A comparative effectiveness study of carotid intervention for long-term stroke prevention in patients with severe asymptomatic stenosis from a large integrated health system.

OBJECTIVE: The results of current prospective trials comparing the effectiveness of carotid endarterectomy (CEA) vs standard medical therapy for long-term stroke prevention in patients with asymptomatic carotid stenosis (ACS) will not be available for several years. In this study, we compared the observed effectiveness of CEA and standard medical therapy vs standard medical therapy alone to prevent ipsilateral stroke in a contemporary cohort of patients with ACS. METHODS: This cohort study was conducted in a large integrated health system in adult subjects with 70% to 99% ACS (no neurologic symptom within 6 months) with no prior ipsilateral carotid artery intervention. Causal inference methods were used to emulate a conceptual randomized trial using data from January 1, 2008, through December 31, 2017, for comparing the event-free survival over 96 months between two treatment strategies: (1) CEA within 12 months from cohort entry vs (2) no CEA (standard medical therapy alone). To account for both baseline and time-dependent confounding, inverse probability weighting estimation was used to derive adjusted hazard ratios, and cumulative risk differences were assessed based on two logistic marginal structural models for counterfactual hazards. Propensity scores were data-adaptively estimated using super learning. The primary outcome was ipsilateral anterior ischemic stroke. RESULTS: The cohort included 3824 eligible patients with ACS (mean age: 73.7 years, 57.9% male, 12.3% active smokers), of whom 1467 underwent CEA in the first year, whereas 2297 never underwent CEA. The median follow-up was 68 months. A total of 1760 participants (46%) died, 445 (12%) were lost to follow-up, and 158 (4%) experienced ipsilateral stroke. The cumulative risk differences for each year of follow-up showed a protective effect of CEA starting in year 2 (risk difference = 1.1%, 95% confidence interval: 0.5%-1.6%) and persisting to year 8 (2.6%, 95% confidence interval: 0.3%-4.8%) compared with patients not receiving CEA. CONCLUSIONS: In this contemporary cohort study of patients with ACS using rigorous analytic methodology, CEA appears to have a small but statistically significant effect on stroke prevention out to 8 years. Further study is needed to appropriately select the subset of patients most likely to benefit from intervention.

Ultrasound-guided carotid sheath block for carotid endarterectomy surgery in a high-risky patient and literature review.

Carotid endarterectomy (CEA) surgery is generally performed for patients who under the risk of ischemic cerebral stroke due to the critical obstruction of the carotid artery. Ischemic complications may occur during the surgery. So, the awakeness of the patient is very important during the surgery. Regional anesthesia techniques may be performed instead of general anesthesia for shunt placement during CEA surgery. Herein, we aimed to share our successful US-guided carotid sheath block experience for anesthesia management during CEA surgery.

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.

Natural History of Asymptomatic Moderate Carotid Artery Stenosis in a Large Community-Based Cohort.

BACKGROUND: Moderate carotid artery stenosis is a poorly defined risk factor for ischemic stroke. As such, practice recommendations are lacking. In this study, we describe the long-term risk of stroke in patients with moderate asymptomatic stenosis in an integrated health care system. METHODS: All adult patients with asymptomatic moderate (50%-69%) internal carotid artery stenosis between 2008 and 2012 were identified, with follow-up through 2017. The primary outcome was acute ischemic stroke attributed to the ipsilateral carotid artery. Stroke rates were calculated using competing risk analysis. Secondary outcomes included disease progression, ipsilateral intervention, and long-term survival. RESULTS: Overall, 11 614 arteries with moderate stenosis in 9803 patients were identified. Mean age was 74.2±9.9 years with 51.4% women. Mean follow-up was 5.1±2.9 years. There were 180 ipsilateral ischemic strokes (1.6%) identified (crude annual risk, 0.31% [95% CI, 0.21%-0.41%]), of which thirty-one (17.2%) underwent subsequent intervention. Controlling for death and intervention as competing risks, the cumulative incidence of stroke was 1.2% (95% CI, 1.0%-1.4%) at 5 years and 2.0% (95% CI, 1.7%-2.4%) at 10 years. Of identified strokes, 50 (27.8%) arteries had progressed to severe stenosis or occlusion. During follow-up, there were 17 029 carotid studies performed in 5951 patients, revealing stenosis progression in 1674 (14.4%) arteries, including 1614 (13.9%) progressing to severe stenosis and 60 (0.5%) to occlusion. The mean time to stenosis progression was 2.6±2.1 years. Carotid intervention occurred in 708 arteries (6.1%). Of these, 66.1% (468/708) had progressed to severe stenosis. The overall mortality rate was 44.5%, with 10.5% of patients lost to follow-up. CONCLUSIONS: In this community-based sample of patients with asymptomatic moderate internal carotid artery stenosis followed for an average of 5 years, the cumulative incidence of stroke is low out to 10 years. Future research is needed to optimize management strategies for this population.

