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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.

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.

Abstract Background Stroke is a heavy burden in modern society, and carotid artery disease is a major cause. The role of the extracellular matrix (ECM) in the development and progression of carotid artery disease has become a popular research focus. However, there is no published bibliometric analysis to derive the main publication features and trends in this scientific area. We aim to conduct a bibliometric analysis to reveal current status of ECM in carotid artery disease and to predict future hot spots. Methods We searched and downloaded articles from the Web of Science Core Collection with “Carotid” and “Extracellular Matrix” as subject words from 1990 to 2021. The complete bibliographic data were analyzed by Bibliometrics, BICOMB, gCLUTO and CiteSpace softwares. Results Since 1990, the United States has been the leader in the number of publications in the field of ECM in carotid artery disease, followed by China, Japan and Germany. Among institutions, Institut National De La Sante Et De La Recherche Medicale Inserm, University of Washington Seattle and Harvard University are in the top 3. “Arteriosclerosis Thrombosis and Vascular Biology” is the most popular journal and “Circulation” is the most cited journal. “Clowes AW”, “Hedin Ulf” and “Nilsson Jan” are the top three authors of published articles. Finally, we investigated the frontiers through the strongest citation bursts, conducted keyword biclustering analysis, and discovered five clusters of research hotspots. Our research provided a comprehensive analysis of the fundamental data, knowledge organization, and dynamic evolution of research about ECM in carotid artery disease. Conclusions The field of ECM in carotid artery disease has received increasing attention. We summarized the history of the field and predicted five future hotspots through bibliometric analysis. This study provided a reference for researchers in this fields, and the methodology can be extended to other fields.

Introduction Stroke remains the second leading cause of death worldwide, a common cause of which is intracranial atherosclerotic stenosis (ICAS). Medical treatment is recommended as first-line therapy for treating ICAS, but the recurrence rate remains high. Drug-coated balloon (DCB) angioplasty has been designed to lower the risk of recurrent stenosis, holding therapeutic promise in the treatment of ICAS. However, the benefits of DCB require further evaluation.Methods and analysis The Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols was followed to develop this protocol. We will systematically search online databases including Cochrane Central Register of Controlled Trials, PubMed, Web of Science, EMBASE, China Biological Medicine Database, ClinicalTrials.gov and WHO ICTRP from 1 January 2011 to the date of search. This will be supplemented by a manual search of unpublished and ongoing trials to manually select articles for inclusion. Inclusion criteria are randomised or quasi-randomised clinical trials and observational studies that investigated DCB or medical treatment for patients with a symptomatic ICAS of 50%–99%. The primary outcome is short-term composite safety including death of any cause, or non-fatal stroke. Secondary outcomes include long-term death or stroke, restenosis, neurological rehabilitation, quality of life and other complications. The available data will be analysed using meta-analysis, if appropriate. The evaluation of heterogeneity and biases will be guided by the Cochrane Handbook for Systematic Reviews of Interventions.Ethics and dissemination This systematic review does not require ethical approval as all available data from eligible studies will be anonymous with no concerns regarding privacy. Our findings will be disseminated through international conferences and peer-reviewed publications. Additional data from the study are available on request to corresponding authors via email.PROSPERO registration number CRD42022341607.

