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.

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.

Application of bedside HINTS, ABCD2 score and truncal ataxia to differentiate cerebellar-brainstem stroke from vestibular neuritis in the emergency room.

BACKGROUND AND PURPOSE: Acute vestibular syndrome (AVS) typically manifests as isolated dizziness or vertigo with no apparent neurological impairments. However, distinguishing life-threatening stroke from innocuous peripheral vestibular lesions in the emergency room (ER) remains challenging. This study aimed to explore the ability of the head impulse-nystagmus-test of skew (HINTS) combined with truncal ataxia or ABCD2 score to differentiate stroke from peripheral vestibular disease in patients with AVS in the ER. METHODS: We prospectively recruited 121 patients with AVS from December 2022 to June 2023, 69 of whom presented with vestibular neuritis (VN) and the remaining with posterior circulation stroke (PCS). We analysed the HINTS results, truncal ataxia and ABCD2 score and compared the sensitivity and specificity among HINTS, truncal ataxia, ABCD2 score and their combinations using the McNemar test for paired samples. RESULTS: HINTS combined with grade 2-3 truncal ataxia achieved significantly higher sensitivity than that of isolated HINTS in differentiating PCS from VN (100% vs 88.5%, p=0.031). The specificity of HINTS plus grade 2-3 truncal ataxia did not significantly differ from that of isolated HINTS (p=0.125); however, the combination of ABCD2 score and HINTS did not improve the diagnostic accuracy. The sensitivity of ABCD2 score ≥4 plus grade 2-3 truncal ataxia was significantly higher than those of isolated ABCD2 score ≥4 or isolated grade 2-3 truncal ataxia (p=0.016 and p<0.001, respectively) and not significantly lower than that of isolated HINTS (p=0.508). CONCLUSION: Compared with the ABCD2 score, the truncal ataxia is of more valuable assistance to HINTS in differentiating PCS. Although the combination of ABCD2 score and truncal ataxia has a significant implication, it is not a replacement for HINTS.

Inflammatory marker profiles and in-hospital neurological deterioration in patients with acute minor ischemic stroke.

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

Intracerebral hemorrhage-induced brain injury in mice: The role of peroxiredoxin 2-Toll-like receptor 4 inflammatory axis.

BACKGROUND: Peroxiredoxin 2 (Prx2), an intracellular protein that regulates redox reactions, released from red blood cells is involved in inflammatory brain injury after intracerebral hemorrhage (ICH). Toll-like receptor 4 (TLR4) may be crucial in this process. This study investigated the role of the Prx2-TLR4 inflammatory axis in brain injury following experimental ICH in mice. METHODS: First, C57BL/6 mice received an intracaudate injection of autologous arterial blood or saline and their brains were harvested on day 1 to measure Prx2 levels. Second, mice received an intracaudate injection of either recombinant mouse Prx2 or saline. Third, the mice were co-injected with autologous arterial blood and conoidin A, a Prx2 inhibitor, or vehicle. Fourth, the mice received a Prx2 injection and were treated with TAK-242, a TLR4 antagonist, or saline (intraperitoneally). Behavioral tests, magnetic resonance imaging, western blot, immunohistochemistry/immunofluorescence staining, and RNA sequencing (RNA-seq) were performed. RESULTS: Brain Prx2 levels were elevated after autologous arterial blood injection. Intracaudate injection of Prx2 caused brain swelling, microglial activation, neutrophil infiltration, neuronal death, and neurological deficits. Co-injection of conoidin A attenuated autologous arterial blood-induced brain injury. TLR4 was expressed on the surface of microglia/macrophages and neutrophils and participated in Prx2-induced inflammation. TAK-242 treatment attenuated Prx2-induced inflammation and neurological deficits. CONCLUSIONS: Prx2 can cause brain injury following ICH through the TLR4 pathway, revealing the Prx2-TLR4 inflammatory axis as a potential therapeutic target.

