Carotid stenting: is there an operator effect? A pooled analysis from the carotid stenting trialists' collaboration.

BACKGROUND AND PURPOSE: Randomized clinical trials show higher 30-day risk of stroke or death after carotid artery stenting compared with surgery. We examined whether operator experience is associated with 30-day risk of stroke or death in the Carotid Stenting Trialists' Collaboration database. METHODS: The Carotid Stenting Trialists' Collaboration is a pooled individual patient database including all patients recruited in 3 randomized trials of stenting versus endarterectomy for symptomatic carotid stenosis (Endarterectomy Versus Angioplasty in patients with Symptomatic Severe Carotid Stenosis trial, Stent-Protected Angioplasty versus Carotid Endarterectomy trial, and International Carotid Stenting Study). Lifetime carotid artery stenting experience, lifetime experience in stenting procedures excluding the carotid, and annual number of procedures performed within the trial (in-trial volume), divided into tertiles, were used to measure operator experience. The outcome event was the occurrence of any stroke or death within 30 days of the procedure. The analysis was done per protocol. RESULTS: Among 1546 patients who underwent carotid artery stenting, 120 (7.8%) had a stroke or death within 30 days of the procedure. The 30-day risk of stroke or death did not differ according to operator lifetime carotid artery stenting experience (P=0.8) or operator lifetime stenting experience excluding the carotid (P=0.7). In contrast, the 30-day risk of stroke or death was significantly higher in patients treated by operators with low (mean ≤3.2 procedures/y; risk 10.1%; adjusted risk ratio=2.30 [1.36-3.87]) and intermediate annual in-trial volumes (3.2-5.6 procedures/y; 8.4%; adjusted risk ratio=1.93 [1.14-3.27]) compared with patients treated by high annual in-trial volume operators (>5.6 procedures/y; 5.1%). CONCLUSIONS: Carotid stenting should only be performed by operators with annual procedure volume ≥6 cases per year

Class IA PI3Kinase Regulatory Subunit, p85α, Mediates Mast Cell Development through Regulation of Growth and Survival Related Genes

Stem cell factor (SCF) mediated KIT receptor activation plays a pivotal role in mast cell growth, maturation and survival. However, the signaling events downstream from KIT are poorly understood. Mast cells express multiple regulatory subunits of class 1A PI3Kinase (PI3K) including p85α, p85β, p50α, and p55α. While it is known that PI3K plays an essential role in mast cells; the precise mechanism by which these regulatory subunits impact specific mast cell functions including growth, survival and cycling are not known. We show that loss of p85α impairs the growth, survival and cycling of mast cell progenitors (MCp). To delineate the molecular mechanism (s) by which p85α regulates mast cell growth, survival and cycling, we performed microarray analyses to compare the gene expression profile of MCps derived from WT and p85α-deficient mice in response to SCF stimulation. We identified 151 unique genes exhibiting altered expression in p85α-deficient cells in response to SCF stimulation compared to WT cells. Functional categorization based on DAVID bioinformatics tool and Ingenuity Pathway Analysis (IPA) software relates the altered genes due to lack of p85α to transcription, cell cycle, cell survival, cell adhesion, cell differentiation, and signal transduction. Our results suggest that p85α is involved in mast cell development through regulation of expression of growth, survival and cell cycle related genes

Carotid stenting: Is there an operator effect? A pooled analysis from the carotid stenting trialists' collaboration

Background and Purpose Randomized clinical trials show higher 30-day risk of stroke or death after carotid artery stenting compared with surgery. We examined whether operator experience is associated with 30-day risk of stroke or death in the Carotid Stenting Trialists’ Collaboration database. Methods The Carotid Stenting Trialists’ Collaboration is a pooled individual patient database including all patients recruited in 3 randomized trials of stenting versus endarterectomy for symptomatic carotid stenosis (Endarterectomy Versus Angioplasty in patients with Symptomatic Severe Carotid Stenosis trial, Stent-Protected Angioplasty versus Carotid Endarterectomy trial, and International Carotid Stenting Study). Lifetime carotid artery stenting experience, lifetime experience in stenting procedures excluding the carotid, and annual number of procedures performed within the trial (in-trial volume), divided into tertiles, were used to measure operator experience. The outcome event was the occurrence of any stroke or death within 30 days of the procedure. The analysis was done per protocol. Results Among 1546 patients who underwent carotid artery stenting, 120 (7.8%) had a stroke or death within 30 days of the procedure. The 30-day risk of stroke or death did not differ according to operator lifetime carotid artery stenting experience (P=0.8) or operator lifetime stenting experience excluding the carotid (P=0.7). In contrast, the 30-day risk of stroke or death was significantly higher in patients treated by operators with low (mean ≤3.2 procedures/y; risk 10.1%; adjusted risk ratio=2.30 [1.36–3.87]) and intermediate annual in-trial volumes (3.2–5.6 procedures/y; 8.4%; adjusted risk ratio=1.93 [1.14–3.27]) compared with patients treated by high annual in-trial volume operators (&gt;5.6 procedures/y; 5.1%). Conclusions Carotid stenting should only be performed by operators with annual procedure volume ≥6 cases per year.</p