Carotid revascularisation versus medical treatment for asymptomatic carotid artery stenosis.

OBJECTIVES: This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To compare the safety and efficacy of carotid revascularisation plus best medical treatment with best medical treatment alone in people with asymptomatic carotid artery stenosis.

Anatomical predispositions for silent cerebral infarction post carotid artery stenting: A retrospective cohort.

BACKGROUND: Silent cerebral infarction (SCI) that manifests following carotid artery stenting (CAS) has been postulated to correlate with cognitive decline, the onset of dementia, and an increased risk of subsequent cerebrovascular events. This investigation aimed to thoroughly examine the potential anatomical predispositions that are linked to the occurrence of SCI post-CAS, and further develop a predictive nomogram that could accurately forecast the risk of SCI post-CAS. METHODS: The present investigation conducted a retrospective examination of datasets from 250 individuals presenting with carotid artery stenosis who had been subjected to CAS within a tertiary healthcare institution from June 2020 to November 2021. Stratified by the procedural date, participants were allocated into a training cohort and a validation cohort. A nomogram was constructed predicated on salient prognostic determinants discerned via a multivariate logistic regression analysis. RESULTS: An aggregate of 184 patients were incorporated into the study, of which 60 (32.6%) manifested SCI, whereas 124 (67.4%) did not. Within the training cohort (n=123), age (OR 1.08, 95%CI 1.01-1.16; P=0.034), aortic arch type (Type III vs. I: OR 10.79, 95%CI 2.12-54.81; P=0.005), aortic arch variant (OR 47.71, 95%CI 6.05-376.09; P<0.001), common carotid artery (CCA) ostium lesions (OR 6.93, 95%CI 1.49-32.32; P=0.014), and proximal tortuosity index (TI) (OR 1.01, 95%CI 1.00-1.02; P=0.029) were demarcated as standalone risk predispositions for SCI subsequent to CAS. The concordance index (C-index) for the training cohort's nomogram stood at 0.89 (95% CI, 0.84-0.95). Moreover, the said nomogram exhibited commendable efficacy within the validation cohort (C-index=0.94) as well as the entire participant base (C-index=0.90). Furthermore, the decision curve analysis illustrated the exemplary clinical applicability of the nomogram. CONCLUSIONS: The findings of this inquiry underscore that age, aortic arch type, aortic arch variant, CCA ostium lesions, and proximal TI serve as independent determinants linked with SCI post-CAS. The formulated nomogram, predicated on these risk factors, possesses robust prognostic significance and might serve as a valuable adjunct to inform clinical decision-making.

Qualifying Event and Recurrence of Ischemic Stroke in Symptomatic Artery Occlusion: A Post Hoc Analysis of CMOSS.

BACKGROUND: The authors aimed to elucidate the relationship between latest ischemic event and the incidence of subsequent ischemic stroke in patients with symptomatic artery occlusion. METHODS AND RESULTS: We analyzed the association between qualifying event-the latest ischemic event (transient ischemic attack [TIA] or stroke)-and the incidence of ipsilateral ischemic stroke in patients with symptomatic artery occlusion treated with medical therapy alone in CMOSS (Carotid or Middle Cerebral Artery Occlusion Surgery Study). The incidence of CMOSS primary outcomes, including any stroke or death within 30 days after randomization or ipsilateral ischemic stroke between 30 days and 2 years, between the bypass surgical and medical groups, stratified by qualifying events, was also compared. Of the 165 patients treated with medical therapy alone, 75 had a TIA and 90 had a stroke as their qualifying event. The incidence of ipsilateral ischemic stroke did not significantly differ between patients with a TIA and those with a stroke as their qualifying event (13.3% versus 6.7%, P=0.17). In multivariate analysis, the qualifying event was not associated with the incidence of ipsilateral ischemic stroke. There were no significant differences in the CMOSS primary outcomes between the surgical and medical groups, regardless of the qualifying event being TIA (10.1% versus 12.2%, P=0.86) or stroke (6.7% versus 8.9%, P=0.55). CONCLUSIONS: Among patients with symptomatic artery occlusion and hemodynamic insufficiency, the risk of subsequent ipsilateral ischemic stroke does not appear to be lower in patients presenting with a TIA compared with those with a stroke. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01758614.

