Association between untreated and treated blood pressure levels and cognitive decline in community-dwelling middle-aged and older adults in China: a longitudinal study.

BACKGROUND: Optimal blood pressure (BP) levels to reduce the long-term risk of cognitive decline remains controversial. We aimed to investigate the association between BP and anti-hypertensive treatment status with cognitive decline in older adults. METHODS: This study used data from the China Health and Retirement Longitudinal Study. Cognitive function was assessed at year 2011, 2013, 2015, and 2018. Global cognitive Z-score was calculated as the average score of episodic memory and mental intactness. BP were measured at the first and second wave. Pulse pressure (PP) was calculated as systolic BP (SBP) minus diastolic BP. Cumulative BP was calculated as the area under the curve using BP measurements from 2011 to 2013. Linear mixed models were used to assess the longitudinal association between BP-related measurements and cognitive decline. RESULTS: We included 11,671 participants (47.3% men and mean age 58.6 years). Individual with BP > 140/90 mm Hg or taking anti-hypertensive medication were independently associated with accelerated cognitive decline (ß=-0.014, 95% CI: -0.020 to -0.007). Individuals with anti-hypertensive medication use, but with controlled SBP to less than 120 mm Hg did not have a significantly increased risk of cognitive decline compared with normotension (ß=-0.003, 95% CI: -0.021 to 0.014). Individuals on anti-hypertensive treatment with PP of more than 70 mm Hg had a significantly higher risk of cognitive decline (ß=-0.033, 95% CI: -0.045 to -0.020). Regardless of anti-hypertensive treatment status, both elevated baseline and cumulative SBP and PP were found to be independently associated with accelerated cognitive decline. CONCLUSIONS: Cumulatively elevated SBP, PP and uncontrolled BP were associated with subsequent cognitive decline. Effectively controlling BP with anti-hypertensive treatment may be able to preserve cognitive decline in older adults.

Cumulative remnant cholesterol burden increases the risk of cardiovascular disease among young adults.

BACKGROUND: Previous studies have shown that remnant cholesterol (RC) was associated with cardiovascular disease (CVD) among middle-aged or older adults. However, lack of evidence on long-term exposures to RC and their role in CVD risk among young adults. We thus aimed to explore the association between cumulative RC burden and CVD in young adults. METHODS: We enrolled participants younger than 45 years free of CVD history in the Kailuan Study who completed the first three health examinations from 2006 to 2010. Cumulative RC burden included cumulative RC burden score, time-weighted cumulative RC, exposure duration of high RC, and time course of RC accumulation. The outcome was the incidence of CVD. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) between cumulative RC burden and CVD risk. RESULTS: A total of 15,219 participants were included (73.70% male, median age 39.13 years). During a median follow-up duration of 8.71 years (interquartile range: 8.4-9.15 years), 502 individuals developed CVD. After adjustment for traditional cardiovascular risk factors, highest risk of CVD was observed in participants with the highest cumulative RC burden score (HR, 1.66; 95% CI, 1.29-2.12), the highest quartile time-weighted cumulative RC (HR,1.50; 95% CI, 1.15-1.96), the longest exposure duration of high RC (HR, 1.71; 95% CI, 1.21-2.42), and those with cumulative RC burden and positive slope (HR, 1.79; 95% CI, 1.35-2.36). CONCLUSIONS: Cumulative RC burden increased the risk of CVD among young adults, suggesting that maintaining low RC levels throughout young adulthood may minimize CVD risk.

Elevated gut microbiota metabolite bile acids confer protective effects on clinical prognosis in ischemic stroke patients.

Background: There is evidence of an association between the gut microbiota and progression of stroke. However, the relationship between gut microbial metabolites, specifically bile acids (BAs), and post-ischemic stroke disability and poor functional outcomes remains unexplored. Methods: Patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA) in the Third China National Stroke Registry were grouped according to total bile acid (TBA) quartile on admission. Association of TBA with disability and poor functional outcomes were evaluated using logistic regression models and restricted cubic splines. Results: Data for 9,536 patients were included. After adjusting for confounders, the risks of disability and poor functional outcomes were significantly lower in the highest TBA quartile than in the lowest TBA quartile at the 3-month follow-up, with respective odds ratios (ORs) of 0.65 (95% confidence interval [CI] 0.55-0.78; p < 0.001) and 0.66 (95% CI 0.55-0.78, p < 0.001). Each standard deviation increase in the TBA level reduced the risks of disability and poor functioning outcomes by 10% (adjusted ORs 0.9 [95% CI 0.83-0.98; p = 0.01] and 0.9 [95% CI 0.83-0.97; p < 0.001], respectively). This association remained similar at the 1-year follow-up. After stratification by TOAST subtype, the risk of disability or a poor functional outcome in patients with the large-artery atherosclerosis or "other" subtype was significantly lower in the highest quartile than in the lowest quartile (p < 0.05). Conclusion: Serum TBA is an independent risk factor for disability and poor functional outcomes after AIS or TIA, and exerts a protective effects on brain.