[Tongdu Tiaoshen acupuncture combined with carotid endarterectomy for carotid artery stenosis: a randomized controlled trial].

OBJECTIVE: To observe the clinical therapeutic effect of Tongdu Tiaoshen acupuncture combined with carotid endarterectomy (CEA) and simple CEA on carotid artery stenosis (CAS). METHODS: A total of 60 patients with CAS were randomized into an observation group (30 cases, 2 cases dropped off) and a control group (30 cases, 3 cases dropped off). Both groups were treated with eversion CEA (eCEA). The conventional treatment of internal medicine and antiplatelet drugs i.e. aspirin enteric-coated tablet and clopidogrel hydrogen sulfate tablet were given in the control group for 4 weeks. On the basis of the treatment in the control group, Tongdu Tiaoshen acupuncture was applied at Baihui (GV 20), Fengfu (GV 16), Yamen (GV 15), cervical Jiaji (EX-B 2), Dazhui (GV 14), etc. in the observation group, once a day, 1-day rest was taken after 6-day treatment, 2 weeks were as one course and totally 2 courses were required. The carotid intima-media thickness (IMT) before and after treatment was detected by ultrasonic diagnostic apparatus, the TCM symptom score was compared before and after treatment and in the follow-up of 6 months after treatment, the clinical efficacy was evaluated in the two groups. The occurrence of endpoints within 1 year was recorded. RESULTS: After treatment, the carotid IMT and TCM symptom scores were decreased compared before treatment in the both groups (P<0.05), and the changes in the observation group were greater than the control group (P<0.05). In the follow-up, the TCM symptom scores were decreased compared before treatment in the both groups (P<0.05). The total effective rate was 96.4% (27/28) in the observation group, which was superior to 88.9% (24/27) in the control group (P<0.05). There were 1 case of stoke in the observation group and 2 cases of stroke in the control group within 1-year follow-up, and there was no significant difference in the number of endpoints between the two groups within 1 year (P>0.05). CONCLUSION: Tongdu Tiaoshen acupuncture combined with CEA can effectively reduce the IMT in patients with CAS, improve the TCM symptom score, the efficacy is superior to simple CEA treatment.