Potential of body mass index as a screening indicator for extracranial-intracranial bypass surgery in patients with symptomatic artery occlusion: a post-hoc analysis of the CMOSS trial.

BACKGROUND: To investigate the association between body mass index (BMI) and the incidence of ischemic stroke in patients with symptomatic artery occlusion, and further to evaluate the utility of BMI as a screening tool for identifying candidates for extracranial-intracranial bypass surgery. MATERIALS AND METHODS: We analyzed the relationship between BMI and the occurrence of ipsilateral ischemic stroke (IIS) among patients receiving only medical management in the Carotid or Middle cerebral artery Occlusion Surgery Study (CMOSS). Additionally, we compared the primary endpoint of CMOSS-stroke or death within 30 days, or IIS after 30 days up to two years-among patients with varying BMIs who underwent either surgery or medical treatment. RESULTS: Of the 165 patients who treated medically only, 16 (9.7%) suffered an IIS within two years. BMI was independently associated with the incidence of IIS (hazard ratio: 1.16 per kg/m2; 95% confidence interval: 1.06-1.27). The optimal BMI cutoff for predicting IIS was 24.5 kg/m2. Patients with BMI ≥24.5 kg/m2 experienced a higher incidence of IIS compared to those with BMI <24.5 kg/m2 (17.4% vs. 0.0%, P<0.01). The incidence of the CMOSS primary endpoint was significantly different between the surgical and medical groups for patients with BMI ≥24.5 kg/m2 (5.3% vs. 19.8%, P<0.01) and those with BMI <24.5 kg/m2 (10.6% vs. 1.4%; P=0.02). Surgical intervention was independently associated with a reduced rate of the CMOSS primary endpoint in patients with BMI ≥24.5 kg/m2. CONCLUSION: Data from the CMOSS trial indicate that patients with BMI ≥24.5 kg/m2 are at a higher risk of IIS when treated medically only and appear to derive greater benefit from bypass surgery compared to those with lower BMIs. Given the small sample size and the inherent limitations of retrospective analyses, further large-scale, prospective studies are necessary to confirm these findings.

In Vivo Classification and Characterization of Carotid Atherosclerotic Lesions with Integrated 18F-FDG PET/MRI.

BACKGROUND: The aim of this study was to exploit integrated PET/MRI to simultaneously evaluate the morphological, component, and metabolic features of advanced atherosclerotic plaques and explore their incremental value. METHODS: In this observational prospective cohort study, patients with advanced plaque in the carotid artery underwent 18F-FDG PET/MRI. Plaque morphological features were measured, and plaque component features were determined via MRI according to AHA lesion-types. Maximum standardized uptake values (SUVmax) and tissue to background ratio (TBR) on PET were calculated. Area under the receiver-operating characteristic curve (AUC) and net reclassification improvement (NRI) were used to compare the incremental contribution of FDG uptake when added to AHA lesion-types for symptomatic plaque classification. RESULTS: A total of 280 patients with advanced plaque in the carotid artery were recruited. A total of 402 plaques were confirmed, and 87 of 402 (21.6%) were symptomatic plaques. 18F-FDG PET/MRI was performed a mean of 38 days (range 1-90) after the symptom. Increased stenosis degree (61.5% vs. 50.0%, p < 0.001) and TBR (2.96 vs. 2.32, p < 0.001) were observed in symptomatic plaques compared with asymptomatic plaques. The performance of the combined model (AHA lesion type VI + stenosis degree + TBR) for predicting symptomatic plaques was the best among all models (AUC = 0.789). The improvement of the combined model (AHA lesion type VII + stenosis degree + TBR) over AHA lesion type VII model for predicting symptomatic plaques was the highest (AUC = 0.757/0.454, combined model/AHA lesion type VII model), and the NRI was 50.7%. CONCLUSIONS: Integrated PET/MRI could simultaneously evaluate the morphological component and inflammation features of advanced atherosclerotic plaques and provide supplementary optimization information over AHA lesion-types for identifying vulnerable plaques in atherosclerosis subjects to achieve further stratification of stroke risk.

