Brain ischemia causes systemic Notch1 activity in endothelial cells to drive atherosclerosis.

Stroke leads to persistently high risk for recurrent vascular events caused by systemic atheroprogression that is driven by endothelial cell (EC) activation. However, whether and how stroke induces sustained pro-inflammatory and proatherogenic endothelial alterations in systemic vessels remain poorly understood. We showed that brain ischemia induces persistent activation, the upregulation of adhesion molecule VCAM1, and increased senescence in peripheral ECs until 4 weeks after stroke onset. This aberrant EC activity resulted from sustained Notch1 signaling, which was triggered by increased circulating Notch1 ligands DLL1 and Jagged1 after stroke in mice and humans. Consequently, this led to increased myeloid cell adhesion and atheroprogression by generating a senescent, pro-inflammatory endothelium. Notch1- or VCAM1-blocking antibodies and the genetic ablation of endothelial Notch1 reduced atheroprogression after stroke. Our findings revealed a systemic machinery that induces the persistent activation of peripheral ECs after stroke, which paves the way for therapeutic interventions or the prevention of recurrent vascular events following stroke.

Reteplase versus Alteplase for Acute Ischemic Stroke.

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.).

Tenecteplase for Ischemic Stroke at 4.5 to 24 Hours without Thrombectomy.

BACKGROUND: Tenecteplase is an effective thrombolytic agent for eligible patients with stroke who are treated within 4.5 hours after the onset of stroke. However, data regarding the effectiveness of tenecteplase beyond 4.5 hours are limited. METHODS: In a trial conducted in China, we randomly assigned patients with large-vessel occlusion of the middle cerebral artery or internal carotid artery who had salvageable brain tissue as identified on perfusion imaging and who did not have access to endovascular thrombectomy to receive tenecteplase (at a dose of 0.25 mg per kilogram of body weight; maximum dose, 25 mg) or standard medical treatment 4.5 to 24 hours after the time that the patient was last known to be well (including after stroke on awakening and unwitnessed stroke). The primary outcome was the absence of disability, which was defined as a score of 0 or 1 on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability), at day 90. The key safety outcomes were symptomatic intracranial hemorrhage and death. RESULTS: A total of 516 patients were enrolled; 264 were randomly assigned to receive tenecteplase and 252 to receive standard medical treatment. Less than 2% of the patients (4 in the tenecteplase group and 5 in the standard-treatment group) underwent rescue endovascular thrombectomy. Treatment with tenecteplase resulted in a higher percentage of patients with a modified Rankin scale score of 0 or 1 at 90 days than standard medical treatment (33.0% vs. 24.2%; relative rate, 1.37; 95% confidence interval, 1.04 to 1.81; P = 0.03). Mortality at 90 days was 13.3% with tenecteplase and 13.1% with standard medical treatment, and the incidence of symptomatic intracranial hemorrhage within 36 hours after treatment was 3.0% and 0.8%, respectively. CONCLUSIONS: In this trial involving Chinese patients with ischemic stroke due to large-vessel occlusion, most of whom did not undergo endovascular thrombectomy, treatment with tenecteplase administered 4.5 to 24 hours after stroke onset resulted in less disability and similar survival as compared with standard medical treatment, and the incidence of symptomatic intracranial hemorrhage appeared to be higher. (Funded by the National Natural Science Foundation of China and others; TRACE-III ClinicalTrials.gov number, NCT05141305.).

Progress in Noninvasive Low-Intensity Focused Ultrasound Neuromodulation.

Low-intensity focused ultrasound represents groundbreaking medical advancements, characterized by its noninvasive feature, safety, precision, and broad neuromodulatory capabilities. This technology operates through mechanisms, for example, acoustic radiation force, cavitation, and thermal effects. Notably, with the evolution of medical technology, ultrasound neuromodulation has been gradually applied in treating central nervous system diseases, especially stroke. Furthermore, burgeoning research areas such as sonogenetics and nanotechnology show promising potential. Despite the benefit of low-intensity focused ultrasound the precise biophysical mechanism of ultrasound neuromodulation still need further exploration. This review discusses the recent and ongoing developments of low-intensity focused ultrasound for neurological regulation, covering the underlying rationale to current utility and the challenges that impede its further development and broader adoption of this promising alternative to noninvasive therapy.