Application of Dual-Layer Spectral-Detector Computed Tomography Angiography in Identifying Symptomatic Carotid Atherosclerosis: A Prospective Observational Study.

BACKGROUND: Dual-layer spectral-detector dual-energy computed tomography angiography (DLCTA) can distinguish components of carotid plaques. Data on identifying symptomatic carotid plaques in patients using DLCTA are not available. METHODS AND RESULTS: In this prospective observational study, patients with carotid plaques were enrolled and received DLCTA. The attenuation for both polyenergetic image and virtual monoenergetic images (40, 70, 100, and 140 keV), as well as Z-effective value, were recorded in the noncalcified regions of plaques. Logistic regression models were used to assess the association between attenuations of DLCTA and the presence of symptomatic carotid plaques. In total, 100 participants (mean±SD age, 64.37±8.31 years; 82.0% were men) were included, and 36% of the cases were identified with the symptomatic group. DLCTA parameters were different between 2 groups (symptomatic versus asymptomatic: computed tomography [CT] 40 keV, 152.63 [interquartile range (IQR), 70.22-259.78] versus 256.78 [IQR, 150.34-408.13]; CT 70 keV, 81.28 [IQR, 50.13-119.33] versus 108.87 [IQR, 77.01-165.88]; slope40-140 keV, 0.91 [IQR, 0.35-1.87] versus 1.92 [IQR, 0.96-3.00]; Z-effective value, 7.92 [IQR, 7.53-8.46] versus 8.41 [IQR, 7.94-8.92]), whereas no difference was found in conventional polyenergetic images. The risk of symptomatic plaque was lower in the highest tertiles of attenuations in CT 40 keV (adjusted odds ratio [OR], 0.243 [95% CI, 0.078-0.754]), CT 70 keV (adjusted OR, 0.313 [95% CI, 0.104-0.940]), Z-effective values (adjusted OR, 0.138 [95% CI, 0.039-0.490]), and slope40-140 keV (adjusted OR, 0.157 [95% CI, 0.046-0.539]), with all P values and P trends <0.05. The areas under the curve for CT 40 keV, CT 70 keV, slope 40 to 140 keV, and Z-effective values were 0.64, 0.61, 0.64, and 0.63, respectively. CONCLUSIONS: Parameters of DLCTA might help assist in distinguishing symptomatic carotid plaques. Further studies with a larger sample size may address the overlap and improve the diagnostic accuracy.

Patterns of atrial fibrillation, relevant cardiac structural and functional changes predict functional and cognitive outcomes in patients with ischemic stroke and atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) pattern, relevant cardiac changes are important predictors of outcomes in AF, but their impact on patients with ischemic stroke and AF remained unclear. We aimed to explore the impact of AF patterns, cardiac structural and functional markers on long-term functional and cognitive outcomes in ischemic stroke patients with AF. METHODS: Ischemic stroke patients diagnosed with AF were enrolled in this retrospective cohort study. AF pattern was defined by both traditional and novel classification, in which patients were divided into AF diagnosed after stroke (AFDAS) and known before stroke (KAF). Left atrial (LA) diameter, left ventricular ejection fraction (LVEF), natriuretic peptide (BNP) and cardiac troponin (cTnI) were dichotomized according to the median value. Outcomes include poor functional outcome and cognitive impairment at the 1-year follow-up. Multivariable logistic regression was performed to validate the association between AF pattern, parameters of cardiac change and functional and cognitive outcome. RESULTS: A total of 377 patients were included. Non-paroxysmal AF patients had a higher risk of poor functional outcome (OR = 3.59, P < 0.0001) and cognitive impairment (OR = 2.38, P = 0.019) than paroxysmal AF patients, while there were no differences between AFDAS and KAF. Lower LVEF (OR = 1.83, P = 0.045) and higher BNP (OR = 2.66, P = 0.001) were associated with poor functional outcome. Lower LVEF (OR = 2.86, P = 0.004), higher LA diameter (OR = 2.72, P = 0.008) and BNP (OR = 2.31, P = 0.023) were associated with cognitive impairment. CONCLUSIONS: AF type and related cardiac markers can serve as predictors for poor functional and cognitive outcomes. Comprehensive cardiac assessment and monitoring should be strengthened after stroke.