Systemic-inflammatory indices and clinical outcomes in patients with anterior circulation acute ischemic stroke undergoing successful endovascular thrombectomy.

Background: There is a lack of comprehensive profile assessment on complete blood count (CBC)-derived systemic-inflammatory indices, and their correlations with clinical outcome in patients with anterior circulation acute ischemic stroke (AIS) who achieved successful recanalization by endovascular thrombectomy (EVT). Methods: Patients with anterior circulation AIS caused by large vessel occlusion (AIS-LVO) were retrospectively screened from December 2018 to December 2022. Systemic-inflammatory indices including ratios of neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), platelet-to-lymphocyte (PLR), and platelet-to-neutrophil (PNR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and aggregate inflammation systemic index (AISI) on admission and the first day post-EVT were calculated. Their correlations with symptomatic intracranial hemorrhage (sICH) and unfavorable 90-day functional outcome (modified Rankin Scale score of 3-6) were analyzed. Results: A total of 482 patients [65 (IQR, 56-72) years; 33 % female] were enrolled, of which 231 (47.9 %) had unfavorable 90-day outcome and 50 (10.4 %) developed sICH. Day 1 neutrophil and monocyte counts, NLR, MLR, PLR, SII, SIRI, and AISI were increased, while lymphocyte and PNR were decreased compared to their admission levels. In multivariate analyses, neutrophil count, NLR, SII, and AISI on day 1 were independently associated with 90-day functional outcome. Moreover, day 1 neutrophil count, NLR, MLR, PLR, PNR, SII, and SIRI were independently linked to the occurrence of sICH. No admission variables were identified as independent risk factors for patient outcomes. Conclusion: CBC-derived systemic-inflammatory indices measured on the first day after successful EVT are predictive of 90-day functional outcome and the sICH occurrence in patients with anterior circulation AIS-LVO.

Impact of immediate postrecanalization cooling on outcome in acute ischemic stroke patients with a large ischemic core: prospective cohort study.

BACKGROUND: Patients with large acute ischemic strokes (AIS) often have a poor prognosis despite successful recanalization due to multiple factors including reperfusion injury. The authors aim to describe our preliminary experience of endovascular cooling in patients with a large AIS after recanalization. METHODS: From January 2021 to July 2022, AIS patients presenting with large infarcts (defined as ASPECTS ≤5 on noncontrast CT or ischemic core ≥50 ml on CT perfusion) who achieved successful recanalization after endovascular treatment were analyzed in a prospective registry. Patients were divided into targeted temperature management (TTM) and non-TTM group. Patients in the TTM group received systemic cooling with a targeted core temperature of 33° for at least 48 h. The primary outcome is 90-day favorable outcome [modified Rankin Scale (mRS) 0-2]. The secondary outcomes are 90-day good outcome (mRS 0-3), mortality, intracranial hemorrhage and malignant cerebral edema within 7 days or at discharge. RESULTS: Forty-four AIS patients were recruited (15 cases in the TTM group and 29 cases in the non-TTM group). The median Alberta Stroke Program Early CT Score (ASPECTS) was 3 (2-5). The median time for hypothermia duration was 84 (71.5-147.6) h. The TTM group had a numerically higher proportion of 90-day favorable outcomes than the non-TTM group (46.7 vs. 27.6%, P=0.210), and no significant difference were found regarding secondary outcomes (all P>0.05). The TTM group had a numerically higher rates of pneumonia (66.7 vs. 58.6%, P=0.604) and deep vein thrombosis (33.3 vs. 13.8%, P=0.138). Shivering occurred in 4/15 (26.7%) of the TTM patients and in none of the non-TTM patients (P=0.009). CONCLUSIONS: Postrecanalization cooling is feasible in patients with a large ischemic core. Future randomized clinical trials are warranted to validate its efficacy.

Vascular Endothelial Growth Factor and Ischemic Stroke Risk: A Mendelian Randomization Study.

