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Ning Li,1 Jia Zhang,1,2 Si-Jia Li,1 Yang Du,1,2 Qi Zhou,2 Hong-Qiu Gu,2 Xing-Quan Zhao1– 3 1Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2China National Clinical Research Center for Neurological Diseases, Beijing, People’s Republic of China; 3Research Unit of Artificial Intelligence in Cerebrovascular Disease, Chinese Academy of Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Xing-Quan Zhao, Beijing Tiantan Hospital, Capital Medical University, No. 119 South 4th Ring West Road, Fengtai District, Beijing, 100070, People’s Republic of China, Tel +86-13501031486, Email zxq@vip.163.comBackground: The presence of mild deficit is the most common reason for nonuse of intravenous alteplase in ischemic stroke. We analyzed within a national prospective cohort on whether patients with minor stroke can benefit from intravenous alteplase.Methods: This observational study included patients with acute ischemic stroke with a National Institutes of Health Stroke Scale (NIHSS) score 0 to 5 at admission. The short-term outcomes at discharge and 3-month were analyzed including the modified Rankin Scale score, gait speed, Montreal Cognitive Assessment, Patient Health Questionnaire-9, General Anxiety Disorder-7 and Stroke Impact Scale-16. Multivariate regression models were performed to evaluate the association between intravenous thrombolysis and clinical outcomes.Results: A total of 1876 consecutive patients were included in the current analyses with 102 patients (5.4%) received alteplase and 1774 patients (94.5%) were in non-alteplase group. We found that 10.9% patients presented unfavorable functional outcome with a mRS ≥ 2 at 3-month. Patients with alteplase treatment had a more favorable outcome in SIS-16 at discharge (OR, 5.45; 95% CI, 2.22– 8.68) and 3-month after stroke (OR, 2.34; 95% CI, 0.17– 4.50). There was an association of alteplase with better gait speed in the restricted sample of age > 60 (OR,0.14; 95% CI, 0.02– 0.25), while an unfavorable effect was found in anxiety (OR, 2.23; 95% CI, 2.23, 0.91– 3.55) and depression (OR, 1.54; 95% CI, 0.17– 2.91) in female.Conclusion: Alteplase showed a suggestive benefit in function and motor outcomes in patients with low NIHSS score of 0– 5. Meanwhile, female seemed more inclined to post-stroke emotional problems after alteplase treatment, which should be further explored in the future.Keywords: alteplase, minor stroke, ischemic, outcomes

Background: Recombinant prourokinase (rhPro-UK) is a specific plasmin activator, which has been approved to treat acute myocardial infarction in China., Aim: This phase 3 trial aimed to further demonstrate the efficacy and safety of rhPro-UK in patients with acute ischemic stroke (AIS) within 4.5 h of symptom onset., Methods and Design: RhPro-UK in AIS within 4.5 h of stroke onset trial-2 (PROST-2) is a multicenter, prospective randomized, open-label, blinded end-point, non-inferiority, recombinant tissue plasmin activator (rt-PA)-controlled, phase 3 trial. A total of 1552 patients who are eligible for intravenous thrombolytic therapy from 72 clinical sites will be randomly assigned to receive either rhPro-UK 35 mg (15 mg bolus + 20 mg infusion/30 min) or rt-PA 0.9 mg/kg (10% bolus + 90% infusion/1 h)., Study Outcomes: The primary outcome is the proportion of patients with a modified Rankin Scale (mRS) score of 0-1 at 90 days. Secondary efficacy outcomes include the proportion of patients with mRS score of 0-2, the distribution of mRS, self-care ability in daily life on the Barthel Index at 90 days, the proportion of subjects with ⩾ 4 points decrease in National Institutes of Health Stroke Scale (NIHSS) score or NIHSS score ⩽ 1 from baseline at 24 h and 7 days after treatment. Safety outcomes are symptomatic intracranial hemorrhage (sICH) and major systematic bleeding within 7 days as well as death from all causes within 90 days., Discussion: The results from the PROST-2 trial will comprehensively elucidate the efficacy and safety profile of rhPro-UK as a potential alternative agent for stroke thrombolysis., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT05700591., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Alteplase is the standard agent used in early reperfusion therapy, but alternative thrombolytic agents are needed. The efficacy and safety of reteplase as compared with alteplase in patients with acute ischemic stroke are unclear., Methods: We randomly assigned patients with ischemic stroke within 4.5 hours after symptom onset in a 1:1 ratio to receive intravenous reteplase (a bolus of 18 mg followed 30 minutes later by a second bolus of 18 mg) or intravenous alteplase (0.9 mg per kilogram of body weight; maximum dose, 90 mg). The primary efficacy outcome was an excellent functional outcome, defined as a score of 0 or 1 on the modified Rankin scale (range, 0 [no neurologic deficit, no symptoms, or completely recovered] to 6 [death]) at 90 days. The primary safety outcome was symptomatic intracranial hemorrhage within 36 hours after symptom onset., Results: A total of 707 patients were assigned to receive reteplase, and 705 were assigned to receive alteplase. An excellent functional outcome occurred in 79.5% of the patients in the reteplase group and in 70.4% of those in the alteplase group (risk ratio, 1.13; 95% confidence interval [CI], 1.05 to 1.21; P<0.001 for noninferiority and P = 0.002 for superiority). Symptomatic intracranial hemorrhage within 36 hours after disease onset was observed in 17 of 700 patients (2.4%) in the reteplase group and in 14 of 699 (2.0%) of those in the alteplase group (risk ratio, 1.21; 95% CI, 0.54 to 2.75). The incidence of any intracranial hemorrhage at 90 days was higher with reteplase than with alteplase (7.7% vs. 4.9%; risk ratio, 1.59; 95% CI, 1.00 to 2.51), as was the incidence of adverse events (91.6% vs. 82.4%; risk ratio, 1.11; 95% CI, 1.03 to 1.20)., Conclusions: Among patients with ischemic stroke within 4.5 hours after symptom onset, reteplase was more likely to result in an excellent functional outcome than alteplase. (Funded by China Resources Angde Biotech Pharma and others; RAISE ClinicalTrials.gov number, NCT05295173.)., (Copyright © 2024 Massachusetts Medical Society.)