Rehabilitation with brain-computer interface and upper limb motor function in ischemic stroke: A randomized controlled trial.

BACKGROUND: Upper limb motor dysfunction is a major problem in the rehabilitation of patients with stroke. Brain-computer interface (BCI) is a kind of communication system that converts the "ideas" in the brain into instructions and has been used in stroke rehabilitation. This study aimed to investigate the efficacy and safety of BCI in rehabilitation training on upper limb motor function among patients with ischemic stroke. METHODS: This was an investigator-initiated, multicenter, randomized, open-label, blank-controlled clinical trial with blinded outcome assessment conducted at 17 centers in China. Patients were assigned in a 1:1 ratio to the BCI group or the control group based on traditional rehabilitation training. The primary efficacy outcome is the difference in improvement of the Fugl-Meyer Assessment upper extremity (FMA-UE) score between two groups at month 1 after randomization. The safety outcomes were any adverse events within 3 months. FINDINGS: A total of 296 patients with ischemic stroke were enrolled and randomly allocated to the BCI group (n = 150) and the control group (n = 146). The primary efficacy outcomes of FMA-UE score change from baseline to 1 month were 13.17 (95% confidence interval [CI], 11.56-14.79) in the BCI group and 9.83 (95% CI, 8.19-11.47) in the control group (mean difference between groups was 3.35; 95% CI, 1.05-5.65; p = 0.0045). Adverse events occurred in 33 patients (22.00%) in the BCI group and in 31 patients (21.23%) in the control group. CONCLUSIONS: BCI rehabilitation training can further improve upper limb motor function based on traditional rehabilitation training in patients with ischemic stroke. This study was registered at ClinicalTrials.gov: NCT04387474. FUNDING: This work was supported by the National Key R&D Program of China (2018YFC1312903), the National Key Research and Development Program of China (2022YFC3600600), the Training Fund for Open Projects at Clinical Institutes and Departments of Capital Medical University (CCMU2022ZKYXZ009), the Beijing Natural Science Foundation Haidian original innovation joint fund (L222123), the Fund for Young Talents of Beijing Medical Management Center (QML20230505), and the high-level public health talents (xuekegugan-02-47).

Association between BMI-based metabolic phenotypes and prevalence of intracranial atherosclerotic stenosis: a cross-sectional study.

BACKGROUND: Obesity and metabolic syndrome (MetS) have been acknowledged to commonly co-exist and lead to increased risks of stroke, whereas the association between various BMI-based metabolic phenotypes and development of intracranial atherosclerotic stenosis (ICAS) remained controversial. METHODS: A total of 5355 participants were included from the Asymptomatic Polyvascular Abnormalities Community (APAC) study. Participants were categorized into six groups according to their body mass index (BMI) and MetS status. ICAS was assessed using transcranial Doppler (TCD) Ultrasonography. Logistic regression was employed to evaluate the association between BMI-based metabolic phenotypes and ICAS. RESULTS: 704 participants were diagnosed with ICAS. Compared to the metabolic healthy normal weight (MH-NW) group, the metabolic unhealthy normal weight (MUH-NW) group demonstrated a higher risk of ICAS (full-adjusted odds ratio [OR], 1.91; 95% confidence interval [CI], 1.42-2.57), while no significant association was observed in the metabolic unhealthy obesity (MUO) group (full-adjusted OR, 1.07; 95% CI, 0.70-1.65) and other metabolic healthy groups regardless of BMI. The results were consistent across gender, age, smoking, alcohol intake, and physical activity subgroups. CONCLUSION: The present study suggested that MUH-NW individuals had a significant association with increased risk of ICAS compared with MH-NW individuals.

Intensive Versus Standard Blood Pressure Management after Endovascular Therapy for Acute Ischemic Stroke: A Systematic Review and Meta-analysis.

Prospective clinical studies on blood pressure (BP) management targets after endovascular therapy (EVT) for acute ischemic stroke (AIS) have recently been published. Our objective was to assess the impact on clinical outcomes of BP management guided by established systolic BP (SBP) targets within the first 24 hours after successful EVT. Four randomized controlled trials (RCTs) including 1556 participants across 5 SBP target settings identified from 5 databases up to September 6, 2023 were included in this systematic review and meta-analysis. All the intensive SBP target groups in these RCTs were combined to facilitate head-to-head comparisons. Patients receiving intensive SBP management had lower risk of 90-day functional independence as assessed by the modified Rankin scale score (relative risk [RR], 0.81; 95% confidence interval [CI], 0.72 to 0.91; I2, 12%), excellent outcomes (RR,0.86; 95% CI, 0.75 to 0.99; I2, 7%), favorable outcomes (RR, 0.85; 95% CI, 0.78 to 0.92; I2, 0%), and quality of life (standardized mean difference, -0.22; 95% CI, -0.35 to -0.10; I2,0%). There were no differences in the probability of any intracerebral hemorrhage (RR, 1.04; 95% CI, 0.92 to 1.19; I2,0%), symptomatic intracerebral hemorrhage (RR, 1.10; 95% CI, 0.76 to 1.60; I2, 0%), stroke-related death (RR, 1.16; 95% CI, 0.80 to 1.68; I2, 0%), or parenchymal hematoma (RR, 1.71; 95% CI, 0.74 to 3.98; I2, 47%) between SBP targets. This meta-analysis provides evidence from RCTs suggesting that intensive SBP control (target<160 mm Hg) may be detrimental to clinical outcomes in AIS patients with successful reperfusion after EVT.

