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Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Background and Aim: Symptomatic intracranial hemorrhage (sICH) was the most serious complication associated with alteplase intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients. However, the relationship between serum sodium levels and post-thrombolysis symptomatic intracranial hemorrhage has not been investigated. Therefore, the aim of this study was to investigate the relationship between pre-thrombolysis serum sodium levels and sICH after IVT, as well as to explore the optimal pre-thrombolysis serum sodium levels for lowering the risk of sICH following IVT., Methods: From July 1, 2017 to April 30, 2023, out-of-hospital AIS patients who received IVT in the emergency department were enrolled in this study. Serum sodium levels were measured at admission prior to IVT, and National Institutes of Health Stroke Scale scores were continuously assessed during and after thrombolysis. Routine follow-up neuroimaging was performed between 22 to 36 h after IVT. Initially, three logistic regression models and restricted cubic splines (RCS) were established to investigate the relationship between serum sodium levels and post-thrombolysis sICH. Furthermore, to evaluate the predictive value of serum sodium for post-thrombolysis sICH, we compared area under the receiver operating characteristic curve (AUROC) and net reclassification improvement (NRI) before and after incorporating serum sodium into traditional models. Finally, subgroup analysis was conducted to explore interactions between serum sodium levels and other variables., Results: A total of 784 AIS patients who underwent IVT were enrolled, among whom 47 (6.0%) experienced sICH. The median serum sodium concentration for all patients was 139.10 [interquartile ranges (IQR): 137.40-141.00] mmol/L. Patients who developed sICH had lower serum sodium levels than those without sICH [138.20(IQR:136.00-140.20) vs. 139.20(IQR:137.40-141.00), p  = 0.031]. Logistic regression analysis (model 3) revealed a 14% reduction in the risk of post-thrombolysis sICH for every 1 mmol/L increase in serum sodium levels after adjusting for confounding variables ( p  < 0.001). The risk of post-thrombolysis sICH was minimized within the serum sodium range of 139.1-140.9 mmol/L compared to serum sodium concentration below 137.0 mmol/L [odds ratio (OR) = 0.33, 95% confidence interval (CI): 0.13-0.81] in model3. Furthermore, there was a significant trend of decreasing risk for sICH as serum sodium concentrations increased across the four quartiles ( P for trend = 0.036). The RCS analysis indicated a statistically significant reduction in the risk of sICH as serum sodium levels increased when the concentration was below 139.1 mmol/L. Incorporating serum sodium into traditional models improved their predictive performance, resulting in higher AUROC and NRI values. Subgroup analysis suggested that early infarct signs (EIS) appeared to moderate the relationship between serum sodium and sICH ( p  < 0.05)., Conclusion: Lower serum sodium levels were identified as independent risk factors for post-thrombolysis sICH. Maintaining pre-thrombolysis serum sodium concentrations above 139.1 mmol/L may help reduce the risk of post-thrombolysis sICH., 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. The reviewer ZC declared a shared affiliation with the authors XW, ZJ, DX, RZ, and HL at the time of review., (Copyright © 2024 Wu, Jiang, Xu, Zhang and Li.)

Introduction: Symptomatic intracranial hemorrhage (sICH) is a serious complication of acute ischemic stroke (AIS) after endovascular treatment (EVT). Limited data exist regarding predictors and clinical implications of sICH after EVT, underscoring the significance of identifying risk factors to enhance prevention strategies. Therefore, the main objective of this study was to evaluate the incidence of sICH and identify its predictors after EVT in patients with large infarct core-AIS in the pre-circulation stage., Methods: Using data from the EVT for the Pre-circulation Large Infarct Core-AIS Study, we enrolled patients who were treated with EVT from the Prospective Multicenter Cohort Study of Early Treatment in Acute Stroke (MAGIC) registry. Baseline demographics, medical history, vascular risk factors, blood pressure, stroke severity, radiographic features, and EVT details were collected. The patients were classified into three groups: without intracranial hemorrhage (ICH), with asymptomatic intracranial hemorrhage (aICH), and sICH, based upon the occurrence of sICH. The main outcomes were the occurrence of sICH according to the Heidelberg Bleeding Classification and functional condition at 90 days. Multivariate logistic regression analysis and receiver operating characteristic (ROC) curves were used to identify independent predictors of sICH after EVT., Results: The study recruited a total of 490 patients, of whom 13.3% ( n  = 65) developed sICH. Patients with sICH had less favorable outcomes than those without intracranial hemorrhage (ICH) and those with aICH (13.8% vs. 43.5% vs. 32.2%, respectively; p  < 0.001). The overall mortality was 41.8% ( n  = 205) at 90 days post-EVT. The univariate analysis revealed significant differences among the three groups in terms of blood glucose levels at admission, probability of favorable outcomes, incidence of brain herniation, and 90-day mortality. The multifactorial logistic regression analysis revealed that the blood glucose level at admission [odds ratio (OR) 1.169, p  < 0.001, confidence interval (CI) 1.076-1.269] was an independent predictor of sICH. A blood glucose level of 6.95 mmol/L at admission was the best predictor of sICH, with an area under the ROC curve (AUC) of 0.685 (95% CI: 0.616-0.754)., Discussion: The study findings demonstrated that the probability of sICH after EVT was 13.3% in patients with pre-circulation large infarct core-AIS, and sICH increased the risk of an unfavorable prognosis. Higher blood glucose levels at admission were associated with sICH after EVT in patients with pre-circulation large infarct core AIS. These findings underscore the importance of early management strategies to mitigate this risk., 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 © 2024 Yang, Yang, Shi, Ni, Fan, Xu, Ma, Yang, Wang, Zi, Yang and Hao.)