Retinal structure and vessel density changes in cerebral small vessel disease.

Background: Cerebral small vessel disease (CSVD) attaches people's attention in recent years. In this study, we aim to explore retinal structure and vessel density changes in CSVD patients. Methods: We collected information on retinal metrics assessed by optical coherence tomography (OCT) and OCT angiography and CSVD characters. Logistic and liner regression was used to analyze the relationship between retinal metrics and CSVD. Results: Vessel density of superficial retinal capillary plexus (SRCP), foveal density- 300 length (FD-300), radial peripapillary capillary (RPC) and thickness of retina were significantly lower in CSVD patients, the difference only existed in the thickness of retina after adjusted relevant risk factors (OR (95% CI): 0.954 (0.912, 0.997), p = 0.037). SRCP vessel density showed a significant downward trend with the increase of CSVD scores (ß: -0.087, 95%CI: -0.166, -0.008, p = 0.031). SRCP and FD-300 were significantly lower in patients with lacunar infarctions and white matter hypertensions separately [OR (95% CI): 0.857 (0.736, 0.998), p = 0.047 and OR (95% CI): 0.636 (0.434, 0.932), p = 0.020, separately]. Conclusion: SRCP, FD-300 and thickness of retina were associated with the occurrence and severity of total CSVD scores and its different radiological manifestations. Exploring CSVD by observing alterations in retinal metrics has become an optional research direction in future.

A clinically actionable and explainable real-time risk assessment framework for stroke-associated pneumonia.

The current medical practice is more responsive rather than proactive, despite the widely recognized value of early disease detection, including improving the quality of care and reducing medical costs. One of the cornerstones of early disease detection is clinically actionable predictions, where predictions are expected to be accurate, stable, real-time and interpretable. As an example, we used stroke-associated pneumonia (SAP), setting up a transformer-encoder-based model that analyzes highly heterogeneous electronic health records in real-time. The model was proven accurate and stable on an independent test set. In addition, it issued at least one warning for 98.6 % of SAP patients, and on average, its alerts were ahead of physician diagnoses by 2.71 days. We applied Integrated Gradient to glean the model's reasoning process. Supplementing the risk scores, the model highlighted critical historical events on patients' trajectories, which were shown to have high clinical relevance.

Autonomic dysfunction and treatment strategies in intracerebral hemorrhage.

AIMS: Autonomic dysfunction with central autonomic network (CAN) damage occurs frequently after intracerebral hemorrhage (ICH) and contributes to a series of adverse outcomes. This review aims to provide insight and convenience for future clinical practice and research on autonomic dysfunction in ICH patients. DISCUSSION: We summarize the autonomic dysfunction in ICH from the aspects of potential mechanisms, clinical significance, assessment, and treatment strategies. The CAN structures mainly include insular cortex, anterior cingulate cortex, amygdala, hypothalamus, nucleus of the solitary tract, ventrolateral medulla, dorsal motor nucleus of the vagus, nucleus ambiguus, parabrachial nucleus, and periaqueductal gray. Autonomic dysfunction after ICH is closely associated with neurological functional outcomes, cardiac complications, blood pressure fluctuation, immunosuppression and infection, thermoregulatory dysfunction, hyperglycemia, digestive dysfunction, and urogenital disturbances. Heart rate variability, baroreflex sensitivity, skin sympathetic nerve activity, sympathetic skin response, and plasma catecholamine concentration can be used to assess the autonomic functional activities after ICH. Risk stratification of patients according to autonomic functional activities, and development of intervention approaches based on the restoration of sympathetic-parasympathetic balance, would potentially improve clinical outcomes in ICH patients. CONCLUSION: The review systematically summarizes the evidence of autonomic dysfunction and its association with clinical outcomes in ICH patients, proposing that targeting autonomic dysfunction could be potentially investigated to improve the clinical outcomes.