Tongdu Tiaoshen acupuncture combined with carotid endarterectomy for carotid artery stenosis: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the clinical therapeutic effect of Tongdu Tiaoshen acupuncture combined with carotid endarterectomy (CEA) and simple CEA on carotid artery stenosis (CAS).@*METHODS@#A total of 60 patients with CAS were randomized into an observation group (30 cases, 2 cases dropped off) and a control group (30 cases, 3 cases dropped off). Both groups were treated with eversion CEA (eCEA). The conventional treatment of internal medicine and antiplatelet drugs i.e. aspirin enteric-coated tablet and clopidogrel hydrogen sulfate tablet were given in the control group for 4 weeks. On the basis of the treatment in the control group, Tongdu Tiaoshen acupuncture was applied at Baihui (GV 20), Fengfu (GV 16), Yamen (GV 15), cervical Jiaji (EX-B 2), Dazhui (GV 14), etc. in the observation group, once a day, 1-day rest was taken after 6-day treatment, 2 weeks were as one course and totally 2 courses were required. The carotid intima-media thickness (IMT) before and after treatment was detected by ultrasonic diagnostic apparatus, the TCM symptom score was compared before and after treatment and in the follow-up of 6 months after treatment, the clinical efficacy was evaluated in the two groups. The occurrence of endpoints within 1 year was recorded.@*RESULTS@#After treatment, the carotid IMT and TCM symptom scores were decreased compared before treatment in the both groups (P<0.05), and the changes in the observation group were greater than the control group (P<0.05). In the follow-up, the TCM symptom scores were decreased compared before treatment in the both groups (P<0.05). The total effective rate was 96.4% (27/28) in the observation group, which was superior to 88.9% (24/27) in the control group (P<0.05). There were 1 case of stoke in the observation group and 2 cases of stroke in the control group within 1-year follow-up, and there was no significant difference in the number of endpoints between the two groups within 1 year (P>0.05).@*CONCLUSION@#Tongdu Tiaoshen acupuncture combined with CEA can effectively reduce the IMT in patients with CAS, improve the TCM symptom score, the efficacy is superior to simple CEA treatment.

Local versus general anaesthesia for carotid endarterectomy.

BACKGROUND: Carotid endarterectomy may significantly reduce the risk of stroke in people with recently symptomatic, severe carotid artery stenosis. However, there are significant perioperative risks that may be minimised by performing the operation under local rather than general anaesthetics. This is an update of a Cochrane Review first published in 1996, and previously updated in 2004, 2008, and 2013. OBJECTIVES: To determine whether carotid endarterectomy under local anaesthetic: 1) reduces the risk of perioperative stroke and death compared with general anaesthetic; 2) reduces the complication rate (other than stroke) following carotid endarterectomy; and 3) is acceptable to individuals and surgeons. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and two trials registers (to February 2021). We also reviewed reference lists of articles identified. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing the use of local anaesthetics to general anaesthetics for people having carotid endarterectomy were eligible. DATA COLLECTION AND ANALYSIS: Three review authors independently extracted data, assessed risk of bias, and evaluated quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) tool. We calculated a pooled Peto odds ratio (OR) and corresponding 95% confidence interval (CI) for the following outcomes that occurred within 30 days of surgery: stroke, death, ipsilateral stroke, stroke or death, myocardial infarction, local haemorrhage, and arteries shunted. MAIN RESULTS: We included 16 RCTs involving 4839 participants, of which 3526 were obtained from the single largest trial (GALA). The main findings from our meta-analysis showed that, within 30 days of operation, neither incidence of stroke nor death were significantly different between local and general anaesthesia. Of these, the incidence of stroke in the local and general anaesthesia groups was 3.2% and 3.5%, respectively (Peto odds ratio (OR) 0.91, 95% confidence interval (CI) 0.66 to 1.26; P = 0.58; 13 studies, 4663 participants; low-quality evidence). The rate of ipsilateral stroke under both types of anaesthesia was 3.1% (Peto OR 1.03, 95% CI 0.71 to 1.48; P = 0.89; 2 studies, 3733 participants; low-quality evidence). The incidence of stroke or death in the local anaesthesia group was 3.5%, while stroke or death incidence was 4.1% in the general anaesthesia group (Peto OR 0.85, 95% CI 0.62 to 1.16; P = 0.31; 11 studies, 4391 participants; low-quality evidence). A lower rate of death was observed in the local anaesthetic group but evidence was of low quality (Peto OR 0.61, 95% CI 0.35 to 1.06; P = 0.08; 12 studies, 4421 participants). AUTHORS' CONCLUSIONS: The incidence of stroke and death were not convincingly different between local and general anaesthesia for people undergoing carotid endarterectomy. The current evidence supports the choice of either approach. Further high-quality studies are still needed as the evidence is of limited reliability.

Anesthetic choice during transcarotid artery revascularization and carotid endarterectomy affects the risk of myocardial infarction.