Impact of Off-Hour Admission on In-Hospital Outcomes for Patients With Stroke Receiving Reperfusion Therapy in China.

BACKGROUND: The structure and staffing of hospitals greatly impact patient outcomes, with frequent changes occurring during nights and weekends. This retrospective cohort study assessed the impact of admission timing on in-hospital management and outcomes for patients with stroke receiving reperfusion therapy in China using data from a nationwide registry. METHODS: Data from patients receiving reperfusion therapy were extracted from the Chinese Stroke Center Alliance. Hospital admission time was categorized according to day/evening versus night and weekday versus weekend. Primary outcomes were in-hospital death or discharge against medical advice, hemorrhage transformation, early neurological deterioration, and major adverse cardiovascular events. Logistic regression was performed to compare in-hospital management performance and outcomes based on admission time categories. RESULTS: Overall, 42 381 patients received recombinant tissue-type plasminogen activator (r-tPA) therapy, and 5224 underwent endovascular treatment (EVT). Patients admitted during nighttime had a higher probability of receiving r-tPA therapy within 4.5 hours from onset or undergoing EVT within 6 hours from onset compared with those admitted during day/evening hours (adjusted odds ratio, 1.04 [95% CI, 1.01-1.08]; P=0.021; adjusted odds ratio, 1.72 [95% CI, 1.59-1.86]; P<0.001, respectively). However, no significant difference was observed between weekend and weekday admissions for either treatment. No notable differences were noted between weekends and weekdays or nighttime and daytime periods in door-to-needle time for r-tPA or door-to-puncture time for EVT initiation. Furthermore, weekend or nighttime admission did not have a significant effect on the primary outcomes of r-tPA therapy or EVT. Nevertheless, in patients undergoing EVT, a higher incidence of pneumonia was observed among those admitted at night compared with those admitted during day/evening hours (adjusted odds ratio, 1.22 [95% CI, 1.05-1.42]; P=0.011). CONCLUSIONS: Patients admitted at nighttime were more likely to receive r-tPA therapy or EVT within the time window recommended in the guidelines. However, patients receiving EVT admitted at night had an increased risk of pneumonia.

Subtype-Specific Association of Mitochondrial DNA Copy Number With Poststroke/TIA Outcomes in 10†241 Patients in China.

BACKGROUND: Mitochondrial DNA copy number (mtDNA-CN) is associated with the severity and mortality in patients with stroke, but the associations in different stroke subtypes remain unexplored. METHODS: We conducted an observational prospective cohort analysis on patients with ischemic stroke or transient ischemic attack enrolled in the Third China National Stroke Registry. We applied logistic models to assess the association of mtDNA-CN with functional outcome (modified Rankin Scale score, 3-6 versus 0-2) and Cox proportional hazard models to assess the association with stroke recurrence (treating mortality as a competing risk) and mortality during a 12-month follow-up, adjusting for sex, age, physical activity, National Institutes of Health Stroke Scale at admission, history of stroke and peripheral artery disease, small artery occlusion, and interleukin-6. Subgroup analyses stratified by age and stroke subtypes were conducted. RESULTS: The Third China National Stroke Registry enrolled 15 166 patients, of which 10 241 with whole-genome sequencing data were retained (mean age, 62.2 [SD, 11.2] years; 68.8% men). The associations between mtDNA-CN and poststroke/transient ischemic attack outcomes were specific to patients aged ≤65 years, with lower mtDNA-CN significantly associated with stroke recurrence in 12 months (subdistribution hazard ratio, 1.15 per SD lower mtDNA-CN [95% CI, 1.04-1.27]; P=5.2×10-3) and higher all-cause mortality in 3 months (hazard ratio, 2.19 [95% CI, 1.41-3.39]; P=5.0×10-4). Across subtypes, the associations of mtDNA-CN with stroke recurrence were specific to stroke of undetermined cause (subdistribution hazard ratio, 1.28 [95% CI, 1.11-1.48]; P=6.6×10-4). In particular, lower mtDNA-CN was associated with poorer functional outcomes in stroke of undetermined cause patients diagnosed with embolic stroke of undetermined source (odds ratio, 1.53 [95% CI, 1.20-1.94]; P=5.4×10-4), which remained significant after excluding patients with recurrent stroke (odds ratio, 1.49 [95% CI, 1.14-1.94]; P=3.0×10-3). CONCLUSIONS: Lower mtDNA-CN is associated with higher stroke recurrence rate and all-cause mortality, as well as poorer functional outcome at follow-up, among stroke of undetermined cause, embolic stroke of undetermined source, and younger patients.