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.

Prevalence, risk factors and prognostic value of atrial fibrillation detected after stroke after haemorrhagic versus ischaemic stroke.

BACKGROUND AND OBJECTIVES: Prior evidence suggests that atrial fibrillation detected after stroke (AFDAS) is distinct from known atrial fibrillation (KAF), with particular clinical characteristics and impacts on outcomes in ischaemic stroke. However, the results remained inconsistent in ischaemic stroke, and the role of AFDAS in haemorrhagic stroke remains unclear. Therefore, we aimed to estimate the prevalence, risk factors and prognostic value of AFDAS in haemorrhagic stroke in comparison with ischaemic stroke. METHODS: This was a multicentre cohort study. Patients who had an ischaemic and haemorrhagic stroke hospitalised in the Chinese Stroke Center Alliance hospitals were enrolled and classified as AFDAS, KAF or sinus rhythm (SR) based on heart rhythm. Univariate and multivariate logistic regression analyses were used to assess the prevalence, characteristics, risk factors and outcomes of AFDAS, KAF and SR in different stroke subtypes. RESULTS: A total of 913 163 patients, including 818 799 with ischaemic stroke, 83 450 with intracerebral haemorrhage (ICH) and 10 914 with subarachnoid haemorrhage (SAH), were enrolled. AFDAS was the most common in ischaemic stroke. There were differences in the risk factor profile between stroke subtypes; older age is a common independent risk factor shared by ischaemic stroke (OR 1.06, 95% CI 1.06 to 1.06), ICH (OR 1.08, 95% CI 1.07 to 1.09) and SAH (OR 1.07, 95% CI 1.05 to 1.10). Similar to KAF, AFDAS was associated with an increased risk of in-hospital mortality compared with SR in both ischaemic stroke (OR 2.23, 95% CI 1.94 to 2.56) and ICH (OR 2.84, 95% CI 1.84 to 4.38). DISCUSSION: There are differences in the prevalence, characteristics and risk factors for AFDAS and KAF in different stroke subtypes. AFDAS was associated with an increased risk of mortality compared with SR in both ischaemic stroke and ICH. Rhythm monitoring and risk factor modification after both ischaemic and haemorrhagic stroke are essential in clinical practice. More emphasis and appropriate treatment should be given to AFDAS.

Clinical significance of the Microbleed Anatomical Rating Scale score in ischemic stroke patients treated with intravenous thrombolysis.

BACKGROUND: Conflicting results were shown on the relationship between cerebral microbleeds (CMBs) burden and functional outcomes in patients treated with intravenous tissues plasminogen activator (IV tPA). We aimed to investigate the relationship between CMBs burden and functional outcomes using the Microbleed Anatomical Rating Scale (MARS) and determine its optimal cutoff value. METHODS: A retrospective study was conducted to include patients treated with IV tPA in our stroke center, and the MARS was used to assess the CMBs burden. Other clinical data including demographic factors, stroke severity, vascular risk factors, and clinical outcomes were also documented. Another mediation analysis was performed to investigate whether early neurological improvement could mediate the association between MARS and functional outcomes. RESULTS: A total of 408 patients were included. A cutoff value of 1.5 could predict functional outcomes in patients treated with IV tPA. Based on that cutoff value, MARS showed an independent relationship with functional outcomes [adjusted OR (Odds Ratio) 0.841, 95% confidence interval (CI) 0.720-0.982, P = .029]. A shift analysis showed that higher MARS score (MARS ≥1.5) was related with poor functional outcome according to mRS score distribution (OR = 0.519, 95% CI 0.336-0.803, P = .003). Total effect (indirect + direct effect) was calculated and showed in figure. Early neurological improvement mediated 24% of the effect of MARS score on functional outcomes. CONCLUSION: Our study showed that MARS could be a potential method to assess the functional outcome based on CMBs in patients treated with IV tPA, and MARS score ≥ 1.5 might be an optimal threshold for poor functional outcome.