Background: Bilirubin has both antioxidative and prooxidative properties. The study aimed to explore the relationship between serum bilirubin and hemorrhagic transformation (HT) after intravenous thrombolysis in patients with acute ischemic stroke., Methods: The patients receiving intravenous thrombolysis with alteplase were retrospectively analyzed. HT was defined as new intracerebral hemorrhage in follow-up computed tomography images within 24-36 h after thrombolysis. Symptomatic intracranial hemorrhage (sICH) was defined as HT accompanied by worsening neurological function. Multivariate logistic regression and spline regression models were performed to investigate the relationship between serum bilirubin levels and the risk of HT and sICH., Results: Among 557 included patients, 71 (12.7%) were diagnosed with HT and 28 (5.0%) developed sICH. Patients with HT had significant higher baseline serum total bilirubin, direct bilirubin, and indirect bilirubin levels than those without HT. Multivariable logistic regression analysis indicated that patients with higher serum bilirubin levels, including total bilirubin (OR 1.05, 95% CI 1.01-1.08, p  = 0.006), direct bilirubin (OR 1.18, 95% CI 1.05-1.31, p  = 0.004), and indirect bilirubin (OR 1.06, 95% CI 1.02-1.10, p  = 0.005) had increased risk of HT. Furthermore, multiple-adjusted spline regression models excluded nonlinear association between serum bilirubin levels and HT ( p  > 0.05 for nonlinearity). Similar results were present between serum bilirubin and sICH., Conclusion: The data showed the positively linearly relationship between serum bilirubin levels and the risk of HT and sICH in patients with acute ischemic stroke undergoing intravenous thrombolysis., 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 © 2023 Chen, Yang, Xu, Fu and Huang.)

Some evidence suggests a possible influence of liver disease on stroke prognosis. We investigated the association between fibrosis-4 (FIB-4) score, a marker of liver disease, and the 3-month outcome in patients with ischemic stroke undergoing intravenous thrombolysis. We also evaluated the rate of symptomatic intracranial hemorrhage after thrombolysis. In this prospective cohort study, we enrolled consecutive patients with ischemic stroke treated with thrombolysis who had a 3-month follow-up. The FIB-4 score was calculated and the validated cut-off values were used to indicate high/low risk of advanced liver fibrosis. The primary outcome was 3-month poor prognosis estimated as a modified Rankin scale score ≥3. Of the 264 included patients, 131 (49.62%) had a 3-month mRS ≥3, with a significantly higher FIB-4 score, compared to those with a mRS <3 score ( adj p <0.001). When adjusted for possible confounders by multivariate logistic regression, FIB-4 score remained a significant predictor of poor outcome (OR 1.894, p = 0.011), along with history of atrial fibrillation (OR 3.488, p = 0.017), admission NIHSS score (OR 1.305, p < 0.001), and low values of hemoglobin (OR 0.730, p < 0.001). Mechanical thrombectomy had a favorable effect on patients' outcome (OR 0.201, p = 0.005). The risk of poor 3-month outcome was significantly higher among the 32 patients (12.1%) with high risk of severe fibrosis ( p = 0.007). FIB-4 score values were also related to symptomatic intracranial hemorrhage ( p = 0.004), specifically among patients with high probability of advanced hepatic fibrosis ( p = 0.037). FIB-4 score can be considered as a promising independent predictor of poor prognosis in patients with acute ischemic stroke undergoing intravenous thrombolysis., 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 © 2023 Norata, Lattanzi, Broggi, Rocchi, Bartolini and Silvestrini.)

