Intensive Ambulance-Delivered Blood-Pressure Reduction in Hyperacute Stroke.

BACKGROUND: Treatment of acute stroke, before a distinction can be made between ischemic and hemorrhagic types, is challenging. Whether very early blood-pressure control in the ambulance improves outcomes among patients with undifferentiated acute stroke is uncertain. METHODS: We randomly assigned patients with suspected acute stroke that caused a motor deficit and with elevated systolic blood pressure (≥150 mm Hg), who were assessed in the ambulance within 2 hours after the onset of symptoms, to receive immediate treatment to lower the systolic blood pressure (target range, 130 to 140 mm Hg) (intervention group) or usual blood-pressure management (usual-care group). The primary efficacy outcome was functional status as assessed by the score on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days after randomization. The primary safety outcome was any serious adverse event. RESULTS: A total of 2404 patients (mean age, 70 years) in China underwent randomization and provided consent for the trial: 1205 in the intervention group and 1199 in the usual-care group. The median time between symptom onset and randomization was 61 minutes (interquartile range, 41 to 93), and the mean blood pressure at randomization was 178/98 mm Hg. Stroke was subsequently confirmed by imaging in 2240 patients, of whom 1041 (46.5%) had a hemorrhagic stroke. At the time of patients' arrival at the hospital, the mean systolic blood pressure in the intervention group was 159 mm Hg, as compared with 170 mm Hg in the usual-care group. Overall, there was no difference in functional outcome between the two groups (common odds ratio, 1.00; 95% confidence interval [CI], 0.87 to 1.15), and the incidence of serious adverse events was similar in the two groups. Prehospital reduction of blood pressure was associated with a decrease in the odds of a poor functional outcome among patients with hemorrhagic stroke (common odds ratio, 0.75; 95% CI, 0.60 to 0.92) but an increase among patients with cerebral ischemia (common odds ratio, 1.30; 95% CI, 1.06 to 1.60). CONCLUSIONS: In this trial, prehospital blood-pressure reduction did not improve functional outcomes in a cohort of patients with undifferentiated acute stroke, of whom 46.5% subsequently received a diagnosis of hemorrhagic stroke. (Funded by the National Health and Medical Research Council of Australia and others; INTERACT4 ClinicalTrials.gov number, NCT03790800; Chinese Trial Registry number, ChiCTR1900020534.).

Identification and characterization of extrachromosomal circular DNA in large-artery atherosclerotic stroke.

Extrachromosomal circular DNA (eccDNA) is a new biomarker and regulator of diseases. However, the role of eccDNAs in large-artery atherosclerotic (LAA) stroke remains unclear. Through high-throughput circle-sequencing technique, the length distribution, genomic characteristic and motifs feature of plasma eccDNA from healthy controls (CON) and patients with LAA stroke were analysed. Then, the potential functions of the annotated eccDNAs were investigated using GO and KEGG pathway analyses. EccDNAs mapped to the reference genome showed SHN3 and BCL6 were LAA stroke unique transcription factors. The genes of differentially expressed eccDNAs between LAA stroke patients and CON were mainly involved in axon/dendrite/neuron projection development and maintenance of cellular structure via Wnt, Rap1 and MAPK pathways. Moreover, LAA stroke unique eccDNA genes played a role in regulation of coagulation and fibrinolysis, and there were five LAA stroke unique eccDNAs (Chr2:12724406-12724784, Chr4:1867120-186272046, Chr4:186271494-186271696, Chr7:116560296-116560685 and Chr11:57611780-5761192). Additionally, POLR2C and AURKA carried by ecDNAs (eccDNA size >100 kb) of LAA stroke patients were significantly associated with development of LAA stroke. Our data firstly revealed the characteristics of eccDNA in LAA stroke and the functions of LAA stroke unique eccDNAs and eccDNA genes, suggesting eccDNA is a novel biomarker and mechanism of LAA stroke.