OBJECTIVE: Previous studies have shown no differences in the outcomes of transcarotid artery revascularization (TCAR) performed with general anesthesia (GA) vs local or regional anesthesia (LRA). To date, no study has specifically compared the outcomes of TCAR to those of carotid endarterectomy (CEA) stratified by anesthetic type. The aim of the present study was to identify the effect of the anesthetic type on the outcomes of TCAR vs CEA. METHODS: Patients undergoing CEA and TCAR for carotid artery stenosis from 2016 to 2019 in the Vascular Quality Initiative were included. We excluded patients who had undergone concomitant procedures, patients with more than two stented lesions, and patients who had undergone the procedure for a nonatherosclerotic indication. Propensity score matching was performed between the two procedures stratified by the anesthetic type for age, sex, race, presenting symptoms, major comorbidities (ie, hypertension, diabetes, coronary artery disease, congestive heart failure, chronic obstructive pulmonary disease, chronic kidney disease), previous coronary artery bypass grafting or percutaneous transluminal coronary intervention, previous CEA or carotid artery stenting, degree of ipsilateral stenosis, the presence of contralateral occlusion, and preoperative medications. Intergroup differences between the treatment groups and differences in the perioperative outcomes were tested using the McNemar test for categorical variables and the paired t test or Wilcoxon matched pairs signed rank test for continuous variables, as appropriate. The relative risk (RR) and 95% confidence intervals (CIs) were estimated as the ratio of the probability of the outcome event for the patients treated within each treatment group. RESULTS: A total of 65,337 patients were included. Of the 65,337 patients, 59,664 had undergone carotid revascularization under GA (91%). When performed with LRA, TCAR and CEA had similar rates of stroke, death, and MI. However, when performed with GA, patients undergoing TCAR had a 50% decreased risk of MI compared with those undergoing CEA under GA (0.5% vs 1.0%; RR, 0.50; 95% CI, 0.32-0.80; P < .01). When stratified by symptomatic status, patients undergoing TCAR with GA for symptomatic carotid disease had a 67% decreased risk of MI compared with those undergoing CEA with GA for symptomatic disease (0.4% vs 1.2%; RR, 0.33; 95% CI, 0.15-0.75; P < .01). In contrast, no difference was found in the risk of MI between patients undergoing CEA vs TCAR for asymptomatic carotid disease (0.6% vs 0.9%; RR, 0.64; 95% CI, 0.37-1.14; P = .13). CONCLUSIONS: The results from the present study have confirmed previous studies suggesting that TCAR confers a lower risk of MI compared with CEA. However, our findings demonstrated no differences in the MI rates between TCAR and CEA when performed with LRA. Patients undergoing TCAR under GA had lower rates of MI compared with patients undergoing CEA under GA. When stratified by symptomatic status, the benefit of TCAR persisted only for the symptomatic patients.

Long-term stroke risk with carotid endarterectomy in patients with severe carotid stenosis.

OBJECTIVE: Informed debate regarding the optimal use of carotid endarterectomy (CEA) for stroke risk reduction requires contemporary assessment of both long-term risk and periprocedural risk. In this study, we report long-term stroke and death risk after CEA in a large integrated health care system. METHODS: All patients with documented severe (70%-99%) stenosis from 2008 to 2012 who underwent CEA were identified and stratified by asymptomatic or symptomatic indication. Those with prior ipsilateral interventions were excluded. Patients were followed up through 2017 for the primary outcomes of any stroke/death within 30 days of intervention and long-term ipsilateral ischemic stroke; secondary outcomes were any stroke and overall survival. RESULTS: Overall, 1949 patients (63.2% male; mean age, 71.3 ± 8.9 years) underwent 2078 primary CEAs, 1196 (58%) for asymptomatic stenosis and 882 (42%) for symptomatic stenosis. Mean follow-up was 5.5 ± 2.7 years. Median time to surgery was 72.0 (interquartile range, 38.5-198.0) days for asymptomatic patients and 21.0 (interquartile range, 5.0-55.0) days for symptomatic patients (P < .001). Most of the patients' demographics and characteristics were similar in both groups. Controlled blood pressure rates were similar at the time of CEA. Baseline statin use was seen in 60.5% of the asymptomatic group compared with 39.9% in the symptomatic group (P < .001), and statin adherence by 80% medication possession ratio was 19.3% asymptomatic vs 12.4% symptomatic (P < .001). The crude overall 30-day any stroke/death rates were 0.9% and 1.5% for the asymptomatic group and the symptomatic group, respectively. The 5-year risk of ipsilateral stroke and a combined end point of any stroke/death by Kaplan-Meier survival analysis were 2.5% and 28.7% for the asymptomatic group and 4.0% and 31.4% for the symptomatic group, respectively. Unadjusted cumulative all-cause survival was 74.2% for the asymptomatic group and 71.8% for the symptomatic group at 5 years. CONCLUSIONS: In a contemporary review of CEA, outcomes for either operative indication show low adverse events perioperatively and low long-term stroke risk up to 5 years. These results are well within consensus guidelines and published trial outcomes and should help inform the discussion around optimal CEA use for severe carotid stenosis.