Objectives: To assess the efficacy and safety of colchicine versus placebo on reducing the risk of subsequent stroke after high risk non-cardioembolic ischaemic stroke or transient ischaemic attack within the first three months of symptom onset (CHANCE-3)., Design: Multicentre, double blind, randomised, placebo controlled trial., Setting: 244 hospitals in China between 11 August 2022 and 13 April 2023., Participants: 8343 patients aged 40 years of age or older with a minor-to-moderate ischaemic stroke or transient ischaemic attack and a high sensitivity C-reactive protein ≥2 mg/L were enrolled., Interventions: Patients were randomly assigned 1:1 within 24 h of symptom onset to receive colchicine (0.5 mg twice daily on days 1-3, followed by 0.5 mg daily thereafter) or placebo for 90 days., Main Outcome Measures: The primary efficacy outcome was any new stroke within 90 days after randomisation. The primary safety outcome was any serious adverse event during the treatment period. All efficacy and safety analyses were by intention to treat., Results: 4176 patients were assigned to the colchicine group and 4167 were assigned to the placebo group. Stroke occurred within 90 days in 264 patients (6.3%) in the colchicine group and 270 patients (6.5%) in the placebo group (hazard ratio 0.98 (95% confidence interval 0.83 to 1.16); P=0.79). Any serious adverse event was observed in 91 (2.2%) patients in the colchicine group and 88 (2.1%) in the placebo group (P=0.83)., Conclusions: The study did not provide evidence that low-dose colchicine could reduce the risk of subsequent stroke within 90 days as compared with placebo among patients with acute non-cardioembolic minor-to-moderate ischaemic stroke or transient ischaemic attack and a high sensitivity C-reactive protein ≥2 mg/L., Trial Registration: ClinicalTrials.gov, NCT05439356., Competing Interests: Declaration of interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: support from National Key R&D Program of China, the National Natural Science Foundation of China, the Capital's Funds for Health Improvement and Research, and Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: Multiple factors play important roles in the occurrence and prognosis of stroke. However, the roles of monogenic variants in all-cause ischaemic stroke have not been systematically investigated. We aim to identify underdiagnosed monogenic stroke in an adult ischaemic stroke/transient ischaemic attack (TIA) cohort (the Third China National Stroke Registry, CNSR-III)., Methods: Targeted next-generation sequencing for 181 genes associated with stroke was conducted on DNA samples from 10 428 patients recruited through CNSR-III. The genetic and clinical data from electronic health records (EHRs) were reviewed for completion of the diagnostic process. We assessed the percentages of individuals with pathogenic or likely pathogenic (P/LP) variants, and the diagnostic yield of pathogenic variants in known monogenic disease genes with associated phenotypes., Results: In total, 1953 individuals harboured at least one P/LP variant out of 10 428 patients. Then, 792 (7.6%) individuals (comprising 759 individuals harbouring one P/LP variant in one gene, 29 individuals harbouring two or more P/LP variants in different genes and 4 individuals with two P/LP variants in ABCC6 ) were predicted to be at risk for one or more monogenic diseases based on the inheritance pattern. Finally, 230 of 792 individuals manifested a clinical phenotype in the EHR data to support the diagnosis of stroke with a monogenic cause. The most diagnosed Mendelian cause of stroke in the cohort was cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. There were no relationships between age or family history and the incidence of first symptomatic monogenic stroke in patients., Conclusion: The rate of monogenic cause of stroke was 2.2% after reviewing the clinical phenotype. Possible reasons that Mendelian causes of stroke may be missed in adult patients who had an ischaemic stroke/TIA include a late onset of stroke symptoms, combination with common vascular risks and the absence of a prominent family history., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The present study aimed to develop a model to predict functional disability at 3 months in patients with acute ischemic stroke (AIS) ( n = 5,406). The primary outcome was functional disability (modified Rankin Scale [mRS] >2) at 3 months. A prediction model including blood biomarkers was developed based on a multivariable logistic regression model, which was internally validated by the 100-time bootstrap method. A nomogram and a web-based calculator were developed for usage in clinical practice. At 3 months, 11% (638/5,406) of the patients had functional disability. Seven independent predictors of functional disability at 3 months were incorporated into the FAITHS 2 model (fasting plasma glucose, age, interleukin-6, stroke history, National Institute of Health Stroke Scale [NIHSS] at admission, sex, and systolic blood pressure). The Area Under Curves (AUCs) were 0.814 (95% confidence interval [CI] 0.796-0.832) and 0.808 (95% CI 0.806-0.810), and the Brier scores were 0.088 ± 0.214 and 0.089 ± 0.003 for the derivation cohort and internal validation, respectively, showing optimal performance of the model. The FAITHS 2 model has excellent potential to be a dependable application for individualized clinical decision making., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The modified Rankin Scale change score (ΔmRS) is useful for evaluating acute poststroke functional improvement or deterioration. We investigated the relationship between multiple biomarkers and ΔmRS by analyzing data on 6931 patients with acute ischemic stroke (average age 62.3 ± 11.3 years, 2174 (31.4%) female) enrolled from the Third China National Stroke Registry (CNSR-III) and 15 available biomarkers. Worse outcomes at 3 months were defined as ΔmRS 3m-discharge ≥1 (ΔmRS 3m-discharge  = mRS 3m -mRS discharge ). Adjusted odds ratios (aORs) and their 95% confidence intervals (CIs) were calculated from logistic regression models. At 3-months poststroke, 1026 (14.8%) patients experienced worse outcomes. The highest quartiles of white blood cells (WBCs) (aOR [95%CI],1.37 [1.12-1.66]), high-sensitivity C-reactive protein (hs-CRP) (1.37 [1.12-1.67]), interleukin-6 (IL-6) (1.43 [1.16-1.76]), interleukin-1 receptor antagonist (IL-1Ra) (1.46 [1.20-1.78]) and YKL-40 (1.31 [1.06-1.63]) were associated with an increased risk of worse outcomes at 3 months. Results remained stable except for YKL-40 when simultaneously adding multiple biomarkers to the basic traditional-risk-factor model. Similar results were observed at 6 and 12 months after stroke. This study indicated that WBCs, hs-CRP, IL-6, IL-1Ra, and YKL-40 were significantly associated with worse outcomes in acute ischemic stroke patients, and all inflammatory biomarkers except YKL-40 were independent predictors of worse outcomes at 3 months., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Edaravone dexborneol is believed to be a novel cytoprotective drug, demonstrating a synergistic combination of antioxidative and anti-inflammatory properties in animal models. The Treatment of Acute Ischaemic Stroke with Edaravone Dexborneol (TASTE) trial demonstrated its superior efficacy over edaravone alone for acute ischaemic stroke (AIS) patients. However, its efficacy in individuals undergoing endovascular therapy (EVT) remains uncertain., Aim: To clarify the rationale and design of the TASTE II (TASTE-2) trial., Design: The TASTE-2 is a multicentre, double-blind, randomised, placebo-controlled trial designed to evaluate the efficacy and safety of edaravone dexborneol in patients with AIS and large-vessel occlusion in the anterior circulation. The eligible participants, presenting with a National Institute of Health Stroke Scale score between 6 and 25 (range 0-42, with larger values suggesting severe neurological dysfunction) and an Alberta Stroke Program Early Computed Tomography Score ranging from 6 to 10 (range 0-10, with smaller values suggesting larger infarction) within the initial 24 hours after symptom onset, will be randomly allocated to either the edaravone dexborneol group or the placebo group in equal proportions prior to thrombectomy. The treatment will be continuously administered for a duration of 10-14 days. A follow-up period of 90 days will be implemented for all participants., Study Outcomes: The primary efficacy outcome is defined as achieving favourable functional independence, measured by a modified Rankin Scale of 0-2 at 90 days. The primary safety outcome focuses on the incidence of serious adverse events., Discussion: The TASTE-2 trial will provide evidence to determine whether the administration of edaravone dexborneol in AIS patients undergoing EVT could yield significant improvements in neurological function., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: The aim of the study was to analyze the association between inflammatory marker profiles and in-hospital neurological deterioration (ND) in acute ischemic stroke (AIS) patients., Methods: Data from patients with minor AIS from the Third China National Stroke Registry were analyzed. Inflammatory cytokine levels within 24 h of admission were measured. The primary outcome was in-hospital ND (an increase in National Institutes of Health Stroke Scale score ≥4 from admission to discharge). Associations were evaluated using odds ratios (ORs) and 95% confidence intervals (CIs) derived from logistic regression models. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were used to evaluate incremental predictive values., Results: A total of 4031 patients (1246 women, 30.9%) with a median age of 62 years were included. In-hospital ND occurred in 121 patients (3%). Each standard-deviation increase in interleukin (IL)-6 (OR, 1.17 [95% CI, 1.06-1.31]) and high-sensitivity C-reactive protein (hsCRP) (OR, 1.43 [95% CI, 1.24-1.66]) levels was associated with increased in-hospital ND risk. Incremental predictive values for adding IL-6 (IDI, 0.012; NRI, 0.329) but not hsCRP levels to the conventional risk factors were found., Conclusion: In minor AIS, hsCRP and IL-6 levels were associated with in-hospital ND, including IL-6 levels in prognostic models improved risk classification., (© 2024 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Background: Given the swift advancements in artificial intelligence (AI), the utilisation of AI-based clinical decision support systems (AI-CDSSs) has become increasingly prevalent in the medical domain, particularly in the management of cerebrovascular disease., Aims: To describe the design, rationale and methods of a cluster-randomised multifaceted intervention trial aimed at investigating the effect of cerebrovascular disease AI-CDSS on the clinical outcomes of patients who had a stroke and on stroke care quality., Design: The GOLDEN BRIDGE II trial is a multicentre, open-label, cluster-randomised multifaceted intervention study. A total of 80 hospitals in China were randomly assigned to the AI-CDSS intervention group or the control group. For eligible participants with acute ischaemic stroke in the AI-CDSS intervention group, cerebrovascular disease AI-CDSS will provide AI-assisted imaging analysis, auxiliary stroke aetiology and pathogenesis analysis, and guideline-based treatment recommendations. In the control group, patients will receive the usual care. The primary outcome is the occurrence of new vascular events (composite of ischaemic stroke, haemorrhagic stroke, myocardial infarction or vascular death) at 3 months after stroke onset. The sample size was estimated to be 21 689 with a 26% relative reduction in the incidence of new composite vascular events at 3 months by using multiple quality-improving interventions provided by AI-CDSS. All analyses will be performed according to the intention-to-treat principle and accounted for clustering using generalised estimating equations., Conclusions: Once the effectiveness is verified, the cerebrovascular disease AI-CDSS could improve stroke care and outcomes in China., Trial Registration Number: NCT04524624., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The performance of intravenous tenecteplase in patients who had an acute ischaemic stroke with large/medium vessel occlusion or severe stenosis in an extended time window remains unknown. We investigated the promise of efficacy and safety of different doses of tenecteplase manufactured in China, in patients who had an acute ischaemic stroke with large/medium vessel occlusion beyond 4.5-hour time window., Methods: The CHinese Acute tissue-Based imaging selection for Lysis In Stroke-Tenecteplase was an investigator-initiated, umbrella phase IIa, open-label, blinded-endpoint, Simon's two-stage randomised clinical trial in 13 centres across mainland China. Participants who had salvageable brain tissue on automated perfusion imaging and presented within 4.5-24 hours from time of last seen well were randomised to receive 0.25 mg/kg tenecteplase or 0.32 mg/kg tenecteplase, both with a bolus infusion over 5-10 s. The primary outcome was proportion of patients with promise of efficacy and safety defined as reaching major reperfusion without symptomatic intracranial haemorrhage at 24-48 hours after thrombolysis. Assessors were blinded to treatment allocation. All participants who received tenecteplase were included in the analysis., Results: A total of 86 patients who had an acute ischaemic stroke identified with anterior large/medium vessel occlusion or severe stenosis were included in this study from November 2019 to December 2021. All of the 86 patients enrolled either received 0.25 mg/kg (n=43) or 0.32 mg/kg (n=43) tenecteplase, and were available for primary outcome analysis. Fourteen out of 43 patients in the 0.25 mg/kg tenecteplase group and 10 out of 43 patients in the 0.32 mg/kg tenecteplase group reached the primary outcome, providing promise of efficacy and safety for both doses based on Simon's two-stage design., Discussion: Among patients with anterior large/medium vessel occlusion and significant penumbral mismatch presented within 4.5-24 hours from time of last seen well, tenecteplase 0.25 mg/kg and 0.32 mg/kg both provided sufficient promise of efficacy and safety., Trial Registration Number: ClinicalTrials.gov Registry (NCT04086147, https://clinicaltrials.gov/ct2/show/NCT04086147)., Competing Interests: Competing interests: XC reported grant support from the National Natural Science Foundation of China and Science and Technology Commission of Shanghai Municipality. YS reported honoraria from Boehringer Ingelheim (China) Investment Co. The other authors report no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: Reteplase is the third generation of alternative thrombolytic agent. We hypothesis that reteplase will be non-inferior to alteplase in achieving excellent functional outcome at 90 days among eligible patients with acute ischaemic stroke., Methods and Design: Reteplase versus alteplase for acute ischaemic stroke within 4.5 hours (RAISE) trial is a multicentre, prospective, randomised, open-label, blinded endpoint (PROBE), controlled phase 3 non-inferiority trial. A total of 1412 eligible patients will be randomly assigned to receive either reteplase at a dose of 18 mg+ 18 mg or alteplase 0.9 mg/kg at a ratio of 1:1. An independent data monitoring committee will review the trail's progress and safety data., Study Outcomes: The primary efficacy outcome of this study is proportion of individuals attaining an excellent functional outcome, defined as modified Rankin Scale (mRS) 0-1 at 90 days. The secondary efficacy outcomes encompass favourable functional outcome defined as mRS 0-2, major neurological improvement on the National Institutes of Health Stroke Scale, ordinal distribution of mRS and Barthel Index score of at least 95 points at 90 days. The primary safety outcomes are symptomatic intracranial haemorrhage at 36 hours within 90 days., Discussion: The RAISE trial will provide crucial insights into the selection of thrombolytic agents for stroke thrombolysis., Trial Registration Number: NCT05295173., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: This study aimed to investigate factors associated with undergoing dysphagia screening (DS) and developing pneumonia, as well as the relationship between DS and pneumonia in patients with intracerebral haemorrhage (ICH)., Design: Our study was a cross-sectional hospital-based retrospective study., Study Design and Settings: We derived data from the China Stroke Centre Alliance, a nationwide clinical registry of ICH from 1476 participating hospitals in mainland China. To identify predictors for pneumonia, multivariable logistic regression models were used to identify patient characteristics that were independently associated with DS and pneumonia., Participants: We included 31 546 patients in this study with patient characteristics, admission location, medical history, hospital characteristics and hospital grade from August 2015 to July 2019., Primary and Secondary Outcome Measures: The primary outcomes were DS and pneumonia during acute hospitalisation., Results: In total, 25 749 (81.6%) and 7257 (23.0%) patients with ICH underwent DS and developed pneumonia. Compared with patients without pneumonia, those who developed pneumonia were older and had severe strokes (Glasgow Coma Scale 9-13: 52.7% vs 26.9%). Multivariable analyses revealed that a higher pneumonia risk was associated with dysphagia (OR, 4.34; 95% CI, 4.02 to 4.68), heart failure (OR, 1.85; 95% CI, 1.24 to 2.77) and smoking (OR, 1.12; 95% CI, 1.12 to 0.20). DS was associated with lower odds of pneumonia (OR, 0.65; 95% CI, 0.44 to 0.95)., Conclusion: Our findings further confirm that dysphagia is an independent risk factor for pneumonia; one-fifth of patients with ICH did not undergo DS. However, comprehensive dysphagia evaluation and effective management are crucial. Nursing processes ensure the collection of complete and accurate information during evaluation of patients. There is a need to increase the rate of DS in patients with ICH, especially those with severe stroke or older. Further, randomised controlled trials are warranted to determine the effectiveness of DS on clinical outcomes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: Nonvalvular atrial fibrillation (NVAF) is a risk factor for stroke. This study was undertaken to determine the influence of NVAF on the mortality and recurrent stroke after a minor stroke event., Methods: Data were derived from the Third China National Stroke Registry (CNSR-III) which enrolled 15,166 subjects during August 2015 through March 2018 in China. Patients with minor stroke (NIHSS ≤ 5) within 24 h after onset were included. Clinical outcomes including all-cause mortality, cardiovascular death, recurrent ischemic stroke, and recurrent hemorrhagic stroke were collected. The Cox proportional hazards models were used to determine the association between NVAF and clinical outcomes., Results: A total of 4,753 patients were included in our study. Of them, 222 patients had NVAF (4.7%) (mean age, 71.1 years) and 4,531 patients were without AF (95.3%) (mean age, 61.4 years). NVAF was associated with 12-month cardiovascular mortality in both univariate (hazards ratio [HR], 4.13; 95% confidence interval [CI], 1.84 to 9.31; P < 0.001) and multivariate analyses (HR, 4.66; 95% CI, 1.79 to 12.15; P = 0.001). There was no difference in the in-hospital ischemic stroke recurrence rate between the two groups (HR, 0.45 [95% CI, 0.19 to 1.05] P = 0.07 at discharge). However, patients with NVAF had a lower rate of recurrent ischemic stroke at medium- (3 months and 6 months) and long-term (12 months) follow-up (HR, 0.33 [95% CI, 0.16 to 0.68] P = 0.003 at 3 months; 0.49 [95% CI, 0.27 to 0.89] P = 0.02 at 6 months; 0.55 [95% CI, 0.32 to 0.94] P = 0.03 at 12 months, respectively) compared with those without. There was no difference in all-cause mortality and hemorrhagic stroke between the two groups during follow-up., Conclusions: Minor stroke patients with NVAF were at higher risk of cardiovascular death but had a lower rate of recurrent ischemic stroke compared to those without during the subsequent year after stroke event. A more accurate stroke risk prediction model for NVAF is warranted for optimal patient care strategies., (© 2023. The Author(s).)