Safety and Efficacy of Reteplase Versus Alteplase for Acute Ischemic Stroke: A Phase 2 Randomized Controlled Trial.

BACKGROUND: Reteplase is a more affordable new-generation thrombolytic with a prolonged half-life. We aimed to determine the safety dose range of reteplase for patients with acute ischemic stroke within 4.5 hours of onset. METHODS: This is a multicenter, prospective, randomized controlled, open-label, blinded-end point phase 2 clinical trial. Patients with acute ischemic stroke aged between 18 and 80 years who were eligible for standard intravenous thrombolysis were enrolled from 17 centers in China and randomly assigned (1:1:1) to receive intravenous reteplase 12+12 mg, intravenous reteplase 18+18 mg, or intravenous alteplase 0.9 mg/kg. The primary safety outcome was symptomatic intracranial hemorrhage (SITS definition) within 36 hours. The primary efficacy outcome was the proportion of patients with the National Institutes of Health Stroke Scale score of no more than 1 or a decrease of at least 4 points from the baseline at 14 days after thrombolysis. RESULTS: Between August 2019 and May 2021, 180 patients were randomly assigned to reteplase 12+12 mg (n=61), reteplase 18+18 mg (n=67), or alteplase (n=52). Four patients did not receive the study agent. Symptomatic intracranial hemorrhage occurred in 3 of 60 (5.0%) in the reteplase 12+12 mg group, 1 of 66 (1.5%) in the reteplase 18+18 mg group, and 1 of 50 (2.0%) in the alteplase group (P=0.53). The primary efficacy outcome in the modified intention-to-treat population occurred in 45 of 60 (75.0%) in the reteplase 12+12 mg group (odds ratio, 0.85 [95% CI, 0.35-2.06]), 48 of 66 (72.7%) in the reteplase 18+18 mg group (odds ratio, 0.75 [95% CI, 0.32-1.78]), and 39 of 50 (78.0%) in alteplase group. CONCLUSIONS: Reteplase was well tolerated in patients with acute ischemic stroke within 4.5 hours of onset in China with a similar efficacy profile to alteplase. The efficacy and appropriate dosage of reteplase for patients with acute ischemic stroke need prospective validation. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04028518.

Hemodynamic Impairment of Blood Pressure and Stroke Mechanisms in Symptomatic Intracranial Atherosclerotic Stenosis.

