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Background: Carotid endarterectomy (CEA) for the prevention of upcoming vascular and cerebral events is necessary in patients with high-grade stenosis (≥70%). In the framework of the Italian National project Age.It, a pilot study was proposed aiming at the discovery of a molecular signature with predictive potential of carotid stenosis comparing 65+ asymptomatic and symptomatic inpatients., Methods: A total of 42 inpatients have been enrolled, including 26 men and 16 women, with a mean age of 74 ± 6 years. Sixteen symptomatic and 26 asymptomatic inpatients with ≥70% carotid stenosis underwent CEA, according to the recommendations of the European Society for Vascular Surgery and the Society for Vascular Surgeons. Plaque biopsies and peripheral blood samples from the same individuals were obtained. Hematobiochemical analyses were conducted on all inpatients, and plasma cytokines/molecules, such as microRNAs (miRs), IL-6, sIL-6Ralpha, sgp130, myostatin (GDF8), follistatin, activin A, CXCL9, FGF21, and fibronectin, were measured using the ELISA standard technique. MiR profiles were obtained in the discovery phase including four symptomatic and four asymptomatic inpatients (both plasma and plaque samples), testing 734 miRs. MiRs emerging from the profiling comparison were validated through RT-qPCR analysis in the total cohort., Results and Conclusion: The two groups of inpatients differ in the expression levels of blood c-miRs-126-5p and -1271-5p (but not in their plaques), which are more expressed in symptomatic subjects. Three cytokines were significant between the two groups: IL-6, GDF8, and CXCL9. Using receiver operating characteristic (ROC) analysis with a machine learning-based approach, the most significant blood molecular signature encompasses albumin, C-reactive protein (CRP), the percentage of monocytes, and CXCL9, allowing for the distinction of the two groups (AUC = 0.83, 95% c.i. [0.85, 0.81], p = 0.0028). The potential of the molecular signature will be tested in a second cohort of monitored patients, allowing the application of a predictive model and the final evaluation of cost/benefit for an assessable screening test., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Capri, Fronterrè, Collura, Giampieri, Carrino, Feroldi, Ciurca, Conte, Olivieri, Ullo, Pini, Vacirca, Astolfi, Vasuri, La Manna, Pasquinelli and Gargiulo.)

Introduction: Carotid endarterectomy (CEA) in patients with asymptomatic carotid stenosis (ACAS) remains a subject of debate. Current recommendations are based on randomized trials conducted over 20 years ago and improvements in medical therapies may have reduced the risk of cerebral ischemic events (CIE). This study presents a mid-term analysis of results from an ongoing prospective observational study of ACAS patients to assess their CIE risk in a real-world setting., Methods: This is a prospective observational cohort study of patients with ACAS >60 % (NASCET criteria) identified in a single duplex ultrasonography (DUS) vascular laboratory (trial registered: NCT04825080). Patients were not considered for CEA due to their short life expectancy (<3 year) or absence of signs of plaque vulnerability (ulceration, ipoechogenic core). Patient enrollment started in January 2019 and ended in March 2020 with a targeted sample size of 300 patients.A 5-year follow-up was scheduled. Clinical characteristics, risk factors, and medical therapies were documented, and, when necessary, the best medical therapy (BMT), involving antiplatelet agents, blood pressure control, and statins, was recommended during clinical visits. The primary endpoint was to asses CIEs (including strokes, transient ischemic attacks, amaurosis-fugax) ipsilateral to ACAS along with plaque progression rate and patients survival. Follow-up involved annual clinical visit and carotid DUS examination, complemented by telephone interviews at six-month intervals., Results: The study included 307 patients, with an average age of 80 ± 7 years, of whom 55 % were male. Contralateral stenosis exceeding 60 % was present in 61 (20 %) patients. Seventy-seven percent of patients were on BMT. At a mean follow-up of 41±9 months, 7 ispilateral strokes and 9 TIAs occurred, resulting in 14 CIEs (2 patients experienced both TIA and stroke). According to Kaplan-Meier analysis, the 4-year CIE rate was 6±2 %, with an annual CIE rate of 1.5 %. Fifty-eight (19 %) patients had a stenosis progression which was associated with a higher 4-year estimated CIE rate compared to patients with stable plaque (10.3 % vs 3.2 %, P=.01). Similarly, a contralateral carotid stenosis >60 % was associated with a higher 4-year estimated CIE rate: 11.7 % vs 2.9 %, P=.002. These factors were independently associated with high risk for CIE at the multivariate COX analysis: Hazard Ratio (HR): 3.2; 95 % Confidence Interval: 1.1-9.2 and HR: 3.6; 95 % CI: 1.2-10.5., Conclusion: The mid-term results of this prospective study suggest that the incidence of CIE in ACAS patients should not be underestimated, with plaque progression and contralateral stenosis serving as primary predictors of CIEs., Competing Interests: Declaration of Competing Interest No conflicts of interest., (Copyright © 2023. Published by Elsevier Inc.)