Naoxueshu Oral Liquid Accelerates Post-Craniotomy Hematoma Absorption in Patients: An Open-Label, Multicenter, and Randomized Controlled Trial.

OBJECTIVE: To investigate whether Naoxueshu Oral Liquid (NXS) could promote hematoma absorption in post-craniotomy hematoma (PCH) patients. METHODS: This is an open-label, multicenter, and randomized controlled trial conducted at 9 hospitals in China. Patients aged 18-80 years with post-craniotomy supratentorial hematoma volume ranging from 10 to 30 mL or post-craniotomy infratentorial hematoma volume less than 10 mL, or intraventricular hemorrhage following cranial surgery were enrolled. They were randomly assigned at a 1:1 ratio to the NXS (10 mL thrice daily for 15 days) or control groups using a randomization code table. Standard medical care was administered in both groups. The primary outcome was the percentage reduction in hematoma volume from day 1 to day 15. The secondary outcomes included the percentage reduction in hematoma volume from day 1 to day 7, the absolute reduction in hematoma volume from day 1 to day 7 and 15, and the change in neurological function from day 1 to day 7 and 15. The safety was closely monitored throughout the study. Moreover, subgroup analysis was performed based on age, gender, history of diabetes, and etiology of intracerebral hemorrhage (ICH). RESULTS: A total of 120 patients were enrolled and randomly assigned between March 30, 2018 and April 15, 2020. One patient was lost to follow-up in the control group. Finally, there were 119 patients (60 in the NXS group and 59 in the control group) included in the analysis. In the full analysis set (FAS) analysis, the NXS group had a greater percentage reduction in hematoma volume from day 1 to day 15 than the control group [median (Q1, Q3): 85% (71%, 97%) vs. 76% (53%, 93%), P<0.05]. The secondary outcomes showed no statistical significance between two groups, either in FAS or per-protocol set (P>0.05). Furthermore, no adverse events were reported during the study. In the FAS analysis, the NXS group exhibited a higher percentage reduction in hematoma volume on day 15 in the following subgroups: male patients, patients younger than 65 years, patients without diabetes, or those with initial cranial surgery due to ICH (all P<0.05). CONCLUSIONS: The administration of NXS demonstrated the potential to promote the percentage reduction in hematoma volume from day 1 to day 15. This intervention was found to be safe and feasible. The response to NXS may be influenced by patient characteristics. (Registration No. ChiCTR1800017981).

Two cases of venous thromboembolism in siblings after splenectomy due to a novel PROC gene mutation.

BACKGROUND: Venous thromboembolism(VTE)is a common multifactorial disease. Anticoagulant protein deficiency is the most usual hereditary thrombophilia in the Chinese people, which includes protein C(PC), protein S and antithrombin deficiencies. CASE PRESENTATION: A retrospective analysis was conducted on clinical manifestations, laboratory tests, genetic information, and other relevant data of siblings diagnosed with VTE in 2020 at the Department of Pediatrics of Shenzhen Second People's Hospital. The proband, a 12-year-old female, was admitted to the hospital in December 2020 with a complaint of pain in the left lower limb for four days. The examination found that the PC activity was 53%, and B-ultrasound showed bilateral thrombosis of the great saphenous vein in the thigh segment. The proband's younger brother, a 10-year-old male, was admitted to the hospital in January 2021 due to right lower limb pain for two weeks. PC activity is 40%. B-ultrasound showed superficial venous thrombosis in the left lower limb and upper limb. Both siblings suffered from thalassemia and underwent splenectomy before recurrent thrombosis occurred. The proband's mother was asymptomatic, and her PC activity was 45%. Both cases were treated with warfarin anticoagulation, and their symptoms improved. The proband's mother was found to have a heterozygous mutation at this locus through Sanger sequencing. CONCLUSION: Protein C deficiency should be considered for venous thromboembolism in childhood. The heterozygous mutation 1204 A > G in PROC exon 9 in this family is reported for the first time.

Anesthesia on Clinical Outcomes in an Extended Time Window During Endovascular Stroke Therapy: Exploratory Analysis of the ANGEL-ACT Registry.