Objective: Network pharmacology is a bioinformatics-based research strategy for identifying the mechanisms of drugs and promoting drug development. This study used network pharmacology to investigate the mechanism of the Loulu-Cremastrae Pseudobulbus drug pair treating breast cancer (BC)., Materials and Methods: The ingredients and potential targets of the drug pair were searched with Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCSMP). National Center for Biotechnology Information (NCBI) and gene cards were used to search the targets of BC. Networks of "drugs-components-targets" and protein-protein interaction were constructed through Cytoscape. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were carried out through common targets. Using AutoDock tool, molecular docking was performed to verify the binding between key targets and compounds., Results: Finally, we selected 6 active compounds from the drug pair. A total of 61 targets were associated with the drug pair, and 15,295 targets were related to BC. 55 common targets were obtained after the intersection. The key targets included Transcription factor Jun (JUN), Heat shock protein HSP 90-alpha (HSP90AA1), and Caspase-3(CASP3). 327 terms were obtained by GO analysis. 78 pathways (p < 0.05) were identified through KEGG analysis. Molecular docking indicated that important compounds combined well with key targets., Conclusions: Various active compounds, including beta-sitosterol, 2-methoxy-9,10-dihydrophenanthrene-4,5-diol, and stigmasterol, can regulate multiple signaling pathways related to BC, such as the estrogen and prolactin signaling pathways, playing therapeutic roles in BC.

Aim: Post-stroke inflammation increases the risk of functional disability through enlarged cerebral infarct size directly and follow-up stroke event indirectly. We aimed to use post-stroke proinflammatory cytokine interleukin-6 (IL-6) as a marker of inflammatory burden and quantify post-stroke inflammation's direct and indirect effect on functional disability., Methods: We analyzed patients with acute ischemic stroke admitted to 169 hospitals in the Third China National Stroke Registry. Blood samples were collected within 24 h of admission. Stroke recurrence and functional outcome measured by the modified Rankin scale (mRS) were assessed via face-to-face interviews at 3 months. Functional disability was defined as an mRS score ≥2. Mediation analyses under the counterfactual framework were performed to examine the potential causal chain in which stroke recurrence may mediate the relationship between IL-6 and functional outcome., Results: Among the 7053 analyzed patients, the median (interquartile range [IQR]) NIHSS score was 3 (1-5), and the median (IQR) level of IL-6 was 2.61 (1.60-4.73) pg/mL. Stroke recurrence was observed in 458 (6.5%) patients, and functional disability was seen in 1708 (24.2%) patients at the 90-day follow-up. Per stand deviation (4.26 pg/mL) increase in the concentration of IL-6 was associated with an increased risk of stroke recurrence (adjusted odds ratio [aOR], 1.19; 95% CI, 1.09-1.29) and disability (aOR, 1.22; 95% CI, 1.15-1.30) within 90 days. Mediation analyses revealed that 18.72% (95% CI, 9.26%-28.18%) of the relationship between IL-6 and functional disability was mediated by stroke recurrence., Conclusions: Stroke recurrence mediates less than 20% of the association between IL-6 and functional outcome at 90 days among patients with acute ischemic stroke. In addition to typical secondary prevention strategies for preventing stroke recurrence, more attention should be paid to novel anti-inflammatory therapy to improve functional outcomes directly., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Background: Lack of high-quality national-level data on in-hospital ischaemic stroke hinders the development of tailored strategies for this subgroup's identification, treatment, and management., Methods: We analyzed and compared clinical characteristics, in-hospital management measures, and outcomes, including death or discharge against medical advice (DAMA), major adverse cardiovascular events (MACEs), disability at discharge, and in-hospital complications between in-hospital and community-onset ischaemic stroke enrolled in the Chinese Stroke Center Association registry from August 2015 to December 2022., Findings: The cohort comprised 14,948 in-hospital and 1,366,898 community-onset ischaemic stroke patients. In-hospital ischaemic stroke exhibited greater stroke severity, higher prevalence of comorbidities, more pre-admission medications, and had suboptimal management measures, for example, the onset-to-needle time within 4.5 h (83.3% vs. 93.1%; difference, -9.8% [-11.4% to -8.3%]), and antithrombotics at discharge (78.6% vs. 90.0%; difference, -11.4% [95% CI, -12.1% to -10.7%]). After adjusting for covariates, in-hospital ischaemic stroke remains associated with higher risks of unfavorable outcomes, including in-hospital death/DAMA (13.9% vs. 8.6%; adjusted risk difference [aRD], 2.2% [95% CI, 1.8%-2.7%]; adjusted odds ratio [aOR], 1.35 [95% CI, 1.25-1.45]), MACE (12.6% vs. 6.5%; aRD, 4.1% [95% CI, 3.5%-4.7%]; aOR, 1.68 [95% CI, 1.52-1.85]), and complications (23.7% vs. 12.1%; aRD, 6.5% [95% CI, 5.1%-7.9%]; aOR, 1.72 [95% CI, 1.64-1.80]), except for disability at discharge (41.1% vs. 33.1%; aRD, 0.4% [95% CI, -1.7% to 2.5%]; aOR, 0.99 [95% CI, 0.88-1.11])., Interpretation: In-hospital ischaemic stroke demonstrated more severe strokes, worse vascular risk profiles, suboptimal management measures, and worse outcomes compared to community-onset ischaemic stroke. This emphasizes the urgent need for improved hospital systems of care and targeted quality improvement initiatives for better outcomes in in-hospital ischaemic stroke., Funding: National Key R&D Programme of China and Beijing Hospitals Authority., Competing Interests: All authors declare no competing interests., (© 2023 The Author(s).)

In order to more effectively monitor and interfere with enemy signals, it is particularly important to accurately and efficiently identify the intercepted signals and estimate their parameters in the increasingly complex electromagnetic environment. Therefore, in non-cooperative situations, it is of great practical significance to study how to accurately detect direct sequence spread spectrum (DSSS) signals in real time and estimate their parameters. The traditional time-delay correlation algorithm encounters the challenges such as peak energy leakage and false peak interference. As an alternative, this paper introduces a Pseudo-Noise (PN) code period estimation method utilizing a one-dimensional (1D) convolutional neural network based on the residual network (CNN-ResNet). This method transforms the problem of spread spectrum code period estimation into a multi-classification problem of spread spectrum code length estimation. Firstly, the In-phase/Quadrature(I/Q) two-way of the received DSSS signals is directly input into the CNN-ResNet model, which will automatically learn the characteristics of the DSSS signal with different PN code lengths and then estimate the PN code length. Simulation experiments are conducted using a data set with DSSS signals ranging from -20 to 10 dB in terms of signal-to-noise ratios (SNRs). Upon training and verifying the model using BPSK modulation, it is then put to the test with QPSK-modulated signals, and the estimation performance was analyzed through metrics such as loss function, accuracy rate, recall rate, and confusion matrix. The results demonstrate that the 1D CNN-ResNet proposed in this paper is capable of effectively estimating the PN code period of the non-cooperative DSSS signal, exhibiting robust generalization abilities.

Background: Rehabilitation improves functional recovery in subarachnoid hemorrhage (SAH) patients, and assessing patients for rehabilitation is the first step in this process. However, little is known about clinical practice in China regarding the assessment and provision of rehabilitation for patients with SAH., Methods: To identify patients hospitalized with SAH and to analyze rehabilitation assessment rates, we used data for 11,234 SAH patients admitted to 861 hospitals from the China Stroke Center Alliance from August 2015 to July 2019. We examined factors for rehabilitation assessment and analyzed the relationship between rehabilitation assessment and outcomes in these patients., Results: Among 11,234 patients with SAH, 6,513 (58.0%) were assessed for rehabilitation. Assessed patients had an increased length of stay (mean ± SD days: 17.3 ± 12.5 versus 11.6 ± 10.5, P = 49.4), a higher Glasgow Coma Scale (GCS) score on admission (mean ± SD GCS score: 12.3 ± 3.8 versus 11.8 ± 4.4, P = 12.2), and were more likely to be admitted to the stroke unit (19.6% versus 13.8%, P = 15.6). In multivariable analysis, factors associated with an increased likelihood of a rehabilitation assessment (p < 0.05) included a longer length of stay (odds ratio [OR], 1.04; 95% confidence interval (CI), 1.04 to 1.05) and care such as dysphagia screening (OR, 1.88; 95% CI, 1.73 to 2.04), DVT prophylaxis (OR, 1.56; 95% CI, 1.41 to 1.72) and vessel evaluation (OR, 1.80; 95% CI, 1.63 to 1.98). For the multivariate analysis of outcomes, patients undergoing rehabilitation assessment had a longer length of stay (OR, 1.96; 95% CI, 1.81 to 2.12), a higher modified Rankin Scale (mRS) score at discharge (OR, 1.49; 95% CI, 1.36 to 1.64), and higher rates of discharge to a rehabilitation center (OR, 3.23; 95% CI, 1.81-5.75)., Conclusion: More than two-fifths of SAH patients were not assessed for rehabilitation. Rates vary considerably among hospital grades, and there is a need to improve adherence to recommended care for SAH patients., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Women with stroke differ from men in terms of risk factors, treatment, and outcomes. However, previous inconsistent results in China hampered the development of tailored sex-specific strategies for ischemic stroke management. We performed a nationwide serial cross-sectional survey to obtain national-level estimates to assess the 10-year trends in sex differences in cardiovascular risk factors, in-hospital management, and outcomes in China from 2005 to 2015., Methods: We used a two-stage random sampling design, economic-geographical region-stratified random sampling for hospitals first and then systematic sampling for patients, to obtain a nationally representative sample of ischemic strokes in China in 2005, 2010, and 2015. We extracted data on clinical characteristics, management measures (diagnostic tests, interventions, and secondary prevention treatments), in-hospital outcomes (all-cause in-hospital mortality, discharge against medical advice [DAMA], and a composite outcome of in-hospital death and DAMA), and comorbidities. We applied weights proportional to the inverse sampling fraction of hospitals within each stratum and the inverse sampling fraction of patients within each hospital., Results: A total of 26,900 ischemic stroke admissions were analyzed. Compared to men, women had a much lower prevalence of current smokers and a slightly higher prevalence of hypertension, diabetes, dyslipidemia, and atrial fibrillation at admission. Prevalence differences between sex in these cardiovascular risk factors were stable except for atrial fibrillation (decreased from 3.7% [95% CI: 1.8% to 5.7%] to 1.3% [95% CI: 0.5% to 2.0%]) and current smoker (increased from -18.0 [95% CI: -20.2% to -15.9%] to -25.6% [95% CI: -26.6% to -24.6%]). From 2005 to 2015, in-hospital management and outcomes were improved both for women and men, and sex differences in cerebrovascular assessment, cervical vessels assessment, and transthoracic echocardiography/transesophageal echocardiography were improved as well. However, women increased more slowly than men in the administration of clopidogrel (from 0.3% [95% CI: -0.9% to 1.4%) to -7.3% [95% CI: -8.7% to -6.0%]) and aspirin plus clopidogrel (0.3% [95% CI: -5.0% to 1.1%] to -5.0% [95% CI: -6.2% to -3.9%])., Conclusion: Compared to men, women patients with ischemic stroke had a steadily higher prevalence of cardiovascular risk factors, a slower increase rate in the administration of key secondary prevention drugs, and comparable in-hospital outcomes. More effort should be paid to the treatment and control of cardiovascular risk factors and also to the prescription of antiplatelets at discharge for women.

