One month follow-up of carotid endarterectomy with in-hospital preoperative aspirin monotherapy and postoperative dual antiplatelet therapy in asymptomatic and symptomatic patients: A multi-center study.

Background: There is currently no consensus regarding the optimal perioperative antiplatelet strategy for carotid artery surgery. This multicentre study aimed to analyse the association between preoperative aspirin monotherapy following postoperative dual antiplatelet therapy (DAPT) and the risk for stroke and death after carotid endarterectomy (CEA). Methods: This cohort study included 821 patients with carotid artery stenosis who underwent CEA. Primary outcomes included any stroke or death up to the one-month postoperative follow-up. Multilevel multivariate regression analyses and descriptive statistics were performed. Results: Patients were predominantly male (53 %), with a mean age of 66.2 years. The primary outcome occurred in 1.6 % of patients. Univariate and multivariate analyses revealed that patients with chronic obstructive pulmonary disease (COPD) exhibited a high risk for stroke or death (P = 0.011). The occurrence of any local complications in the neck was accompanied by an increase in diastolic blood pressure (DBP) (P = 0.007). Patients with a high systolic blood pressure (SBP) (P = 0.002) experienced a longer operative duration. The length of hospital stay was longer in the patients with COPD (P = 0.020), minor stroke (P = 0.011), and major stroke (P = 0.001). A positive linear correlation was found between SBP and operative duration in the overall population (ß 0.4 [95 % confidence interval (CI) 0.1-0.7]; P = 0.002). The resultant curve for DBP and any local complications in the neck exhibited a two-stage change and one breakpoint in the entire population (k = 68 mmHg, <68; odds ratio [OR] 0.9 [95 % CI 0.7-1.1], P = 0.461; ≥68: OR 1.1 [95 % CI 1.0-1.1], P = 0.003). Conclusions: Preoperative aspirin monotherapy and postoperative DAPT were safe and effective antiplatelet treatments for patients who underwent CEA.

Retrospective, multicenter study of surgical treatment for carotid body tumors with or without preoperative embolization.

Background: Carotid body tumor (CBT) is the most common head and neck paraganglioma. Whether preoperative embolization benefits CBT patients who will receive surgical resection is still controversial. Methods: In this multi-center retrospective study, we collected data from patients with CBT who received surgical treatment without (group A) or with preoperative embolization (group B) from 2011 to 2019. The primary outcome was the rate of death or stroke after 3 years of follow-up. The secondary outcomes of the study were length of operation (LOO), intraoperative blood loss (IBL), length of stay (LOS), rate of recurrence, and rate of cranial nerve (CN) injuries. Descriptive statistics were used to analyze the demographics, clinical characteristics, complications, and follow-up results of the patients. Results: Between January 2011 and October 2019, 261 consecutive patients (107 male and 154 female) entered analysis. After 3 years of follow-up, no patient died in both groups. Only three patients with stroke were detected: 2/226 (0.9%) in group A vs. 1/35 (2.9%) in group B (p = .308). The LOO in group A was 132.6 ± 64.6 min compared with 152.9 ± 40.4 min in group B (p = .072). IBL in group A was 375.4 ± 497.8 ml compared with 448.0 ± 270.8 ml in group B (p = .400). LOS in group A was 8.3 ± 2.0 days compared with 7.4 ± 1.7 days in group B (p = .016). Seventy-two CN injuries were detected: 65/226 (28.8%) in group A vs. 7/35 (20.0%) in group B (p = .281). There were 65 temporary CN injuries (59 in group A vs. 6 in group B) (p = .254) and seven permanent CN injuries (6 in group A vs. 1 in group B) (p = .945). Three most frequently injured cranial nerves were the pharyngeal branch and superior laryngeal nerve (12.3%), recurrent laryngeal nerve (7.7%) and vagus nerve (7.3%). Conclusion: There was insufficient evidence to support the efficacy of preoperative embolization. CBT resection alone had a similar rate of stoke, recurrence, and CN injuries when compared with CBT resection with preoperative arterial embolization. Meanwhile, CBT resection alone did not increase LOO and IBL.

Long-Term Surgical Outcomes of Carotid Body Tumors With Pathological Fibrosis: A Cohort Study.