Risk factors and Outcomes of Dysphagia Among Patients Hospitalized with Acute Intracerebral Hemorrhage: Findings from the Chinese Stroke Center Alliance.

Objective: Dysphagia is a common and severe symptom of acute stroke; however, few studies investigated the prevalence of and risk factors of dysphagia among intracerebral hemorrhage (ICH) patients. We aimed to determine the prevalence and risk factors for dysphagia among acute ICH patients, and assess its impact on outcome of hospitalization. Methods: We collected data of ICH patients from the Chinese Stroke Center Alliance (CSCA) from August 2015 to July 2019 retrospectively. Univariate analysis and multivariable analysis were conducted to identify the factors associated with dysphagia and the outcomes of hospitalization. Results: 32 581 eligible ICH patients were included in the final analysis. According to the results of the swallowing function assessment, patients were divided into 24 084 (73.9%) non-dysphagia group and 8497 (26.1%) dysphagia group. Compared with the non-dysphagia group, the dysphagia group had poor outcomes, including higher incidence of pneumonia (60.2% vs 17.3%, OR 4.82, 95% CI 4.53-5.13) and in-hospital mortality (3.5% vs 0.3%, OR 5.96, 95% CI 4.41-8.06), longer length of stay (P < .01), higher hospitalization cost (P < .01), and higher medicine cost (P < .01). In multivariable analysis, the incidence of dysphagia was independently associated with older age (OR 1.10, 95% CI 1.09-1.11), male sex (OR 1.13, 95% CI 1.06-1.20), arrival at the hospital by emergency medical services (OR 2.11, 95% CI 1.99-2.24), lower Glasgow Coma Scale (GCS) score (per point decrease) (OR 0.78, 95% CI 0.77-0.78), history of ICH (OR 1.25, 95% CI 1.17-1.35), and higher glucose level (OR 1.09, 95% CI 1.07-1.10). Conclusions: More than one-quarter of acute ICH patients were diagnosed with dysphagia, which was associated with poor hospital outcomes. The early identification and management of dysphagia may reduce the possibility of stroke-associated pheumonia, shorten the length of hospital stay, and reduce medical cost.

Effects of rhythm-control and rate-control strategies on cognitive function and dementia in atrial fibrillation: a systematic review and meta-analysis.

BACKGROUND: Growing evidence suggests that atrial fibrillation (AF) is an independent risk factor for cognitive impairment and dementia, even in the absence of thromboembolic events and stroke. Whether rhythm-control therapy can protect cognitive function remains unclear. We aimed to evaluate the efficacy of rhythm-control strategies in patients with AF regarding cognitive function and dementia risk. METHODS: We systematically searched the PubMed, Embase and Cochrane Library databases for randomised clinical trials, cohort and case-control studies evaluating the associations between rhythm-control strategies and cognitive function outcomes up to May 2023. We assessed the risk of bias using the ROBINS-I and the Cochrane risk-of-bias tool. Both fixed- and random-effects models were used to create summary estimates of risk. RESULTS: We included a total of 14 studies involving 193,830 AF patients. In the pooled analysis, compared with rate-control, rhythm-control therapy was significantly associated with a lower risk of future dementia (hazard ratio (HR) 0.74; 95% confidence interval (CI) 0.62-0.89; I2 = 62%). Among the rhythm-control strategies, AF ablation is a promising treatment that was related to significantly lower risks of overall dementia (HR 0.62; 95% CI 0.56-0.68; I2 = 42%), Alzheimer's disease (HR 0.78; 95% CI 0.66-0.92; I2 = 0%) and vascular dementia (HR 0.58; 95% CI 0.42-0.80; I2 = 31%). Pooled results also showed that compared with patients without ablation, those who underwent AF ablation had significantly greater improvement in cognitive score (standardized mean difference (SMD) 0.85; 95% CI 0.30-1.40; P = 0.005; I2 = 76%). CONCLUSIONS: Rhythm-control strategies, especially ablation, are effective in protecting cognitive function, reducing dementia risk and thus improving quality of life in AF patients.