Carotid Endarterectomy with Modified Eversion Technique: Results of a Single Center.

BACKGROUND: Carotid endarterectomy (CEA) has a wide range of approaches based on personal expertise and preference. We evaluated our outcome with CEA with modified eversion technique (meCEA) under local anesthesia and whether the surgeon's experience could influence it. METHODS: at our Institution, 837 patients underwent CEA across 8 years. Although the surgical technique was standardized, 2 groups were considered further: meCEA performed by a single Senior Operator (Group A) and meCEA performed by 4 young Consultants (Group B). RESULTS: A selective shunting policy was needed in 5.1%, together with general anesthesia. Overall operative time was 63.9 ± 15.1 minutes (61.4 ± 12.5 and 66 ± 16.9 minutes in Group A and Group B respectively; P < 0.001) and cross-clamp time 19.3 ± 2.9 minutes (19.0 ± 3.2 vs. 19.5 ± 2.8, P = 0.009). At 30 days, 0.7% TIA and 0.8% strokes were recorded. No differences (p = N.S.) between the 2 study groups in terms of postoperative neurological complications, with postoperative ipsilateral strokes always < 1%. At a median imaging follow-up of 22.5 months, the overall percentage of restenosis was 3.7%, with no difference between the 2 groups (P = 0.954). Twenty-two patients (2.6%) underwent reintervention for significant restenosis, and none of them had an ipsilateral stroke or TIA. Freedom from reintervention for restenosis at 24 months was 97.9% in Group A and 95.9% in Group B, with no between-group difference (P = 0.14). At the median survival follow-up of 37 months, the overall survival rate at 24 months was 97.9%in Group A, and 97.9% in Group B, with no between-group difference (P = 0.070). CONCLUSIONS: In our experience, CEA with a modified technique is safe and achieves comparable outcomes to those of other established techniques. The reported short cross-clamp time, also in less experienced hands, is an additional strength.

Linoleic Acid Status in Cell Membranes Inversely Relates to the Prevalence of Symptomatic Carotid Artery Disease.

BACKGROUND AND PURPOSE: The red blood cell fatty acid composition objectively reflects the long-term dietary intake of several fatty acids. In patients undergoing carotid endarterectomy, we explored whether red blood cell status of selected fatty acids related to symptomatic carotid artery disease. METHODS: We included patients with symptomatic (n=22) and asymptomatic (n=23) carotid artery disease. We determined all-C18:1 trans, linoleic acid (LA, C18:2n6), alpha-linolenic acid (C18:3n3), and the omega-3 index (sum of eicosapentaenoic [C20:5n3] and docosahexaenoic [C22:6n3] acids) in both red blood cells and carotid plaque phospholipids by gas-chromatography. RESULTS: In a multivariate logistic regression analysis, we only observed a significant association for LA, whose red blood cell status was inversely related to symptomatic carotid artery disease (odds ratio, 0.116 [95% CI, 0.022-0.607], P=0.011, for each 1-SD increase). A similar result was observed for LA in carotid plaque phospholipids. CONCLUSIONS: Cell membrane enrichment in LA, which reflects its intake, was inversely related to symptomatic carotid disease. This increases evidence supporting a favorable role of dietary LA in vascular health.