CONTEXT: Circulating neutrophils and long noncoding RNAs (lncRNAs) play various roles in intracranial atherosclerotic stenosis (ICAS). OBJECTIVE: Our study aimed to detect differentially expressed (DE) lncRNAs and mRNAs in circulating neutrophils and explore the pathogenesis of atherosclerosis from the perspective of neutrophils. METHODS: Nineteen patients with ICAS and 15 healthy controls were enrolled. The peripheral blood of the participants was collected, and neutrophils were separated. The expression profiles of lncRNAs and mRNAs in neutrophils from five patients and five healthy controls were obtained, and DE lncRNAs and mRNAs were selected. Six lncRNAs were selected and validated using quantitative reverse transcription–polymerase chain reaction (qRT-PCR), and ceRNA and lncRNA-RNA binding protein (RBP)-mRNA networks were constructed. Correlation analysis between lncRNAs and mRNAs was performed. Functional enrichment annotations were also performed. RESULTS: Volcano plots and heat maps displayed the expression profiles and DE lncRNAs and mRNAs, respectively. The qRT-PCR results revealed that the four lncRNAs showed a tendency consistent with the expression profile, with statistical significance. The ceRNA network revealed three pairs of regulatory networks: lncRNA RP3-406A7.3-NAGLU, lncRNA HOTAIRM1-MVK/IL-25/GBF1/CNOT4/ANKK1/PLEKHG6, and lncRNA RP11-701H16.4-ZNF416. The lncRNA-RBP-mRNA network showed five pairs of regulatory networks: lncRNA RP11-701H16.4-TEK, lncRNA RP11-701H16.4-MED17, lncRNA SNHG19-NADH-ubiquinone oxidoreductase core subunit V1, lncRNA RP3-406A7.3-Angel1, and lncRNA HOTAIRM1-CARD16. CONCLUSIONS: Our study identified and verified four lncRNAs in neutrophils derived from peripheral blood, which may explain the transcriptional alteration of neutrophils during the pathophysiological process of ICAS. Our results provide insights for research related to the pathogenic mechanisms and drug design of ICAS.

Introduction Intracranial atherosclerotic stenosis (ICAS) is a common cause of stroke worldwide. However, whether the treatment options for symptomatic ICAS is stent placement or medical therapy alone is still controversial. At present, three multicentre randomised controlled trials (RCTs) have been published, but their research designs are also slightly different and the conclusions are not completely consistent. Therefore, we plan to conduct a systematic review and individual patient data (IPD) meta-analysis of randomised clinical trials to ascertain safety and efficacy of stenting versus medical therapy alone for symptomatic patients with intracranial arterial stenosis.Methods and analyses We will identify RCTs comparing stenting vs medical therapy alone in patients with symptomatic ICAS stenosis (70%–99%) through a systematic search, mainly including PubMed, MEDLINE, EMBASE, the Cochrane Library and ClinicalTrials.gov. Individual-level patient data for a prespecified list of variables will be sought from authors of all eligible studies. The primary outcome was a composite of stroke or death within 30 days, or stroke in territory of qualifying artery beyond 30 days after randomisation. IPD meta-analysis will be conducted with a one-stage approach.Ethics and dissemination Ethical approval and individual patient consent will not be required in most cases since this IPD meta-analysis will use pseudoanonymised data from RCTs. Results will be disseminated through peer-reviewed journals and international conferences.PROSPERO registration number CRD42022369922.

Introduction Cerebrovascular intervention is an excellent option to treat cerebrovascular diseases. Interventional access is a prerequisite and a foundation for cerebrovascular intervention, which is crucial to the success of an intervention. Although transfemoral arterial access (TFA) has become a popular and acceptable method of access for cerebrovascular angiography and intervention in clinical practice, it has some drawbacks that limit the usage in cerebrovascular interventions. Therefore, transcarotid arterial access (TCA) has been developed in cerebrovascular interventions. We aim to conduct a systematic review to compare the safety and efficacy of TCA with TFA for cerebrovascular intervention.Methods and analysis In this protocol, Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols were followed. PubMed, Embase, Web of Science and the Cochrane Central Register of Controlled Trials will be searched mainly from 1 January 2004, to the formal search date. Additionally, reference lists and clinical trial registries will be searched. We will include clinical trials with more than 30 participants, which reported the endpoints of stroke, death and myocardial infarction. Two investigators will independently select studies, extract data and assess bias risk. A standardised mean difference with 95% CI will be presented for continuous data, and a risk ratio with 95% CI will be presented for dichotomous data. On inclusion of sufficient studies, subgroup analysis and sensitivity analysis will be conducted. The funnel plot and Egger’s test will be used to assess publication bias.Ethics and dissemination As only published sources will be used in this review, ethical approval is not required. We will publish the results in a peer-reviewed journal.PROSPERO registration number CRD42022316468.