OBJECTIVE: To compare the surgical outcomes of carotid body tumor (CBT) with or without pathological fibrosis, and evaluate the associated factors of fibrous CBT (FCBT). MATERIALS AND METHODS: Paraffin-embedded tissues of 236 patients with unilateral CBTs at our center were retrospectively reviewed from January 2008 to May 2020. Based on the pathologic features, CBTs were divided into FCBT and conventional CBT (CCBT) groups. The clinical data and surgical outcomes of the two groups were compared. RESULTS: Of 236 patients, 53 had FCBT and 183 had CCBT. FCBTs showed higher vascular invasion (24.53%), marked pleomorphism (22.64%), internal carotid artery reconstruction (37.74%), estimated blood loss (559.62 cm3), and postoperative nerve injury (49.06%), with lower 10-year recurrence- (89.2%) and major adverse event-free survival (87.3%) compared to CCBTs. Nerve injury was correlated with the Shamblin grade; major adverse events and nerve injury were both correlated with pathological fibrosis. CONCLUSION: Compared with CCBT, FCBT is prone to increased recurrence, metastasis, major adverse events, and nerve injury risk. Early surgical resection, routine excision of surrounding abnormal lymph nodes, and closer clinical surveillance in FCBT patients are recommended.

C-C motif ligand 8 promotes atherosclerosis via NADPH oxidase 2/reactive oxygen species-induced endothelial permeability increase.

Chemokines have been reported to play important roles in atherosclerotic development. Recently, we found C-C motif ligand 8 (CCL8), a rarely studied chemokine in atherosclerosis, was highly expressed in the endothelium of advanced human carotid plaques. We hypothesized whether CCL8 promotes atherosclerosis through endothelial dysfunction. Apolipoprotein E-deficient mice under the Western diet were used to construct atherosclerosis models. Adeno-associated viruses (AAV) with CCL8 and the CCL8-antibody were injected into mice respectively to conduct CCL8 overexpression and suppression. The results showed that atherosclerotic lesions were significantly increased in the AAV-CCL8 group, while, lesions in the aortic sinus were reduced in the CCL8-antibody group. With CCL8 treatment (200 ng/ml, 24 h) in vitro, the permeability of human aortic endothelial cells (HAECs) increased and the expression of junctional proteins Zonula occluden-1, and Vascular endothelial cadherin were decreased. This effect was dependent on reactive oxygen species (ROS) generation, which could be blocked by l-Ascorbic acid and Apocynin. Results showed that NADPH oxidase 2 (NOX2) expression also increased with CCL8 stimulation and the ROS, and permeability increase of HAECs could be inhibited when NOX2 interfered with the specific siRNA. Additionally, we further found ERK1/2, PI3K-AKT, and NF-κB pathways were involved in the activation of CCL8. Our results indicated that CCL8 might also play important roles in atherosclerosis and this effect, at least in part, was caused by NOX2/ROS-induced endothelial permeability increase. This study might contribute to a deeper understanding of the connection between chemokines and atherosclerosis.

Predictors of Ipsilateral New Ischemic Lesions on Diffusion-Weighted Imaging after Carotid Artery Stenting in Asymptomatic Patients: A Retrospective Observational Study with Conventional Multicontrast MRI.

BACKGROUND: The purpose of this study was to identify the independent risk factors for ipsilateral new ischemic lesions (NILs) during carotid artery stenting (CAS). METHODS: In patients treated with CAS, the association between postoperative ipsilateral NILs on diffusion-weighted imaging (DWI) and patient demographics, intraoperative factors, the presence of plaque components, the semiquantitative grading of component size on multicontrast magnetic resonance imaging (MRI) were retrospectively analyzed. RESULTS: Ipsilateral NILs on DWI were detected in 85 (39.2%) patients. The debris was observed on the surface embolic protection devices in 70.97% of patients. Univariate analysis showed that different stages of intraplaque hemorrhage (IPH) (along with lipid-rich necrotic core [LRNC]) (P < 0.001), size of IPH (P < 0.001), calcification (CA) (P = 0.045), and LRNC (without IPH) (P < 0.001) as well as postdilation (P < 0.001)), stent type (P = 0.001), and aortic arch ulcer (P = 0.004) were associated with postoperative ipsilateral NILs. Multivariate logistic regression analysis showed that the acute and recent IPH (along with LRNC) (odds ratio [OR]: 5.77, P < 0.002 and OR: 28.66, P < 0.001, respectively), LRNC size in Grade 2 (OR: 6.10, P < 0.001) were independent risk factors for ipsilateral NILs. Aortic arch ulcer (OR: 3.44, P = 0.002), postdilation (OR: 4.72, P = 0.04) and open cell stent (OR: 2.88, P < 0.016) were also significantly related to ipsilateral NILs on DWI after CAS. There was a significant correlation between IPH at different stages and their grade of size (correlation coefficient: 0.89; P < 0.001). CONCLUSION: The IPH and larger LRNC along with the aortic arch ulcer, postdilation and open cell stent are associated with increased risk of ipsilateral NILs on DWI after CAS procedure. Preoperative staging of IPH and semiquantitative grading of size of plaque components based on multi-contrast MRI may be useful for predicting ipsilateral cerebral ischemic events after CAS.

