Jijun Shi

Patients with mild acute ischemic stroke (AIS) (NIHSS score ≤5) remain at substantial risk for early neurological deterioration (END) and poor functional outcomes despite receiving standard dual antiplatelet therapy (DAPT). Tirofiban, a rapid-onset glycoprotein IIb/IIIa receptor inhibitor, may reduce this risk; however, evidence in patients with mild AIS is limited. To determine whether administration of intravenous tirofiban for 48 h followed by DAPT improves the proportion of patients with excellent functional outcomes (modified Rankin Scale [mRS] score 0-1) at 90 days compared with administration of DAPT alone in patients with mild noncardioembolic AIS within 48 h of onset. The TiMIS trial is a prospective, multicenter, open-label, blinded-endpoint (PROBE), randomized controlled study. A total of 688 patients aged 18-80 years with noncardioembolic acute mild ischemic stroke within 48 h of symptom onset will be enrolled across 20 centers in China. Participants are randomized 1:1 to intravenous tirofiban for 48 h sequentially followed by DAPT or DAPT alone. The primary outcome is the proportion of patients with excellent functional outcomes at 90 days. Secondary outcomes include END, changes in the NIHSS score, good functional outcome, mRS score shift, incidence of new ischemic stroke and composite cardiovascular events, and safety endpoints (symptomatic intracerebral hemorrhage, all-cause mortality and severe bleeding events). This trial provides crucial evidence on whether early intravenous tirofiban with sequential DAPT offers superior benefits over standard care in patients with mild AIS, potentially guiding future antithrombotic strategies. ClinicalTrials.gov (NCT07095790).

While early National Institutes of Health Stroke Scale (NIHSS) scores are predictive of outcomes in patients with acute ischemic stroke (AIS), the prognostic value of the discharge NIHSS score after intravenous thrombolysis (IVT) remains unclear. We aimed to determine whether the discharge NIHSS score outperforms baseline, 24-hour, and early change indicators in predicting poor 3-month outcomes (modified Rankin scale [mRS] score of 3-6). In this retrospective cohort study, we analyzed 554 AIS patients who received IVT at our stroke center from May 2022 to March 2024. NIHSS scores were assessed at baseline, 24 h, and discharge. Absolute (baseline minus discharge) and percentage (absolute change/baseline × 100%) NIHSS changes were calculated. Multivariable logistic regression analyses were used to assess the independent correlation between different NIHSS scores and poor outcomes. Predictive performance was evaluated using receiver operating characteristic (ROC) curves, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Discharge NIHSS scores demonstrated superior discriminative ability for poor outcomes (AUC 0.950, 95% CI 0.932-0.969) versus baseline (AUC 0.842), 24-hour (AUC 0.930), absolute change (AUC 0.689), and percentage change (AUC 0.885) (all p < 0.001). The optimal cutoff was 4.5 (sensitivity 90.5%, specificity 86.0%). Adding the discharge NIHSS score to the 24-hour NIHSS score significantly improved reclassification (NRI 123.4%, IDI 9.1%). The discharge NIHSS score consistently outperformed the 24-hour NIHSS score in predicting poor 3-month functional outcomes across all key patient subgroups. This study revealed a notable association between the discharge NIHSS score and poor 3-month outcomes in thrombolysis-eligible patients with AIS, particularly in those with moderate stroke severity. These findings complement the established prognostic value of the 24-hour NIHSS score and may guide postacute care planning.

To investigate the effect of eosinophils on early (END) and delayed neurological deterioration (DND) after mechanical thrombectomy (MT) in patients with acute ischemic stroke (AIS). A total of 442 consecutive AIS patients experiencing MT between May 2017 and January 2023 were analyzed. END and DND were defined as a rise of ≥ 2 points on the National Institutes of Health Stroke Scale (NIHSS) or a fall of ≥ 1 point on the Glasgow Coma Scale or death from baseline to 24 h and from 24 to 72 h, respectively. Multivariate regression analysis, generalize additive models and mediation analysis were used to assess the effect of eosinophils on END and DND and the underlying mechanisms. 113 (25.17%) and 47 (10.63%) patients had END and DND, respectively. Eosinophils was independently associated with END after adjusting potential confounders (odds ratio, 0.00; 95% CI, 0.00–0.80; P = 0.0441), which is consistent with the result of eosinophils (dichotomous) as a categorical variable (odds ratio, 0.40; 95% CI, 0.24–0.68; P = 0.0006). In assessing the relationship between eosinophils and DND, the inflection point was found to be 0.02, and eosinophils were independently correlated with DND at less than 0.02 (odds ratio, 0.00, 95% CI: 0.00–0.00, P = 0.0038); however, eosinophils ceased to be independently correlated with DND after exceeding 0.02 (P = 0.3519). Mediation analyses confirmed that eosinophils contribute to END in patients through symptomatic intracranial hemorrhage (indirect effect: -0.463; 95%CI: -0.902–0.19; P < 0.001). The effects of eosinophils on END and DND are not identical.