Introduction Atherosclerosis is the leading cause of cardiovascular disease (CVD), which is one of the most common causes of morbidity and mortality worldwide. Lipid accumulation and inflammation play a crucial role in the pathogenesis of atherosclerosis. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are an emerging lipid-lowering agent reported as a potential anti-inflammation effect in the prevention of CVD. However, the anti-inflammatory effect is still elusive. Therefore, a systematic review and meta-analysis is needed to analyse the anti-inflammatory effect of PCSK9 inhibitors on atherosclerosis in practice.Methods and analysis This protocol was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols. We will include double-blind, randomised controlled trials that reported changes in the levels of inflammatory markers, with an intervention arm of PCSK9 inhibitors and a treatment duration of more than 2 weeks. The following databases will be mainly searched from 1 January 2003 to the formal search date: PubMed, Embase, Web of Science and the Cochrane Central Register of Controlled Trials. The primary aim is to assess the effect of PCSK9 inhibitors on inflammatory markers, including circulating inflammatory markers such as C-reactive protein, high-sensitivity C-reactive protein, white cell counts, IL-1β, IL-6 and TNF-α and local inflammatory markers such as the most diseased segment target-to-background ratio of the index vessel in adult patients with atherosclerosis. We will assess the quality of evidence, heterogeneity and report bias following the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions.Ethics and dissemination Due to the systematic review being based on published studies, no ethics approval is required. The study results will be presented at international conferences and published in a peer-reviewed journal.PROSPERO registration number CRD42022297710.

Atherosclerosis (AS) is a common cardiovascular disease with complex pathogenesis, in which multiple pathways and their interweaving regulatory mechanism remain unclear. The primary transcription factor NF-κB plays a critical role in AS via modulating the expression of a series of inflammatory mediators under various stimuli such as cytokines, microbial antigens, and intracellular stresses. Endoplasmic reticulum (ER) stress, caused by the disrupted synthesis and secretion of protein, links inflammation, metabolic signals, and other cellular processes via the unfolded protein response (UPR). Both NF-κB and ER stress share the intersection regarding their molecular regulation and function and are regarded as critical individual contributors to AS. In this review, we summarize the multiple interactions between NF-κB and ER stress activation, including the UPR, NLRP3 inflammasome, and reactive oxygen species (ROS) generation, which have been ignored in the pathogenesis of AS. Given the multiple links between NF-κB and ER stress, we speculate that the integrated network contributes to the understanding of molecular mechanisms of AS. This review aims to provide an insight into these interactions and their underlying roles in the progression of AS, highlighting potential pharmacological targets against the atherosclerotic inflammatory process.

Introduction Conventional lipid-lowering agents, including statins, ezetimibe, fibrates, bile acid sequestrants, nicotinic acid, bempedoic acid and Omega-3, are essential to the management of dyslipidaemia. However, these agents have been shown to increase the level of plasma proprotein convertase subtilisin/kexin 9 (PCSK9), a serine protease associated with increased cardiovascular risk. This review aims to investigate the impact of commonly available conventional lipid-lowering agents on circulating PCSK9 levels and lipid profiles.Methods and analysis This protocol is conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. A systematic search will be conducted in the following databases: MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, Web of Science, SCOPUS and ScienceDirect. Additional information will be retrieved from clinical trial registries or from reference list searches. Published and peer-reviewed randomised controlled trials with adults receiving statin, ezetimibe, fibrate, bile acid sequestrant, nicotinic acid, bempedoic acid or Omega-3 monotherapy or in combination for at least 2 weeks, with availability of plasma PCSK9 at the beginning and end of treatment or the net changes in values, will be included. Study selection, data extraction and assessment of the risk of bias will be independently conducted by two investigators. Continuous data will be presented as a standardised mean difference with 95% confidence interval (CI) and dichotomous data as risk ratios with 95% CI. Subgroup analysis and sensitivity analysis will be performed when sufficient studies are included. Publication bias will be assessed with a funnel plot and Egger’s test.Ethics and dissemination Ethics approval is not required as this review will only include data from published sources. The results will be published in a peer-reviewed journal.Patient and public involvement No patient or members of the general public are involved.PROSPERO registration number CRD42022297942.