Background and Purpose: Previous studies have stimulated debates on low-dose alteplase administration in acute ischemic stroke (AIS) among the Asian population. We sought to evaluate the safety and efficacy of low-dose alteplase in Chinese patients with AIS using a real-world registry., Methods: We analyzed data from the Shanghai Stroke Service System. Patients receiving alteplase intravenous thrombolysis within 4.5 hours were included. These patients were divided into the low-dose alteplase group (0.55-0.65 mg/kg) and the standard-dose alteplase group (0.85-0.95 mg/kg). Baseline imbalances were adjusted by using the propensity score matching. The primary outcome was mortality or disability, which was defined as the modified Rankin scale (mRS) score ranging from 2 to 6 at discharge. The secondary outcomes were in-hospital mortality, symptomatic intracranial hemorrhage (sICH) and functional independence (mRS score 0-2)., Results: From January 2019 to December 2020, a total of 1,334 patients were enrolled and 368 (27.6%) were treated with low-dose alteplase. The median age of the patients was 71 years, and 38.8% were female. Our study showed that the low-dose group had significantly higher rates of death or disability (adjusted odds ratio (aOR) = 1.49, 95% confidence interval (CI) [1.12, 1.98]) and less functional independence (aOR = 0.71, 95%CI [0.52, 0.97]) than the standard-dose group. There was no significant difference in sICH or in-hospital mortality between the standard-dose and low-dose alteplase groups., Conclusions: Low-dose alteplase was related to a poor functional outcome without lowering the risk of sICH, compared with standard-dose alteplase for AIS patients in China., 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 © 2023 Xu, Chen, Xie, Wang, Chen, Dong, Dong and Fang.)

Objectives: This study aimed to develop a score including novel putative predictors for predicting the risk of sICH and outcomes after thrombolytic therapy with intravenous (IV) recombinant tissue-type plasminogen activator (r-tPA) in acute ischemic stroke patients., Methods: All patients with acute ischemic stroke treated with IV r-tPA at three university-based hospitals in Chongqing, China, from 2014 to 2019 were retrospectively studied. Potential risk factors associated with sICH (NINDS criteria) were determined with multivariate logistic regression, and we developed our score according to the magnitude of logistic regression coefficients. The score was validated in another independent cohort. Area under the receiver operating characteristic curve (AUC-ROC) was used to assess the performance of the score. Calibration was evaluated using the Hosmer-Lemeshow goodness-of-fit method., Results: The SON 2 A 2 score (0 to 8 points) consisted of history of s moking (no = 1, yes = 0, β = 0.81), o nset-to-needle time (≥3.5 = 1,<3.5=0, β = 0.74), N IH Stroke Scale on admission (>10 = 2, ≤10 = 0, β = 1.22), n eutrophil percentage (≥80.0% = 1, <80% = 0, β = 0.81), A SPECT score (≤11 = 2, >11 = 0, β = 1.30), and a ge (>65 years = 1, ≤65 years = 0, β = 0.89). The SON 2 A 2 score was strongly associated with sICH (OR 1.98; 95%CI 1.675-2.34) and poor outcomes (OR 1.89; 95%CI 1.68-2.13). AUC-ROC in the derivation cohort was 0.82 (95%CI 0.77-0.86). Similar results were obtained in the validation cohort. The Hosmer-Lemeshow test revealed that predicted and observed event rates in derivation and validation cohorts were very close., Conclusion: The SON 2 A 2 score is a simple, efficient, quick, and easy-to-perform scale for predicting the risk of sICH and outcome after intravenous r-tPA thrombolysis within 4.5 h in patients with ischemic stroke, and risk assessment using this test has the potential for early and personalized management of this disease in high-risk patients., 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 © 2022 Ren, He, Du, Liu, Zhou, Bai, Chen, Wu, Song, Zhao and Yang.)