OBJECTIVE: Data on the impact of different anesthesia methods on clinical outcomes in patients with acute ischemic stroke undergoing endovascular therapy (EVT) in extended windows are limited. This study compared clinical outcomes in patients with stroke having general anesthesia (GA), conscious sedation (CS), or local anesthesia (LA) during EVT in extended (>6 h) time windows. METHODS: We conducted an exploratory analysis of data from the ANGEL-ACT registry. The primary outcome was the modified Rankin Scale (mRS) score at 90 days. Secondary outcomes included the proportions of patients with mRS scores of 0 to 1, 0 to 2, and 0 to 3, and safety outcomes were any intracranial hemorrhage (ICH), symptomatic ICH, or mortality within 90 days. Multivariate analyses, inverse probability of treatment weighting, and coarsened exact matching were used to adjust for indication bias. RESULTS: A total of 646 patients were included in the analysis (GA,280; CS, 103; LA, 263). Patients having LA during EVT were more likely to have a favorable mRS score (adjusted odds ratio [aOR]: 1.75; 95% CI: 1.28 to 2.40) and a lower incidence of symptomatic ICH (aOR: 0.33; 95% CI: 0.14 to 0.76) than those having GA group. Similarly, CS was associated with greater odds of favorable 90-day mRS scores compared with GA (aOR: 1.69; 95% CI: 1.11 to 2.56). Posterior circulation stroke was overrepresented in the GA group (29.6%) and may be a reason for the worse outcomes in the GA group. CONCLUSIONS: Patients who received LA or CS had better neurological outcomes than those who received GA within extended time windows in a real-world setting.

Plasma sACE-2 and risk of recurrent stroke: a nested case-control analysis.

Introduction The angiotensin-converting enzyme-2 (ACE-2) and its shedding product [soluble ACE-2 (sACE-2)] are implicated in adverse cardiovascular outcomes. However, the relationship between sACE-2 and stroke recurrence is unknown. Herein, we examined the relationship of sACE-2 with stroke recurrence in patients with ischemic stroke or transient ischemic attack (TIA). Methods Data were obtained from the Third China National Stroke Registry (CNSR-Ⅲ). Eligible cases consisted of 494 patients who developed recurrent stroke within 1-year follow-up, 494 controls were selected using age- and sex- matched with a 1:1 case-control ratio. Conditional logistic regressions were used to evaluate the association between sACE-2 and recurrent stroke. The main outcomes were recurrent stroke within 1 year. Results Among 988 patients included in this study, the median (interquartile range) of sACE-2 was 25.17 (12.29-45.56) ng/mL. After adjustment for conventional confounding factors, the odds ratio with 95% confidence interval in the highest quartile versus the lowest quartile was 1.68 (1.12-2.53) for recurrent stroke within 1-year follow-up. Subgroup analysis showed that the association between elevated plasma level of sACE-2 and stroke recurrence was significant in patients with higher systemic inflammation, as indicated by high sensitivity C reactive protein (hsCRP) ≥ 2 mg/L (adjusted OR: 2.33 [95% CI, 1.15-4.72]) and neutrophil (NEUT) counts ≥ median (adjusted OR: 2.66 [95% CI, 1.35-5.23]), but not significant in patients with lower systemic inflammation. Discussion Elevated plasma sACE-2 concentration was associated with increased risk of recurrent stroke.

Efficacy of ginkgo diterpene lactone meglumine on cognitive function in patients with acute ischemic stroke: a predefined exploratory analysis of a multicenter, double-blind, randomized controlled trial.

BACKGROUND: Ginkgo diterpene lactone meglumine (GDLM) could improve the functional outcome in patients with acute ischemic stroke (AIS). This study aimed to investigate the efficacy of GDLM on cognitive function in patients with AIS. METHODS: This is a predefined exploratory analysis of the Efficacy and Safety of Ginkgo Diterpene Lactone Meglumine in Acute Ischemic Stroke trial, which was primarily designed to investigate the efficacy and safety of GDLM versus placebo on functional outcome at 100 centers in China. Cognitive function was measured using the Montreal Cognitive Assessment (MoCA) test. The primary outcomes were changes of MoCA from baseline to Day 14 and Day 90 after randomization. RESULTS: A total of 3163 patients with completed data on MoCA were enrolled. There was statistically significant difference of changes in MoCA scores between the GDLM group and the placebo group from baseline to Day 14 (mean difference, 0.31; 95% confidence interval [CI], 0.08-0.53; P = 0.007) and to Day 90 after randomization (mean difference, 0.47; 95% CI, 0.22-0.72; P < 0.001). Additionally, GDLM was associated with a higher proportion of patients who reached a clinically significant level of improvement in MoCA from baseline to Day 14 (odds ratio [OR], 1.25; 95% CI, 1.08-1.44; P = 0.002) and Day 90 after randomization (OR, 1.21; 95% CI, 1.03-1.41; P = 0.02). Specially, GDLM could significantly improve the scores of visuo-spatial and executive function and language. CONCLUSIONS: In this predefined analysis of patients with AIS, GDLM could improve the 14-day and 90-day cognitive function compared with the placebo.

LDL-C Levels and Bleeding Risk in Patients Taking DAPT After Minor Ischemic Stroke or TIA.