Abstract Background Stroke is the second leading cause of death worldwide, and 53.4% of stroke survivors suffer from post-stroke cognitive impairment. Post-stroke cognitive impairment can increase hospitalization rate and cost of care and decrease the quality of life of stroke patients. To date, multiple cognitive rehabilitation interventions have been tested in stroke populations with post-stroke cognitive impairment. However, the most efficacious intervention has not been established. This systematic review aims to compare the efficacy of cognitive rehabilitation interventions for patients with post-stroke cognitive impairment. Methods We will search MEDLINE, EMBASE, CENTRAL, PsycINFO, CINAHL, PubMed, and clinical trial registries to identify eligible randomized clinical trials with no restrictions in the date of publication and language. Studies conducted with patients aged 18 or over, with the presence of cognitive impairment after being diagnosed with stroke will be included. Studies will be restricted to randomized controlled trials comparing a cognitive rehabilitation intervention with another intervention. The primary outcome is any clinical changes in the general or specific cognitive domain (e.g., executive function, attention, memory, or perception). The secondary outcomes that will be collected include adverse effects (e.g., stroke, disability, or mortality) and quality of life. Two independent reviewers will assess articles to identify trials eligible for inclusion. Data extraction and risk of bias assessment of the included studies will also be done independently. Any discrepancies will be solved by discussion, or a third reviewer will be consulted if necessary. A meta-analysis will be carried out if appropriate. Discussion This systematic review for patients with post-stroke cognitive impairment will assess the efficacy of cognitive rehabilitation interventions. And our results will help clinical decision-making and support the development of clinical practice guidelines. Trial registration Systematic review registration: PROSPERO CRD42020173988

IntroductionIntracranial atherosclerotic disease (ICAD) is one of the most important etiologies of ischemic stroke, especially in Asia. Although medical treatment was recommended as the first-line therapy for ICAD, the recurrent stroke rate was still high in severe stenosis of ICAD despite aggressive medical treatment. Traditionally, the degree of luminal stenosis is used as the principal index for stroke risk stratification in patients with ICAD, while recent evidence suggested that symptomatic atherosclerotic plaques were characterized by plaque features and hemodynamics. This prospective, longitudinal, and nested case-control study aims to identify multimodal imaging predictors of high-risk patients with ICAD refractory to medical treatment and explore a refined risk stratification model based on the above multimodal imaging predictors.MethodsThis prospective, longitudinal, and nested case-control study includes 400 symptomatic patients with ICAD with 50–99% of stenosis treated with aggressive medical therapy. All patients who meet the eligibility criteria are assessed by multimodal imaging examination from three aspects, including lumen stenosis, plaque characteristics, and hemodynamic features. The enrolled patients receive aggressive medical management, including antiplatelet therapy and cardiovascular risk control. The primary outcome is ischemic stroke or death attributable to the lesion of the target vessel within 1 year. The secondary endpoints are (1) any stroke or death; (2) all-cause mortality; (3) any stroke out of the territory of the responsible lesion; (4) functional outcome with the modified Rankin Scale (mRS).Ethics and DisseminationThis study has been approved by the ethics committee of our center ([2021]083) and has been prospectively registered (Registration No: ChiCTR2100048832). Study findings will be disseminated through peer-reviewed publications and presentations at scientific meetings.