INTRODUCTION: Previous studies have reported controversial relationships between circulating vascular endothelial growth factors (VEGF) and ischemic stroke (IS). This study aims to demonstrate the causal effect between VEGF and IS using Mendelian randomization (MR). METHODS: Summary statistics data from two large-scale genome-wide association studies (GWAS) for 16,112 patients with measured VEGF levels and 40,585 patients with IS were downloaded from public databases and included in this study. A published calculator was adopted for MR power calculation. The primary outcome was any ischemic stroke, and the secondary outcomes were large-artery stroke, cardioembolic stroke, and small-vessel stroke. We used the inverse variance-weighted (IVW) method for primary analysis, supplemented by MR-Egger regression and the weighted median method. RESULTS: Nine SNPs were included to represent serum VEGF levels. The IVW method revealed no strong causal association between VEGF and any ischemic stroke (odds ratio [OR] 1.01, 95% CI 0.99-1.04, p = 0.39), cardioembolic stroke (OR 1.04, 95% CI 0.97-1.12, p = 0.28), large-artery stroke (OR 1.02, 95% CI 0.95-1.09, p = 0.62), and small-vessel stroke (OR 0.98, 95% CI 0.91-1.04, p = 0.46). These findings remained robust in sensitivity analyses. MR-Egger regression suggested no horizontal pleiotropy. CONCLUSIONS: This Mendelian randomization study found no relationship between genetically predisposed serum VEGF levels and risks of IS or its subtypes.

ROS-Induced Endothelial Dysfunction in the Pathogenesis of Atherosclerosis.

Various signaling pathways are regulated by reactive oxygen species (ROS), which are radical oxygen intermediates under normal physiological conditions. However, when the buffering capacity of antioxidant enzymes is exceeded by the accumulation of ROS, oxidative stress, and endothelial cell dysfunction occur, which have been recognized as key contributors to the development of atherosclerosis. In this review, an overview is provided on mechanisms underlying ROS generation in endothelial cells and the involved regulatory pathways. Further, we discuss the ROS induced endothelial cell dysfunction and its relationship with atherosclerosis. Current knowledge on ROS-induced endothelial impairment is presented, characterized by decreased NO bioavailability, intracellular dysfunction and ox-LDL accumulation. Furthermore, biomarkers such as oxidative products of lipid, protein, and nucleotide are discussed as measurements for ROS levels. Novel interventions targeting oxidative stress are listed as potential pharmacotherapies in clinical practice. In conclusion, this review presents a systematic analysis of the mechanisms underlying ROS generation and elucidates how manipulation of these mechanisms can safeguard endothelial cell function.

Incidence and predictors of restenosis following successful recanalization of non-acute internal carotid artery occlusion in 252 cases.

BACKGROUND: Data concerning restenosis following successful recanalization of non-acute internal carotid artery occlusion (ICAO) are scarce. This study was conducted to identify the incidence and predictors of restenosis following successful recanalization of non-acute ICAO. METHODS: We reviewed the incidence of restenosis (defined as >70% restenosis or reocclusion) among 252 consecutive patients with successful recanalization of non-acute ICAO. Baseline, imaging, and surgery-related characteristics were analyzed to assess their association with restenosis. A scoring system was developed to identify high-risk patients for restenosis. RESULTS: During a median follow-up of 12.6 months, restenosis occurred in 56 patients (22.2%), including 39 with reocclusion and 17 with >70% restenosis. The cumulative restenosis rate was 18.0% at 12 months and 24.1% at 24 months. The incidence of stroke was higher in patients with restenosis (25.0% vs 1.5%, P<0.01). Multivariate analysis showed occlusion length (5-10 cm vs <5 cm (hazard ratio (HR) 3.15, 95% confidence interval (95% CI) 1.07 to 9.29); ≥ 10 cm vs <5 cm (HR 5.01, 95% CI 1.73 to 14.49)), residual stenosis ≥30% (HR 3.08, 95% CI 1.79 to 5.30), and internal carotid artery (ICA) wall collapse (HR 1.96, 95% CI 1.12 to 3.44) as independent predictors of restenosis. Point scores proportional to model coefficients were assigned, with scores ranging from 0 to 6. Patients scoring 3-6 had a 4.00 times higher chance of developing restenosis (95% CI 2.35 to 6.79) compared with those scoring 0-2. CONCLUSIONS: Nearly one in five patients experienced restenosis following successful recanalization of non-acute ICAO. Occlusion length, residual stenosis ≥30%, and ICA wall collapse were independently associated with restenosis.

eIF2α-mediated integrated stress response links multiple intracellular signaling pathways to reprogram vascular smooth muscle cell fate in carotid artery plaque.