Aims: Our study aimed to describe the short-, medium-, and long-term outcomes of intravenous thrombolysis in minor stroke, and to explore the relationship between thrombolysis and clinical outcomes., Methods: Our study included ischemic minor stroke patients (National Institutes of Health Stroke Scale score ≤ 5) within 4.5 h from symptom onset from the Third China National Stroke Registry (CNSR-III) between August 2015 and March 2018. The primary outcome was a favorable functional outcome, defined as a modified Rankin Scale (mRS) score of 0-1 at 3 months. The secondary outcomes included mRS score of 0-1 at discharge, 6 months, and 1 year. The safety outcomes were symptomatic intracerebral hemorrhage (sICH) at 24-36 h and all-cause mortality. The association between intravenous thrombolysis and clinical outcomes was studied using multivariable models., Results: A total of 1905 minor ischemic stroke patients were included. Overall 527 patients (28%) received intravenous t-PA (IV t-PA) and 1378 patients (72%) in the non-IV t-PA group. Of them, 18.85% (359/1905) participants had a disabled outcome (defined as mRS score ≥ 2) at discharge, 12.8% (242/1885) at 3 months, 13.9% (262/1886) at 6 months, and 13.9% (260/1871) at 1 year. In multivariable analysis, IV t-PA was associated with favorable functional outcomes at discharge (adjusted odds ratio [aOR] 1.49; 95% confidence interval [CI] 1.13-1.96; p = 0.004), 3 months (aOR 1.51; 95% CI 1.09-2.10; p = 0.01), 6 months (aOR 1.64; 95% CI 1.19-2.27; p = 0.003), and 1 year (aOR 1.52; 95% CI 1.10-2.10; p = 0.01). Symptomatic ICH occurred in 3 (0.6%) patients in IV t-PA versus 2 (0.1%) in the non-IV t-PA group. No significant differences were found in all-cause mortality between the two groups., Conclusions: Intravenous t-PA may be safe and effective in minor stroke (NIHSS ≤ 5) within a 4.5-h window and further randomized controlled trials are warranted., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

With the wide application of direct sequence spread spectrum (DSSS) signals, the comprehensive performance of DSSS communication systems has been continuously improved, making the electronic reconnaissance link in communication countermeasures more difficult. Electronic reconnaissance technology, as the fundamental means of modern electronic warfare, mainly includes signal detection, recognition, and parameter estimation. At present, research on DSSS detection algorithms is mostly based on the correlation characteristics of DSSS signals, and autocorrelation algorithm is the most mature and widely used method in practical engineering. With the continuous development of deep learning, deep-learning-based methods have gradually been introduced to replace traditional algorithms in the field of signal processing. This paper proposes a spread spectrum signal detection method based on convolutional neural network (CNN). Through experimental analysis, the detection performance of the CNN model proposed in this paper on DSSS signals in various situations has been compared and analyzed with traditional autocorrelation detection methods for different signal-to-noise ratios. The experiments verified the estimation performance of the model in this paper under different signal-to-noise ratios, different spreading code lengths, different spreading code types, and different modulation methods and compared it with the autocorrelation detection algorithm. It was found that the detection performance of the model in this paper was higher than that of the autocorrelation detection method, and the overall performance was improved by 4 dB.

During the acute stage of ischemic stroke, it remains unclear how to interpret the low low-density lipoprotein cholesterol (LDL-C) level. We aimed to evaluate the association between LDL-C levels, post-stroke infection, and all-cause mortality. 804,855 ischemic stroke patients were included. Associations between LDL-C levels, infection, and mortality risk were estimated by multivariate logistic regression models and displayed by restricted cubic spline curves. Mediation analysis was performed under counterfactual framework to elucidate the mediation effect of post-stroke infection. The association between LDL-C and mortality risk was U-shaped. The nadir in LDL-C level with the lowest mortality risk was 2.67 mmol/L. Compared with the group with LDL-C = 2.50-2.99 mmol/L, the multivariable-adjusted odds ratio for mortality was 2.22 (95% confidence intervals (CI): 1.77-2.79) for LDL-C <1.0 mmol/L and 1.22 (95% CI: 0.98-1.50) for LDL-C ≥5.0 mmol/L. The association between LDL-C and all-cause mortality was 38.20% (95% CI: 5.96-70.45, P = 0.020) mediated by infection. After stepwise excluding patients with increasing numbers of cardiovascular risk factors, the U-shaped association between LDL-C and all-cause mortality and the mediation effects of infection remained consistent with the primary analysis, but the LDL-C interval with the lowest mortality risk increased progressively. The mediation effects of infection were largely consistent with the primary analysis in subgroups of age ≥65 years, female, body mass index <25 kg/m 2 , and National Institutes of Health Stroke Scale ≥16. During the acute stage of ischemic stroke, there is a U-shaped association between LDL-C level and all-cause mortality, where post-stroke infection is an important mediating mechanism., Competing Interests: Conflicts of interest The authors declare that they have no conflict of interest., (Copyright © 2023 Science China Press. Published by Elsevier B.V. All rights reserved.)

Objectives: Our goal was to determine the risk conferred by elevated total homocysteine (tHcy) levels on recurrent stroke and cardiovascular disease (CVD) events after an ischemic stroke (IS), using data from the Chinese Stroke Center Alliance (CSCA)., Methods: The study consisted of 746,854 total participants with IS. Subjects were split into groups as well as quartiles according to tHcy level. Groups included a hyperhomocysteinemia (HHcy) group with tHcy ≥15 μmol/l and a normohomocysteinemia group (nHcy) with tHcy <15 μmol/l. The determined groups and quartiles underwent multiple logistic regression models with nHcy or quartile 1 as reference groups, respectively. The information from these analyses was adjusted for potential covariates and used to investigate the association between blood tHcy and in-hospital outcomes. Information collected at discharge included in-hospital stroke recurrence and CVD events., Results: The mean [SD] age of participants was 66.2 [12.0] and 37.4% (n = 279,571) were female. The median hospital duration was 11.0 days (interquartile range, 8.0-14.0 days) and 343,346 (46.0%) patients were identified as HHcy cases (tHcy ≥15 μmol/). According to the tHcy quartile, the cumulative rates of stroke recurrence (from lowest quartile to highest) were 5.2%, 5.6%, 6.1%, and 6.6% (P < 0.0001). Similarly, those of CVD events were 5.8%, 6.1%, 6.7%, and 7.2% (P < 0.0001). Compared with the nHcy group, the HHcy group was associated with increased risks of in-hospital stroke recurrence (21912 [6.4%] vs. 22048 [5.5%], with the adjusted odds ratio (OR) 1.08, 95% CI: 1.05 to 1.10) as well as CVD events (24001 [7.0%] vs. 24236 [6.0%], with the adjusted OR: 1.08, 95% CI: 1.06 to 1.10) among patients with IS in the fully adjusted model., Conclusion: HHcy was associated with increased in-hospital stroke recurrence and CVD events among patients with IS. In low-folate regions, tHcy levels may potentially predict in-hospital outcomes after IS.

Importance: Reperfusion therapy is the most effective treatment for acute ischemic stroke but remains underused in China., Objective: To evaluate the effect of a problem-oriented, culturally adapted, targeted quality improvement intervention on reperfusion therapy for patients with acute ischemic stroke in China., Design, Setting, and Participants: In this stepped-wedge cluster randomized clinical trial, patients from 16 secondary and 33 tertiary hospitals in China with acute ischemic stroke within 6 hours of symptom onset were consecutively recruited between July 1, 2018, and June 30, 2020., Interventions: Hospitals were randomly assigned to 1 of 3 sequences to receive the targeted quality improvement intervention (n = 5689), in which workflow reconstruction was promoted to reduce in-hospital reperfusion treatment delays, or usual care (n = 6443), in which conventional stroke care was left to the discretion of the stroke team., Main Outcomes and Measures: The primary outcome was the reperfusion therapy rate, a composite outcome of intravenous recombinant tissue plasminogen activator (IV rtPA) or endovascular thrombectomy (EVT) for eligible patients who arrived within 3.5 or 4.5 hours of symptom onset. Secondary outcomes were the IV rtPA administration rate among eligible patients who arrived within 3.5 hours of symptom onset, the EVT rate among eligible participants who arrived within 4.5 hours of symptom onset, the proportion of patients with door-to-needle time within 60 minutes, the proportion of patients with door-to-puncture time within 90 minutes, in-hospital mortality, and 3-month disability as measured by a modified Rankin Scale score greater than 2., Results: All 12 132 eligible patients (mean [SD] age, 66 [12.1] years; 7759 male [64.0%]) completed the trial. The reperfusion rate was 53.5% (3046 of 5689) for the eligible patients in the intervention period and 43.9% (2830 of 6443) in the control period. No significant improvement in primary outcomes was found for the intervention after adjusting for cluster, period, and imbalanced baseline covariates (adjusted risk difference [ARD], 5.5%; 95% CI, -8.0% to 19.0%; adjusted odds ratio [AOR], 1.26; 95% CI, 0.72-2.21) or for the secondary outcomes. However, significant improvements were found in secondary hospitals for reperfusion therapy (1081 of 1870 patients [57.8%] vs 945 of 2022 patients [42.9%]; ARD, 19.0%; 95% CI, 6.4%-31.6%; AOR, 2.24; 95% CI, 1.29-3.88), IV rtPA administration (1062 of 1826 patients [58.2%] vs 916 of 2170 patients [42.2%]; ARD, 20.3%; 95% CI, 7.4%-33.1%; AOR, 2.37; 95% CI, 1.34-4.19), and EVT (51 of 231 patients [22.1%] vs 37 of 259 patients [14.3%]; ARD, 13.6%; 95% CI, 1.0%-26.3%; AOR, 3.03; 95% CI, 1.11-8.25) in subgroup analyses., Conclusions and Relevance: In this stepped-wedge cluster randomized clinical trial of patients with acute ischemic stroke in China, the use of a targeted quality improvement intervention compared with usual care did not improve the reperfusion therapy rate. However, the intervention may be effective in secondary hospitals., Trial Registration: ClinicalTrials.gov Identifier: NCT03578107.

Background: Somatic mutation contributes to clonal haematopoiesis of indeterminate potential (CHIP) is related to age and associated with a higher risk of stroke and atherosclerotic cardiovascular disease. Here, we investigated the prognostic significance of CHIP in a large first-ever acute ischaemic stroke (AIS) cohort and explored the underlying mechanisms., Methods: We studied a prospective cohort of 6016 patients who had a first-ever AIS in China. Whole-genome sequencing was performed to identify CHIP. High-sensitivity C reactive protein (hs-CRP) levels above 3 mg/L at baseline were defined as hyperinflammation. Recurrent stroke during the 3-month follow-up was the primary outcome., Results: Among the 6016 patients who had a first-ever AIS, with a median age was 62 years (IQR, 54.0‒70.0), 3.70% were identified as CHIP carriers. The most common mutations occurred in the DNMT3A (30.0%) and TET2 (11.4%) genes. During a follow-up of 3 months, the presence of CHIP was associated with recurrent stroke (HR 1.62, 95% CI 1.04 to 2.51, p=0.03), recurrent ischaemic stroke (HR 1.64, 95% CI 1.04 to 2.58, p=0.03) and combined vascular events (HR 1.58, 95% CI 1.02 to 2.44, p=0.04) after adjusting for hsCRP levels at baseline in patients who had a first-ever AIS. Subgroup analysis demonstrated that CHIP was only associated with recurrent stroke when patients under hyperinflammation (OR 3.10, 95% CI 1.92 to 5.00, p<0.001) but not in those without hyperinflammation (OR 0.18, 95% CI 0.03 to 1.04, p=0.06, P interaction =0.002)., Conclusion: Our results suggest that somatic mutations contributing to CHIP increase the risk of short-term recurrent stroke in patients who had a first-ever AIS. Hyperinflammation may be important in the relationship between CHIP and recurrent stroke., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To investigate the association between hyperhomocysteinemia (HHcy) and in-hospital mortality following ischemic stroke (IS), transient ischemic attack (TIA), or intracerebral hemorrhage (ICH)., Methods: Data on patients with ischemic cerebrovascular disease (IS/TIA) or ICH enrolled in the Chinese Stroke Center Alliance (CSCA) from 2015 to 2019 were extracted. Patient characteristics and in-hospital mortality were analyzed and multiple adjusted logistic regression analyses performed to investigate the association between blood tHcy (total homocysteine) and in-hospital mortality in patients with HHcy (tHcy ⩾ 15 µmol) and patients with normohomocysteinemia (nHcy) (tHcy < 15 µmol)., Results: A total of 823,622 participants were included. Mean (SD) age was 65.9 (12.1), and 62.5% (n = 514,888) were male. A total of 379,807 (46.0%) patients were identified as having HHcy, and 70,364 (8.5%) patients had an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m 2 . An eGFR < 60 mL/min/1.73 m 2 was the strongest independent risk factor for HHcy in both patients with IS/TIA (adjusted odds ratio (aOR) 2.67, 95% confidence interval (CI): 2.49-2.86), and those with ICH (2.94, 2.46-3.50). On multivariable logistic regression, after adjusting for potential confounding factors, HHcy was associated with in-hospital mortality (aOR: 1.25, 95% CI: 1.13-1.37 for patients with IS/TIA; aOR: 1.40, 95% CI: 1.12-1.76 for patients with ICH). However, after additionally adjusting for eGFR, this association disappeared among patients with both IS/TIA (aOR: 1.09, 95% CI: 0.99-1.20) and those with ICH (aOR: 1.17, 9% CI: 0.96-1.43)., Conclusion: HHcy was associated with in-hospital mortality among the patients with IS/TIA or ICH but this association disappeared after controlling for eGFR, suggesting HHcy was acting as a marker of poor renal function which itself was the predictor of poor outcome. Our results suggest the prevention and management of renal impairment may be an important measure in the reduction of mortality in patients with HHcy after IS/TIA or ICH.