C-C Motif Chemokine 8 promotes angiogenesis in vascular endothelial cells.

OBJECTIVES: Angiogenesis is an important progress associated with several pathological situations. Several chemokines have been reported to act as regulators of angiogenesis. The current study aimed to find whether C-C Motif Chemokine 8 is involved in angiogenesis regulation. METHODS: To verify whether C-C Motif Chemokine 8 is related to angiogenesis in plaques, carotid plaques were collected from patients with severe carotid stenosis and analysed using CD31 immunohistochemistry and real-time PCR. To further clarify the relation between C-C Motif Chemokine 8 and angiogenesis, human umbilical vein endothelium cells and human dermal microvascular endothelial cells were treated with C-C Motif Chemokine 8 in the presence or absence of C-C motif chemokine receptor 2-Ab and extracellular regulated MAP kinase 1/2 inhibition (FR180204). Proliferation and migration of human umbilical vein endothelium cells and human dermal microvascular endothelial cells were examined with Cell Counting Kit-8 and Transwell chamber assay, respectively. In vitro angiogenesis stimulated by C-C Motif Chemokine 8 was examined using tube formation assay. Ex vivo and in vivo angiogenesis were assessed by mice aortic ring assay and Matrigel plug assay, respectively. C-C motif chemokine receptors of human umbilical vein endothelium cells were examined with real-time PCR, and C-C motif chemokine receptor 1, C-C motif chemokine receptor 2, extracellular regulated MAP kinase 1/2 and phosphorylation-extracellular regulated MAP kinase 1/2 were examined with western blotting assay. RESULTS: C-C Motif Chemokine 8 was increased in carotid plaques with severe angiogenesis in both RNA and protein level. C-C Motif Chemokine 8 (5 ng/ml) weakly increased human umbilical vein endothelium cell proliferation, but not on human dermal microvascular endothelial cells. Migration and tube formation could be induced by C-C Motif Chemokine 8 in both human umbilical vein endothelium cells and human dermal microvascular endothelial cells. In mice aortic ring assay and Matrigel plug assay, C-C Motif Chemokine 8 could promote angiogenesis compared to vehicle groups. Phosphorylation of extracellular regulated MAP kinase 1/2 was increased with C-C Motif Chemokine 8 stimulation. The migration and tube formation promoted by C-C Motif Chemokine 8 could be largely blocked by C-C motif chemokine receptor 2-Ab or extracellular regulated MAP kinase 1/2 inhibition (FR180204). CONCLUSIONS: C-C Motif Chemokine 8 could promote both in vitro and in vivo angiogenesis. C-C motif chemokine receptor 2 played an important role in the activation of C-C Motif Chemokine 8 and extracellular regulated MAP kinase 1/2 signalling pathway was involved in this mechanism.

Protective effects of SS-31 against SDHB suppression-mitochondrial dysfunction-EndMT axis-modulated CBT sclerosis and progression.

Sclerosis variant in carotid body tumor (CBT) is characterized by extensive stromal sclerosis, which results in an uncommon pattern of growth that closely resembles that of an invasive malignant neoplasm. However, the clinical significance and the mechanism remains unclear. In this study, we provide evidence that SS-31 exerts protective effects against SDHB suppression-mitochondrial dysfunction-EndMT axis-modulated CBT sclerosis and progression. In human CBT specimens, sclerosis extent was consistently related to decreased recurrence-, death-, systematic metastasis-, and major adverse event-free survival, decreased SDHB expression, and aggravated EndMT. In human umbilical vein endothelial cells (HUVECs), SDHB KD aggravated hypoxia-induced EndMT, mitochondrial dysfunction and metabolic switch, while SS-31 treatment could significantly attenuate these changes caused by SDHB KD and hypoxia. In patient-derived xenograft (PDX) mice models of CBT, we also observed increased tumor growth speed and extent of EndMT, mitochondrial dysfunction, and metabolic switch in sclerosing carotid body tumor (SCBT) group than in conventional carotid body tumor (CCBT) group. And treating with SS-31 could significantly retard SCBT progression by rescuing the mitochondrial dysfunction-induced EndMT. Altogether, these results show that SDHB suppression-mitochondrial dysfunction-EndMT axis is a critical part of the CBT sclerosis and progression, while mitochondria-targeted drug SS-31 exerts an inhibitive effect on the above-mentioned axis, which opens new strategies to prevent and treat malignancies of CBT.