Thalamic Atrophy Plays a Crucial Role in the Effect of Asymptomatic Carotid Stenosis on Cognitive Impairment.

PURPOSE: Our objectives were to assess the abnormalities of subcortical nuclei by combining volume and shape analyses and potential association with cognitive impairment. PATIENTS AND METHODS: Twenty-nine patients with severe ACS of the unilateral internal carotid artery and 31 controls were enrolled between January 2017 to August 2018. All participants underwent a comprehensive neuropsychological evaluation, blood lipid biochemical measurements, and structural magnetic resonance imaging (MRI) to measure subcortical volumes and sub-regional shape deformations. Basic statistics, correction for multiple comparisons. Seventeen ACS patients underwent carotid endarterectomy (CEA) within one week after baseline measurements, cognitive assessments and MRI scans were repeated 6 months after CEA. RESULTS: The ACS patients had higher apolipoprotein B/apolipoprotein A1 (ApoB/ApoA1) ratio and worse performance in all cognitive domains than controls. Moreover, the ACS patients showed more profound thalamic atrophy assessed by shape and volume analysis, especially in the medial dorsal thalamus. No significant differences were found in other subcortical nuclei after multiple comparisons correction. At baseline, thalamic atrophy correlated with cognitive impairment and ApoB/ApoA1 ratio. Furthermore, mediation analysis at baseline showed that the association of carotid intima-media thickness with executive functioning was mediated by thalamic volume. After CEA, cognitive improvement and increase in the bilateral medial dorsal thalamic volume were observed. CONCLUSION: Our study identified the distinct atrophy of subcortical nuclei and their association with cognition in patients with ACS. Assessments of the thalamus by volumetric and shape analysis may provide an early marker for cerebral ischemia and reperfusion after 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.

Elective carotid stenting after urgent best medical treatment suppresses recurrent stroke in patients with symptomatic carotid artery severe stenosis.

OBJECTIVE: Urgent carotid endarterectomy and carotid artery stenting (CAS) for symptomatic advanced carotid artery stenosis is controversial because carry risks of hemorrhagic and thromboembolic complications. As treatments for preventing recurrent stroke have recently advanced, this study evaluated whether elective CAS with urgent best medical therapy reduces recurrent stroke for symptomatic severe carotid artery stenosis. PATIENTS AND METHODS: A total of 131 consecutive patients who underwent CAS for severe stenosis of the carotid artery between 2013-2017 were divided into acute ischemic minor stroke (AIMS) and Asymptomatic groups. The AIMS group comprised 59 patients presenting with minor stroke who underwent elective CAS with oral dual antiplatelet therapy, statin therapy, and add-on oral omega-3 fatty acid ethyl esters from 4 weeks before CAS. The Asymptomatic group comprised 72 patients treated with best medical therapy for 4 weeks before CAS. RESULTS: No recurrent ischemic stroke was observed under urgent best medical treatment before elective CAS in the AIMS group. Although the frequency of vulnerable plaque and degree of stenosis were much higher in the AIMS group, no significant differences were seen in perioperative complications. Baseline serum eicosapentaenoic acid (EPA) levels and EPA/ arachidonic acid (AA) were significantly lower in the AIMS group (p = 0.04, 0.04, respectively) and serum EPA/AA was significantly increased a day before CAS and 3 months after CAS compared with baseline. CONCLUSION: Urgent best medical treatment reduces recurrent stroke and facilitates safe elective CAS in patients with symptomatic and severe carotid artery stenosis.

Examination of the interaction between method of anesthesia and shunting with carotid endarterectomy.