Importance: Evidence on the bleeding risk associated with low-density lipoprotein cholesterol (LDL-C) levels in patients receiving dual antiplatelet therapy (DAPT) remains sparse. Objective: To investigate the association of LDL-C levels with bleeding risk in patients with minor ischemic stroke (MIS) or high-risk transient ischemic attack (HRTIA) receiving DAPT. Design, Setting, and Participants: This cohort study was an analysis of pooled data from 2 randomized, double-blind, placebo-controlled clinical trials in China of patients with MIS or HRTIA who were receiving DAPT: the CHANCE (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events) trial enrolled patients at 114 sites from October 2009 to July 2012, and the CHANCE-2 enrolled patients at 202 centers from September 2019 to March 2021. Both sets of patients were followed up for 90 days. Data analysis was performed from August 2022 to May 2023. Exposures: Baseline LDL-C levels and receipt of ticagrelor-aspirin and clopidogrel-aspirin DAPT. Main Outcomes and Measures: The primary outcome was any bleeding, and the secondary outcome was severe or moderate bleeding within 3 months after randomization. The association of LDL-C levels and all outcomes was assessed by using the Cox proportional hazard model. Hazard ratios (HRs) with 95% CIs were calculated on univariable (unadjusted) Cox regression models. Adjusted HRs (aHRs) and their 95% CIs were calculated on multivariable Cox regression models. Results: In total, 8996 patients with acute MIS or HRTIA who were receiving DAPT were included in the 2 trials, of whom 1066 without serum specimens and 490 patients with missing baseline LDL-C value were excluded. Finally, 7440 patients with DAPT (4486 in the clopidogrel-aspirin group and 2954 in the ticagrelor-aspirin group) were included in this study. The median (IQR) age was 64.32 (56.56-71.30) years, and 2479 patients (33.32%) were women. A total of 270 (3.63%) bleeding events were reported at 3 months, and LDL-C less than 70 mg/dL was associated with an increased risk of both any bleeding (aHR, 1.48; 95% CI, 1.03-2.12), and severe or moderate bleeding (aHR, 2.78; 95% CI, 1.18-6.53). The risk of any bleeding was increased at lower LDL-C levels in the ticagrelor-aspirin group (aHR, 1.71; 95% CI, 1.08-2.72). However, an increased risk of any bleeding was not observed in the clopidogrel-aspirin group (aHR, 1.30; 95% CI, 0.73-2.30). There was no significant association between LDL-C levels and the risk of severe or moderate bleeding in either the ticagrelor-aspirin or clopidogrel-aspirin group. Conclusions and Relevance: These findings suggest that low LDL-C levels are associated with an increased bleeding risk within 3 months among patients with MIS or HRTIA receiving DAPT, especially those taking ticagrelor-aspirin. Weighing the risks and benefits is crucial when simultaneously considering the selection of LDL-C target strategies and DAPT regimens among these patients.

Severity and Remission of Metabolic Dysfunction-Associated Fatty/Steatotic Liver Disease With Chronic Kidney Disease Occurrence.

BACKGROUND: The association of the severity of hepatic steatosis in metabolic dysfunction-associated fatty liver disease (MAFLD)/metabolic dysfunction-associated steatotic liver disease (MASLD) and the remission of MAFLD/MASLD with CKD occurrence is unclear. METHODS AND RESULTS: The study enrolled 79 540 participants from the Kailuan cohort. Hepatic steatosis was diagnosed by ultrasound. MAFLD/MASLD was defined as hepatic steatosis combined with metabolic dysfunction and MASLD further excluded alcohol or other causes of liver disease. Chronic kidney disease (CKD) was defined as estimated glomerular filtration rate<60 mL/min per 1.73 m2 or positive proteinuria (≥1+). Hazard ratio (HR) was calculated by Cox regression models. After a median follow-up of 12.9 years, CKD occurred in 20 465 participants. After adjusting for potential confounders, MAFLD was associated with a higher risk of CKD compared with non-MAFLD (HR, 1.12 [95% CI, 1.09-1.16]), and this risk increased with increasing severity of hepatic steatosis (P-trend<0.001). Consistent findings were observed when MASLD was used as the exposure. Compared with persistent non-MAFLD, no statistical difference was found in the risk of CKD in MAFLD remission (HR, 1.04 [95% CI, 0.95-1.15]); however, MASLD remission still had a higher risk of CKD compared with persistent non-MASLD (HR, 1.15 [95% CI, 1.03-1.27]). When grouped according to the prior severity of hepatic steatosis, there was no statistically significant difference in risk of CKD in mild-MAFLD/MASLD remission compared with persistent non-MAFLD/MASLD, but moderated/severe-MAFLD/MASLD remission still had a higher risk. CONCLUSIONS: The risk of CKD in patients with MAFLD/MASLD increased with the severity of hepatic steatosis. Even after remission of the disease, patients with MAFLD/MASLD with prior moderate to severe hepatic steatosis still had a higher risk of CKD.