Contemporary Outcomes of Open and Endovascular Intervention for Extracranial Carotid Artery Aneurysms: A Single Centre Experience.

OBJECTIVE: The objective of this study was to evaluate the outcomes of open surgery (OS) and endovascular surgery (ES) for extracranial carotid aneurysm (ECCA) in the authors' centre. METHODS: Fifty-seven consecutive patients who were diagnosed with ECCA and underwent intervention from January 2005 to July 2019 at Zhongshan Hospital, Fudan University, were reviewed retrospectively. Patient characteristics and surgical outcomes for OS and ES were analysed. ECCAs were divided into three morphological subgroups: subgroup Ⅰ, no severe tortuosity of the internal carotid artery (ICA) or common carotid artery (CCA) proximal to the aneurysm, tortuosity of the aneurysm and 1 cm of peri-aneurysmal carotid artery ≤ 90°; subgroup Ⅱ, severe ICA or CCA tortuosity proximal to the aneurysm, tortuosity of the aneurysm and 1 cm of peri-aneurysmal carotid artery ≤ 90°; subgroup Ⅲ, aneurysm tortuosity and 1 cm peri-aneurysmal carotid artery > 90°. RESULTS: 35 patients underwent OS, 20 patients underwent ES and 2 patients underwent OS after the failure of ES. Thirty-six cases were classified in subgroup Ⅰ, 11 cases in subgroup Ⅱ, and 10 cases in subgroup Ⅲ. ES was achieved successfully in all 18 cases of subgroup I, but failed in three of four cases in subgroups Ⅱ and Ⅲ. With a mean duration of 62.9 ± 44.5 months of follow up, five deaths were recorded in the OS group, two of which were caused by ipsilateral stroke and three were not neurologically related. There was no stroke or death in the ES group during follow up. One case of stroke and two cases of death occurred in symptomatic patients, while one case of stroke and three cases of death occurred in asymptomatic patients. CONCLUSION: This series demonstrates that ES may be a safe and durable option for ECCA in subgroup Ⅰ, while in subgroups Ⅱ and Ⅲ, ES alone may be difficult to apply. A 30 day stroke rate around 5% existed in ECCAs with interventions, which should be considered before the intervention.

A Systematic Review and Updated Metaanalysis for Carotid Near-Occlusion.

BACKGROUND: Carotid near-occlusion (CNO) is distal luminal collapse of the internal carotid artery beyond a tight stenosis. CNO is a relatively rare condition accounting for 3% in symptomatic carotid stenosis and about 20% in severe (≥70%) symptomatic stenosis. The optimal treatment for CNO remains controversial. METHODS: This systematic review and metaanalysis were performed in accordance with the Meta-analysis of Observational Studies in Epidemiology guidelines (MOOSE). We searched MEDLINE, the Cochrane Library, and EMBASE for articles published from inception date to November 2018. Methodological Index for Non-randomized Studies (MINORS) was used to evaluate the methodological quality of studies. We defined primary outcome as any stroke, death and myocardial infarction (MI) within 30 days after intervention and the operative risks of carotid endarterectomy (CEA) and carotid artery stenting (CAS) were evaluated by the incidence rate (IR) of the primary outcome. Secondary outcome was defined as ipsilateral stroke, neurogenic or cardiac death and MI during the follow-up. Long-term risk was evaluated by the IR of secondary outcome. The analyses used the IRs of secondary outcome and restenosis per person-year (p-y) were performed to evaluate long-term risk and restenosis. Pooled analyses of different therapy groups were calculated. RESULTS: Twenty-eight articles of 26 studies met the inclusion criteria and were eligible for pooled analysis. Pooled IR of secondary outcome was 4.26 per 100 p-ys (95% CI, 2.92-6.20 per 100 p-ys) in intervention group (heterogeneity, I2 = 56.1%, P < 0.01; Egger test, P = 0.73) and 13.3 per 100 p-ys (95% CI, 5.54-31.95 per 100 p-ys) in best medical treatment (BMT) group (heterogeneity, I2 = 88.3%, P < 0.01; Egger test, P = 0.76). No significant difference was demonstrated in operative risk (CEA: 4.82%, 95% confidence interval [CI]: 3.07-7.55%; CAS: 5.39%, 95% CI: 3.69-7.88%) and long-term risk (CEA: 4.47 per 100 p-ys, 95% CI: 3.35-5.97 per 100 p-ys; CAS: 4.71 per 100 p-ys, 95% CI: 2.37-9.37 per 100 p-ys) between CEA and CAS group. CONCLUSIONS: BMT alone may be not enough to support a better prognosis than CEA or CAS for patients with CNO. No significant difference was found between patients with CNO who underwent CAS and CEA in both perioperative period and long-term follow-up.