PurposeIn recent years, metabolic syndrome has risen in prevalence and brought a heavy disease burden to modern society. As the representative aspect of metabolic syndrome, obesity has been shown to be related to an increased risk of stroke. Given that visceral adipose tissue (VAT) forms the fundamental basis of central obesity, we sought to explore a causal relationship between VAT and stroke by using mendelian randomization (MR) methods.MethodsBased on two large genome-wide association studies (GWAS) including 325,153 and 35,762 cases of VAT and stroke, respectively, we conducted a MR study which has the inherent advantage of reducing the noise of confounding and reverse causation.ResultsVAT had a significant causal association with ischemic stroke (OR, per 1kg increase in VAT mass, 1.30; 95% CI, 1.18 ~ 1.45; P = 5.87E-07) as opposed to intracranial hemorrhage (ICH) (OR, 1.15; 95% CI, 0.70 ~ 1.88, P = 5.81E-01) as evaluated with inverse-variance weighting (IVW). Regarding subtypes of ischemic stroke, there was a significant causal effect for cardioembolic stroke (OR, 1.34; 95% CI, 1.13 ~ 1.58, P = 8.07E-04), and potential causal effect for small-vessel stroke (OR, 1.32; 95% CI, 1.06 ~ 1.65, P = 1.39E-02) and large-artery atherosclerotic stroke (OR, 1.33; 95% CI, 1.03 ~ 1.70, P = 2.59E-02).ConclusionsThis study provides potential evidence for a causal role of VAT in ischemic stroke and could suggest novel genetical therapeutic strategies for distinct subtypes of ischemic stroke.

Abstract Background Occlusive atherosclerotic disease of the anterior cerebral circulation is one of the most common causes of anterior circulation ischemia and stroke. Treatment options include medical therapies (including antiplatelet use, blood pressure control, lipid reduction, and lifestyle modification) and extracranial-intracranial bypass surgery (such as superficial temporal artery-middle cerebral artery bypass). However, the optimal treatment remains unclear. The objective of this study will be to compare the efficacy of and extracranial-intracranial bypass surgery with that of other medical therapy in adult patients with occlusive atherosclerotic disease of the anterior cerebral circulation. Methods This is the study protocol for a systematic review. We will search MEDLINE, EMBASE, Web of Science, and the Cochrane Library (from January 1980 onwards). We will include randomized controlled trials, quasi-experimental studies (non-randomized, interrupted time series), and observational studies (e.g., cohort studies and case-control studies), examining the efficacy of extracranial-intracranial bypass surgery compared to other treatments for adult patients with occlusive atherosclerotic disease of anterior cerebral circulation. Two team members will independently screen all citations, full-text articles, and abstract data. Potential conflicts will be resolved through discussion. The primary outcome will include stroke or death. The secondary outcomes will include intracranial hemorrhage, transient ischemic attack, and myocardial infarction. The study methodological quality (or bias) will be appraised using appropriate tools. If feasible, we will conduct random effects meta-analysis. Additional analyses will be conducted to explore the potential sources of heterogeneity (e.g., study design, geographical location, or risk of bias). Discussion This review will evaluate the evidence on the efficacy of extracranial-intracranial bypass surgery for adult patients with occlusive atherosclerotic disease of the anterior cerebral circulation. We anticipate that our findings will be of interest to patients, their families, caregivers, healthcare professionals, and in making optimal treatment selection. Implications for future clinical and epidemiological research will be discussed. Systematic review registration PROSPERO CRD42018105513