Signature and function of plasma exosome-derived circular RNAs in patients with hypertensive intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is one of the major causes of death and disability, and hypertensive ICH (HICH) is the most common type of ICH. Currently, the outcomes of HICH patients remain poor after treatment, and early prognosis prediction of HICH is important. However, there are limited effective clinical treatments and biomarkers for HICH patients. Although circRNA has been widely studied in diseases, the role of plasma exosomal circRNAs in HICH remains unknown. The present study was conducted to investigate the characteristics and function of plasma exosomal circRNAs in six HICH patients using circRNA microarray and bioinformatics analysis. The results showed that there were 499 differentially expressed exosomal circRNAs between the HICH patients and control subjects. According to GO annotation and KEGG pathway analyses, the targets regulated by differentially expressed exosomal circRNAs were tightly related to the development of HICH via nerve/neuronal growth, neuroinflammation and endothelial homeostasis. And the differentially expressed exosomal circRNAs could mainly bind to four RNA-binding proteins (EIF4A3, FMRP, AGO2 and HUR). Moreover, of differentially expressed exosomal circRNAs, hsa_circ_00054843, hsa_circ_0010493 and hsa_circ_00090516 were significantly associated with bleeding volume and Glasgow Coma Scale score of the subjects. Our findings firstly revealed that the plasma exosomal circRNAs are significantly involved in the progression of HICH, and could be potent biomarkers for HICH. This provides the basis for further research to pinpoint the best biomarkers and illustrate the mechanism of exosomal circRNAs in HICH.

Process Evaluation of an Ambulance-Delivered Early Intensive Blood Pressure-Lowering Stroke Trial: Design, Rationale, and Reflection.

INTRODUCTION: The fourth INTEnsive ambulance-delivered blood pressure Reduction in hyper-ACute stroke Trial (INTERACT4) is a large-scale, multicenter, prospective, randomized, open-label, blinded endpoint assessment trial, initiated in an ambulance in China, aiming at evaluating the effectiveness and safety of prehospital blood pressure (BP) lowering in patients with suspected acute stroke and elevated BP. A prespecified process evaluation is intended to explore the implementation of the trial intervention, provide support to interpret the trial outcomes and put forward suggestions to scale up the intervention in broader settings in the future. METHODS: This process evaluation is a mixed-methods design, and follows the Normalization Process Theory (NPT) and the UK Medical Research Council (UK MRC) guidance. Fidelity, reach, acceptability, appropriateness, adoption, sustainability, and relevant contextual factors and mechanisms affecting the implementation of prehospital early intensive BP-lowering treatment will be analyzed. Semi-structured interviews with ambulance staff, ward and emergency department clinicians, and nurses are undertaken to explore perceptions of the intervention, contextual factors, and potential suggestions for future implementation in practice. Data from observational records, surveys, conventional monitoring data, on-site records, and case report forms will be analyzed to understand background care and context. CONCLUSION: The process evaluation of INTERACT4 will provide insights for the implementation of prehospital early intensive BP-lowering intervention in different health systems and help better explain the trial results for further scale up.

Thromboelastography-Guided Antiplatelet Therapy for Patients with Ischemic Cerebrocardiovascular Diseases: A Systematic Review and Meta-Analysis.

INTRODUCTION: The effectiveness of thromboelastography (TEG)-guided antiplatelet therapy in patients with ischemic cerebrocardiovascular diseases is not well-established. This systematic review evaluates the efficacy and safety of TEG-guided antiplatelet therapy compared to standard treatment in patients with ischemic cerebrocardiovascular diseases. METHODS: Randomized controlled trials (RCTs) and observational studies comparing TEG-guided antiplatelet therapy with standard therapy in patients suffering from ischemic stroke (IS) or coronary artery disease (CAD) were identified. The primary efficacy measure was a composite of ischemic and hemorrhagic events. Secondary efficacy measures included any ischemic events, while safety was assessed by the occurrence of bleeding events. RESULTS: Ten studies involving 4 RCTs and 6 observational studies with a total of 1,678 patients were included. When considering a composite of ischemic and hemorrhagic events in RCTs, a significant reduction was observed in IS or CAD patients under TEG-guided therapy compared to standard therapy (OR: 0.45, 95% CI: 0.27-0.75, p = 0.002). After pooling RCTs and observational studies together, compared to standard antiplatelet therapy, TEG-guided therapy significantly reduced the risk of a composite of ischemic and hemorrhagic events (OR: 0.26, 95% CI: 0.19-0.37; p < 0.00001), ischemic events (OR: 0.28, 95% CI: 0.19-0.41; p < 0.00001), and bleeding events (OR: 0.31, 95% CI: 0.16-0.62; p = 0.0009) in patients with IS or CAD. CONCLUSION: TEG-guided antiplatelet therapy appears to be both effective and safe for patients with IS or CAD. These findings support the use of TEG testing to tailor antiplatelet therapy in individuals with ischemic cerebrocardiovascular diseases.