BACKGROUND: Although the choice of anesthesia during carotid endarterectomy (CEA) does not seem to increase the risk of perioperative stroke, it might affect the outcomes of shunting during CEA. This study aims to evaluate whether the choice of anesthesia modifies the association between shunting and in-hospital stroke/death after CEA. METHODS: We retrospective reviewed all CEA cases performed between 2003 and 2017 in the Vascular Quality Initiative. Patients were divided into three groups: (1) no shunting during CEA (n = 29,227 [48.4%]), (2) routine shunting (n = 28,673 [47.5%]), and (3) selective shunting based on an intraoperative indication (n = 2499 [4.1%]). Multivariable logistic regression analysis was used to study the interaction between anesthesia (local anesthesia [LA]/regional anesthesia [RA] vs general anesthesia [GA]) and intraoperative shunting (no shunting vs routine and selective shunting) during CEA in predicting the risk of in-hospital stroke/death after CEA. RESULTS: The final cohort included 60,399 patients. The majority of CEA cases (90.2%) were performed under GA. Of the study cohort, 29,227 (48.4%) underwent CEA without shunting, 28,673 patients (47.5%) had routine shunting, and the remaining (n = 2499 [4.1%]) were selectively shunted. The interaction between intraoperative shunting and anesthesia in predicting in-hospital stroke/death was statistically significant (P < .05). When CEA is performed under LA/GA, routine shunting was associated with 3.5 times the adjusted odds of in-hospital stroke/death after CEA (odds ratio [OR], 3.5; 95% confidence interval [CI], 1.8-6.8; P < .001) compared with no shunting, whereas selective shunting was associated with 7.1 the odds (OR, 7.1; 95% CI, 3.5-14.7; P < .001). In contrast, under GA, there was no significant association between routine shunting and in-hospital stroke/death (OR, 1.2; 95% CI, 1.0-1.5; P = .12), whereas selective shunting was associated with 1.7 times the odds (OR, 1.7; 95% CI, 1.2-2.4; P < .01) compared with not performing shunting during CEA. CONCLUSIONS: The use of LA/RA is associated with increased odds of stroke/death compared with GA when intraoperative shunting is performed. The effect of anesthesia is more pronounced in patients who develop clamp-related ischemia and undergo selective shunting. More controlled studies are needed to explain these findings and validate them.

General Anesthesia Versus Local Anesthesia in Carotid Endarterectomy: A Systematic Review and Meta-Analysis.

OBJECTIVE: The choice of anesthetic technique in carotid endarterectomy (CEA) has been controversial. This study compared the outcomes of general anesthesia (GA) and local anesthesia (LA) in CEA. DESIGN: Systematic review and meta-analysis of comparative studies. SETTING: Hospitals. PARTICIPANTS: Adult patients undergoing CEA with either LA or GA. INTERVENTIONS: The effects of GA and LA on CEA outcomes were compared. MEASUREMENTS AND MAIN RESULTS: PubMed, OVID, Scopus, and Embase were searched to June 2018. Thirty-one studies with 152,376 patients were analyzed. A random effect model was used, and heterogeneity was assessed with the I2 and chi-square tests. LA was associated with shorter surgical time (weighted mean difference -9.15 min [-15.55 to -2.75]; p = 0.005) and less stroke (odds ratio [OR] 0.76 [0.62-0.92]; p = 0.006), cardiac complications (OR 0.59 [0.47-0.73]; p < 0.00001), and in-hospital mortality (OR 0.72 [0.59-0.90]; p = 0.003). Transient neurologic deficit rates were similar (OR 0.69 [0.46-1.04]; p = 0.07). Heterogeneity was significant for surgical time (I2 = 0.99, chi-square = 1,336.04; p < 0.00001), transient neurologic deficit (I2 = 0.41, chi-square = 28.81; p = 0.04), and cardiac complications (I2 = 0.42, chi-square = 43.32; p = 0.01) but not for stroke (I2 = 0.22, chi-square = 30.72; p = 0.16) and mortality (I2 = 0.00, chi-square = 21.69; p = 0.65). Randomized controlled trial subgroup analysis was performed, and all the aforementioned variables were not significantly different or heterogenous. CONCLUSION: The results from this study showed no inferiority of using LA to GA in patients undergoing CEA. Future investigations should be reported more systematically, preferably with randomization or propensity-matched analysis, and thus registries will facilitate investigation of this subject. Anesthetic choice in CEA should be individualized and encouraged where applicable.

