovium obtained from normal individuals and OA patients. These explants were subjected to macrophage depletion and/or cytokine stimulation in order to regulate/deplete the residing macrophage population. Supernatant was collected following a 12-day treatment phase and subjected to inflammatory secretome analysis. sMPCs from the explants were subsequently placed under 21-day chondrogenic differentiation and levels of type II collagen (Col2a), Aggrecan (Acan), and Sox9 gene expression was quantified. RESULTS: Inflammatory secretome analysis from OA patients revealed the presence of pro-inflammatory analytes following pro- and anti-inflammatory cytokine stimulation and/or macrophage depletion. Additionally, chondrogenic differentiation of sMPCs was heterogeneously impacted across all OA patients following pro-/anti-inflammatory cytokine stimulation and/or macrophage depletion. CONCLUSION: Tissue resident synovial macrophages can regulate the chondrogenic differentiation of sMPCs after cytokine stimulation in a patient specific manner. The secretion profile of OA synovium was also responsive to cytokine stimulation and/or macrophage depletion as observed by the largely pro-inflammatory milieu upregulated following cytokine stimulation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12950-016-0120-9) contains supplementary material, which is available to authorized users

Additional file 1: Figure S1. of Characterizing heterogeneity in the response of synovial mesenchymal progenitor cells to synovial macrophages in normal individuals and patients with osteoarthritis

Immunofluorescent examination of synovial explants with or without clodronate treatment. Whole-mount immunofluorescent staining of CD68+ Macrophages (FITC). Isolated synovial biopsies before 12-Day sMPC outgrowth phase (A-B). Isolated synovial biopsies after 12-Day sMPC outgrowth phase where 1000 μM clodronate disodium [CLOD (+)] treatment on days 3,6, & 9 post seeding. (TIF 15841 kb