Coil embolization of renal artery bifurcation and branch aneurysms with flow preservation.

OBJECTIVE: Coil embolization is one of the most common endovascular approaches to treatment of renal artery aneurysms (RAAs). The purpose of this retrospective study was to compare complications, mortality, and morbidity associated with sac packing, coil trapping, and inflow occlusion. METHODS: The records of all patients with RAAs treated with coil embolization at our center from June 2003 to May 2017 were retrospectively reviewed. Demographics of the patients, aneurysm characteristics, management strategies, perioperative and long-term outcomes, and complications were analyzed. RESULTS: A total of 52 patient records were reviewed; 28 patients received sac packing and 24 patients underwent coil trapping/inflow occlusion. There was no significant difference in patients' demographics or RAA characteristics between the groups. The mean aneurysm diameter was 25.6 ± 8.4 mm in the sac packing group and 31.1 ± 16.8 mm in the coil trapping/inflow occlusion group (P = .130). Most aneurysms in the sac packing group originated from the main renal artery bifurcation (67.9%), whereas in the coil trapping/inflow occlusion group, most aneurysms originated from the renal segmental branch arteries (54.2%). The immediate technical success rate was 100%, and the in-hospital mortality rate was 0% in both groups. Sac packing was more likely to be associated with endoleak immediately after the procedure (28.6% vs 8.3%; P = .065). The overall perioperative complication rate was not statistically different between the groups (7.1% vs 16.7%; P = .284). The mean duration of follow-up was 37.67 ± 29.84 months and 49.35 ± 28.11 months in the sac packing and coil trapping/inflow occlusion groups, respectively (P = .192). No deaths related to RAAs or aneurysm rupture occurred in either group. The overall morbidity rate was similar between groups (12.5% vs 25%; P = .284). Partial renal infarction occurred in two and five patients in the sac packing and coil trapping/inflow occlusion groups, respectively (8.3% vs 25%; P = .132). Impaired renal function was more frequent after coil trapping/inflow occlusion (0% vs 15%; P = .049). A single patient in the sac packing group required further intervention for reperfusion of the aneurysmal sac at 4 months (4.2% vs 0%; P = .356). CONCLUSIONS: Sac packing might be a safe and effective way to treat RAAs located at the main bifurcation or in branch arteries and may be preferable to coil trapping/inflow occlusion, considering the potential loss of functional renal mass.

Contemporary Results of Endovascular Repair of Isolated Abdominal Aortic Dissection with Unibody Bifurcated Stent Grafts.

OBJECTIVES: To report the midterm safety and efficacy of the Aegis™-B (Microport, Shanghai, China) unibody bifurcated stent graft for endovascular treatment of isolated abdominal aortic dissection (IAAD). BACKGROUND: Isolated abdominal aorta dissection (IAAD) is a rare event. Endovascular stent grafts seem to offer an efficient therapeutic approach to treat IAAD. However, the relatively small diameter of the infrarenal aorta and aortic bifurcation remains the main anatomical limitation to endovascular repair. METHODS: Between 2008 and 2015, we retrospectively evaluated 32 IAAD patients (21 men; mean age 58 ± 18 years), who underwent endovascular repair using Aegis™-B unibody bifurcated stent graft. Narrow proximal landing zone and narrow distal aorta was present in 11 (34.4%) patients and 10 (31.3%) patients, respectively. In the follow-up period, aortic remodeling was observed with computed tomography angiography. RESULTS: All patients were treated by endovascular means, with a primary technical success rate of 100%. During a mean follow-up period of 30.71 ± 16.36 months (range, 8-56 months), no death, rupture, stent fracture, material failure, or device migration was observed. Complete false lumen thrombosis was observed in all patients at 1 year, and all patients were free from false lumen growth in the follow-up. CONCLUSIONS: Endovascular treatment of IAAD using the Aegis™-B system appears to be safe and effective. Results from this study suggest this algorithm can provide stable, secure fixation for IAAD patients with narrow proximal landing zone, and distal aorta.