Background: Carotid arterial atherosclerotic stenosis is a well-recognized pathological basis of ischemic stroke; however, its underlying molecular mechanisms remain unknown. Vascular smooth muscle cells (VSMCs) play fundamental roles in the initiation and progression of atherosclerosis. Organelle dynamics have been reported to affect atherosclerosis development. However, the association between organelle dynamics and various cellular stresses in atherosclerotic progression remain ambiguous. Methods: In this study, we conducted transcriptomics and bioinformatics analyses of stable and vulnerable carotid plaques. Primary VSMCs were isolated from carotid plaques and subjected to histopathological staining to determine their expression profiles. Endoplasmic reticulum (ER), mitochondria, and lysosome dynamics were observed in primary VSMCs and VSMC cell lines using live-cell imaging. Moreover, the mechanisms underlying disordered organelle dynamics were investigated using comprehensive biological approaches. Results: ER whorls, a representative structural change under ER stress, are prominent dynamic reconstructions of VSMCs between vulnerable and stable plaques, followed by fragmented mitochondria and enlarged lysosomes, suggesting mitochondrial stress and lysosomal defects, respectively. Induction of mitochondrial stress alleviated ER stress and autophagy in an eukaryotic translation initiation factor (eIF)-2α-dependent manner. Furthermore, the effects of eIF2α on ER stress, mitochondrial stress, and lysosomal defects were validated using clinical samples. Conclusion: Our results indicate that morphological and functional changes in VSMC organelles, especially in ER whorls, can be used as reliable biomarkers for atherosclerotic progression. Moreover, eIF2α plays an important role in integrating multiple stress-signaling pathways to determine the behavior and fate of VSMCs.

PCSK9 increases vulnerability of carotid plaque by promoting mitochondrial dysfunction and apoptosis of vascular smooth muscle cells.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) has been recognized as a novel lipid-lowing target. Recent clinical studies suggested the value of inhibiting PCSK9 in decreasing the vulnerability of coronary plaques. However, the evidence of PCSK9-regulated evolution of unstable carotid plaques is unclear, which has limited the use of PCSK9 inhibitor in carotid plaques. This study aimed to determine the effect and molecular mechanisms of PCSK9 on vulnerability of carotid plaques, to provide potential therapeutic targets for stabilizing carotid plaques. METHODS: The expression of PCSK9 in stable and unstable carotid plaques were examined in tissue and plasma. Human aortic vascular smooth muscle cells (VSMCs) and carotid VSMCs were employed to transfect lentivirus for overexpression and knockdown of PCSK9, respectively. Morphological and functional changes of mitochondria were observed by live-cell imaging. Cell apoptosis was evaluated by propidium iodide staining. RNA-sequencing and biological examinations were performed to explore and validate the underlying mechanisms. Truncated plasmids were employed to identify the functional domain of PCSK9 in regulation of VSMCs' mitochondrial morphology, function and apoptosis. RESULTS: Clinically, PCSK9 was closely related with vulnerability of human carotid plaques. Increased expression of PCSK9 in human VSMCs was accompanied by higher level of apoptosis. At subcellular level of VSMCs, the morphology of mitochondria was shifted toward the fission state, followed by mitochondrial dysfunction. Inhibition of p38 MAPK activation partially rescued the above morphological and behavioral changes caused by PCSK9. Furthermore, inhibiting of dynamin-related protein 1 (DRP1) attenuated PCSK9-related mitochondrial dysfunction and cell apoptosis. The 1-149aa domain of PCSK9 protein was essential to achieve functional regulation to VSMCs. CONCLUSION: Our findings demonstrated that PCSK9 induced morphology-related mitochondrial dysfunction and apoptosis of VSMCs, which may be related to increased vulnerability of carotid plaque.

First-in-human experience of sirolimus coated balloon for symptomatic intracranial artery stenosis.