Low HALP (Hemoglobin, Albumin, Lymphocyte, and Platelet) Score Increases the Risk of Post-Stroke Cognitive Impairment: A Multicenter Cohort Study.

Objective: The HALP (hemoglobin, albumin, lymphocyte, and platelet) score is a novel indicator that measures systemic inflammation and nutritional status that has not been correlated with the risk of post-stroke cognitive impairment in patients with acute ischemic stroke or transient ischemic attack (TIA). Methods: Study participants were recruited from 40 stroke centers in China. The HALP score was derived using a weighted sum of hemoglobin, albumin, lymphocytes and platelets, and study participants were categorized into 4 groups of equal sizes based on quartiles cutoffs of the HALP score. The Montreal Cognitive Assessment (MoCA)-Beijing Cognitive Assessment Scale (MoCA-Beijing) was performed at 2 weeks and 12 months following stroke onset. Post-stroke cognitive impairment was considered in patients with MoCA-Beijing≤22. Multiple logistic regression methods were employed to evaluate the relationship between the HALP score and the subsequent risk of developing post-stroke cognitive impairment. Results: The study population comprised 1022 patients (mean age 61.6±11.0 years, 73% men). The proportion of individuals with MoCA-Beijing≤22 at 2 weeks was 49.2% and 32.4% at one year. Patients in the lowest quartile of HALP score (<36.56) were observed to harbor the highest risk of post-stroke cognitive impairment at 12 months post-stroke/TIA compared to those in the highest quartile (odds ratio=1.59, 95% CI=1.07-2.37, p=0.022), and lower domain scores for executive function, naming, and attention. There were no statistically significant differences between patients in the different quartiles of HALP score and HALP score at 2 weeks post-stroke/TIA. Conclusion: The HALP score is a simple score that could stratify the risk of post-stroke cognitive impairment in stroke/TIA patients to facilitate early diagnosis and interventions.

One-Year Outcomes of Early Therapy With Ticagrelor vs Clopidogrel in CYP2C19 Loss-of-Function Carriers With Stroke or TIA Trial.