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.

The effects of music on anxiety and pain in patients during carotid endarterectomy under regional anesthesia: A randomized controlled trial.

OBJECTIVE: Music can be used as an alternative method to decrease anxiety in awake patients during surgical procedures. The aim of this study was to test the hypothesis that listening to music during carotid endarterectomy (CEA) under regional anesthesia decreases the patient's anxiety and pain. DESIGN: A multicenter, prospective, randomized controlled trial. SETTING: Patients undergoing carotid endarterectomy under cervical plexus block. INTERVENTIONS: Patients scheduled for carotid endarterectomy under cervical plexus block were randomized into two groups: Music Group and Control Group. MAIN OUTCOME MEASURES: The primary endpoint of this study was the difference in intraoperative anxiety in patients with or without music during CEA under regional anesthesia, and the secondary endpoints were intraoperative and postoperative pain, use of additional local anesthetics, use of intravenous analgesics, patient and surgeon satisfaction and complications. Anxiety was assessed using State Trait Anxiety Inventory (STAI) and numeric rating scale (NRS). Visual analog scale (VAS) was used for pain assessment. RESULTS: The postoperative STAI scores were similar in both groups (p = 0.839). The NRS scores measured immediately after the end of the surgery were statistically higher in Music Group (p = 0.001). The intraoperative anxiety statistically increased in Music Group, when the scores of the intraoperative responses to the questions of "are you relaxed?" and "are you calm?" were compared. (p = 0.0001 and p = 0.0001, respectively). There were no statistical differences in terms of the amount of intraoperative and postoperative analgesic used (p = 0.801, p = 0.773, respectively). The intraoperative VAS scores, postoperative VAS scores, patient and surgeon satisfaction scores were similar in both groups (p = 0.586, p = 0.185, p = 0.302 and p = 0.599, respectively). Systolic, diastolic and mean arterial blood pressure and heart rate were no different between Music Group and Control Group at any of all time points during the intraoperative period. Surgical side and contralateral side cerebral rSO2 values are similar in both groups (p = 0.438, p = 0.397, respectively). CONCLUSIONS: Music use in CEA under regional anesthesia increased intraoperative patient anxiety, and had no effect on intraoperative and postoperative pain or patient satisfaction.

Patient Satisfaction with General versus Local Anesthesia during Carotid Endarterectomy.

BACKGROUND AND STUDY AIMS: Both general and local anesthesia are used in our department for carotid endarterectomy (CEA). The decision as to which anesthetic technique to use during surgery is made individually. The aim of our study was to evaluate patient satisfaction and preference with the anesthesia type used. MATERIAL AND METHODS: The satisfaction of a group of 205 patients with regard to anesthesia used and their future preferences were evaluated prospectively through a questionnaire. The reasons for dissatisfaction were assessed. RESULTS: CEA was performed under general anesthesia (GA) in 159 cases (77.6%) and under local anesthesia (LA) in 46 cases (22.4%). In the GA group, 148 patients (93.1%) were satisfied; 30 patients (65.2%) in the LA group were satisfied (p < 0.0001). The reason for dissatisfaction with GA were postoperative nausea and vomiting (7 patients), postoperative psychological alteration (3), and fear of GA (1). The reasons for dissatisfaction with LA were intraoperative pain (9 patients), intraoperative discomfort and stress (5), and intraoperative breathing problems (2). Of the GA group, 154 (96.9%) patients would prefer GA again, and of the LA group, 28 (60.9%) patients would prefer LA if operated on again (p < 0.0001). Overall, 172 patients (83.9%) would prefer GA in the future, and 33 patients (16.1%) would prefer LA. CONCLUSION: Overall patient satisfaction with CEA performed under both GA and LA is high. Nevertheless, in the GA group, patient satisfaction and future preference were significantly higher. Both GA and LA have advantages and disadvantages for CEA. An optimal approach is to make use of both anesthetic techniques based on their individual indications and patient preference.