Background/Objective: Venous thromboembolism (VTE) remains a significant challenge in neurocritical care, with limited tailored risk assessment tools available for clinical practice. This study aimed to develop and validate a practical prediction model to support VTE prevention strategies in neurocritical patients. Methods: A total of 605 neurocritical patients were retrospectively enrolled in the neurologic intensive care unit (NICU) from May 2022 to April 2024. The eligible patients were randomly divided into a training dataset and a testing dataset in a ratio of 7:3. Variables with significant univariate effects in the training dataset were selected for multivariable stepwise regression analysis. The model fitting goodness was tested using the Hosmer–Lemeshow test, the area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the model discrimination, and decision curve analysis (DCA) was used to test the clinical value of the model. Results: The final model identified age, length of stay in the NICU, activated partial thromboplastin time (APTT), D‐dimer, tracheotomy duration, pulmonary infection, antibiotic use, and dehydrating agents as key predictors. The nomogram demonstrated excellent discrimination (AUC 0.763, 95% CI: 0.714–0.811 in the training dataset; AUC 0.809, 95% CI: 0.732–0.885 in the testing cohort), strong calibration (Hosmer–Lemeshow test: p = 0.126 [training]; p = 0.823 [testing]) and consistent clinical net benefit across prevention thresholds (10%–40% risk probability). Conclusions: The risk prediction model developed in this study can effectively predict VTE occurrence in neurocritical patients with good discrimination and clinical utility, providing a valuable tool for identifying high‐risk individuals and performing early prevention and treatment measures.

A rare case of ischemic stroke in a young adult demonstrating coexistence of moyamoya disease and carotid web in angiography was reported. Early recognition and prompt intervention should be stressed in individuals with cryptogenic stroke.

Background: Serum uric acid (UA) and the neutrophil-to-lymphocyte ratio (NLR) have been reported to be associated with outcomes in acute ischemic stroke (AIS). However, whether UA is related to the prognosis of AIS patients undergoing intravenous thrombolysis (IVT) remains inconclusive. We sought to explore the combined effect of UA and NLR on the prognosis of AIS treated with IVT. Methods: A total of 555 AIS patients receiving IVT treatment were enrolled. Patients were categorized into four groups according to the levels of UA and NLR: LNNU (low NLR and normal UA), LNHU (low NLR and high UA), HNNU (high NLR and normal UA), and HNHU (high NLR and high UA). Multivariable logistic regression analysis was used to evaluate the value of serum UA level and NLR in predicting prognosis. The primary outcomes were major disability (modified Rankin scale (mRS) score 3–5) and death within 3 months. Results: After multivariate adjustment, a high NLR (≥ 3.94) increased the risk of 3-month death or major disability (OR, 2.23; 95% CI, 1.42 to 3.55, p < 0.001). However, there was no statistically significant association between a high UA level (≥ 313.00 µmol/L) and clinical outcome. HNHU was associated with a 5.09-fold increase in the risk of death (OR, 5.09; 95% CI, 1.31–19.83; P value = 0.019) and a 1.98-fold increase in the risk of major disability (OR, 1.98; 95% CI 1.07–3.68; P value = 0.030) in comparison to LNNU. Conclusions: High serum UA levels combined with high NLR were independently associated with 3-month death and major disability in AIS patients after IVT.

Background Corin, a physical activator of atrial natriuretic peptide, has been associated with hypertension with unclear mechanisms. Here, we aimed to examine whether CORIN gene methylation was involved in the underlying molecular mechanisms. Methods DNA methylation levels of CORIN were measured by target bisulfite sequencing using genomic DNA isolated from peripheral blood mononuclear cells in 2498 participants in the Gusu cohort (discovery sample) and 1771 independent participants (replication sample). We constructed a mediation model with DNA methylation as the predictor, serum corin as the mediator, and hypertension as the outcome, adjusting for covariates. Multiple testing was controlled by false discovery rate (FDR) approach. Results Of the 9 CpGs assayed, hypermethylation at all CpGs were significantly associated with a lower level of blood pressure in the discovery sample and eight associations were also significant in the replication sample (all FDR-adjusted pConclusions These results suggest that hypermethylation in the CORIN gene is associated with a lower odds of prevalent hypertension and may be involved in the role of corin in blood pressure regulation.