BACKGROUND: The drug coated balloon is a promising endovascular therapy for intracranial atherosclerosis (ICAS), potentially combining the advantages of primary angioplasty and antiproliferative drugs. Previous studies have focused on the paclitaxel coated balloon, revealing promising outcomes in the treatment of ICAS, while concerns about the neurotoxicity of paclitaxel were reported. Sirolimus was shown to have less neurotoxicity in the canine cerebral vasculature. The feasibility and safety of a sirolimus coated balloon (SCB) for ICAS have never been evaluated in humans. We assessed the first-in-human feasibility and safety of SCBs for treating symptomatic patients with severe ICAS. METHODS: This prospective, open label, single arm cohort study was designed to enroll patients with transient ischemic attacks or non-disabling, non-perforator territory ischemic stroke caused by severe ICAS (70-99%) and following at least 3 weeks after the onset of ischemic symptoms. The primary outcome was stroke or death within 30 days. All patients were followed up to detect restenosis at 6 months. RESULTS: A total of 60 eligible patients were enrolled with an average age of 59.4±10.8 years. The technical success rate of SCBs for ICAS was 100%. Seven patients (11.7%) required stenting because of flow limited dissections or elastic retraction. Three patients (5.0%) had 30 day strokes, including two ischemic strokes and one hemorrhagic stroke. An additional three patients had recurrent stroke or death during follow-up. Ten patients had restenosis but only two had symptoms. CONCLUSIONS: SCBs may be feasible and safe in selected patients with symptomatic ICAS, with high grade stenosis (70-99%). Further studies are warranted.

Alterations of Hemostatic Molecular Markers During Acute Large Vessel Occlusion Stroke.

BACKGROUND: This study aimed to investigate regional levels of TAT (thrombin-antithrombin complex), PIC (plasmin-α2 plasmin inhibitor complex), t-PAIC (tissue plasminogen activator-plasminogen activator inhibitor complex), sTM (soluble thrombomodulin), and D-dimer, along with their associations with clinical and procedural characteristics in patients with acute ischemic stroke undergoing endovascular thrombectomy. METHODS AND RESULTS: We retrospectively analyzed 166 consecutive patients with acute ischemic stroke (62±11.54 years of age, 34.3% women) using prospectively maintained clinical databases and blood samples from local ischemic (proximal to thrombus) and systemic (femoral artery, self-control) arterial compartments. Levels of TAT, PIC, t-PAIC, and D-dimer were significantly elevated, whereas sTM was significantly reduced, in local ischemic regions compared with their systemic levels. Each 1-unit increase in ischemic TAT (adjusted odds ratio [aOR], 1.086 [95% CI, 1.03-1.145]; P=0.002; area under the curve [AUC], 0.833) and PIC (aOR, 1.337 [95% CI, 1.087-1.644]; P=0.006; AUC, 0.771) correlated significantly with higher symptomatic intracranial hemorrhage risk. Additionally, each 1-unit increase in ischemic TAT (aOR, 1.076 [95% CI, 1.016-1.139]; P=0.013; AUC, 0.797), PIC (aOR, 1.554 [95% CI, 1.194-2.022]; P=0.001; AUC, 0.798), and sTM (aOR, 0.769 [95% CI, 0.615-0.961]; P=0.021; AUC, 0.756) was significantly associated with an increased risk of an unfavorable 90-day outcome (modified Rankin scale of 3-6). These hemostatic molecules, individually or combined, significantly improved the predictive power of conventional risk factors, as evidenced by significant increases in net reclassification improvement and integrated discrimination improvement (all P<0.01). CONCLUSIONS: We observed a hyperactive state of the coagulation-fibrinolysis system within the local ischemic region during hyperacute stroke. Rapid automated measurement of hemostatic molecular markers, particularly TAT, PIC, and sTM, during intra-arterial procedures may provide additional information for stroke risk stratification and therapeutic decision-making, and warrants further investigation.

Exosomes From IgE-Stimulated Mast Cells Aggravate Asthma-Mediated Atherosclerosis Through circRNA CDR1as-Mediated Endothelial Cell Dysfunction in Mice.