BACKGROUND: Hemodynamic impairment of blood pressure may play a crucial role in determining the mechanisms of stroke in symptomatic intracranial atherosclerotic stenosis). We aimed to elucidate this issue and assess the impacts of modifications to blood pressure on hemodynamic impairment. METHODS: From the Third China National Stroke Registry III, computed fluid dynamics modeling was performed using the Newton-Krylov-Schwarz method in 339 patients with symptomatic intracranial atherosclerotic stenosis during 2015 to 2018. The major exposures were translesional systolic blood pressure (SBP) drop and poststenotic mean arterial pressure (MAP), and the major study outcomes were cortex-involved infarcts and borderzone-involved infarcts, respectively. Multivariate logistic regression models and the bootstrap resampling method were utilized, adjusting for demographics and medical histories. RESULTS: In all, 184 (54.3%) cortex-involved infarcts and 70 (20.6%) borderzone-involved infarcts were identified. In multivariate logistic model, the upper quartile of SBP drop correlated with increased cortex-involved infarcts (odds ratio, 1.92 [95% CI, 1.03-3.57]; bootstrap analysis odds ratio, 2.07 [95% CI, 1.09-3.93]), and the lower quartile of poststenotic MAP may correlate with increased borderzone-involved infarcts (odds ratio, 2.07 [95% CI, 0.95-4.51]; bootstrap analysis odds ratio, 2.38 [95% CI, 1.04-5.45]). Restricted cubic spline analysis revealed a consistent upward trajectory of the relationship between translesional SBP drop and cortex-involved infarcts, while a downward trajectory between poststenotic MAP and borderzone-involved infarcts. SBP drop correlated with poststenotic MAP negatively (rs=-0.765; P<0.001). In generating hemodynamic impairment, simulating blood pressure modifications suggested that ensuring adequate blood pressure to maintain sufficient poststenotic MAP appears preferable to the reverse approach, due to the prolonged plateau period in the association between the translesional SBP drop and cortex-involved infarcts and the relatively short plateau period characterizing the correlation between poststenotic MAP and borderzone-involved infarcts. CONCLUSIONS: This research elucidates the role of hemodynamic impairment of blood pressure in symptomatic intracranial atherosclerotic stenosis-related stroke mechanisms, underscoring the necessity to conduct hemodynamic assessments when managing blood pressure in symptomatic intracranial atherosclerotic stenosis.

Dual Antiplatelet Therapy After Embolic Stroke of Undetermined Source: A Subgroup Analysis of the CHANCE-2 Trial.

BACKGROUND: The atherosclerotic sources of embolism are a significant contributor to embolic stroke of undetermined source (ESUS). However, there is limited evidence for the efficacy of intensive dual antiplatelet therapy for ESUS. We conducted an investigation to determine whether gene-directed dual antiplatelet therapy could reduce the risk of recurrent stroke in patients with ESUS. METHODS: CHANCE-2 (Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events-II) was an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled trial that objectively compared ticagrelor plus aspirin and clopidogrel plus aspirin in patients with minor stroke or transient ischemic attack who carried CYP2C19 loss-of-function alleles in China. All study participants were classified into ESUS and non-ESUS groups for the prespecified exploratory analysis. Cox proportional hazards models were used to assess the interaction of the state of ESUS with the effects of dual antiplatelet therapy with ticagrelor-aspirin versus clopidogrel-aspirin, adjusting for sociodemographic and clinical factors. RESULTS: The subgroup analysis comprised 5796 participants (90.4% of the total 6412 participants) in the CHANCE-2 trial, with a median age of 64.9 years (range, 57.0-71.4 years), of whom 1964 (33.9%) were female. These participants underwent diffusion-weighted imaging as part of the study protocol. After systematic evaluation, 15.2% of patients (881/5796) were deemed to have ESUS. The incidence of stroke recurrence in patients with ESUS was found to be 5.6% in the ticagrelor-aspirin group and 9.2% in the clopidogrel-aspirin group (hazard ratio, 0.57 [95% CI, 0.33-0.99]; P=0.04). In patients without ESUS, the respective incidence rates were 5.6% and 7.5% (hazard ratio, 0.72 [95% CI, 0.58-0.90]; P<0.01). The P value was 0.56 for the treatment × ESUS status interaction effect. CONCLUSIONS: In this prespecified exploratory analysis, ticagrelor with aspirin was superior to clopidogrel with aspirin for preventing stroke at 90 days in patients with acute ischemic stroke or transient ischemic attack who carried CYP2C19 loss-of-function alleles and were classified as ESUS. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04078737.

Disrupted pattern of rich-club organization in structural brain network from prediabetes to diabetes: A population-based study.