Background: Fine particulate matter (PM2.5) is a risk factor for stroke, and patients with pre-existing diseases appear to be particularly susceptible. We conducted a case-crossover study to examine the association between short-term exposure to fine particulate matter (PM2.5) and hospital admission for stroke in individuals with atrial fibrillation (AF), hypertension, diabetes, or hyperlipidemia., Methods: Patients diagnosed with acute ischemic stroke (AIS) were recruited from 2015 to 2017 in Chinese Stroke Center Alliances. We estimated daily PM2.5 average exposures with a spatial resolution of 0.1° using a data assimilation approach combining satellite measurements, air model simulations, and monitoring values. Conditional logistic regression was used to assess PM2.5-related stroke risk in patients with pre-existing medical co-morbidities., Results: A total of 155,616 patients diagnosed with AIS were admitted. Patients with a history of AF ( n  = 15,430), hypertension ( n  = 138,220), diabetes ( n  = 43,737), or hyperlipidemia ( n  = 16,855) were assessed separately. A 10 µg/m 3 increase in daily PM2.5 was associated with a significant increase in AIS for individuals with AF at lag 4 (odds ratio (OR), 1.008; 95% confidence interval (CI), 1.002-1.014), and with hypertension (OR, 1.008; 95% CI, 1.006-1.010), diabetes (OR, 1.006; 95% CI, 1.003-1.010), and hyperlipidemia (OR, 1.007; 95% CI, 1.001-1.012) at lags 0-7. Elderly (⩾ 65 years old) and female patients with AF had significantly higher associations at lag 5 (OR, 1.009; 95% CI, 1.002-1.015) and lag 5 (OR, 1.010; 95% CI, 1.002-1.018), respectively., Conclusion: Short-term exposure to PM2.5 is significantly associated with hospital admission for stroke in individuals with pre-existing medical histories, especially in older or female patients with AF. Preventive measures to reduce PM2.5 concentrations are particularly important in individuals with other medical co-morbidities.

Objectives: Evidence shows that rehabilitation is the most effective strategy to reduce the disability rate of patients with stroke. However, there is limited understanding about the factors associated with rehabilitation assessment among patients with intracerebral hemorrhage (ICH) in China. We aimed to investigate the factors associated with rehabilitation assessment in patients with ICH and the relationship between rehabilitation assessment and hospitalization outcomes., Methods: Data from 85,664 patients with ICH admitted to 1,312 hospitals between 1 August 2015 and 31 July 2019 were analyzed. A multivariable logistic regression model accounting for in-hospital clustering was used to identify patient and hospital factors associated with rehabilitation assessment during acute hospitalization., Results: A total of 62,228 (72.6%) patients with ICH underwent rehabilitation assessments. In multivariable analyses, factors associated with an increased likelihood of undergoing a rehabilitation assessment (P < .05) included a higher Glasgow Coma Scale score on admission, a history of hypertension, a history of peripheral vascular disease, dysphagia screening, carotid vessel imaging, and a longer length of hospital stay. Conversely, patients admitted to the intensive care unit and tertiary-grade hospitals were less likely to undergo rehabilitation assessments during hospitalization for ICH., Discussion: This study showed that the rate of rehabilitation assessment was 74.2%, which is low. Rehabilitation assessment was associated with longer hospital stays and lower mortality. Therefore, patients with acute cerebral haemorrhage should undergo comprehensive and professional rehabilitation assessment.

Background: Stroke is the leading cause of mortality in China, with limited evidence of in-hospital burden obtained from nationwide surveys. We aimed to monitor and track the temporal trends and rural-urban disparities in cerebrovascular risk factors, management and outcomes from 2005 to 2015., Methods: We used a two-stage random sampling survey to create a nationally representative sample of patients admitted for ischaemic stroke in 2005, 2010 and 2015. We sampled participating hospitals with an economic-geographical region-stratified random-sampling approach first and then obtained patients with a systematic sampling approach. We weighed our survey data to estimate the national-level results and assess changes from 2005 to 2015., Results: We analysed 28 277 ischaemic stroke admissions from 189 participating hospitals. From 2005 to 2015, the estimated national hospital admission rate for ischaemic stroke per 100 000 people increased (from 75.9 to 402.7, P trend <0.001), and the prevalence of risk factors, including hypertension, diabetes, dyslipidaemia and current smoking, increased. The composite score of diagnostic tests for stroke aetiology assessment (from 0.22 to 0.36, P trend <0.001) and secondary prevention treatments (from 0.46 to 0.70, P trend <0.001) were improved. A temporal decrease was found in discharge against medical advice (DAMA) (from 15.2% (95% CI 13.7% to 16.7%) to 8.6% (8.1% to 9.0%); adjusted P trend =0.046), and decreases in in-hospital mortality (0.7% in 2015 vs 1.8% in 2005; adjusted OR (aOR) 0.52; 95% CI 0.32 to 0.85) and the composite outcome of in-hospital mortality or DAMA (8.4% in 2015 vs 13.9% in 2005; aOR 0.65; 95% CI 0.47 to 0.89) were observed. Disparities between rural and urban hospitals narrowed; however, disparities persisted in in-hospital management (brain MRI: rural-urban difference from -14.4% to -11.2%; cerebrovascular assessment: from -20.3% to -16.7%; clopidogrel: from -2.1% to -10.3%; anticoagulant for atrial fibrillation: from -10.9% to -8.2%) and in-hospital outcomes (DAMA: from 2.7% to 5.0%; composite outcome of in-hospital mortality or DAMA: from 2.4% to 4.6%)., Conclusions: From 2005 to 2015, improvements in hospital admission and in-hospital management for ischaemic stroke in China were found. A temporal improvement in DAMA and improvements in in-hospital mortality and the composite outcome of in-hospital mortality or DAMA were observed. Disparities between rural and urban hospitals generally narrowed but persisted., Competing Interests: Competing interests: JPB reported consulting for the Ohio Department of Health and serving on committees for the Centers for Disease Control and Prevention (CDC) Paul Coverdell National Acute Stroke Registry. GCF reported being a member of the GWTG steering committee and receiving grant funding from Patient Centered Outcomes Research Institute (PCORI) and the National Institutes of Health. LHS reports being the chair of the GWTG-Stroke Clinical Workgroup and of the American Stroke Association Advisory Committee of the American Heart Association; grant funding and non-financial support from Genentech for late window thrombolysis; grant funding from PCORI and the DCRI on stroke outcomes research; national PI of the StrokeAF Study by Medtronic; and scientific consulting for the Joint Commission, CDC and the Massachusetts Department of Public Health. No other disclosures were reported., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Introduction: In the context of modern guideline-based strategies, new validations of prognostic scores for predicting early stroke risk are needed. We aimed to compare the validity of the ABCD series scores and assess the incremental values of risk components for predicting in-hospital stroke events in patients with transient ischemic attack (TIA)., Patients and Methods: We abstracted data from the Chinese Stroke Center Alliance (CSCA), a nationwide registry with 68,433 TIA patients admitted within 7 days of symptom onset from 1476 hospitals. TIA was defined by time-based criteria according to the World Health Organization (WHO). The discrimination of ABCD, ABCD2, ABCD2-I, and ABCD3 scores for predicting in-hospital stroke events was assessed by the area under the receiver-operating characteristics curves (AUC). The incremental predictive values of added risk predictor were determined by net reclassification improvement (NRI) and integrated discrimination improvement (IDI)., Results: A total of 29,286 TIA patients were included, of whom 1466 (5.0%) had in-hospital stroke events. Compared with ABCD2-I score (AUC 0.79, 95% confidence interval [CI] 0.77-0.80), ABCD (AUC 0.58, 95% CI 0.57-0.60), ABCD2 (AUC 0.58, 95% CI 0.56-0.59), and ABCD3 (AUC 0.58, 95% CI 0.56-0.60) had lower predictive utility. An incremental value was observed when adding infarction on DWI (IDI = 0.0597, NRI = 1.1036) into ABCD2 score to be ABCD2-I., Conclusion: The traditional scales utilizing medical history (ABCD, ABCD2, and ABCD3 scores) show fair ability for predicting in-hospital stroke events after TIA, but the ABCD2-I score, which adds infarction on DWI, improves the predictive ability., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© European Stroke Organisation 2022.)

Background and Objectives: To explore the regional discrepancy of the adherence to guideline-recommended stroke interventions for the stroke belt division (north vs south), the economic development division (east vs middle vs west), and potential interaction., Methods: We conducted a retrospective observational study using data from the Chinese Stroke Center Alliance from August 2015 to August 2019. The primary outcome was hospital personnel adherence to 11 individual guideline-recommended treatments. The coprimary outcomes included 2 summary measures: a composite score (range, 0 [nonadherence] to 1 [perfect adherence]) and an all-or-none binary outcome for adherence to evidence-based stroke. Regional disparities were assessed according to the stroke belt division and the economic development division and the interaction between these 2 divisions. Multivariate regression models with generalized estimating equations were used to analyze the outcomes., Results: This study included 838,229 patients with acute ischemic stroke from 1,473 hospitals. The overall quality of care in the nonbelt regions (southern China) was higher than in the stroke belt regions (northern China), as reflected by a higher composite score (0.77 vs 0.75; adjusted odds ratio 1.03 [95% CI 1.02-1.04]; p < 0.001) and a higher all-or-none measure (25.5% vs 22.0%; 1.32 [1.17-1.49], p < 0.001). Patients in the East and Central had higher odds of using intravenous tissue-type plasminogen activator (East: 1.81 [95% CI 1.51-2.18], p < 0.001; Central: 1.57 [95% CI 1.26-1.95], p < 0.001), early antithrombotic medications (East: 1.77 [1.49-2.11], p < 0.001; Central: 1.37 [1.12-1.66], p < 0.001), lipid-lowering medications (East: 1.29 [1.08-1.53], p < 0.001), and deep vein thrombosis prophylaxis (East: 1.28 [1.08-1.50], p = 0.003) compared with those in the West. Patients in the nonbelt regions had higher odds of getting dysphagia screening (1.82 [1.55-2.13], p < 0.001) and rehabilitation assessment (which though varied among different economic development levels). Reflected by significant interaction effects, for patients in the East, those in the nonbelt regions had greater odds of receiving anticoagulation (1.62 [1.34-1.96]; p < 0.001) but lower odds of receiving antithrombotic (0.63 [0.52-0.77]; p < 0.001) and antidiabetic medications (0.87 [0.77-0.99]; p = 0.03); for patients in the West, those in the nonbelt regions were less likely to receive antihypertensive (0.64 [0.46-0.88]; p = 0.004) and antidiabetic (0.66 [0.54-0.81]; p < 0.001) medications., Discussion: Stroke care performance measures differed across regions, along the stroke belt division, and the economic development division. The overall quality of care in the non-stroke belt regions was higher than that in the stroke belt regions. The 2 divisions had interaction effects on several individual measures., (© 2022 American Academy of Neurology.)