BACKGROUND: IgE has been known for mediating endothelial cell dysfunction and mast cell (MC) activation to fuel asthma-aggravated high-fat diet-induced atherosclerosis. However, it remains unclear for the mechanism of asthma-mediated atherosclerosis, especially the potential involvement of IgE in the exacerbation of asthma-mediated atherosclerosis with a standard laboratory diet, and the cross talk between endothelial cells and MCs. METHODS: Asthma-mediated atherosclerosis mice models under a standard laboratory diet and FcεR1 knock-out mice were used to determine the role of IgE-FcεR1 signaling in asthma-mediated atherosclerosis, which was assessed by Oil Red O staining and immunohistochemistry. Various in vitro assays including nanoparticle tracking analysis and transmission electron microscopy were used to evaluate exosome characteristics. Immunofluorescence and fluorescent in situ hybridization approaches were used to evaluate the effect and mechanism of MC-secreted exosomes encapsulated circular RNA CDR1as (cerebellar degeneration-related 1 antisense) on endothelial cells in vivo and in vitro. Finally, cohort studies examined the plasma CDR1as levels in patients with atherosclerosis with or without allergies. RESULTS: Asthma mice with a standard laboratory diet showed increased atherosclerotic lesions and inflammatory infiltration depending on IgE-FcεR1 signal. FcεR1 knockout mice and blockage of IgE-FcεR1 signaling with IgE monoclonal antibody, omalizumab, all significantly alleviated asthma-mediated atherosclerosis and vascular inflammatory remodeling. Anti-inflammation with dexamethasone and stabilization of MC with cromolyn partially alleviated atherosclerotic lesions and mitigated the inflammatory infiltration in arteries. Mechanistically, IgE stimulation upregulates MC CDR1as expression in exosomes and upregulates the endothelial cell adhesive factors VCAM-1 (vascular cell adhesion molecule-1) and ICAM-1 (intercellular adhesion molecule-1) via the CDR1as-FUS (fused in sarcoma)-phos-p65 axis. Knockdown of CDR1as in vivo significantly decreased the endothelial adhesion function and mitigated asthma-mediated atherosclerosis. Furthermore, a cohort study indicated higher plasma CDR1as levels in patients with atherosclerosis with allergies than in patients with atherosclerosis and healthy controls. CONCLUSIONS: Exosomes from IgE-stimulated MCs aggravated atherosclerosis through circular RNA CDR1as-mediated endothelial dysfunction, providing a novel insight into asthma-mediated atherosclerosis and potential diagnostic and therapeutic targets.

Evolution pattern estimated by computed tomography perfusion post-thrombectomy predicts outcome in acute ischemic stroke.

OBJECTIVES: Computed tomography perfusion (CTP) and computed tomography angiography (CTA) have been recommended to select acute ischemic stroke (AIS) patients for endovascular thrombectomy (EVT) but are not widely used for post-treatment evaluation. We aimed to observe abnormalities in CTP and CTA before and after EVT and evaluate post-EVT CTP and CTA as potential tools for improving clinical outcome prediction. METHODS: Patients with AIS who underwent EVT and received CTP and CTA before and after EVT were retrospectively evaluated. The ischemic core was defined as the volume of relative cerebral blood flow <30% and hypoperfusion as the volume of Tmax >6 s. A reduction in hypoperfusion volume >90% between baseline and post-EVT CTP was defined as tissue optimal reperfusion (TOR). The 90-day modified Rankin scale was used to evaluate the clinical outcome. RESULTS: Eighty-three patients were included. Patients with an absent ischemic core or with TOR after EVT had a higher rate of modified Thrombolysis in Cerebral Ischemia score 2c-3 and recanalization of post-treatment vessel condition based on follow-up CTA. Multivariable logistic regression revealed that the baseline ischemic core volume (OR:0.934, p=0.009), TOR (OR:8.322, p=0.029) and immediate NIHSS score after EVT (OR:0.761, p=0.012) were factors significantly associated with good clinical outcome. Combining baseline ischemic core volume and TOR with immediate NIHSS score after EVT showed greatest performance for good outcome prediction after EVT(AUC=0.921). CONCLUSIONS: The addition of pretreatment and post-treatment CTP information to purely clinical NIHSS scores might help to improve the efficacy for good outcome prediction after EVT.