The network nature of the brain is gradually becoming a consensus in the neuroscience field. A set of highly connected regions in the brain network called "rich-club" are crucial high efficiency communication hubs in the brain. The abnormal rich-club organization can reflect underlying abnormal brain function and metabolism, which receives increasing attention. Diabetes is one of the risk factors for neurological diseases, and most individuals with prediabetes will develop overt diabetes within their lifetime. However, the gradual impact of hyperglycemia on brain structures, including rich-club organization, remains unclear. We hypothesized that the brain follows a special disrupted pattern of rich-club organization in prediabetes and diabetes. We used cross-sectional baseline data from the population-based PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE) study, which included 2218 participants with a mean age of 61.3 ± 6.6 years and 54.1% females comprising 1205 prediabetes, 504 diabetes, and 509 normal control subjects. The rich-club organization and network properties of the structural networks derived from diffusion tensor imaging data were investigated using a graph theory approach. Linear mixed models were used to assess associations between rich-club organization disruptions and the subjects' glucose status. Based on the graphical analysis methods, we observed the disrupted pattern of rich-club organization was from peripheral regions mainly located in frontal areas to rich-club regions mainly located in subcortical areas from prediabetes to diabetes. The rich-club organization disruptions were associated with elevated glucose levels. These findings provided more details of the process by which hyperglycemia affects the brain, contributing to a better understanding of the potential neurological consequences. Furthermore, the disrupted pattern observed in rich-club organization may serve as a potential neuroimaging marker for early detection and monitoring of neurological disorders in individuals with prediabetes or diabetes.

Tungstate Intercalated NiFe Layered Double Hydroxide Enables Long-Term Alkaline Seawater Oxidation.

Renewable electricity-driven seawater splitting presents a green, effective, and promising strategy for building hydrogen (H2)-based energy systems (e.g., storing wind power as H2), especially in many coastal cities. The abundance of Cl- in seawater, however, will cause severe corrosion of anode catalyst during the seawater electrolysis, and thus affect the long-term stability of the catalyst. Herein, seawater oxidation performances of NiFe layered double hydroxides (LDH), a classic oxygen (O2) evolution material, can be boosted by employing tungstate (WO4 2-) as the intercalated guest. Notably, insertion of WO4 2- to LDH layers upgrades the reaction kinetics and selectivity, attaining higher current densities with ≈100% O2 generation efficiency in alkaline seawater. Moreover, after a 350 h test at 1000 mA cm-2, only trace active chlorine can be detected in the electrolyte. Additionally, O2 evolution follows lattice oxygen mechanism on NiFe LDH with intercalated WO4 2-.

Differential effect of ticagrelor versus clopidogrel by homocysteine levels on risk of recurrent stroke: a post hoc analysis of the CHANCE-2 trial.

BACKGROUND: Elevated homocysteine levels are associated with increased blood coagulation and platelet activity and may modulate the response to antiplatelet therapies. We aimed to investigate the effects of homocysteine levels on the efficacy and safety of ticagrelor-acetylsalicylic acid (ASA) versus clopidogrel-ASA among patients with minor stroke or transient ischemic attack who carried CYP2C19 loss-of-function alleles. METHODS: We conducted a post hoc analysis of the CHANCE-2 (The Clopidogrel in High-risk Patients with Acute Nondisabling Cerebrovascular Events-II) trial. Participants were randomly assigned to treatment with ticagrelor-ASA or clopidogrel-ASA. We categorized participants into groups with elevated and non-elevated homocysteine levels, based on the median level. The primary efficacy outcome was recurrent stroke within 90-day follow-up. The primary safety outcome was severe or moderate bleeding within 90 days. RESULTS: A total of 2740 participants were randomly assigned to receive ticagrelor-ASA and 2700 to receive clopidogrel-ASA. Use of ticagrelor-ASA was associated with a reduced risk of recurrent stroke among participants with elevated homocysteine levels (74 [5.3%] v. 119 [8.5%]; hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.45-0.81), but not among those with non-elevated levels (86 [6.4%] v. 87 [6.7%]; HR 0.97, 95% CI 0.71-1.32; p = 0.04 for interaction). When analyzed as a continuous variable, the benefits of ticagrelor-ASA with regard to recurrent stroke increased as homocysteine levels increased (p = 0.04 for interaction). No significant interaction between homocysteine levels and treatment with regard to severe or moderate bleeding was observed (p = 0.7 for interaction). We found a significant interaction between homocysteine levels and therapy with regard to recurrent stroke in females (p = 0.04 for interaction) but not males. INTERPRETATION: In comparison with clopidogrel-ASA, ticagrelor-ASA conferred more benefit to patients with elevated homocysteine levels, particularly to female patients, in this secondary analysis of a randomized controlled trial involving patients with minor ischemic stroke or TIA. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT04078737.