Background: Little is known about the impact of prevalent dementia on in-hospital outcomes of patients with incident stroke in China. Using data from the Chinese Stroke Center Alliance (CSCA), we aim to quantify the prevalence of pre-stroke dementia and whether this group is at higher risk of adverse in-hospital outcomes compared to those without pre-stroke dementia., Methods: We used multivariable logistic regression models to assess the associations between pre-stroke dementia and ambulation by day 2, in-hospital mortality, in-hospital complications, and being discharged home. Covariates included age, sex, comorbidities [dyslipidemia, atrial fibrillation, peripheral vascular disease (PVD), smoking, and alcohol use], medication history (antiplatelet drugs or lipid-lowering drugs), stroke severity [measured by the National Institute of Health Stroke Scale (NIHSS)], administration of intravenous tissue plasminogen activator (IV tPA) within 4.5 hours of stroke onset, and receipt of deep vein thrombosis (DVT) prophylaxis if indicated., Results: In the final analytic sample of 559,070 ischemic stroke patients with no prior stroke history enrolled across 1,476 hospitals, those with pre-stroke dementia (n=1,511; 0.3%) were older and more likely to be female. Despite having received similar treatment, patients with pre-stroke dementia had lower odds of ambulating by day 2 [odds ratio (OR) =0.69; 95% confidence interval (CI): 0.62-0.78], higher odds of in-hospital mortality (OR =2.01; 95% CI: 1.35-2.99) or complications (OR =2.17; 95% CI: 1.93-2.44), and lower odds of being discharged home compared to those without pre-stroke dementia (OR =0.71; 95% CI: 0.62-0.83)., Conclusions: Worse in-hospital outcomes among patients with pre-stroke dementia may be explained by pre-existing cognitive impairment that limited their ability to advocate for care needs. Further research is needed to determine whether a different care pathway or additional attention from clinicians is necessary for patients with pre-stroke dementia., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-723/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

China faces the greatest challenge from stroke in the world. According to results from the Global Burden of Disease Study 2019, there were 3.94 million new stroke cases, 28.76 million prevalent cases and 2.19 million deaths due to stroke in China in 2019. Furthermore, stroke is also the leading cause of disability-adjusted life-year (DALY) in China, the number of DALYs reached 45.9 million in 2019. Several recent large-scale epidemiological surveys have updated the data on pre-existing conditions contributed to stroke. The age-adjusted prevalence of overweight among Chinese adults aged 18-69 years was 34.4%, and the prevalence of obesity was 16.8% in 2018. 50.9% of Chinese adults ≥18 years of age without history of hypertension had prehypertension in 2018. The weighted prevalence of hypertension in adults was 27.5% in 2018. The weighted prevalence of total diabetes and pre-diabetes diagnosed by the American Diabetes Association criteria were 12.8% and 35.2%, respectively, among Chinese adults ≥18 years of age in 2017. The weighted atrial fibrillation prevalence was 1.8% among Chinese adults ≥45 years of age and equates to being present in an estimated 7.9 million people in China. Data from 1672 tertiary public hospitals in the Hospital Quality Monitoring System (HQMS) showed that 3 411 168 stroke cases were admitted during 2019. Of those, 2 818 875 (82.6%) were ischaemic strokes (ISs), 485 474 (14.2%) were intracerebral haemorrhages (ICHs), 106 819 (3.1%) were subarachnoid haemorrhages (SAHs). The average age was 66 years old, and 59.6% were male. A total of 1379 (<0.1%), 2604 (0.5%), 1250 (1.2%) paediatric strokes (age <18 years) were identified among IS, ICH and SAH, respectively. Over one-third (1 231 519 (36.1%)) of the stroke cases were covered by urban resident basic medical insurance, followed by urban employee basic medical insurance (891 103 (26.1%)) and new rural cooperative medical schema (543 108 (15.9%)). The leading risk factor was hypertension (57.3% for IS, 69.9% for ICH and 44.1% for SAH), and the leading comorbidity was pneumonia or pulmonary infection (10.4% for IS, 34.6% for ICH and 29.7% for SAH). In-hospital death/discharge against medical advice rate was 8.5%, ranging from 6.0% for IS to 20.6% for SAH. The median and IQR of length of stay was 9.0 (6.0-13.0) days, ranging from 10.0 (7.0-13.0) in IS to 14.0 (8.0-22.0) in ICH. Similar data from 2847 secondary public hospitals or private hospitals in the HQMS were also reported. Data from HQMS showed that higher proportions of interprovincial admission to other provinces were seen in Inner Mongolia, Anhui, Tibet and Beijing. Higher proportions of interprovincial admission from other provinces were seen in Beijng, Tianjin, Shanghai and Ningxia. Data from 323 601 strokes from 1337 hospitals in the Chinese Stroke Center Alliance during 2019 demonstrated that the composite scores of guideline-recommended key performance indicators for patients with IS, ICH and SAH were 0.78±0.20, 0.69±0.27 and 0.60±0.31, respectively., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: We aimed to investigate factors related to the 90-day poor prognosis (mRS≥3) in patients with transient ischemic attack (TIA) or minor stroke, construct 90-day poor prognosis prediction models for patients with TIA or minor stroke, and compare the predictive performance of machine learning models and Logistic model., Method: We selected TIA and minor stroke patients from a prospective registry study (CNSR-III). Demographic characteristics,smoking history, drinking history(≥20g/day), physiological data, medical history,secondary prevention treatment, in-hospital evaluation and education,laboratory data, neurological severity, mRS score and TOAST classification of patients were assessed. Univariate and multivariate logistic regression analyses were performed in the training set to identify predictors associated with poor outcome (mRS≥3). The predictors were used to establish machine learning models and the traditional Logistic model, which were randomly divided into the training set and test set according to the ratio of 70:30. The training set was used to construct the prediction model, and the test set was used to evaluate the effect of the model. The evaluation indicators of the model included the area under the curve (AUC) of the discrimination index and the Brier score (or calibration plot) of the calibration index., Result: A total of 10967 patients with TIA and minor stroke were enrolled in this study, with an average age of 61.77 ± 11.18 years, and women accounted for 30.68%. Factors associated with the poor prognosis in TIA and minor stroke patients included sex, age, stroke history, heart rate, D-dimer, creatinine, TOAST classification, admission mRS, discharge mRS, and discharge NIHSS score. All models, both those constructed by Logistic regression and those by machine learning, performed well in predicting the 90-day poor prognosis (AUC >0.800). The best performing AUC in the test set was the Catboost model (AUC=0.839), followed by the XGBoost, GBDT, random forest and Adaboost model (AUCs equal to 0.838, 0, 835, 0.832, 0.823, respectively). The performance of Catboost and XGBoost in predicting poor prognosis at 90-day was better than the Logistic model, and the difference was statistically significant(P<0.05). All models, both those constructed by Logistic regression and those by machine learning had good calibration., Conclusion: Machine learning algorithms were not inferior to the Logistic regression model in predicting the poor prognosis of patients with TIA and minor stroke at 90-day. Among them, the Catboost model had the best predictive performance. All models provided good discrimination., (© 2022. The Author(s).)

Background: Sex differences in stroke outcomes are crucial to secondary prevention, but previous reports showed inconsistent results. We aimed to explore the sex differences in stroke outcomes in the Third China National Stroke Registry, a prospective multicenter registry study., Methods: Among the 15 166 patients enrolled between 2015 and 2018, 9038 patients with acute ischemic stroke (AIS) were included. The primary outcomes were stroke recurrence, mortality, and unfavorable functional outcome (modified Rankin Scale > 2) at 3, 6, and 12 months. Cox regression model was used for stroke recurrence and mortality and logistic regression was used for the unfavorable functional outcome, and adjusted as follows: (1) Model 1: without adjustment; (2) Model 2: adjusted for potential risk factors, National Institutes of Health Stroke Scale at admission, prestroke modified Rankin Scale, tPA (tissue-type plasminogen activator) treatment, TOAST (Trial of ORG 10172 in Acute Stroke Treatment) classification, and onset-to-door time; (3) Model 3: adjusted for covariates from model 2 in addition to blood pressure and blood serum covariates. Multiple imputation was used for missing values, and sensitivity analyses were conducted to describe sex differences by age groups., Results: One-third (2802/9038) of the patients were women. Women were significantly older than men (64.78±10.84 versus 61.26±11.42, P <0.001). In the fully adjusted model, female patients were more likely to have unfavorable functional outcomes at 3 months (odds ratio, 1.28 [1.09-1.50]), especially among patients aged 65 years or older (odds ratio, 1.39 [1.14-1.70]), but no difference was discovered in patients aged <65 years. There were no sex differences in stroke recurrence and mortality at 3, 6, or 12 months or unfavorable functional outcomes at 6 or 12 months after adjustment., Conclusions: Compared with men, women with AIS were less likely to have favorable outcomes at 3 months in China, especially among those over 65 years of age. Experts should aim to tailor secondary prevention strategies for high-risk patients.