Systemic Immune-Inflammation Response is Associated with Futile Recanalization After Endovascular Treatment.

BACKGROUND: Frequent incidence of futile recanalization decreases the benefit of endovascular treatment (EVT) in acute ischemic stroke. We hypothesized that the inflammation and immune response after ischemic are associated with futile recanalization. We aimed to investigate the correlation of admission systemic immune-inflammation index (SII) with futile recanalization post EVT. METHODS: Patients with successful recanalization (modified Thrombolysis in Cerebral Ischemia angiographic score 2b-3) and maintained artery recanalized after 24 h of EVT were chosen from a prospective nationwide registry study. Futile recanalization was defined as a poor functional outcome (modified Rankin Scale score 3-6) at 90 days, irrespective of a successful recanalization. At admission, SII was calculated as (platelet count × neutrophil count)/lymphocyte count/100. Logistic regression analysis helped to test the relationship of SII with futile recanalization. RESULTS: Among the 1,002 patients included, futile recanalization occurred in 508 (50.70%). No matter whether tested as quartiles or continuous variables, SII was significantly associated with futile recanalization (P < 0.05), and for every one standard deviation increase of SII, the risk of futile recanalization elevated by 22.3% (odds ratio 1.223, 95% confidence interval 1.053-1.444, P = 0.0093). Moreover, no significant interactions could be observed between SII or SII quartiles and age, baseline National Institutes of Health Stroke Scale scores, onset-to-recanalization time, and modified Thrombolysis in Cerebral Ischemia angiographic scores (all P for interaction > 0.05). CONCLUSIONS: Early SII elevation was associated with an increased risk of futile recanalization among patients with EVT. Our results indicated that therapeutic drug targeting hyperreactive immune-inflammation response might be helpful for reducing the incidence of futile recanalization.

Sex and Age Differences in the Association Between Metabolic Dysfunction-Associated Fatty Liver Disease and Heart Failure: A Prospective Cohort Study.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a risk factor for heart failure (HF) occurrence, but it remains unclear whether the association between MAFLD and HF differs in different sexes and ages. METHODS: A total of 96 576 participants of Kailuan Study were included. MAFLD was defined as presence of hepatic steatosis and metabolic dysfunction and classified as mild and significant by ultrasound. Hazard ratios (HRs) were calculated by Cox regression models. RESULTS: After a median follow-up of 14.0 years, 2939 participants developed HF. Adjusting for confounding factors, mild-MAFLD (HR, 1.27 [95% CI, 1.16-1.39]) and significant-MAFLD (HR, 1.45 [95% CI, 1.31-1.63]) were associated with a higher risk of HF in all participants, and the risk differed by sex (Pinteraction<0.05) and age (Pinteraction<0.001). Compared with non-MAFLD participants, in women, significant-MAFLD was associated with an 84% (HR, 1.84 [95% CI, 1.43-2.37]) increased risk of HF; however, in men, the risk was 36% (HR, 1.36 [95% CI, 1.20-1.53]). In participants under 45 years, mild-MAFLD and significant-MAFLD had a 55% (HR, 1.55 [95% CI, 1.07-2.25]) and 172% (HR, 2.72 [95% CI, 1.87-3.97]) increased risk of HF; however, in participants over 65 years, even significant-MAFLD did not associate with a higher risk of HF (HR, 1.11 [95% CI, 0.92-1.34]). Afterwards, we stratified all participants by both sex and age and found that the risk of MAFLD-associated HF decreased with age in men (Pinteraction<0.05) and women (Pinteraction<0.05), but the sex difference in this risk was only present in participants younger than 45 years (Pinteraction<0.05). CONCLUSIONS: MAFLD greatly increased the risk of HF in women, especially young women. With increasing age, MAFLD-related risk of HF decreased and the difference between men and women disappeared.

Clinical and neuroimaging association between neuropsychiatric symptoms and nutritional status across the Alzheimer's disease continuum: a longitudinal cohort study.

OBJECTIVES: To investigate the association between neuropsychiatric symptoms (NPS) and nutritional status, and explore their shared regulatory brain regions on the Alzheimer's disease (AD) continuum. DESIGN: A longitudinal, observational cohort study. SETTING: Data were collected from the Chinese Imaging, Biomarkers, and Lifestyle study between June 1, 2021 and December 31, 2022. PARTICIPANTS: Overall, 432 patients on the AD continuum, including amnestic mild cognitive impairment and AD dementia, were assessed at baseline, and only 165 patients completed the (10.37 ± 6.08) months' follow-up. MEASUREMENTS: The Mini-Nutritional Assessment (MNA) and Neuropsychiatric Inventory (NPI) were used to evaluate nutritional status and NPS, respectively. The corrected cerebral blood flow (cCBF) measured by pseudo-continuous arterial spin labeling of the dietary nutrition-related brain regions was analyzed. The association between the NPS at baseline and subsequent change in nutritional status and the association between the changes in the severity of NPS and nutritional status were examined using generalized linear mixed models. RESULTS: Increased cCBF in the left putamen was associated with malnutrition, general NPS, affective symptoms, and hyperactivity (P < 0.05). The presence of general NPS (ß = -1.317, P = 0.003), affective symptoms (ß = -1.887, P < 0.001), and appetite/eating disorders (ß = -1.714, P < 0.001) at baseline were associated with a decline in the MNA scores during follow-up. The higher scores of general NPI (ß = -0.048), affective symptoms (ß = -0.181), and appetite/eating disorders (ß = -0.416; all P < 0.001) were longitudinally associated with lower MNA scores after adjusting for confounding factors. CONCLUSIONS: We found that baseline NPS were predictors of a decline in nutritional status on the AD continuum. The worse the severity of affective symptoms and appetite/eating disorders, the poorer the nutritional status. Furthermore, abnormal perfusion of the putamen may regulate the association between malnutrition and NPS, which suggests their potentially common neural regulatory basis.