Implementation of early prophylaxis for deep-vein thrombosis in intracerebral hemorrhage patients: an observational study from the Chinese Stroke Center Alliance.

BACKGROUND: There is substantial evidence to support the use of several methods for preventing deep-vein thrombosis (DVT) following intracerebral hemorrhage (ICH). However, the extent to which these measures are implemented in clinical practice and the factors influencing patients' receipt of preventive measures remain unclear. Therefore, we aimed to evaluate the rate of the early implementation of DVT prophylaxis and the factors associated with its success in patients with ICH. METHODS: This study enrolled 49,950 patients with spontaneous ICH from the Chinese Stroke Center Alliance (CSCA) between August 2015 and July 2019. Early DVT prophylaxis implementation was defined as an intervention occurring within 48 h after admission. Univariate and multivariate logistic regression analyses were conducted to identify the rate and factors associated with the implementation of early prophylaxis for DVT in patients with ICH. RESULTS: Among the 49,950 ICH patients, the rate of early DVT prophylaxis implementation was 49.9%, the rate of early mobilization implementation was 29.49%, and that of pharmacological prophylaxis was 2.02%. Factors associated with an increased likelihood of early DVT prophylaxis being administered in the multivariable model included receiving early rehabilitation therapy (odds ratio [OR], 2.531); admission to stroke unit (OR 2.231); admission to intensive care unit (OR 1.975); being located in central (OR 1.879) or eastern regions (OR 1.529); having a history of chronic obstructive pulmonary disease (OR 1.292), ischemic stroke (OR 1.245), coronary heart disease or myocardial infarction (OR 1.2); taking antihypertensive drugs (OR 1.136); and having a higher Glasgow Coma Scale (GCS) score (OR 1.045). Conversely, being male (OR 0.936), being hospitalized in tertiary hospitals (OR 0.778), and having a previous intracranial hemorrhage (OR 0.733) were associated with a lower likelihood of early DVT prophylaxis being administered in patients with ICH. CONCLUSIONS: The implementation rate of early DVT prophylaxis among Chinese patients with ICH was subpar, with pharmacological prophylaxis showing the lowest prevalence. Various controllable factors exerted an impact on the implementation of early DVT prophylaxis in this population.

Thrombocytopenia and In-hospital outcomes in patients with acute ischemic stroke undergoing intravenous thrombolysis: Findings from a nationwide registry study in China.

BACKGROUND AND OBJECTIVE: Our study aimed to evaluate the associations between platelet count (PC) and in-hospital outcomes for patients with stroke after rt-PA intravenous thrombolysis. METHODS: We identified patients who had been hospitalized with a primary diagnosis of stroke and had received rt-PA intravenous thrombolysis from June 2015 to July 2019 at participating hospitals in the Chinese Stroke Center Alliance. PC measured before intravenous thrombolysis was categorized into the following four groups: severe thrombocytopenia (PC < 100 × 109/L), mild thrombocytopenia (100 ≤ PC < 150 × 109/L), normal PC (150 ≤ PC ≤ 450 × 109/L), and thrombocythemia (PC > 450 × 109/L). Outcomes were determined from clinical data collected during hospitalization. The primary clinical outcome was symptomatic intracranial hemorrhage (sICH). Secondary outcomes were mortality, bleeding events, gastrointestinal (GI) hemorrhage, and in-hospital stroke recurrence. We used multivariate logistic regression models to evaluate the associations between PC and outcomes. RESULTS: We included 44,882 individuals with a median age of 66 years, of whom 34.7 % were female, 951 (2.1 %) had severe thrombocytopenia, 7218 (16.1 %) had mild thrombocytopenia, 36,522 (81.4 %) had a normal PC, and 191 (0.4 %) had thrombocythemia. Both severe and mild thrombocytopenia groups had higher risks of bleeding events (adjusted OR 1.30; 95 % CI,1.01-1.67; p = 0.045; adjusted OR 1.32; 95 % CI,1.19-1.46; p < 0.001) and sICH (adjusted OR 1.48;95 % CI,1.13-1.94; p = 0.005; adjusted OR 1.43;95 % CI,1.27-1.60; p < 0.001) than the normal PC group. Patients with 100 ≤ PC < 150 × 109/L also had a higher risk of in-hospital stroke recurrence (adjusted OR 1.12; 95 % CI,1.02-1.22; p = 0.02). CONCLUSIONS: Intravenous thrombolysis brings a high risk of sICH given PC < 150 × 109/L, especially PC < 100 × 109/L. It indicated that PC < 100 × 109/L is a reasonable contraindication to thrombolysis.