Background: Symptomatic intracranial hemorrhage (sICH) is a terrible complication after intravenous alteplase in stroke, and numerous biomarkers have been investigated. However, the change of biomarkers to sICH has not been well determined., Aim: To investigate the association between the change of biomarkers and sICH., Methods: This is a prospective cohort study, and patients with sICH within 24 h after thrombolysis were enrolled, while patients without sICH were matched by propensity score matching with a ratio of 1:1. The blood samples were collected before and 24 h after intravenous thrombolysis (IVT), and preset 49 serum biomarkers were measured by microarray analysis. Protein function enrichment analyses were performed to detect the association between the change of biomarkers and sICH., Results: Of consecutive 358 patients, 7 patients with sICH in 24 h were assigned to the sICH group, while 7 matched patients without any ICH were assigned to the non-sICH group. A total of 9 biomarkers were found to significantly change before vs. after thrombolysis between groups, including increased biomarkers, such as brain-derived neurotrophic factor, C-C motif chemokine ligand (CCL)-24, interleukin (IL)-6, IL-10, IL-18, and vascular endothelial growth factor, and decreased biomarkers, such as CCL-11, intercellular adhesion molecule-1, and IL-7., Conclusions: This is the first study to identify changes in serum biomarkers in patients with sICH after IVT, and found that 6 neuroinflammatory and 3 neuroprotective biomarkers may be associated with brain injury following post-thrombolytic sICH., Clinical Trial Registration: https://www.clinicaltrials.gov, identifier: NCT02854592., 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 © 2022 Cui, Wang, Zhao, Chen, Sheng, Wang and Chen.)

Background: The triglyceride-glucose (TyG) index has recently been proposed as a reliable marker of insulin resistance. There is insufficient evidence to verify that the TyG index is correlated with functional outcomes and hemorrhagic transformation and in patients with stroke treated with intravenous thrombolysis (IVT)., Methods: We designed a multicenter cohort study, which enrolled patients with acute ischemic stroke treated with IVT between December 2004 and December 2016. The TyG index was divided into tertiles and calculated on a continuous scale. Unfavorable functional outcomes were defined by the modified Rankin Scale of 3-6 at 90 days and the incident rates of symptomatic intracranial hemorrhage (SICH) within 36 h of IVT onset were surveyed. Stroke severity was defined as mild (4-8), moderate (9-15), or high (≥16) based on the National Institutes of Health Stroke Scale (NIHSS) scores., Results: Among 914 enrolled patients, the tertiles of the TyG index were 8.48 for T1, 8.48-9.04 for T2, and 9.04 for T3. T3 showed an increased risk of unfavorable functional outcomes at 90 days [odds ratio (OR): 1.76; P = 0.0132]. The TyG index was significantly associated with unfavorable functional outcomes at 90 days (OR: 1.32; P = 0.0431 per unit increase). No association was found between the TyG index and SICH. These findings were applicable for T3 with stroke of moderate (OR, 2.35; P = 0.0465) and high severity (OR: 2.57, P = 0.0440) patients with stroke., Conclusion: This study supports the strong association between the increased TyG index and increased unfavorable functional outcomes at 90 days in patients with acute ischemic stroke treated with IVT. These findings were found to be robust in patients with moderate and high stroke severity., 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 © 2022 Lin, Hu, Chao, Ho, Chen, Chan, Lin, Sun, Lin, Chen, Lin, Wei, Lin, Lee and Chao.)

Background: Symptomatic intracranial hemorrhage (sICH) after intravenous thrombolysis is closely related to the poor outcome of stroke., Aims: To determine the serum biomarkers associated with sICH based on the INTRECIS study., Methods: Enrolled patients with sICH and without any ICH were matched by propensity score matching with the ratio of 1:1. Preset 49 biomarkers were measured by protein microarray analysis. Gene Ontology and Pathway Enrichment Analysis and protein-protein interaction network (PPI) were analyzed in the identified biomarkers., Results: Of the consecutive 358 patients, eight patients occurred with sICH, which was assigned as an sICH group, while eight matched patients without any ICH were assigned as a Non-sICH group. A total of nine biomarkers were found significantly different between groups, among which the levels of interferon (IFN)-γ and interleukin (IL)-4 were higher, while the levels of C-reactive protein (CRP), glial cell line-derived neurotrophic factor (GDNF), insulin-like growth factor-binding protein (IGFBP)-6, lymphatic vessel endothelial hyaluronan receptor (LYVE)-1, matrix metalloprotein (MMP)-2, plasminogen activator inhibitor (PAI)-1, and platelet-derived growth factor (PDGF)-AA were lower in the sICH group compared with those in the Non-sICH group., Conclusions: Our finding indicated that baseline serum CRP, GDNF, IFN-γ, IGFBP-6, IL-4, LYVE-1, MMP-2, PAI-1, and PDGF-AA levels were associated with post-thrombolytic sICH in stroke., 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 © 2022 Cui, Zhao, Chen, Sheng, Wang, Meng and Chen.)