Background and Purpose: We aimed to determine whether young adults (<50 years) with acute ischaemic stroke (AIS) are more likely to receive intravenous tissue plasminogen activator (IV tPA) and have shorter time to treatment than older patients with stroke., Methods: We analysed data from the Chinese Stroke Center Alliance registry for patients with AIS hospitalised between August 2015 and July 2019. Patients were classified into two groups according to age: young adults (<50 years of age) and older adults (≥50 years of age)., Results: Of 793 175 patients with AIS admitted to 1471 hospitals, 9.1% (71 860) were young adults. Compared with older adults, a higher proportion of young adults received IV tPA among patients without contraindicaitons (7.2% vs 6.1%, adjusted OR (aOR) 1.13, 95% CI 1.10 to 1.17) and among patients without contraindications and with onset-to-door time ≤3.5 hours (23.6% vs 19.3%, aOR 1.20, 95% CI 1.15 to 1.24). We did not observe differences in onset-to-needle time (median hours 2.7 hours) or door-to-needle time (DNT) (median minutes 60 min) between young and older adults. The proportion of DNT ≤30 min, DNT ≤45 min and DNT ≤60 min in young and older IV tPA-treated patients were 16.9% vs 18.8%, 30.2% vs 32.8% and 50.2% vs 54.2%, respectively. Compared with older adults, young adults treated with IV tPA had lower odds of in-hospital mortality (0.5% vs 1.3%, aOR 0.54, 95% CI 0.35 to 0.82) and higher odds of independent ambulation at discharge (61.0% vs 53.6%, aOR 1.15, 95% CI 1.08 to 1.22), and the associations may be partly explained by stroke severity measured by the National Institutes of Health Stroke Scale score., Conclusion: Young adults with AIS were more likely to receive IV tPA than older adults, although there was no difference between the two groups in time to treatment. Compared with older adults, young adults may had better in-hospital outcomes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: Dysphagia is common and is associated with aspiration pneumonia. However, little is known about the prevalence of and factors influencing dysphagia screening (DS) and pneumonia after subarachnoid hemorrhage (SAH)., Methods: We used data on SAH patients admitted to 1476 hospitals from the China Stroke Center Alliance (CSCA) from August 2015 to July 2019 to analyze the rates of DS and pneumonia. We then conducted univariate and multivariable analyses to examine the relationship between DS and pneumonia., Results: Among 4877 SAH patients who were eligible for DS and had complete data on pneumonia status, 3527 (72.3%) underwent DS, and 1006 (20.6%) developed pneumonia. Compared with patients without pneumonia, patients with pneumonia were older (mean: 63.4 vs. 57.8 years of age), had lower Glasgow Coma Scale (GCS) scores at admission (mean: 13.5 vs. 14.3), were more likely to have dysphagia (15.2% vs. 3.3%), and were more likely to have undergone aneurysm isolation (19.1% vs. 10.0%). In multivariable analyses, factors independently associated with a higher risk of pneumonia were dysphagia [odds ratio (OR), 3.77; 95% confidence interval (CI), 2.85-4.98], age (OR, 1.50 per 10-year increase; 95% CI, 1.40-1.60), male sex (OR, 1.23; 95% CI, 1.02-1.49), arrival at the hospital by emergency medical services (OR, 1.36; 95% CI, 1.16-1.58), nimodipine treatment (OR, 1.42; 95% CI, 1.11-1.81), endovascular embolization of aneurysms (OR, 1.23; 95% CI, 1.03-1.47), cerebral ventricular shunt placement (OR, 2.24; 95% CI, 1.41-3.54), and treatment at a higher grade hospital (OR, 1.44; 95% CI, 1.21-1.71)., Conclusion: More than a quarter of patients with SAH did not have documented DS, while one-fifth developed pneumonia. DS performance was associated with a lower risk of pneumonia. Randomized controlled trials may be needed to determine the effectiveness of DS., (© 2022 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Background: Post-stroke inflammation biomarker high-sensitivity C-reactive protein (hsCRP) increases cerebral infarct size and results in functional disability directly, it also contributes to the formation and maturation of atherosclerotic plaques, which increase the risk of stroke recurrence and results in functional disability indirectly. However, no study has quantified how much functional disability was mediated by stroke recurrence., Methods: Patients with acute ischaemic stroke within 7 days and admitted to 169 hospitals in the Third China National Stroke Registry were analyzed. Blood samples were collected within 24 h of admission. Stroke recurrence and functional disability (defined as a modified Rankin scale score ≥ 2) were assessed via face-to-face interviews at three months. Mediation analysis under the counterfactual framework was performed to examine the potential causal chain in which stroke recurrence may mediate the relationship between hsCRP and functional outcome. Sensitivity analyses were performed across different subgroups and on different scales of hsCRP measurement., Findings: Of the 7603 analyzed patients (mean [SD] age, 62.3 [11.3] years; 2392 [31.5%] women), the median (interquartile range [IQR]) of NIHSS score was 3.0 (1.0-6.0). The median (IQR) level of hsCRP was 1.73 (0.81-4.38) mg/L. A total of 496 (6.5%) cases of stroke recurrence and 1884 (24.8%) cases of functional disability were observed at the 90-day follow-up. Each SD increase in the concentration of hsCRP was associated with an increased risk of stroke recurrence (adjusted odds ratio [aOR], 1.11; 95% CI, 1.04-1.18) and disability (aOR, 1.14; 95% CI, 1.08-1.20) within 90 days. Of 1884 functionally disabled patients, only 16.0 % (n = 302) of patients experienced stroke recurrence before functional disability. Stroke recurrence during follow-up explained 16.52% (95% CI, 5.79%-27.25%) of the relationship between hsCRP and functional disability. Sensitivity analyses in different subgroups and on different scales of hsCRP measurement showed comparable results., Interpretation: Stroke recurrence mediates less than 20% of the association between hsCRP and functional disability at 90 days among patients with acute ischaemic stroke. In addition to typical secondary prevention strategies for preventing stroke recurrence, more attention should be paid to novel anti-inflammatory therapy to improve functional outcomes., Funding: Beijing Natural Science Foundation, the National Key R&D Program of China, the National Natural Science Foundation of China, and the Beijing Municipal Science & Technology Commission., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Previous assessments of sex differences for patients with acute ischemic stroke were limited in a specific region or population, narrow scope, or small sample size., Methods: Patients with acute ischemic stroke hospitalized in the China Stroke Center Alliance hospitals were analyzed. Absolute standardized differences (ASDs) were used to assess sex differences in vascular risk factors, guideline-recommended in-hospital management measures and outcomes, including stroke severity (National Institutes of Health Stroke Scale≥16), death/discharge against medical advice, major adverse cardiovascular events, pneumonia, and disability (modified Rankin Scale≥3)., Results: Of 838,229 patients analyzed, 524351 (62.6%) were men and 313,878 (37.4%) were women. Compared with men, women were older (68.6 vs. 64.7 years), had higher prevalence of hypertension (67.7% vs. 62.4%), diabetes (24.7% vs. 19.5%), and atrial fibrillation (7.1% vs. 4.3%), but lower prevalence of smoking (4.5% vs. 56.6%) and drinking (2.6% vs 35.8%) (ASDs >10%). No sex differences were seen in guideline-directed management measures, indicated by risk-adjusted individual measures and the all-or-null summary measure (34.5% vs 34.9%, ASD = 1.0%). Compared to men, women tended to have strokes that were more severe at presentation (6.5% vs. 4.5%, ASD = 8.8%) and more disabilities at discharge (34.9% vs 30.5%, ASD =9.4%). However, all sex-related differences in outcomes were attenuated to null after risk adjustments (ASDs<2%)., Conclusions: Compared to male patients, female patients had more vascular risk factors and received similar in-hospital care. They had strokes that were more severe at presentation and more disabilities at discharge, both of which may be explained by worse vascular risk profiles., (© 2021 European Academy of Neurology.)

Background: Clinical trials have shown that dexmedetomidine might decrease the occurrence of postoperative delirium after major surgery, but neurosurgical patients were excluded from these studies. We aimed to determine the feasibility of conducting a full-scale randomized controlled trial of the effect of prophylactic low-dose dexmedetomidine on postoperative delirium in patients after elective intracranial operation for brain tumors., Methods: In this single-center, parallel-arm pilot randomized controlled trial, adult patients who underwent an elective intracranial operation for brain tumors were recruited. Dexmedetomidine (0.1 μg/kg/hour) or placebo was continuously infused from intensive care unit (ICU) admission on the day of surgery until 08:00 AM on postoperative day one. Adverse events during the study-drug administration were recorded. The primary feasibility endpoint was the occurrence of study-drug interruption. Delirium was assessed twice daily with the Confusion Assessment Method for the ICU during the first five postoperative days. The assessable rate of delirium evaluation was documented., Results: Sixty participants were randomly assigned to receive either dexmedetomidine (n = 30) or placebo (n = 30). The study-drug was stopped in two patients (6.7%) in the placebo group due to desaturation after new-onset unconsciousness and an unplanned reoperation for hematoma evacuation and in one patient (3.3%) in the dexmedetomidine group due to unplanned discharge from the ICU. The absolute difference (95% confidence interval) of study-drug interruption between the two groups was 3.3% (- 18.6 to 12.0%), with a noninferiority P value of 0.009. During the study-drug infusion, no bradycardia occurred, and hypotension occurred in one patient (3.3%) in the dexmedetomidine group. Dexmedetomidine tended to decrease the incidence of tachycardia (10.0% vs. 23.3%) and hypertension (3.3% vs. 23.3%). Respiratory depression, desaturation, and unconsciousness occurred in the same patient with study-drug interruption in the placebo group (3.3%). Delirium was evaluated 600 times, of which 590 (98.3%) attempts were assessable except in one patient in the placebo group who remained in a coma after an unplanned reoperation., Conclusions: The low rate of study-drug interruption and high assessable rate of delirium evaluation supported a fully powered trial to determine the effectiveness of low-dose dexmedetomidine on postoperative delirium in patients after intracranial operation for brain tumors., Trial Registration: The trial was registered at ClinicalTrials.gov (NCT04494828) on 31/07/2020., (© 2021. The Author(s).)

Background and Aims: Spontaneous bacterial peritonitis (SBP) is one of the leading causes of death in patients with liver cirrhosis. We aimed to establish a prognostic model to evaluate the 1-year survival of cirrhosis patients after the first episode of SBP., Methods: A prognostic model was developed based on a retrospective derivation cohort of 309 cirrhosis patients with first-ever SBP and was validated in a separate validation cohort of 141 patients. We used Uno's concordance, calibration curve, and decision curve (DCA) analysis to evaluate the discrimination, calibration, and clinical net benefit of the model., Results: A total of 59 (19.1%) patients in the derivation cohort and 42 (29.8%) patients in the validation cohort died over the course of 1 year. A prognostic model in nomogram form was developed with predictors including age [hazard ratio (HR): 1.25; 95% confidence interval (CI): 0.92-1.71], total serum bilirubin (HR: 1.66; 95% CI: 1.28-2.14), serum sodium (HR: 0.94; 95% CI: 0.90-0.98), history of hypertension (HR: 2.52; 95% CI: 1.44-4.41) and hepatic encephalopathy (HR: 2.06; 95% CI: 1.13-3.73). The nomogram had a higher concordance (0.79) compared with the model end-stage liver disease (0.67) or Child-Turcotte-Pugh (0.71) score. The nomogram also showed acceptable calibration (calibration slope, 1.12; Bier score, 0.15±0.21) and optimal clinical net benefit in the validation cohort., Conclusions: This prediction model developed based on characteristics of first-ever SBP patients may benefit the prediction of patients' 1-year survival., Competing Interests: The authors have no conflict of interests related to this publication., (© 2021 Authors.)

Background Prior studies have shown an increased risk of ischemic stroke (IS) after myocardial infarction (MI); however, there are limited studies concerning the characteristics, in-hospital mortality, and complications of patients with IS with a medical history of MI. We hypothesized that patients with IS with a medical history of MI may experience more severe strokes and have a higher risk of in-hospital mortality and complications than patients with IS without a medical history of MI. Methods and Results Consecutive in-hospital data were extracted from the China Stroke Center Alliance database from August 2015 to July 2019. Patient characteristics, hospital tests, in-hospital mortality, and complications were analyzed and compared in patients with IS with or without a history of MI. Of 893 429 patients with IS, we identified 81 646 (9.1%) patients with a history of MI (MI group). Compared with patients with IS without MI, MI group patients were older, had a lower prevalence of current smoking, had a higher prevalence of a relative medical history, and took more medications before admission. Compared with the group with IS without MI, the MI group had a higher National Institute of Health Stroke Scale score after onset (4.0 versus 3.0; Hodges-Lehmann estimator, 22.5) and a higher proportion of severe strokes (National Institute of Health Stroke Scale score ≥15) (7.1% versus 4.4%; absolute standardized difference=11.6%). In the fully adjusted models, the risk of in-hospital mortality was higher in the MI group (odds ratio [OR], 1.74; 95% CI, 1.57-1.92; P <0.0001). MI group patients also had a higher risk of complications, including urinary tract infection (OR, 1.28; 95% CI, 1.2-1.36; P <0.0001), gastrointestinal bleeding (OR, 1.29; 95% CI, 1.19-1.39; P <0.0001), pneumonia (OR, 1.24; 95% CI, 1.21-1.28; P <0.0001), depression (OR, 1.33; 95% CI, 1.24-1.42; P <0.0001), seizure (OR, 1.35; 95% CI, 1.22-1.49; P <0.0001), atrial fibrillation (OR, 1.78; 95% CI, 1.71-1.86; P <0.0001), and cardiac or respiratory arrest (OR, 1.98; 95% CI, 1.78-2.2; P <0.0001). Conclusions Patients with IS with a medical history of MI have an increased risk of severe stroke, in-hospital mortality, and complications. Studies exploring the underlying mechanisms are needed to improve and tailor stroke treatment strategies.