Statistical Analysis Plan for the INTEnsive Ambulance-Delivered Blood Pressure Reduction in Hyper-ACute Stroke Trial.

INTRODUCTION: Recruitment is complete in the fourth INTEnsive ambulance-delivered blood pressure Reduction in hyper-ACute stroke Trial (INTERACT4), a multicenter, prospective, randomized, open-label, blinded endpoint assessed trial of prehospital blood pressure (BP) lowering initiated in the ambulance for patients with a suspected acute stroke and elevated BP in China. According to the registered and published trial protocol and developed by the blinded trial Steering Committee and Operations team, this manuscript outlines a detailed statistical analysis plan for the trial prior to database lock. METHODS: Patients were randomized (1:1) to intensive (target systolic BP 130-140 mm Hg within 30 min) or guideline-recommended BP management (BP lowering only considered if systolic BP >220 mm Hg) group. Primary outcome is an ordinal analysis of the full range of scores on the modified Rankin scale at 90 days. A modified sample size of 2,320 was estimated to provide 90% power to detect a 22% reduction in the odds (common odds ratio of 0.78) of a worse functional outcome using ordinal logistic regression, on the assumption of 5% patients with missing outcome and 6% patients with a stroke mimic. CONCLUSION: The statistical analysis plan for the trial has been developed to ensure transparent, verifiable, and prespecified analysis and to avoid potential bias in the evaluation of the trial intervention.

Lower Plasma miR-223 Level Is Associated with Clopidogrel Resistance in Acute Coronary Syndrome: A Systematic Review and Meta-Analysis.

Objectives: To evaluate the relationship between the plasma miR-223 expression level and clopidogrel resistance in acute coronary syndrome (ACS) patients. Methods: We performed a search for publications using online databases including PubMed, EMBASE, Cochrane Library, and Chinese Databases (CNKI database, Weipu database, and Wanfang database) from the inception of the databases to June 18, 2023, to identify studies reporting the relationship between the plasma miR-223 level and clopidogrel resistance in ACS patients. Two researchers independently searched and screened to ensure the consistency of the results and assess the quality of the included studies according to the Newcastle-Ottawa scale. A fixed-effects model was used for pooling data with STATA 14.0. Results: Four articles including 399 Chinese ACS patients were eligible for the meta-analysis. Low plasma miR-223 levels were independently correlated with clopidogrel resistance in Chinese ACS patients (OR 0.58, 95% CI: 0.33-1.04). Conclusion: Lower plasma miR-223 levels are associated with clopidogrel resistance in Chinese ACS patients, suggesting that miR-223 may be a potential diagnostic biomarker of clopidogrel resistance.

Influence of tirofiban on stroke outcome after mechanical thrombectomy in acute vertebrobasilar artery occlusion.

BACKGROUND: Even undergoing mechanical thrombectomy (MT), patients with acute vertebrobasilar artery occlusion (AVBAO) still have a high rate of mortality. Tirofiban is a novel antiplatelet agent which is now widely empirically used in acute ischemic stroke (AIS). In this study, we aimed to evaluate the safety and efficacy of tirofiban as adjunctive therapy for MT in AVBAO. METHODS: From October 2016 to July 2021, consecutive AVBAO patients receiving MT were included in the prospective stroke registry. The short-term outcomes were (1) symptomatic intracerebral hemorrhage (sICH); (2) in-hospital death; (3) National Institute of Health Stroke Scale (NIHSS) at discharge. The Long-term outcomes were: (1) modified Rankin Scale (mRS) at 3 months; (2) death at 3 months. RESULTS: A total of 130 eligible patients were included in the study, 64 (49.2%) patients received tirofiban. In multivariate regression analysis, no significant differences were observed in all outcomes between the tirofiban and non-tirofiban group [sICH (adjusted OR 0.96; 95% CI, 0.12-7.82, p = 0.97), in-hospital death (adjusted OR 0.57; 95% CI, 0.17-1.89, p = 0.36), NIHSS at discharge (95% CI, -2.14-8.63, p = 0.24), mRS (adjusted OR 1.20; 95% CI, 0.40-3.62, p = 0.75), and death at 3 months (adjusted OR 0.83; 95% CI, 0.24-2.90, p = 0.77)]. CONCLUSIONS: In AVBAO, tirofiban adjunctive to MT was not associated with an increased risk of sICH. Short-term (in-hospital death, NIHSS at discharge) and long-term outcomes (mRS and death at 3 months) seem not to be influenced by tirofiban use.