Symptomatic carotid stenosis and carotid dissection are acute conditions of extracranial cerebrovascular vessels determining transient ischemic attack or stroke. Medical, surgical, or endovascular management are different options to treat these pathologies. This narrative review focused on the management, from symptoms to treatment, of the acute conditions of extracranial cerebrovascular vessels, including post-carotid revascularization stroke. Symptomatic carotid stenosis (> 50% according to North American Symptomatic Carotid Endarterectomy Trial criteria) with transient ischemic attack or stroke benefits from carotid revascularization-primarily with carotid endarterectomy associated with medical therapy-within 2 weeks from symptom onset to reduce the risk of stroke recurrence. Different from acute extracranial carotid dissection, medical management with antiplatelet or anticoagulant therapy can prevent new neurologic ischemic events, considering stenting only in case of symptom recurrence. Stroke after carotid revascularization can be associated with the following etiologies: carotid manipulation, plaque fragmentation, or clamping ischemia. Medical or surgical management is therefore influenced by the cause and timing of the neurologic events after carotid revascularization. Acute conditions of the extracranial cerebrovascular vessels include a heterogeneous group of pathologies and correct management can reduce symptom recurrence substantially., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To report the characteristics of the prospective observational cohort study "Carotid Asymptomatic Stenosis (CARAS)", including patients with asymptomatic carotid stenosis under medical treatment and their first year of follow-up, in order to estimate the risk of cerebral ischemic events., Methods: This is a prospective observational cohort study of CARAS>60% (Nascet criteria) patients, identified in a single duplex-ultrasonography (DUS) vascular laboratory (trail registration N: NCT04825080). Patient's enrollment started in January 2019 and ended in March 2020 with the follow-up conclusion scheduled in December 2025. The aimed sample size was calculated at 300 patients for a 5-year follow-up. The primary outcome were the incidence of ipsilateral neurologic ischemic events (stokes and transient ischemic attacks [TIA]), plaque progression rate, and survival. The follow-up was scheduled at six-month intervals for clinical visit and annually for DUS examination., Results: a total of 307 patients completed the first follow-up year. The mean age was 81±4 years, 55% were male. Contralateral stenosis >60% was present in 90 (29%) patients. Antiplatelet therapy and statins adherence was 80% and 88%, respectively. During the first year, 3 ispilateral strokes (1%) and 4 TIAs (1.3%) occurred, for a total of 2.3% ipsilateral ischemic events. During the first year, 43 (14%) plaques had a stenosis progression, which was correlated with the occurrence of neurological events (9.3% vs. 1.1%, P=.001, OR: 8.9; 95%CI: 1.9-41); 6 deaths (2%) occurred in the same period., Conclusion: the preliminary one-year results of this prospective study suggest that the overall rate of any ipsilateral ischemic event, and specifically ipsilateral strokes, correlates with plaque progression., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The outcomes of carotid endarterectomy (CEA) are constantly reported in a multitude of studies; however, the specific causes of perioperative stroke have been scarcely investigated. The aim of the present study was to analyze and categorize the causes of perioperative strokes after CEA. Methods: All CEAs performed from 2006 to 2019 in a single center were collected. CEA was routinely performed under general anesthesia, with routine shunting and patching, using cerebral near-infrared spectroscopy monitoring. Carotid exposure technique was classified as either clamped-dissection (CD) or preclamping-dissection (PCD) if the carotid bifurcation was dissected after or prior to carotid clamping. Perioperative and 30-day strokes and their possible mechanisms were evaluated according to preoperative symptoms and surgical technique adopted. Results: Among 1760 CEAs performed, 30 (1.7%) perioperative strokes occurred. 14 (47%) were identified upon emergence from general anesthesia, and 16 (53%) were noted in the first 30 days following intervention. Stroke etiology was categorized as follows: technical (acute thrombosis or intimal flap or due to intraoperative complications), embolic (no recognized technical defect), hemorrhagic, or contralateral. Symptomatic patients had a significantly higher rate of any type of stroke than asymptomatic patients (3.8% vs 0.9%, P = .0001). CD was protective for postoperative stroke (0.9% vs 3.1%, P = .001) in both symptomatic and asymptomatic patients (2.5% vs 5.9%, P = .05; 0.4% vs 1.9%, P = .005), particularly for the cohort in which symptomatic patients (0.7% vs 3.2%, P = .04) suffered postoperative embolic stroke. Conclusion: Perioperative stroke in CEA may be multifactorial in etiology, including a result of technical errors. A CD technique may help reduce the incidence of perioperative stroke.