Background: Intracranial cerebral atherosclerosis (ICAS) is a leading etiology of ischemic stroke. The diagnosis and assessment of intracranial stenosis are shifting from anatomic to hemodynamic for better risk stratification. However, the relationships between lesion geometry and translesional pressure gradient have not been clearly elucidated.Methods: Patients with symptomatic unifocal M1 middle cerebral artery (M1-MCA) stenosis were consecutively recruited. The translesional pressure gradient was measured with a pressure wire and was recorded as both mean distal/proximal pressure ratios (Pd/Pa) and translesional pressure difference (Pa–Pd). Lesion geometry measured on angiography was recorded as diameter stenosis, minimal lumen diameter, and lesion length. The correlations between pressure-derived and angiography-derived indices were then analyzed.Results: Forty-three patients were analyzed. A negative correlation was found between Pd/Pa and diameter stenosis (r = −0.371; p = 0.014) and between Pa – Pd and minimal lumen diameter (r = −0.507; p = 0.001). A positive correlation was found between Pd/Pa and minimal lumen diameter (r = 0.411; p = 0.006) and between Pa – Pd and diameter stenosis (r = 0.466; p = 0.002).Conclusions: In a highly selected ICAS subgroup, geometric indices derived from angiography correlate significantly with translesional pressure gradient indices. However, the correlation strength is weak-to-moderate, which implies that anatomic assessment could only partly reflect hemodynamic status. Translesional pressure gradient measured by pressure wire may serve as a more predictive marker of ICAS severity. More factors need to be identified in further studies.

Objective: To investigate the impact of timing on the safety and efficacy of stenting for ICAS, we reviewed high-volume randomized controlled trials or prospective cohort studies of stenting for intracranial atherosclerotic artery stenosis (ICAS) after the SAMMPRIS trial.Methods: We included randomized controlled trials or prospective cohort studies since 2011 (the publication of the SAMMPRIS trial), evaluating the outcomes of intracranial stenting for ICAS patients. The primary outcomes were perioperative and 1-year stroke or death rate. The interaction of timing and outcomes were shown on trend plots. Overall meta-analysis and subgroup analysis by timing of intracranial stenting were conducted.Results: Fourteen studies with a total of 1,950 patients were included. The perioperative and post-operative stroke or death rates decreased with the time of stenting to the qualifying events. The perioperative stroke rate was significantly higher in patients treated within 21 days after the qualifying events, compared to those beyond 21 days (IRR = 1.60, 95%CI: 1.10–2.33; p = 0.014), similar relationships were obtained for both post-procedural (IRR = 1.61, 95%CI: 1.02–2.55; p = 0.042) and 1-year (IRR = 1.51, 95%CI: 1.10–2.08; p = 0.012) stroke or death rate.Conclusions: The timing of intracranial stenting may influence the safety and efficacy outcomes of stenting. Intracranial stenting within 21 days from the qualifying events may confer a higher risk of stroke or death. More studies are needed to confirm the impact of timing and the proper cut-off value.

Objective: The current study aims to analyze the risk factors of new cerebral infarctions in the distribution of basilar artery (BA) detected by diffusion-weighted imaging (DWI) after endovascular treatment in patients with severe BA stenosis.Methods: Data was collected from the electronic medical records of patients with severely atherosclerotic basilar artery stenosis (≥70%) who underwent endovascular treatment. The plaque characteristics, including the plaque distribution, plaque burden, plaque enhancement index, remodeling ratio, and stenosis degree, were evaluated qualitatively and quantitatively using high-resolution magnetic resonance imaging (HR-MRI) and digital subtraction angiography (DSA). The characteristics of the procedure, such as the type of treatment, balloon diameter, balloon length, stent diameter, and stent length, were analyzed.Results: A total of 107 patients with severe basilar artery stenosis (≥70%) who underwent endovascular treatment were enrolled. The study participants included 77 men and 30 women, with an average age of 61.6 ± 8.1 years. The rate of postoperative new cerebral infarctions was 55.1% (59/107), of which 74.6% (44/59) were caused by artery-to-artery embolism, 6.8% (4/59) due to perforator occlusion, and 18.6% (11/59) were caused by a mixed mechanism. Twelve of 59 patients had ischemic events, with nine cases of stroke and three cases of transient ischemic attacks (TIA). The plaque burden in the DWI-positive group was significantly larger than that in the DWI-negative group (3.7% vs. −8.5%, p = 0.016). Positive remodeling was more common in the DWI-positive group than in the DWI-negative group (35.6% vs. 16.7%, p = 0.028). Smoking was inversely correlated with the rate of new cerebral infarctions (odds ratio, 0.394; 95% confidence interval, 0.167–0.926; p = 0.033).Conclusion: The plaque characteristics are not associated with new cerebral infarctions in the distribution of BA, although a large plaque burden and positive remodeling are more likely to appear in patients with new cerebral infarctions after BA stenting, which warrants further studies with a larger sample size. As for smoking, the inverse correlation with new cerebral infarctions in the BA territory needs large-scale prospective randomized controlled trials to verify.