Safety and efficacy of edaravone combined with alteplase for patients with acute ischemic stroke: A systematic review and meta-analysis.

Early administration of edaravone for acute ischemic stroke patients (AIS) receiving intravenous thrombolysis (IVT) has a potential neuroprotective effect. This study aimed to estimate the safety and efficacy of edaravone for AIS patients receiving IVT. We searched PubMed, Embase, Cochrane Library and Chinese Databases (CNKI database, Weipu database, and Wanfang database) for randomized controlled trials (RCT) from the inception of the database to 20 July 2020. Efficacy outcome was reduced National Institutes of Health Stroke Scale (NIHSS) score before and after treatment. Safety outcomes were intracranial hemorrhage (ICH) and mortality. Review Manager 5.3 and Stata 14.0 was used to perform the meta-analysis. A total of 1877 AIS patients from 17 studies were included, 939 (50.03%) patients received edaravone combined with alteplase treatment. Compared with alteplase alone, combined treatment reduced the NIHSS score (MD=3.95,95% CI 2.92-4.99, I² = 92%) and ICH (OR=0.44,95% CI 0.29-0.66, I² =0%) during hospitalization. There was no significant association between combined treatment and mortality during follow-up (OR=0.43,95% CI 0.13-1.42, I² =0%). Conclusions: Edaravone combined with alteplase seems to be safe and effective for AIS patients' short term outcomes.

Stroke Care in the First Affiliated Hospital of Chengdu Medical College during the COVID-19 Outbreak.

Coronavirus disease-2019 (COVID-19) has become a pandemic disease globally. The First Affiliated Hospital of Chengdu Medical College has adopted telestroke to make stroke care accessible in remote areas. During the period January 2020 to March 2020, there was no COVID-19 case reported in our stroke center. A significant reduction of stroke admission was observed between the ischemic stroke group (235 vs. 588 cases) and the intracerebral hemorrhage group (136 vs. 150 cases) when compared with the same period last year (p < 0.001). The mean door-to-needle time (DNT) and door-to-puncture time (DPT) was 62 and 124 min, respectively. Compared to the same period last year, a significant change was observed in DNT (62 ± 12 vs. 47 ± 8 min, p = 0.019) but not in DPT (124 ± 58 vs. 135 ± 23 min, p = 0.682). A total of 46 telestroke consultations were received from network hospitals. Telestroke management in the central hospital was performed on 17 patients. Of them, 3 (17.6%) patients had brain hernia and died in hospital and 8 (47.1%) patients were able to ambulation at discharge and had a modified Rankin Scale of 0-2 at 3 months. The COVID-19 pandemic impacted stroke care significantly in our hospital, including prehospital and in-hospital settings, resulting in a significant drop in acute ischemic stroke admissions and a delay in DNT. The construction of a telestroke network enabled us to extend health-care resources and make stroke care accessible in remote areas. Stroke education and public awareness should be reinforced during the COVID-19 pandemic.

The impact of mindfulness on nurses' perceived professional benefits: the mediating roles of workplace spirituality and work-life balance.