Importance: Stroke represents a significant burden on the health care system of China. The Chinese Stroke Center Alliance was launched in 2015 to monitor and improve care quality and outcomes for patients with acute stroke and transient ischemic attack (TIA)., Objective: To evaluate the clinical characteristics, management, and in-hospital clinical outcomes and complications among patients with stroke or TIA in China., Design, Setting, and Participants: This quality improvement study assessed stroke or TIA admissions to 1476 participating hospitals in the Chinese Stroke Center Alliance between August 1, 2015, and July 31, 2019., Exposures: Stroke types and calendar year., Main Outcomes and Measures: Eleven guideline-based admission or discharge management measures and 2 summary measures: an all-or-none binary outcome and a composite score (range, 0 [nonadherence] to 1 [perfect adherence]) for adherence to evidence-based stroke and TIA care and in-hospital clinical outcomes, including death or discharge against medical advice (DAMA), major adverse cardiovascular events (MACEs), including ischemic stroke, hemorrhagic stroke, TIA, or myocardial infarction; and in-hospital complications., Results: Of 1 006 798 patients with stroke or TIA (mean [SD] age, 65.7 [12.2] years; 383 500 [38.1%] female), 838 229 (83.3%) had an ischemic stroke, 64 929 (6.4%) had TIA, 85 705 (8.5%) had intracerebral hemorrhage (ICH), and 11 241 (1.1%) had subarachnoid hemorrhage (SAH). Management measures varied by cerebrovascular event type, with the mean (SD) composite score ranging from 0.57 (0.31) in SAH to 0.83 (0.24) in TIA. Poor outcomes and complications were highest among patients with SAH (21.9%; 95% CI, 21.0%-22.8% in-hospital death or DAMA; 9.6%; 95% CI, 9.1%-10.2% MACEs; and 31.4%; 95% CI, 30.6%-32.3% in-hospital complications) and patients with ICH (17.2%; 95% CI, 16.9%-17.5% in-hospital death or DAMA; 9.3%; 95% CI, 9.1%-9.5% MACEs; and 31.3%; 95% CI, 31.0%-31.6% in-hospital complications), followed by patients with ischemic stroke (6.1%; 95% CI, 6.0%-6.1% in-hospital death or DAMA; 6.3%; 95% CI, 6.3%-6.4% MACEs; and 12.8%; 95% CI, 12.7%-12.9% in-hospital complications), and lowest in patients with TIA (5.0%; 95% CI, 4.8%-5.2% in-hospital death or DAMA; 2.4%; 95% CI, 2.3%-2.5% MACEs; and 0.8%; 95% CI, 0.7%-0.8% in-hospital complications). Temporal improvements in management measures were observed from 2015 to 2019, especially in administration of intravenous recombinant tissue plasminogen activator (+60.3% relatively; 95% CI, 52.9%-70.5%), dysphagia screening (+14.7% relatively; 95% CI, 14.0%-15.6%), and use of anticoagulants for atrial fibrillation (+31.4% relatively; 95% CI, 25.7%-37.3%). Temporal improvements in in-hospital death or DAMA (-9.7% relatively; 95% CI, -9.6% to -8.5%) and complications (-27.1% relatively; 95% CI, -28.6% to -25.3) were also observed., Conclusions and Relevance: In this quality improvement study, performance measure adherence and poor outcomes and complications varied by cerebrovascular event type; although there were substantial improvements over time, these results suggest that support for the use of evidence-based practices is needed.

Background: Lowering low-density lipoprotein cholesterol (LDL-C) is crucial for secondary stroke prevention in stroke patients with preexisting cardiovascular diseases (CVD) or cerebrovascular diseases (CeVD). However, data on attainment of guideline-recommended LDL-C levels are lacking., Methods: We analyzed data from the Chinese Stroke Center Alliance (CSCA) program for patients with ischemic stroke and transient ischemic attack (TIA) hospitalized between August 2015 and July 2019. Participants were classified into different disease groups according to preexisting CeVD (stroke/TIA) or CVD [coronary heart disease (CHD) or myocardial infarction (MI)]., Results: Of 858,509 patients presenting with an acute stroke/TIA, 251,176 (29.3%) had a preexisting CeVD, 44,158 (5.1%) had preexisting CVD, 33,070 (3.9%) had concomitant preexisting CeVD and CVD, and 530,105 (61.7%) had no documented history of CeVD/CVD. Overall, only 397,596 (46.3%) met the target for LDL-C <2.6 mmol/L, 128,177 (14.9%) for LDL-C <1.8 mmol/L and 55,275 (6.4%) for LDL-C <1.4 mmol/L, and patients with concomitant CeVD and CVD had higher attainment rates than other disease groups (P<0.001). Despite improvements over time in the proportion of patients who attain LDL-C targets (P for trend <0.05), it remains suboptimal. Younger age, women, having a history of hypertension or dyslipidemia, current smoking or drinking, and being admitted to hospitals located in eastern China were associated with lower odds of meeting the LDL-C goals., Conclusions: Overall attainment of guideline LDL-C targets in a population of stroke/TIA patients is low and indicates the need for better management of dyslipidemia, particularly for high-risk stroke patients with pre-existing CeVD or CVD., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/atm-21-1467). The authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

Importance: Adherence to oral anticoagulants (OACs) per guideline recommendations is crucial in reducing ischemic stroke and systemic thromboembolism in high-risk patients with ischemic stroke and atrial fibrillation. However, data on OAC use are underreported in China., Objective: To assess adherence to the Chinese Stroke Association or the American Heart Association/American Stroke Association's clinical management guideline-recommended prescription of OACs, the temporal improvement in adherence, and the risk factors associated with OAC prescriptions., Design, Setting, and Participants: This quality improvement study was conducted at 1430 participating hospitals in the Chinese Stroke Center Alliance (CSCA) among patients with ischemic stroke and atrial fibrillation enrolled in the CSCA between August 1, 2015, and July 31, 2019., Exposure: Calendar year., Main Outcomes and Measures: Adherence to the Chinese Stroke Association or the American Heart Association/American Stroke Association's clinical management guideline-recommended prescribing of OACs (warfarin and non-vitamin K OACs, including dabigatran, rivaroxaban, apixaban, and edoxaban) at discharge., Results: Among 35 767 patients (18 785 women [52.5%]; mean [SD] age, 75.5 [9.2] years) with previous atrial fibrillation at admission, the median CHA2DS2-VASc (cardiac failure or dysfunction, hypertension, age 65-74 [1 point] or ≥75 years [2 points], diabetes, and stroke, transient ischemic attack or thromboembolism [2 points]-vascular disease, and sex category [female]) score was 4.0 (interquartile range, 3.0-5.0); 6303 (17.6%) were taking OACs prior to hospitalization for stroke, a rate that increased from 14.3% (20 of 140) in the third quarter of 2015 to 21.1% (118 of 560) in the third quarter of 2019 (P < .001 for trend). Of 49 531 eligible patients (26 028 men [52.5%]; mean [SD] age, 73.4 [10.4] years), 20 390 (41.2%) had an OAC prescription at discharge, an increase from 23.2% (36 of 155) in the third quarter of 2015 to 47.1% (403 of 856) in the third quarter of 2019 (P < .001 for trend). Warfarin was the most commonly prescribed OAC (11 956 [24.2%]) and had the largest temporal increase (from 5.8% [9 of 155] to 20.7% [177 of 856]). Older age (adjusted odds ratio [aOR] per 5 year increase, 0.89;95% CI, 0.89-0.90), lower levels of education (aOR for below elementary school, 0.84; 95% CI, 0.74-0.95 ), lower income (aOR for ≤¥1000 [$154], 0.66; 95% CI, 0.59-0.73), having new rural cooperative medical scheme insurance (aOR, 0.92; 95% CI, 0.87-0.96), prior antiplatelet use (aOR, 0.70; 95% CI, 0.66-0.74), having several cardiovascular comorbid conditions (including stroke or transient ischemic attack [aOR, 0.78; 95% CI, 0.75-0.82], hypertension [aOR, 0.84; 95% CI, 0.80-0.89], diabetes [aOR, 0.91; 95% CI, 0.83-0.99], dyslipidemia [aOR, 0.87; 95% CI, 0.80-0.94], carotid stenosis [aOR, 0.83; 95% CI, 0.69-0.98], and peripheral vascular disease [aOR, 0.80; 95% CI, 0.71-0.90]), and admission to secondary hospitals (aOR, 0.71; 95% CI, 0.68-0.74) or hospitals located in the central region of China (aOR, 0.80; 95% CI, 0.75-0.84) were associated with not being prescribed an OAC at discharge., Conclusions and Relevance: This quality improvement study suggests that, despite significant improvement over time, OAC prescriptions remained low. Efforts to increase OAC prescriptions, especially non-vitamin K OACs, are needed for vulnerable subgroups by age, socioeconomic status, and presence of comorbid conditions.

Background and Purpose: We performed a systemic review and meta-analysis to elucidate the effectiveness and safety of dual antiplatelet (DAPT) therapy with P2Y12 inhibitors (clopidogrel/ticagrelor) and aspirin versus aspirin monotherapy in patients with mild ischemic stroke or high-risk transient ischemic attack., Methods: Following Preferred Reported Items for Systematic Review and Meta-Analysis standards for meta-analyses, Medline, Embase, Cochrane Central Register of Controlled Trials, and the Cochrane Library were searched for randomized controlled trials that included patients with a diagnosis of an acute mild ischemic stroke or high-risk transient ischemic attack, intervention of DAPT therapy with clopidogrel/ticagrelor and aspirin versus aspirin alone from January 2012 to July 2020. The outcomes included subsequent stroke, all-cause mortality, cardiovascular death, hemorrhage (mild, moderate, or severe), and myocardial infarction. A DerSimonian-Laird random-effects model was used to estimate pooled risk ratio (RR) and corresponding 95% CI in R package meta. We assessed the heterogeneity of data across studies with use of the Cochran Q statistic and I 2 test., Results: Four eligible trials involving 21 493 participants were included in the meta-analysis. DAPT therapy started within 24 hours of symptom onset reduced the risk of stroke recurrence by 24% (RR, 0.76 [95% CI, 0.68-0.83], I 2 =0%) but was not associated with a change in all-cause mortality (RR, 1.30 [95% CI, 0.90-1.89], I 2 =0%), cardiovascular death (RR, 1.34 [95% CI, 0.56-3.17], I 2 =0%), mild bleeding (RR, 1.25 [95% CI, 0.37-4.29], I 2 =94%), or myocardial infarction (RR, 1.45 [95% CI, 0.62-3.39], I 2 =0%). However, DAPT was associated with an increased risk of severe or moderate bleeding (RR, 2.17 [95% CI, 1.16-4.08], I 2 =41%); further sensitivity tests found that the association was limited to trials with DAPT treatment duration over 21 days (RR, 2.86 [95% CI, 1.75-4.67], I 2 =0%) or ticagrelor (RR, 2.17 [95% CI, 1.16-4.08], I 2 =37%) but not within 21 days or clopidogrel., Conclusions: In patients with noncardioembolic mild stroke or high-risk transient ischemic attack, DAPT with aspirin and clopidogrel/ticagrelor is more effective than aspirin alone for recurrent stroke prevention with a small absolute increase in the risk of severe or moderate bleeding.

Background: Although hyperuricemia frequently associates with respiratory diseases, patients with severe coronavirus disease 2019 (COVID-19) and severe acute respiratory syndrome (SARS) can show marked hypouricemia. Previous studies on the association of serum uric acid with risk of adverse outcomes related to COVID-19 have produced contradictory results. The precise relationship between admission serum uric acid and adverse outcomes in hospitalized patients is unknown., Methods: Data of patients affected by laboratory-confirmed COVID-19 and admitted to Leishenshan Hospital were retrospectively analyzed. The primary outcome was composite and comprised events, such as intensive care unit (ICU) admission, mechanical ventilation, or mortality. Logistic regression analysis was performed to explore the association between serum concentrations of uric acid and the composite outcome, as well as each of its components. To determine the association between serum uric acid and in-hospital adverse outcomes, serum uric acid was also categorized by restricted cubic spline, and the 95% confidence interval (CI) was used to estimate odds ratios (OR)., Results: The study cohort included 1854 patients (mean age, 58 years; 52% women). The overall mean ± SD of serum levels of uric acid was 308 ± 96 µmol/L. Among them, 95 patients were admitted to ICU, 75 patients received mechanical ventilation, and 38 died. In total, 114 patients reached composite end-points (have either ICU admission, mechanical ventilation or death) during hospitalization. Compared with a reference group with estimated baseline serum uric acid of 279-422 µmol/L, serum uric acid values ≥ 423 µmol/L were associated with an increased risk of composite outcome (OR, 2.60; 95% CI, 1.07- 6.29) and mechanical ventilation (OR, 3.01; 95% CI, 1.06- 8.51). Serum uric acid ≤ 278 µmol/L was associated with an increased risk of the composite outcome (OR, 2.07; 95% CI, 1.18- 3.65), ICU admission (OR, 2.18; 95% CI, 1.17- 4.05]), and mechanical ventilation (OR, 2.13; 95% CI, 1.06- 4.28), as assessed by multivariate analysis., Conclusions: This study shows that the association between admission serum uric acid and composite outcome of COVID-19 patients was U-shaped. In particular, we found that compared with baseline serum uric acid levels of 279-422 µmol/L, values ≥ 423 µmol/L were associated with an increased risk of composite outcome and mechanical ventilation, whereas levels ≤ 278 µmol/L associated with increased risk of composite outcome, ICU admission and mechanical ventilation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chen, Lu, Gu, Li, Zhang, Lio, Luo, Zhang, Hu, Lan, Chen, Xie and Pan.)