Introduction Carotid endarterectomy (CEA), carotid artery stenting (CAS) and best medical therapy (BMT) are the major treatments used for significant asymptomatic carotid artery stenosis (ACAS, ≥50%). However, the widespread use of lipid-lowering drugs in this century has improved BMT outcomes. This study aims to compare the treatment efficacy of current BMT, CEA+BMT and CAS+BMT in patients with significant ACAS.Methods and analysis This protocol was designed based on the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. Publication time for studies will be set from 1 January 2000 to 1 June 2020. We will search three databases: PubMed, EMBASE and The Cochrane Library. Suitable randomised controlled studies will be screened. The primary outcomes will include short-term and long-term mortality, stroke and myocardial infarction. OR and HR for dichotomous data and time-to-event data with 95% CIs will be calculated. Treatment effects among different therapies will be ranked according to the surface under the cumulative ranking curve and mean rank. A comprehensive evaluation of the risk of bias, heterogeneity and transitivity will be performed before data synthesis. Consistency and evidence quality will also be assessed.Ethics and dissemination There will be no need for ethics approval as this systematic review is a summary and analysis of existing literature. Final results may be presented in international conferences or a peer-reviewed journal.PROSPERO registration number CRD42019138942.

Understanding asymptomatic moyamoya disease (aMMD), for which treatment options are currently limited, is key to the development of therapeutic strategies that will slow down the progression of this disease, as well as facilitate the discovery of therapeutic targets for symptomatic MMD. Newly found transfer RNA-derived small RNAs (tsRNAs) perform potential regulatory functions in neovascularization, which is a well-known pathological manifestation of MMD. In this study, the neutrophilic tsRNA transcriptome in aMMD was profiled using next-generation RNA sequencing in five patients and five matched healthy subjects. A negative binominal generalized log-linear regression was used to identify differentially expressed (DE)-tsRNAs in aMMD. Gene Ontology and functional pathway analyses were used to identify biological pathways involved with the targeted genes of the DE-tsRNAs. Four tsRNAs were selected and validated using quantitative reverse transcription polymerase chain reaction. In total, 186 tsRNAs were DE between the two groups. Pathophysiological events, including immune response, angiogenesis, axon guidance, and metabolism adjustment, were enriched for the DE-tsRNAs. The expression levels of the four DE-tsRNAs were consistent with those in the neutrophilic transcriptome. These aberrantly expressed tsRNAs and their targeted pathophysiological processes provide a basis for potential future interventions for aMMD.

Intracranial atherosclerotic stenosis (ICAS) is a common cause of transient ischemic attack (TIA) and ischemic stroke. Endovascular treatment, including balloon angioplasty alone, balloon-mounted stents, and self-expandable stent placement with or without prior angioplasty, is an alternative to medical treatment for the prevention of recurrent TIA or ischemic stroke in patients with ICAS. Although the SAMMPRIS and VISSIT trials supported medical management alone against endovascular treatments, both randomized controlled trials (RCT) were criticized due to flaws relating to patient-, intervention-, and operator-related factors. In this review, we discuss the current debate regarding these aspects and suggest approaches to solve current controversies in the future. In our opinion, endovascular treatment in carefully selected patients, individualized choice of endovascular treatment subtypes, and an experienced multidisciplinary team managing the patient in the pre-, peri- and post-procedural period have the potential to provide safe and efficious treatment of patients with symptomatic ICAS.