This study delves into the effects of mindfulness on workplace spirituality, work-life balance, and perceived professional benefits among nurses operating in the high-pressure environments of hospitals in Jiangxi Province, China. Utilizing a robust sample of 303 valid questionnaires and employing partial least squares (PLS) analysis, the research uncovers a significant positive relationship between mindfulness and workplace spirituality. Furthermore, it demonstrates how both workplace spirituality and work-life balance serve as crucial mediators in enhancing nurses' perception of their professional benefits. The findings illuminate the potential of mindfulness training in substantially elevating job satisfaction and reducing burnout among nurses. The study not only reinforces the value of mindfulness in the healthcare sector but also advocates for its integration into professional development programs and healthcare policies. By doing so, it aims to bolster the overall wellbeing and professional effectiveness of nurses facing the myriad challenges inherent in demanding healthcare environments. This study contributes to the growing discourse on mindfulness in occupational settings, highlighting its pivotal role in enhancing both the personal wellbeing and professional capabilities of healthcare professionals.

METTL3-mediated methylation of CYP2C19 mRNA may aggravate clopidogrel resistance in ischemic stroke patients.

Background: N6-methyladenosine (m6A) is the most frequently occurring interior modification in eukaryotic messenger RNA (mRNA), and abnormal mRNA modifications can affect many biological processes. However, m6A's effect on the metabolism of antiplatelet drugs for the prevention of ischemic stroke (IS) remains largely unclear. Methods: We analyzed the m6A enzymes and m6A methylation in peripheral blood samples of IS patients with/without clopidogrel resistance (CR), and the peripheral blood and liver of rat models with/without CR. We also compared the effect of m6A methylation on the expression of the drug-metabolizing enzymes (CYP2C19 and CYP2C6v1) in CR and non-CR samples. Results: Methyltransferase-like 3 (METTL3), an m6A enzyme, was highly expressed in the peripheral blood of patients with CR, and in both the peripheral blood and liver of rats with CR. This enzyme targets CYP2C19 or CYP2C6v1 mRNA through m6A methylation, resulting in low expression of CYP2C19 or CYP2C6v1 mRNA. Consequently, this leads to decreased clopidogrel metabolism and CR. Conclusion: The METTL3-mediated methylation of CYP2C19 mRNA may aggravate CR in IS patients.

Prior statin use in acute ischemic stroke patients with mechanical thrombectomy: A prospective cohort study in China.

BACKGROUND AND PURPOSE: Mechanical thrombectomy (MT) has been proven to be effective for selected patients with acute ischemic stroke (AIS). However, conflicting findings have suggested the association between prior statin use and outcomes in AIS patients with MT, with a particular lack of information in the Chinese population. Via a prospective cohort study, we explored the safety and efficacy of prior statin use in Chinese AIS patients with MT. METHODS: We consecutively enrolled AIS patients treated with MT from the First Affiliated Hospital of Chengdu Medical College and Nanjing First Hospital between June 2015 and June 2022 who were under prior statin use or not. Safety and efficacy outcomes were prospectively followed. The primary outcomes were defined as 90-day favorable outcomes (mRS score 0-2). Secondary outcomes included successful recanalization (TICI≥2b), early neurological improvement (decrease of National Institutes of Health Stroke Scale (NIHSS) score ≥ 4 points at 24 h), symptomatic intracerebral hemorrhage (sICH), and death at 90 days. RESULTS: We enrolled 334 patients in total, 50 of whom (15.0%) undertaken statins administration before AIS. 117 (35.0%) patients had favorable outcomes at 90 days, 288 (86.2%) patients had successful recanalization, 108 (32.3%) patients achieved early neurological improvement, 41 (12.3%) patients had sICH and 73 (21.9%) patients died within 90 days. The 90-day favorable outcomes were not significantly different (adjusted OR=0.853, 95% CI 0.449-1.620, P = 0.626) between prior statins use group and no statins use group. There was no significant difference in recanalization (adjusted OR=1.466, 95% CI 0.536-4.009, P = 0.456), early neurological improvement (adjusted OR=1.568, 95% CI 0.811-3.032, P = 0.181), sICH (adjusted OR=0.850, 95% CI 0.325-2.224, P = 0.741), ICH (adjusted OR=1.029, 95% CI 0.479-2.490, P = 0.942), and 90-day mortality (adjusted OR=0.381, 95% CI 0.091-1.586, P = 0.185) between the two groups. CONCLUSIONS: Prior statin use may be safe for Chinese AIS patients with MT, but its efficacy warrants further research.

Keep Moving to Retain the Healthy Self: The Influence of Physical Exercise in Health Anxiety among Chinese Menopausal Women.