Background: The endovascular treatment of peripheral artery obstructive disease in Trans-Atlantic Inter-Society (TASC) C and D lesions involving the aortic bifurcation is a matter of debate. The aim of this study is to evaluate the technical and clinical success of kissing stenting in this context and to analyze predictors of outcome., Methods: All patients treated for aortoiliac TASC C and D lesions with kissing stenting (from 2012 to 2017) in a 6-year period were retrospectively analyzed. Preoperative anatomical features were evaluated by reviewing computed tomography angiography images to identify severe iliac calcifications (SICs) versus not SIC (NSICs). Primary end points were as follows: technical success (TS), procedural success, primary patency (PP), and clinical success (CS). Secondary end points were as follows: secondary patency, assisted patency, survival, mid-term procedure-related complications, and risk factors that affected TS and mid-term results., Results: In a 6-year period, 51 patients fulfilled the inclusion criteria. TS was achieved in 49 (96.1%) cases. Thirty-one patients (60.8%) received a dual antiplatelet therapy (DAPT) for at least 1 month after the procedure. 30-day CS was 94.1%. Median follow-up was 45.7 months (IQR: 24.5, 8-86 range). The CS was 92.6% at 3 years, with a PP of 86.8% and a secondary patency of 93.2% at 3 years. Six (13.2%) iliac axis occluded during the first follow-up year. NSIC was statistically and independently associated with a lower PP (73% vs. 96%, P = 0.03); DAPT was statistically and independently associated with higher PP than single antiplatelet therapy (96% vs. 75%, P = 0.03); these results were confirmed by Cox regression analysis (HR: 0.14, 95%, IC: 0.01-0.89, P = 0.05 for DAPT analysis; HR: 6.8, 95%, IC: 1.21-59, P = 0.05 for NSIC analysis)., Conclusions: Endovascular treatment for TASC C-D is an effective technique. Postoperative stent occlusion is higher in patients with no DAPT and it usually occurs during the first postoperative year. Preoperative NSIC lesions are associated with reduced PP at 3 years of follow-up., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Atherosclerosis is considered a chronic inflammatory disease of arteries associated with the aging process. Many risk factors have been identified and they are mainly related to life-styles, gene-environment interactions and socioeconomic status. Carotid and coronary artery diseases are the two major atherosclerotic conditions, being the primary cause of stroke and heart attack, respectively. Nevertheless, carotid plaque assumes particular aspects not only for the specific molecular mechanisms, but also for the types of atheroma which may be associated with a better or a worst prognosis. The identification of circulating blood biomarkers able to distinguish carotid plaque types (stable or vulnerable) is a crucial step for the improvement of adequate therapeutic approaches avoiding or delaying endarterectomy in the oldest old individuals (> 80 years), a population predicted to growth in the next years. The review highlights the most recent knowledge on carotid plaque molecular mechanisms, focusing on microRNAs (miRs), as a site-specific accelerated aging within the conceptual framework of Geroscience for new affordable therapies., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: The best timing for carotid endarterectomy in patients with stroke is still matter of debate, particularly in case of significant cerebral ischemic lesion or neurological deterioration. The present review and meta-analysis aimed to report the best evidence in the outcome of patients submitted to urgent (<48h) or standard elapsing time (<2-week) CEA for stroke and to evaluate the impact of cerebral ischemic lesion size and clinical manifestation in the postoperative outcome., Evidence Acquisition: A systematic review and meta-analysis was performed by searching through Scopus and PubMed all papers reporting carotid endarterectomy (CEA) outcome (stroke and stroke/death) in patients who suffered a stable stroke, treated within 48h and 2 weeks from symptoms. A subgroup analysis of studies reporting the presence and size of cerebral lesion and clinical manifestation was planned. The pooled 30-day stroke and stroke/death risk (effect size) was expressed by crude percentage and 95% confidence interval (CI), by random effect model., Evidence Synthesis: Sixteen studies were included in the meta-analysis, 7 reporting the CEA outcome performed <48h from stroke and 13 reporting the outcome of CEA performed <2-week. The effect size of stroke and stroke/death of CEA performed <48h from symptoms was 7.4% (95% CI: 3.7-11.2) and 7.9% (95% CI: 4.0-11.8) respectively, and for CEA <2-week was 4.5% (95% CI: 2.8-6.3) and 5.4% (95% CI: 3.4-7.4) respectively. The authors agreed in considering the severity of stroke and the volume of the cerebral ischemic lesion a risk factor for postoperative complication however, due to the extremely high heterogeneity of the studies data, the effect size was not calculated. Two studies evaluated the effect of the cerebral ischemic lesion distribution; the presence of a border-zone infarct was associated with a significant increase in the risk of postoperative stroke/death rate compared with territorial cerebral ischemic lesion (OR: 6.0; 95%CI 1.1-32.0)., Conclusions: CEA for patients with a recent stroke is associated with 5.4% and 7.9% of stroke/death. A large volume of the cerebral ischemic lesion and a deteriorated neurological status are associated with a higher perioperative risk; urgent carotid revascularization seems to further increase this risk.