Background Fractional flow reserve is widely used in coronary disease management, with a threshold of 0.80. However, similar thresholds are unclear in functional assessment of intracranial atherosclerotic stenosis (ICAS). Objective To investigate the potential threshold values in functional assessment of ICAS by studying the relation between pressure-derived indexes and perfusion parameters derived from arterial spin labeling (ASL). Methods Patients were consecutively screened between June 2019 and December 2020. The translesional gradient indices were measured by pressure guidewire under resting-state conditions and recorded as mean distal/proximal pressure ratios (Pd/Pa) and translesional pressure difference (Pa-Pd). Preoperative and postoperative cerebral blood flow (CBF) bilaterally and the relative cerebral blood flow ratio (rCBF) were measured and recorded by ASL imaging. Patients were defined as having reversible hemodynamic insufficiency only if the preoperative rCBF was <0.9 and the postoperative rCBF≥0.9. Preoperative and postoperative Pd/Pa or Pa-Pd values of those patients were used to calculate the threshold. Results Twenty-five patients (19 men, 6 women) with a mean age of 56.7±9.4 years were analyzed. Seventeen patients (68%) had lesions at the M1 segment of the middle cerebral artery, eight patients (32%) had lesions in the intracranial internal carotid artery. In 14 of the 25 patients, the preoperative rCBF was <0.9 and the postoperative rCBF≥0.9. Cut-off values of Pd/ Pa=0.81 and Pa-Pd=8 mm Hg were suggested to be associated with hemodynamic insufficiency. Conclusions In a highly selected subgroup with ICAS, cut-off values of translesional pressure gradients (Pd/Pa=0.81 or Pa-Pd=8 mm Hg) were preliminarily established, which may facilitate clinical decision-making in the management of ICAS. [ABSTRACT FROM AUTHOR]

Background The efficacy of percutaneous transluminal angioplasty and stenting (PTAS) relative to medical management in treating symptomatic intracranial arterial stenosis (ICAS) varies based on the qualifying artery. This study aims to evaluate PTAS compared with medical therapy alone in cases of ICAS involving the internal carotid artery (ICA), middle cerebral artery (MCA), vertebral artery (VA) and basilar artery (BA).Methods This study involves a thorough pooled analysis of individual patient data from two randomised controlled trials, evaluating the efficacy of PTAS in comparison to medical management for symptomatic ICAS with different qualifying arteries. The primary outcome was stroke or death within 30 days postenrolment, or stroke in the region of the qualifying artery beyond 30 days through 1 year. A methodology based on intention-to-treat was employed, and HR accompanied by 95% CIs were used to convey risk estimates.Results The data of 809 individuals were collected from Stenting vs Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis trial and China Angioplasty and Stenting for Symptomatic Intracranial Severe Stenosis trial. Four hundred were designated for PTAS, while 409 were assigned to medical therapy alone. For the primary outcome, patients with symptomatic BA stenosis had a significantly higher risk of receiving PTAS compared with medical therapy (17.17% vs 7.77%; 9.40; HR, 2.38 (1.03 to 5.52); p=0.04). However, PTAS had no significant difference in patients with symptomatic ICA (26.67% vs 16.67%; HR, 1.68 (0.78 to 3.62); p=0.19), MCA (8.28% vs 9.79%; HR, 0.85 (0.42 to 1.74); p=0.66) and VA stenosis (9.52% vs 10.71%; HR, 0.91 (0.32 to 2.62); p=0.86) compared with medical therapy.Conclusions PTAS significantly increases the risk of both short-term and long-term stroke in patients with symptomatic BA stenosis. Without significant technological advancements to mitigate these risks, PTAS offers limited benefits. For symptomatic ICA, MCA and VA stenosis, PTAS provided no significant advantage.

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. [ABSTRACT FROM AUTHOR]