Menopause is a period of high incidence of chronic diseases. Women experience various physical and psychological discomforts during menopause, and hormonal changes exacerbate mood swings in menopausal women and also cause them to begin to experience excessive worry and anxiety about their health problems. This study was a cross-sectional survey investigating the relationship between physical activity and women's health anxiety. Using cluster sampling, a valid sample of 455 females aged 45-50 was collected from 78 communities in five municipal districts in Changsha, China, and AMOS v.23 was adopted to construct a structural equation model to verify the hypotheses. The results indicate that interpersonal competence and emotional intelligence are negatively associated with health anxiety. Furthermore, interpersonal competence and emotional intelligence mediate the relationship between physical exercise and health anxiety, which means that menopausal women with more physical exercise, higher interpersonal competence, and higher emotional intelligence reported lower health anxiety. Finally, to alleviate menopausal women's health anxiety and reduce their risk of chronic diseases, the government, community, and family should create conditions and opportunities for women to participate in group physical activities.

Ticagrelor Resistance in Cardiovascular Disease and Ischemic Stroke.

Ticagrelor, acting as a reversible platelet aggregation inhibitor of P2Y12 receptors (P2Y12R), is regarded as one of the first-line antiplatelet drugs for acute cardiovascular diseases. Though the probability of ticagrelor resistance is much lower than that of clopidogrel, there have been recent reports of ticagrelor resistance. In this review, we summarized the clinical application of ticagrelor and then presented the criteria and current status of ticagrelor resistance. We further discussed the potential mechanisms for ticagrelor resistance in terms of drug absorption, metabolism, and receptor action. In conclusion, the incidences of ticagrelor resistance fluctuated between 0 and 20%, and possible mechanisms mainly arose from its absorption and receptor action. Specifically, a variety of factors, such as the drug form of ticagrelor, gut microecology, and the expression and function of P-glycoprotein (P-gp) and P2Y12R, have been shown to be associated with ticagrelor resistance. The exact mechanisms of ticagrelor resistance warrant further exploration, which may contribute to the diagnosis and treatment of ticagrelor resistance.

Platelet transfusion for spontaneous intracerebral hemorrhage with prior antiplatelet: A systematic review and meta-analysis.

BACKGROUND: Recent studies have highlighted the unfavorable prognosis of patients with spontaneous intracerebral hemorrhage (ICH) who have received prior antiplatelet therapy (PAP). Platelet infusion therapy (PIT) is commonly administered to such patients at many medical institutions, but its efficacy remains a subject of debate. METHODS: To address this uncertainty, we conducted a comprehensive search of PubMed, EMBASE, and Cochrane Library databases for eligible studies published before June 30, 2023. Our primary outcomes of interest were favorable functional outcome and mortality, while secondary outcomes included the incidence of hematoma expansion and adverse events associated with PIT. Meta-analysis was performed using Review Manager 5.3. RESULTS: Our analysis included 1 randomized controlled trial (RCT) and 6 retrospective studies, involving a total of 577 patients. Pooled analysis revealed that PIT did not contribute to a better favorable functional outcome at the 3-month follow-up (OR = 0.49, 95% CI 0.27-0.89) among ICH patients with PAP. Furthermore, PIT did not significantly reduce the risk of mortality (OR = 0.79, 95% CI 0.40-1.55) or hematoma expansion (OR = 1.15, 95% CI 0.65-2.01). Notably, no significant differences in serious adverse events were observed between patients who underwent PIT and those who did not. CONCLUSIONS: Based on the available evidence, there is no indication that PIT can enhance the prognosis of spontaneous ICH patients with prior antiplatelet therapy, although this treatment approach appears to be safe. Therefore, routine recommendation of PIT for ICH patients with prior antiplatelet therapy is not warranted.

Update on the INTEnsive ambulance-delivered blood pressure Reduction in hyper-ACute stroke Trial (INTERACT4): progress and baseline features in 2053 participants.