BACKGROUND AND OBJECTIVES: The Ticagrelor or Clopidogrel with Aspirin in High-Risk Patients with Acute Nondisabling Cerebrovascular Events II (CHANCE-2) trial showed that among Chinese patients with minor ischemic stroke or transient ischemic attack (TIA) who were carriers of CYP2C19 loss-of-function alleles, dual-antiplatelet therapy with ticagrelor-aspirin reduced the 90-day risk of stroke without increased severe or moderate bleeding compared with clopidogrel-aspirin. However, whether dual-antiplatelet therapy with ticagrelor was superior to clopidogrel beyond the 90 days of follow-up remained unclear. In this study, we reported 1-year follow-up outcomes of the CHANCE-2 trial. METHODS: The CHANCE-2 trial is a randomized, double-blind, placebo-controlled trial at 202 centers in China. Patients with a minor stroke or TIA who carried CYP2C19 loss-of-function alleles were randomized within 24 hours after symptom onset, in a 1:1 ratio, to receive ticagrelor and placebo clopidogrel or to receive clopidogrel and placebo ticagrelor for 90 days; both groups received aspirin for the first 21 days. After day 90, treatment was as per the choice of the clinician and the patient. RESULTS: Among 6,412 patients, the proportion of patients on ticagrelor plus aspirin, clopidogrel plus aspirin, ticagrelor alone, clopidogrel alone, aspirin alone, other antiplatelet, and no antiplatelet beyond month 3 to 1 year was 0.09%, 1.56%, 0.13%, 2.66%, 73.65%, 0.78%, and 21.13% in the ticagrelor-aspirin group and 0.03%, 1.63%, 0.19%, 2.60%, 72.83%, 0.66%, and 22.06% in the clopidogrel-aspirin group, respectively. The primary outcome of new stroke occurred in 252 patients (7.91%) in the ticagrelor-aspirin group and 310 patients (9.73%) in the clopidogrel-aspirin group by 1 year of follow-up (hazard ratio 0.80; 95% CI 0.68-0.95; p = 0.007); new stroke beyond 3 months to 1 year occurred in 61 patients (2.07%) and 67 patients (2.32%) (p = 0.48), respectively. Primary safety outcome of severe or moderate bleeding occurred in 17 patients (0.53%) in the ticagrelor-aspirin group and 20 patients (0.63%) in the clopidogrel-aspirin group (p = 0.61). DISCUSSION: For CYP2C19 loss-of-function allele carriers, early dual-antiplatelet therapy with ticagrelor is superior to clopidogrel at 1 year in reducing recurrent stroke. TRIAL REGISTRATION INFORMATION: URL: clinicaltrials.gov. Unique identifier: NCT04078737. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with minor stroke or TIA with TIACYP2C19 loss-of-function, ticagrelor plus aspirin for 21 days is superior to clopidogrel plus aspirin in reducing the 1-year risk of recurrent stroke.

Outcomes associated to the time to treatment with intravenous tenecteplase for acute ischaemic stroke: subgroup analysis of the TRACE-2 randomised controlled clinical trial.

BACKGROUND: The benefit of intravenous alteplase in acute ischaemic stroke (AIS) is time-dependent. Tenecteplase is non-inferior to alteplase among patients with AIS. We aimed to delineate the association of the stroke onset to treatment time (OTT) with tenecteplase compared with alteplase on therapeutic benefit and clinical risks. METHODS: This is a post hoc analysis of the Tenecteplase Reperfusion therapy in Acute ischaemic Cerebrovascular Events-2 an open-label, randomised, controlled, non-inferior trial. A total of 1430 AIS within 4.5 hours onset at 53 sites in China from 12 June 2021 to 29 May 2022 were randomly assigned (1:1) to receive either tenecteplase 0.25 mg/kg or alteplase 0.9 mg/kg. The primary efficacy outcome was the proportion of participants with a modified Rankin Scale score of 0-1 at 90 days. A post hoc subgroup analysis was conducted with the OTT divided into three intervals (0-90 min, 91-180 min and 181-270 min). The primary safety outcome was symptomatic intracranial haemorrhage within 36 hours post-thrombolytic treatment. RESULTS: Treatment was initiated within 270 min of stroke onset in 1412 patients who were randomly allocated to either tenecteplase (n=707) or alteplase (n=705). The OR of primary efficacy outcome was similar as OTT increased (p=0.84). Adjusted odds of an excellent functional outcome were 0.99 (95% CI 0.37 to 2.67) for 0-90 min, 1.23 (95% CI 0.88 to 1.71) for 91-180 min and 1.21 (95% CI 0.88 to 1.65) for 181-270 min. All were in favour of the tenecteplase group. Meta-analysis of 2949 patients yielded a pooled risk difference of 5.54 (95% CI -0.18 to 11.26; p=0.82) in favour of tenecteplase for more than 180 min and 1.77 (95% CI -2.66 to 6.20; p=0.58) for 0-180 min. CONCLUSIONS: In AIS patients who were treated with either tenecteplase or alteplase within 4.5 hours onset, there was no difference observed in the efficacy and safety between the two groups at the three different OTT time intervals.

Rationale and design of ProUrokinase in Mild IsChemic strokE (PUMICE): a multicentre, prospective, randomised, open-label, blinded-endpoint controlled trial.