Background: Symptomatic intracranial hemorrhage (sICH) is a devastating complication of endovascular treatment (EVT) in patients with acute ischemic stroke (AIS) and is associated with high risk of disability and mortality. This study intended to evaluate the predictors of sICH after EVT in patients with large vessel occlusion (LVO)-induced AIS., Methods: We conducted a retrospective review on consecutive AIS patients who underwent EVT in our University hospital between January 2019 and August 2020. The patients were classified into two groups based upon the occurrence of sICH. The main outcomes were the occurrence of sICH using the Heidelberg Bleeding Classification and functional condition at 90 days. Multivariate logistic regression analysis and receiver operating characteristics (ROC) curves were used to identify independent predictors of sICH after EVT., Results: Three hundred and 69 patients were enrolled in the study, of which 16.8% ( n = 62) developed sICH. Favorable neurological outcome was lower in patients with sICH than in patients without sICH (6.5 vs. 43.3%; P < 0.001), with the overall mortality being 112 (30.4%) at 90 days post- EVT. Results from univariate analysis showed significant differences between the two groups in the prevalence of diabetes, initial Alberta Stroke Program Early CT Score (ASPECTS) score, National Institutes of Health Stroke Scale (NIHSS) score after operation, the levels of fasting blood glucose (FBG), neutrophil to lymphocyte ratio (NLR), platelets (PLT), and thrombin time (TT) at admission. Multivariate logistic regression analysis showed that FBG ≥ 7.54 mmol/L (OR: 2.765; 95% confidence interval [CI]: 1.513-5.054), NLR ≥ 5.48 (OR: 2.711; 95% CI: 1.433-5.128), TT at admission ≥ 16.25 s (OR: 2.022; 95% CI: 1.115-3.667), and NIHSS score within 24 h after the operation ≥ 10 (OR: 3.728; 95% CI: 1.516-9.170) were independent predictors of sICH. The combination of NLR ≥ 5.48, FBG ≥ 7.54 mmol/L, TT at admission ≥ 16.25 s, and NIHSS score within 24 h after the operation ≥ 10 generated an optimal prediction model (AUC: 0.723)., Conclusion: Higher levels of FDG, NLR, TT at admission, and NIHSS score after operation were associated with sICH after EVT in patients with LVO-induced AIS., 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 © 2022 Shen, Ma, Jiao, Chen, Xue, Li, Li, Song and Huang.)

Background and Purpose: There is limited information on symptomatic intracranial hemorrhage (sICH) in stroke patients without thrombolysis. This study aimed to evaluate the risk factors of sICH and the association between sICH and the prognosis at 3 and 12 months in acute ischemic stroke patients without thrombolysis. Methods: Data originated from the Chinese Acute Ischemic Stroke Treatment Outcome Registry. Univariate analysis and multivariate logistic regression were used to screen the risk factors of sICH. Multivariable logistic regression models were used to assess the association of sICH with poor outcome and all-cause mortality. Results: Totally, 9,484 patients were included, of which 69 (0.73%) had sICH. Atrial fibrillation (odds ratio [OR], 3.682; 95% confidence interval [CI], 1.945-6.971; p < 0.001), history of tumors (OR, 2.956; 95% CI, 1.115-7.593; p = 0.024), and the National Institutes of Health Stroke Scale (NIHSS) score on admission ([6-15: OR, 2.344; 95% CI, 1.365-4.024; p = 0.002] [>15: OR, 4.731; 95% CI, 1.648-13.583; p = 0.004]) were independently associated with sICH. After adjustment of the confounders, patients with sICH had a higher risk of poor outcome (OR, 1.983; 95% CI, 1.117-3.521; p = 0.018) at 3 months and that of all-cause mortality at 3 (OR, 6.135; 95% CI, 2.328-16.169; p < 0.001) and 12 months (OR, 3.720; 95% CI, 1.513-9.148; p = 0.004). Conclusion: sICH occurred in 0.73% of acute ischemic stroke patients without thrombolysis and was associated with a worse prognosis at 3 and 12 months. Atrial fibrillation, history of tumors, and NIHSS score at admission were independent risk factors of sICH., 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 Shen, Jin, Lu, Sun, Liu, Li, Shu, Tai, Li, Chen, Zhang, Zhang, Sun, Qiu, Wei, Sun and Huang.)