BACKGROUND AND AIMS: Uncertainty persists over the effects of blood pressure (BP) lowering in acute stroke. The INTEnsive ambulance-delivered blood pressure Reduction in hyper-Acute stroke Trial (INTERACT4) aims to determine efficacy and safety of hyperacute intensive BP lowering in patients with suspected acute stroke. Given concerns over the safety of this treatment in the pre-hospital setting, particularly in relation to patients with intracerebral hemorrhage, we provide an update on progress of the study and profile of participants to date. METHODS: INTERACT4 is an ongoing multicentre, ambulance-delivered, randomized, open-label, blinded endpoint trial of pre-hospital BP lowering in patients with suspected acute stroke and elevated BP in China. Patients are randomized via a mobile phone digital system to intensive (target systolic BP [SBP] <140mmHg within 30 min) or guideline-recommended BP management. Primary outcome is an ordinal analysis of the full range of scores on the modified Rankin scale scores at 90 days. RESULTS: Between March 2020 and April 2023, 2053 patients (mean age 70 years, female 39%) were recruited with a mean BP 178/98 mmHg in whom 45% have a diagnosis of primary intracerebral hemorrhage upon arrival at hospital. At the time of presentation to hospital, the mean SBP was 160 and 170mmHg in the intensive and control groups (Δ10 mmHg), respectively. The independent data and safety monitoring board has not identified any safety concerns and recommended continuation of the trial. The sample size was reduced from 3116 to 2320 after meetings in August 2022 as the stroke mimic rate was persistently lower than initially estimated (6% vs 30%). The study is expected to be completed in late 2023 and the results announced in May 2024. CONCLUSIONS: INTERACT4 is on track to provide reliable evidence of the effectiveness of ambulance-delivered intensive BP lowering in patients with suspected acute stroke. TRIAL REGISTRATION: ClinicalTrials.gov NCT03790800 ; registered on 2 January 2019. Chinese Trial Registry ChCTR1900020534 , registered on 7 January 2019.

The Mechanism and Role of N6-Methyladenosine (m6A) Modification in Atherosclerosis and Atherosclerotic Diseases.

N6-methyladenosine (m6A) modification is a newly discovered regulatory mechanism in eukaryotes. As one of the most common epigenetic mechanisms, m6A's role in the development of atherosclerosis (AS) and atherosclerotic diseases (AD) has also received increasing attention. Herein, we elucidate the effect of m6A on major risk factors for AS, including lipid metabolism disorders, hypertension, and hyperglycemia. We also describe how m6A methylation contributes to endothelial cell injury, macrophage response, inflammation, and smooth muscle cell response in AS and AD. Subsequently, we illustrate the m6A-mediated aberrant biological role in the pathogenesis of AS and AD, and analyze the levels of m6A methylation in peripheral blood or local tissues of AS and AD, which helps to further discuss the diagnostic and therapeutic potential of m6A regulation for AS and AD. In summary, studies on m6A methylation provide new insights into the pathophysiologic mechanisms of AS and AD, and m6A methylation could be a novel diagnostic biomarker and therapeutic target for AS and AD.

Excessive Supraventricular Ectopic Activity and the Risk of Atrial Fibrillation and Stroke: A Systematic Review and Meta-Analysis.

BACKGROUND: Excessive supraventricular ectopic activity (ESVEA) is correlated with the development of atrial fibrillation (AF) and is frequently observed in ischemic stroke patients. This meta-analysis aims to summarize the evidence on the association between ESVEA and the risk of AF and stroke. METHODS: PubMed and Embase databases were systematically searched to identify all publications providing relevant data from inception to 23 August 2022. Hazard ratio (HR) and 95% confidence interval (CI) were pooled using fixed-effect or random-effect models. RESULTS: We included 23,272 participants from 20 studies. Pooled results showed that ESVEA was associated with an increased risk of AF in the general population (HR: 2.57; 95% CI 2.16-3.05), increased risk of AF in ischemic stroke patients (HR: 2.91; 95% CI 1.80-4.69), new-onset ischemic stroke (HR: 1.91; 95% CI 1.30-2.79), and all-cause mortality (HR: 1.41; 95% CI 1.24-1.59). Pooled analysis indicated that ESVEA was not associated with recurrent ischemic stroke/transient ischemic attack (TIA) (HR: 1.24; 95% CI 0.91-1.67). CONCLUSIONS: ESVEA is associated with AF, new-onset ischemic stroke, and all-cause mortality.