BACKGROUND AND PURPOSE: Recombinant human prourokinase (rhPro-UK) is a new generation of specific plasminogen activator, that is non-inferior to alteplase in acute ischemic stroke. We aimed to investigate the efficacy and safety of rhPro-UK compared with standard medical treatment in acute mild ischemic stroke within 4.5 hours of symptom onset. METHODS AND DESIGN: Prourokinase in mild ischemic stroke is a multicentre, prospective, randomised, open-label, blinded-endpoint controlled trial. Patients who had an acute ischemic stroke within 4.5 hours from symptom onset and with baseline National Institutes of Health Stroke Scale (NIHSS) score ≤ 5 will be recruited. Patients will be randomly assigned (1:1) to receive intravenous rhPro-UK (35 mg) or standard medical treatment. The follow-up duration will be 90 days. The calculated sample size is 1446. STUDY OUTCOMES: Primary efficacy outcome is an excellent functional outcome, defined as a modified Rankin Scale (mRS) score ≤ 1 at 90 days. Secondary efficacy outcomes include ordinal distribution of mRS at 90 days, mRS score ≤ 2 at 90 days, early neurological improvement at 24 hours (a decrease of NIHSS score ≥ 4 points compared with baseline or NIHSS score ≤ 1 point), Barthel index of 75-100 points at 90 days, quality of life at 90 days, and activities of daily living at 90 days. Safety outcomes are symptomatic intracranial haemorrhage within 36 hours, mortality at 90 days, moderate and severe systematic bleeding at 90 days, and adverse events/serious adverse events within 90 days. DISCUSSION: This large phase III randomised clinical trial will answer the question of whether thrombolysis is beneficial for acute mild ischemic stroke, and may provide evidence for rhPro-UK in patients had an acute mild ischemic stroke within 4.5 hours of symptom onset. TRIAL REGISTRATION NUMBER: NCT05507645.

Predictors of dysphagia screening and pneumonia among patients with intracerebral haemorrhage in China: a cross-sectional hospital-based retrospective study.

OBJECTIVES: This study aimed to investigate factors associated with undergoing dysphagia screening (DS) and developing pneumonia, as well as the relationship between DS and pneumonia in patients with intracerebral haemorrhage (ICH). DESIGN: Our study was a cross-sectional hospital-based retrospective study. STUDY DESIGN AND SETTINGS: We derived data from the China Stroke Centre Alliance, a nationwide clinical registry of ICH from 1476 participating hospitals in mainland China. To identify predictors for pneumonia, multivariable logistic regression models were used to identify patient characteristics that were independently associated with DS and pneumonia. PARTICIPANTS: We included 31 546 patients in this study with patient characteristics, admission location, medical history, hospital characteristics and hospital grade from August 2015 to July 2019. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcomes were DS and pneumonia during acute hospitalisation. RESULTS: In total, 25 749 (81.6%) and 7257 (23.0%) patients with ICH underwent DS and developed pneumonia. Compared with patients without pneumonia, those who developed pneumonia were older and had severe strokes (Glasgow Coma Scale 9-13: 52.7% vs 26.9%). Multivariable analyses revealed that a higher pneumonia risk was associated with dysphagia (OR, 4.34; 95% CI, 4.02 to 4.68), heart failure (OR, 1.85; 95% CI, 1.24 to 2.77) and smoking (OR, 1.12; 95% CI, 1.12 to 0.20). DS was associated with lower odds of pneumonia (OR, 0.65; 95% CI, 0.44 to 0.95). CONCLUSION: Our findings further confirm that dysphagia is an independent risk factor for pneumonia; one-fifth of patients with ICH did not undergo DS. However, comprehensive dysphagia evaluation and effective management are crucial. Nursing processes ensure the collection of complete and accurate information during evaluation of patients. There is a need to increase the rate of DS in patients with ICH, especially those with severe stroke or older. Further, randomised controlled trials are warranted to determine the effectiveness of DS on clinical outcomes.