Effects of brain atrophy and altered functional connectivity on poststroke cognitive impairment.

BACKGROUND AND PURPOSE: Brain atrophy and disrupted functional connectivity are often present in patients with poststroke cognitive impairment (PSCI). This study aimed to explore the relationship between remote brain atrophy, connectional diaschisis and cognitive impairment in ischemic stroke patients to provide valuable information about the mechanisms underlying cognitive function recovery. METHODS: Forty first-time stroke patients with basal ganglia infarcts and twenty-nine age-matched healthy people were enrolled. All participants underwent T1-weighted and functional MRI scans, comprehensive cognitive function assessments at baseline, and 3-month follow-up. Brain volumes were calculated, and the atrophic regions were regarded as regions of interest in seed-based functional connectivity analyses. Pearson correlation analysis was used to explore the relationships among cognitive performance, brain atrophy, and functional connectivity alterations. RESULTS: Compared with healthy participants, stroke patients had worse cognitive performance at baseline and the 3-month follow-up. Worse cognitive performance was associated with smaller bilateral thalamus, left hippocampus, and left amygdala volumes, as well as lower functional connectivity between the left thalamus and the left medial superior frontal gyrus, between the right thalamus and the left median cingulate and paracingulate gyri, between the right hippocampus and the left medial superior frontal gyrus, and between the left amygdala and the right dorsolateral superior frontal gyrus. CONCLUSIONS: In patients with basal ganglia infarction, connectional diaschisis between remote brain atrophy and the prefrontal lobe plays a significant role in PSCI. This finding provides new scientific evidence for understanding the mechanisms of PSCI and indicates that the prefrontal lobe may be a target to improve cognitive function after stroke.

AIRPORT: A Data Consistency Constrained Deep Temporal Extrapolation Method To Improve Temporal Resolution In Contrast Enhanced CT Imaging.

Typical tomographic image reconstruction methods require that the imaged object is static and stationary during the time window to acquire a minimally complete data set. The violation of this requirement leads to temporal-averaging errors in the reconstructed images. For a fixed gantry rotation speed, to reduce the errors, it is desired to reconstruct images using data acquired over a narrower angular range, i.e., with a higher temporal resolution. However, image reconstruction with a narrower angular range violates the data sufficiency condition, resulting in severe data-insufficiency-induced errors. The purpose of this work is to decouple the trade-off between these two types of errors in contrast-enhanced computed tomography (CT) imaging. We demonstrated that using the developed data consistency constrained deep temporal extrapolation method (AIRPORT), the entire time-varying imaged object can be accurately reconstructed with 40 frames-per-second temporal resolution, the time window needed to acquire a single projection view data using a typical C-arm cone-beam CT system. AIRPORT is applicable to general non-sparse imaging tasks using a single short-scan data acquisition.

Hematocrit Predicts Poor Prognosis in Patients with Acute Ischemic Stroke or Transient Ischemic Attack.

This study aims to investigate the association between HCT (Hematocrit) levels and adverse outcomes in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA); 14,832 participants from the China National Stroke Registry-III with AIS or TIA were analyzed. Participants were categorized into quartiles based on baseline HCT levels. The primary outcome was poor functional outcomes (modified Rankin Scale ≥ 3) during three months, with secondary outcomes including all-cause death, stroke recurrence, and combined vascular events. Logistic regression or Cox regression models were used to assess the relationship between HCT and clinical outcomes. Compared to the third quartile, patients in the lowest quartile group showed increased risk of poor functional outcome (adjusted OR: 1.35, 95% CI: 1.15-1.58, p < 0.001), patients in the lowest quartile had a higher risk of all-cause death (adjusted HR: 1.68, 95% CI: 1.06-2.68, p = 0.028), as did those in the highest quartile (adjusted HR: 2.02, 95% CI: 1.26-3.25, p = 0.004). Sensitivity analysis shows that the association of HCT with all-cause death weakened, while the association with poor functional outcome was strengthened after excluding patients with recurrent stroke. Our results indicated that HCT level could be used as a short-term predictor for poor functional outcomes and all-cause death in patients with AIS or TIA.