The impact of intraarterial, intravenous, and combined tirofiban on endovascular treatment for acute intracranial atherosclerotic occlusion.

Background and purpose: Adjunctive tirofiban administration in patients undergoing endovascular treatment (EVT) for acute large vessel occlusion (LVO) has been investigated in several studies. However, the findings are conflict. This study aimed to compare the effect of different administration pathways of tirofiban on patients undergoing EVT for acute LVO with intracranial atherosclerotic disease (ICAD). Methods: Patients were selected from the ANGEL-ACT Registry (Endovascular Treatment Key Technique and Emergency Workflow Improvement of Acute Ischemic Stroke: A Prospective Multicenter Registry Study) and divided into four groups: intra-arterial (IA), intravenous (IV), and intra-arterial plus intravenous (IA+IV) and non-tirofiban. The primary outcome was 90-day ordinal modified Rankin Scale (mRS) score, and the secondary outcomes included the rates of mRS 0-1, 0-2, and 0-3 at 90-day, successful recanalization. The safety outcomes were symptomatic intracranial hemorrhage (sICH) and other safety endpoints. The multivariable logistic regression models adjusting for potential baseline confounders were performed to compare the outcomes. A propensity score matching (PSM) with a 1:1:1:1 ratio was conducted among four groups, and the outcomes were then compared in the post-matched population. Results: A total of 502 patients were included, 80 of which were in the IA-tirofiban group, 73 in IV-tirofiban, 181 in (IA+IV)-tirofiban group, and 168 in the non-tirofiban group. The median (IQR) 90-day mRS score in the four groups of IA, IV, IA+IV, and non-tirofiban was, respectively 3(0-5) vs. 1(0-4) vs. 1(0-4) vs. 3(0-5). The adjusted common odds ratio (OR) for 90-day ordinal modified Rankin Scale distribution with IA-tirofiban vs. non-tirofiban was 0.77 (95% CI, 0.45-1.30, P = 0.330), with IV-tirofiban vs. non-tirofiban was 1.36 (95% CI, 0.78-2.36, P = 0.276), and with (IA+IV)-tirofiban vs. non-tirofiban was 1.03 (95% CI, 0.64-1.64, P = 0.912). The adjusted OR for mRS 0-1 and mRS 0-2 at 90-day with IA-tirofiban vs. non-tirofiban was, respectively 0.51 (95% CI, 0.27-0.98, P = 0.042) and 0.50 (95% CI, 0.26-0.94, P = 0.033). The other outcomes of each group were similar with non-tirofiban group, all P was >0.05. After PSM, the common odds ratio (OR) for 90-day ordinal modified Rankin Scale distribution with IA-tirofiban vs. non-tirofiban was 0.41 (95% CI, 0.18-0.94, P = 0.036), and the OR for mRS 0-1 and mRS 0-2 at 90-day with IA-tirofiban vs. non-tirofiban was, respectively 0.28 (95% CI, 0.11-0.74, P = 0.011) and 0.25 (95% CI, 0.09-0.67, P = 0.006). Conclusions: Intra-arterial administration of tirofiban was associated with worse outcome than non-tirofiban, which suggested that intra-arterial tirofiban had a harmful effect on patients undergoing EVT for ICAD-LVO. Clinical trial registration: http://www.clinicaltrials.gov, Unique identifier: NCT03370939.

Impact of alkaline phosphatase on clinical outcomes in patients with ischemic stroke: a nationwide registry analysis.