Early venous filling after mechanical thrombectomy in acute ischemic stroke due to large vessel occlusion in anterior circulation.

BACKGROUND: The significance of early venous filling (EVF) after mechanical thrombectomy (MT) in acute ischemic stroke (AIS) is not fully understood. In this study, we aimed to investigate the impact of EVF after MT. METHODS: From January 2019 to May 2022, AIS patients with successful recanalization (modified Thrombolysis in Cerebral Infarction score (mTICI) ≥2b) after MT were retrospectively reviewed. EVF was evaluated on final digital subtraction angiography runs after successful recanalization and was categorized into phase subgroups (arterial phase and capillary phase) and pathway subgroups (cortical veins subgroup and thalamostriate veins subgroup), respectively. The impact of EVF subgroups on functional outcomes after successful recanalization were both investigated. RESULTS: A total of 349 patients achieving successful recanalization after MT were included, including 45 patients in the EVF group and 304 patients in the non-EVF group. Multivariable logistic regression analysis showed the EVF group had a higher rate of intracranial hemorrhage (ICH; 66.7% vs 22%, adjusted odds ratio (aOR) 6.805, 95% CI 3.389 to 13.662, P<0.001), symptomatic ICH (sICH; 28.9% vs 4.9%, aOR 6.011, 95% CI 2.493 to 14.494, P<0.001) and malignant cerebral edema (MCE; 20% vs 6.9%, aOR 2.682, 95% CI 1.086 to 6.624, P=0.032) than the non-EVF group. Furthermore, the cortical veins subgroup of EVF had a higher rate of mortality than the thalamostriate veins subgroup (37.5% vs 10.3%, P=0.029). CONCLUSIONS: EVF is independently associated with ICH, sICH and MCE after successful recanalization of MT, but not with favorable outcome and mortality.

Impact of acute silent ischemic lesions on clinical outcomes of carotid revascularization.

BACKGROUND: Previous literature has established an association between acute silent ischemic lesions (ASILs) and elevated susceptibility to future adverse clinical outcomes. The present study endeavors to scrutinize the prognostic significance of preprocedural ASILs, as detected through diffusion-weighted imaging and apparent diffusion coefficient metrics, in relation to subsequent adverse events-namely, stroke, myocardial infarction, and all-cause death-following carotid revascularization in a cohort of patients with symptomatic carotid stenosis. MATERIALS AND METHODS: Subjects were extracted from a comprehensive retrospective dataset involving symptomatic carotid stenosis cases that underwent carotid revascularization at a tertiary healthcare institution in China, spanning January 2019 to March 2022. Of the 2663 initially screened patients (symptomatic carotid stenosis=1600; asymptomatic carotid stenosis=1063), a total of 1172 individuals with symptomatic carotid stenosis were retained for subsequent analysis. Stratification was implemented based on the presence or absence of ASILs. The primary endpoint constituted a composite measure of in-hospital stroke, myocardial infarction, or all-cause death. Both carotid endarterectomy (CEA) and carotid artery stenting (CAS) treatment modalities were individually subjected to propensity score-matched analyses. RESULTS: Among the 584 subjects who underwent CEA, 91 ASIL-positive and 91 ASIL-negative (NASIL) cases were propensity score-matched. Notably, the ASIL cohort demonstrated a statistically significant augmentation in the risk of primary outcomes relative to the NASIL group [10.99 vs. 1.10%; absolute risk difference, 9.89% (95% CI: 3.12-16.66%); RR, 10.00 (95% CI: 1.31-76.52); P =0.01]. Similarly, within the 588 CAS-treated patients, 107 ASIL-positive and 107 NASIL cases were matched, revealing a correspondingly elevated risk of primary outcomes in the ASIL group [9.35 vs. 1.87%; absolute risk difference, 7.48% (95% CI: 1.39-13.56%); RR, 5.00 (95% CI: 1.12-22.28); P =0.02]. CONCLUSIONS: ASILs portend an elevated risk for grave adverse events postcarotid revascularization, irrespective of the specific revascularization technique employed-be it CEA or CAS. Thus, ASILs may serve as a potent biomarker for procedural risk stratification in the context of carotid revascularization.