Comparison of stress hyperglycemia ratio and glycemic gap on acute ICH in-hospital outcomes.

OBJECTIVE: To compare the effect of different indicators on stress-induced hyperglycemia for predicting in-hospital outcomes of acute intracerebral hemorrhage. METHODS: Using data from the Chinese Stroke Center Alliance database, which is a national, multicenter, prospective, and consecutive program. Stress-induced hyperglycemia was described as glycemic gap (GG, defined as fasting blood glucose [FBG] minus estimated average blood glucose) and stress hyperglycemia ratio (SHR, defined as FBG-to-estimated average blood glucose ratio [SHR 1] or FBG-to-HbA1c ratio [SHR 2]). The primary outcome was in-hospital mortality, and the second outcome was hematoma expansion. RESULTS: A total of 71,333 patients with acute intracerebral hemorrhage were included. In multivariate analyses, the highest levels of GG (OR 1.68, 95% CI 1.12-2.51), SHR 1 (OR 1.73, 95% CI 1.15-2.60), and SHR 2 (OR 2.07, 95% CI 1.33-3.23) were associated with in-hospital death (all the p trends <0.01). Only the highest level of SHR 2 (OR 1.24 [1.02-1.51], p trend >0.05) was related to hematoma expansion. No association between GG or SHR 1 and hematoma expansion was observed. The areas under the ROC curve of GG, SHR 1, and SHR 2 for in-hospital mortality were 0.8808 (95% CI 0.8603-0.9014), 0.8796 (95% CI 0.8589-0.9002), and 0.8806 (95% CI 0.8600-0.9012). The areas under the ROC curve of SHR 2 for hematoma expansion were 0.7133 (95% CI 0.6964-0.7302). INTERPRETATION: SHR (FBG-to-HbA1c ratio) was associated with both in-hospital death and hematoma expansion in intracerebral hemorrhage, and might serve as an accessory indicator for the in-hospital prognosis of intracerebral hemorrhage.

Brain structural-functional coupling mechanism in mild subcortical stroke and its relationship with cognition.

OBJECTIVES: Stroke can lead to significant restructuring of brain structure and function. However, the precise changes in the coordination between brain structure and function in subcortical stroke patients remain unclear. We investigated alterations in brain structural-functional coupling (SC-FC coupling) and their impact on cognitive function in subcortical basal ganglia infarction patients. METHODS: The study comprised 40 patients with mild stroke with basal ganglia region infarcts and 29 healthy controls (HC) who underwent multidimensional neuroimaging examination and neuropsychological testing. The subcortical stroke patients were divided into post-stroke cognitive impairment (PSCI) and stroke with no cognitive impairment (NPSCI) groups based on cognitive performance, with 22 individuals undergoing follow-up examination after three months. We investigated differences in brain structural-functional coupling across three groups, and their associations with cognitive functions. RESULTS: Compared to both HC participants and NPSCI, PSCI exhibited significantly reduced structural-functional coupling strength in specific brain regions. After a three-month period, there was observed an increase in structural-functional coupling strength within the frontal lobe (precentral gyrus and paracentral lobule). The strength of SC-FC coupling within the precentral gyrus, precuneus, and paracentral lobule regions demonstrated a decline correlating with the deterioration of cognitive function (MoCA, memory and visual motor speed functions). CONCLUSIONS: After subcortical basal ganglia stroke, PSCI patients demonstrated decreased SC-FC coupling in the frontal lobe region, correlating with multidimensional cognitive impairment. Three months later, there was an increase in SC-FC coupling in the frontal lobe, suggesting a compensatory mechanism during the recovery phase of cognitive impairment following stroke.