Background: Data on the association between serum alkaline phosphatase (ALP) levels and clinical outcomes in patients with ischemic stroke (IS) are inconsistent and limited. Therefore, this study aimed to investigate the correlation between ALP and prognosis in patients with IS. Methods: Patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA) from the Third China National Stroke Registry were divided into four groups according to the quartiles of serum ALP levels on admission. Cox proportional hazards and logistic regression models were used to evaluate the correlation between ALP and the risk of all-cause mortality, disability (modified Rankin Scale (mRS) score 3-5), and poor functional outcomes (mRS score 3-6). Results: A total of 11,405 patients were included in the study. Higher levels of ALP were associated with all-cause mortality at 3 months (adjusted hazard ratio [HR] per standard deviation [SD]: 1.16; 95% confidence interval (CI): 1.07-1.27; p = 0.001) and 1 year (adjusted HR: 1.11; 95% CI: 1.03-1.20; p = 0.010). At the 3-month follow-up, each SD increase of ALP was associated with a 12 and 14% higher risk of disability (adjusted odds ratio (OR): 1.12; 95% CI: 1.06-1.18; p < 0.001) and poor functional outcomes (adjusted OR: 1.14; 95% CI: 1.08-1.20; p < 0.001). Similar results were observed at the 1-year follow-up. Higher ALP levels were associated with an increased risk of all-cause mortality, disability, and poor functional outcomes in patients with "others" subtypes (including other determined etiology and undetermined etiology) (p < 0.05). Conclusion: Elevated ALP levels were associated with an increased risk of all-cause mortality, disability, and poor function outcomes in patients with IS. Heterogeneity was observed among the subtypes of different etiologies.

Sublingual Edaravone Dexborneol for the Treatment of Acute Ischemic Stroke: The TASTE-SL Randomized Clinical Trial.

Importance: Sublingual edaravone dexborneol, which can rapidly diffuse and be absorbed through the oral mucosa after sublingual exposure, is a multitarget brain cytoprotection composed of antioxidant and anti-inflammatory ingredients edaravone and dexborneol. Objective: To investigate the efficacy and safety of sublingual edaravone dexborneol on 90-day functional outcome in patients with acute ischemic stroke (AIS). Design, Setting, and Participants: This was a double-blind, placebo-controlled, multicenter, parallel-group, phase 3 randomized clinical trial conducted from June 28, 2021, to August 10, 2022, with 90-day follow-up. Participants were recruited from 33 centers in China. Patients randomly assigned to treatment groups were aged 18 to 80 years and had a National Institutes of Health Stroke Scale score between 6 and 20, a total motor deficit score of the upper and lower limbs of 2 or greater, a clinically diagnosed AIS symptom within 48 hours, and a modified Rankin Scale (mRS) score of 1 or less before stroke. Patients who did not meet the eligibility criteria or declined to participate were excluded. Intervention: Patients were assigned, in a 1:1 ratio, to receive sublingual edaravone dexborneol (edaravone, 30 mg; dexborneol, 6 mg) or placebo (edaravone, 0 mg; dexborneol, 60 µg) twice daily for 14 days and were followed up until 90 days. Main Outcomes and Measures: The primary efficacy outcome was the proportion of patients with mRS score of 1 or less on day 90 after randomization. Results: Of 956 patients, 42 were excluded. A total of 914 patients (median [IQR] age, 64.0 [56.0-70.0] years; 608 male [66.5%]) were randomly allocated to the edaravone dexborneol group (450 [49.2%]) or placebo group (464 [50.8%]). The edaravone dexborneol group showed a significantly higher proportion of patients experiencing good functional outcomes on day 90 after randomization compared with the placebo group (290 [64.4%] vs 254 [54.7%]; risk difference, 9.70%; 95% CI, 3.37%-16.03%; odds ratio, 1.50; 95% CI, 1.15-1.95, P = .003). The rate of adverse events was similar between the 2 groups (89.8% [405 of 450] vs 90.1% [418 of 464]). Conclusion and Relevance: Among patients with AIS within 48 hours, sublingual edaravone dexborneol could improve the proportion of those achieving a favorable functional outcome at 90 days compared with placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT04950920.

Changes in baPWV and the risk of clinical outcomes: a cohort study of Chinese community-based population.

It has not been fully investigated whether improved arterial stiffness (AS) can reduce the clinical outcomes risk in community population-based study. In this prospective study, a total of 5247 individuals with abnormal AS (at baseline) and repeated brachial-ankle pulse wave velocity (baPWV) measurement before 2018 years were enrolled from the Kailuan Study. According the second baPWV measurement, we divided the participants into two groups, improved AS (defined as transfer elevated AS status to normal) and persistent AS (defined as maintaining elevated AS status). The outcome was a composite event of stroke, myocardial infraction, and all-cause mortality. We used Cox proportional hazards regression to examine the association between AS status at the follow-up and the subsequent outcome. During a median of 5.2 years follow-up, we observed 413 end point events. After adjusted for potential confounders, comparing with the persistent AS group, individuals in the improved AS group had a 43% (hazard ratio [HR], 0.57; 95% confidence interval [CI] 0.35-0.94) decreased the risk of the primary composite events. We also found a baPWV decrease of 1 m/s was associated with a 3% decreased risk (HR, 0.97; 95% CI 0.94-0.99) for primary composite events. We further demonstrated that younger than 60 years, non-smoker, non-hypertension, and non-diabetes were associated with improved the AS status. In conclusion, improving AS status may reduce the risk of clinical events. In the future, more research should be performed to explore the target for improving the AS status.