Locoregional Anaesthesia and Intra-Operative Angiography in Carotid Endarterectomy: 16 Year Results of a Consecutive Single Centre Series.

OBJECTIVE: The benefit of local (LA) over general (GA) anaesthesia and the rationale of intra-operative imaging strategies during carotid endarterectomy (CEA) is debated. This study analysed the associations between patient characteristics, LA, and intra-operative imaging strategies and the in hospital stroke and death rates in elective CEA over a 16 year period. METHODS: All consecutive patients treated by elective CEA between January 2004 and December 2019 (n = 1 872; median age 71 years, 70% male, 37% symptomatic) were included. All patients were assessed neurologically before and within 48 hours after CEA. The primary outcome event was the combined rate of any in hospital stroke or death. Secondary outcome events were the combined rates of any in hospital major stroke (modified Rankin scale [mRS] 3 - 5) or death, stroke, minor stroke (mRS 0 - 2), major stroke, and death alone. To detect changes over time, four quartiles (2004 - 2007, 2008 - 2011, 2012 - 2015, and 2016 - 2019) of this cohort were analysed. Statistical analysis comprised trend tests, and uni- and multivariable logistic regression. RESULTS: Median patient age increased from 68 to 73 years (p < .001). Over time, LA (from 28% to 91%) and intra-operative imaging (angiography 2.8 - 98.1%, duplex ultrasound 0 - 78.2%) was applied more frequently. Surgical techniques did not change. The in hospital stroke or death and major stroke or death rates decreased from 3.7% to 1.5% (p = .041) and from 2.8% to 0.9% (p = .014), respectively, corresponding to a relative risk of decline of 7% and 12% annually. Multivariable analysis revealed that LA (odds ratio [OR] 0.25, 95% confidence interval [CI] 0.1 - 0.62) and intra-operative angiography (OR 0.09, 95% CI 0.10 - 0.81) were associated with lower in hospital major stroke and death rates. CONCLUSION: These data demonstrate a decline in the combined rates of any in hospital major stroke or death after non-emergency CEA over time. Locoregional anaesthesia and intra-operative quality control were associated with these improvements and might be worthwhile in elective CEA.

Designed CXCR4 mimic acts as a soluble chemokine receptor that blocks atherogenic inflammation by agonist-specific targeting.

Targeting a specific chemokine/receptor axis in atherosclerosis remains challenging. Soluble receptor-based strategies are not established for chemokine receptors due to their discontinuous architecture. Macrophage migration-inhibitory factor (MIF) is an atypical chemokine that promotes atherosclerosis through CXC-motif chemokine receptor-4 (CXCR4). However, CXCR4/CXCL12 interactions also mediate atheroprotection. Here, we show that constrained 31-residue-peptides ('msR4Ms') designed to mimic the CXCR4-binding site to MIF, selectively bind MIF with nanomolar affinity and block MIF/CXCR4 without affecting CXCL12/CXCR4. We identify msR4M-L1, which blocks MIF- but not CXCL12-elicited CXCR4 vascular cell activities. Its potency compares well with established MIF inhibitors, whereas msR4M-L1 does not interfere with cardioprotective MIF/CD74 signaling. In vivo-administered msR4M-L1 enriches in atherosclerotic plaques, blocks arterial leukocyte adhesion, and inhibits atherosclerosis and inflammation in hyperlipidemic Apoe-/- mice in vivo. Finally, msR4M-L1 binds to MIF in plaques from human carotid-endarterectomy specimens. Together, we establish an engineered GPCR-ectodomain-based mimicry principle that differentiates between disease-exacerbating and -protective pathways and chemokine-selectively interferes with atherosclerosis.

Associations of Perioperative Variables With the 30-Day Risk of Stroke or Death in Carotid Endarterectomy for Symptomatic Carotid Stenosis.

Background and Purpose- This analysis was performed to assess the association between perioperative and clinical variables and the 30-day risk of stroke or death after carotid endarterectomy for symptomatic carotid stenosis. Methods- Individual patient-level data from the 5 largest randomized controlled carotid trials were pooled in the Carotid Stenosis Trialists' Collaboration database. A total of 4181 patients who received carotid endarterectomy for symptomatic stenosis per protocol were included. Determinants of outcome included carotid endarterectomy technique, type of anesthesia, intraoperative neurophysiological monitoring, shunting, antiplatelet medication, and clinical variables. Stroke or death within 30 days after carotid endarterectomy was the primary outcome. Adjusted risk ratios (aRRs) were estimated in multilevel multivariable analyses using a Poisson regression model. Results- Mean age was 69.5±9.2 years (70.7% men). The 30-day stroke or death rate was 4.3%. In the multivariable regression analysis, local anesthesia was associated with a lower primary outcome rate (versus general anesthesia; aRR, 0.70 [95% CI, 0.50-0.99]). Shunting (aRR, 1.43 [95% CI, 1.05-1.95]), a contralateral high-grade carotid stenosis or occlusion (aRR, 1.58 [95% CI, 1.02-2.47]), and a more severe neurological deficit (mRS, 3-5 versus 0-2: aRR, 2.51 [95% CI, 1.30-4.83]) were associated with higher primary outcome rates. None of the other characteristics were significantly associated with the perioperative stroke or death risk. Conclusions- The current results indicate lower perioperative stroke or death rates in patients operated upon under local anesthesia, whereas a more severe neurological deficit and a contralateral high-grade carotid stenosis or occlusion were identified as potential risk factors. Despite a possible selection bias and patients not having been randomized, these findings might be useful to guide surgeons and anesthetists when treating patients with symptomatic carotid disease.

Intraoperative Completion Studies, Local Anesthesia, and Antiplatelet Medication Are Associated With Lower Risk in Carotid Endarterectomy.

BACKGROUND AND PURPOSE: In Germany, all surgical and endovascular procedures on the carotid bifurcation must be documented in a statutory nationwide quality assurance database. We aimed to analyze the association between procedural and perioperative variables and in-hospital stroke or death rates after carotid endarterectomy. METHODS: Between 2009 and 2014, overall 142 074 elective carotid endarterectomy procedures for asymptomatic or symptomatic carotid artery stenosis were documented in the database. The primary outcome of this secondary data analysis was in-hospital stroke or death. Major stroke or death, stroke, and death, each until discharge were secondary outcomes. Adjusted relative risks (RRs) were assessed by multivariable multilevel regression analyses. RESULTS: The primary outcome occurred in 1.8% of patients, with a rate of 1.4% in asymptomatic and 2.5% in symptomatic patients, respectively. In the multivariable analysis, lower risks of stroke or death were independently associated with local anesthesia (versus general anesthesia: RR, 0.85; 95% confidence interval [CI], 0.75-0.95), carotid endarterectomy with patch plasty compared with primary closure (RR, 0.71; 95% CI, 0.52-0.97), intraoperative completion studies by duplex ultrasound (RR, 0.74; 95% CI, 0.63-0.88) or angiography (RR, 0.80; 95% CI, 0.71-0.90), and perioperative antiplatelet medication (RR, 0.83; 95% CI, 0.71-0.97). No shunting and a short cross-clamp time were also associated with lower risks; however, these are suspected to be confounded. CONCLUSIONS: Local anesthesia, patch plasty compared with primary closure, intraoperative completion studies by duplex ultrasound or angiography, and perioperative antiplatelet medication were independently associated with lower in-hospital stroke or death rates after carotid endarterectomy.