Objective: Transcranial magnetic stimulation (TMS), as a non-invasive means of neuromodulation, plays a crucial role in rehabilitation. Recent studies highlight that modeling the TMS-induced electric field (E-field) is essential to maximize the personalized treatment efficacy. Despite advancements in various E-field calculation methods, classic numerical calculation pipelines remain time-consuming and rely on whole head segmentation, and deep learning-based pipelines suffer from limited interpretability and stability. Methods: We develop a comprehensive pipeline that supports both numerical methods and deep learning methods for TMS targeting and optimization based on local E-field, called PLED. This pipeline mainly consists of local image patch extraction, tissue segmentation, local E-field estimation, and coil placement optimization. Notably, prior information about tissue conductivity and primary E-field from the coil is embedded into the deep learning model. Results: We have conducted extensive experiments on four datasets involving millions of local image patches in total. It is examined that our pipeline runs over 40 times faster on CPU and 100 times faster with GPU acceleration than classic numerical calculation pipelines for coil placement optimization. Meanwhile, compared to other deep learning-based pipelines, our pipeline achieves higher accuracy at most potential stimulation sites across the entire brain. Conclusion: Our proposed pipeline enables rapid, accurate, and robust local E-field estimation and coil placement optimization. Significance: Our pipeline would enhance stimulation efficacy and reduce data processing time in the precise personalized TMS treatment and rehabilitation.

Introduction: Headache ranks as the fifth most common reason for emergency department visits. This common symptom requires careful evaluation to distinguish between benign causes and conditions requiring urgent intervention. Proper triage and assessment of headache in the emergency setting remain challenging, headache may manifest as the sole or predominant presenting symptom in various types of acute stroke, including acute ischemic stroke, subarachnoid hemorrhage (SAH), and intracerebral hemorrhage (ICH). Disorders characterized by prominent headache symptoms, particularly migraine with aura, may elevate the risk of both ischemic and hemorrhagic stroke, underscoring the critical importance of timely imaging to guide appropriate treatment decisions. While CT is fast and widely used, its sensitivity for early ischemia is limited. Previous experimental–clinical study demonstrated that 0.23 T MRI can rapidly and accurately differentiate between stroke types, including cerebral hemorrhage and infarction. However, clinical studies that conduct a comparison of 0.23T MRI and CT in patients with SAH remain unclear. Hypothesis: To evaluate the diagnostic accuracy of portable low-field (0.23 T) MRI for acute SAH. We hypothesized that 0.23 T FLAIR MRI is comparable to CT in detecting SAH. Methods: This study included adults who visited the emergency department of Beijing Tiantan Hospital. Patients who underwent both CT and 0.23T MRI examinations were included in the study. The 0.23-T MRI protocol consisted of diffusion-weighted imaging (DWI), fluid-attenuated inversion recovery (FLAIR), and haematoma enhanced inversion recovery (HEIR) sequences, with a total scan time of 7.2 minutes. Four blinded raters independently assessed image quality and SAH presence. CT served as the reference standard. Sensitivity and specificity of 0.23T MRI for detection of SAH were calculated. Results: We selected 40 cases of SAH, among which 20 patients without positive neurological symptoms. Overall, 0.23-T MRI showed comparable sensitivity and specificity to CT for SAH detection, especially among the patients who underwent scans 24 to 72 hours after the onset of the disease. Figure 1 shows several cases. Conclusion: Low-field 0.23-T FLAIR MRI is comparable to CT in detecting SAH, which indicates that the application of 0.23T low-field MRI in emergency situations maybe reliable.

Low-field (LF) magnetic resonance imaging (MRI) plays a crucial role in assisting clinicians with rapid stroke diagnosis. However, its inherent limitations, such as low signal-to-noise ratio (SNR) and suboptimal image quality, make accurate stroke lesion identification challenging. To address this, we propose a Difference-Guided Conditional Diffusion Model (DGCD-3D) to enhance image quality of LF MRI while preserving structural integrity of stroke lesions. Specifically, the model incorporates a difference-adaptive forward diffusion process that guides the diffusion dynamics based on differences. During training, multi-scale intrinsic features from LF MRI and prior spatial information of stroke lesions are explicitly encoded into the generative process. Furthermore, a time-adaptive multi-loss optimization strategy dynamically balances pixel-wise and perceptual losses at different timesteps. DGCD-3D was evaluated on a large-scale, clinically scarce paired LF-HF MRI dataset (n = 974) acquired within a mean interval of 18.5 min. Experimental results demonstrate that DGCD-3D substantially improves LF MRI image quality (PSNR = 28.26, SSIM = 0.896) and achieves significantly higher consistency with HF MRI in stroke lesion assessment (Spearman's correlation coefficient ρ = 0.732) compared with the LF MRI (ρ = 0.680). Furthermore, a clinical authenticity assessment conducted by six experienced radiologists yielded a confusion rate of 51.6% and a confusion score of 5.64, further confirming the clinical reliability and broad applicability of the proposed approach. The codes and trained models will be released on GitHub: https://github.com/lihao9056/DGCD-3D.

Low-field portable magnetic resonance imaging (pMRI) devices address a crucial requirement in the realm of healthcare by offering the capability for on-demand and timely access to MRI, especially in the context of routine stroke emergency. Nevertheless, images acquired by these devices often exhibit poor clarity and low resolution, resulting in their reduced potential to support precise diagnostic evaluations and lesion quantification. In this paper, we propose a 3D deep learning based model, named Stroke-Aware CycleGAN (SA-CycleGAN), to enhance the quality of low-field images for further improving diagnosis of routine stroke. Firstly, based on traditional CycleGAN, SA-CycleGAN incorporates a prior of stroke lesions by applying a novel spatial feature transform mechanism. Secondly, gradient difference losses are combined to deal with the problem that the synthesized images tend to be overly smooth. We present a dataset comprising 101 paired high-field and low-field diffusion-weighted imaging (DWI), which were acquired through dual scans of the same patient in close temporal proximity. Our experiments demonstrate that SA-CycleGAN is capable of generating images with higher quality and greater clarity compared to the original low-field DWI. Additionally, in terms of quantifying stroke lesions, SA-CycleGAN outperforms existing methods. The lesion volume exhibits a strong correlation between the generated images and the high-field images, with R=0.852. In contrast, the lesion volume correlation between the low-field images and the high-field images is notably lower, with R=0.462. Furthermore, the mean absolute difference in lesion volumes between the generated images and high-field images ( $1.73\pm 2.03$ mL) was significantly smaller than the difference between the low-field images and high-field images ( $2.53\pm 4.24$ mL). It shows that the synthesized images not only exhibit superior visual clarity compared to the low-field acquired images, but also possess a high degree of consistency with high-field images. In routine clinical practice, the proposed SA-CycleGAN offers an accessible and cost-effective means of rapidly obtaining higher-quality images, holding the potential to enhance the efficiency and accuracy of stroke diagnosis in routine clinical settings. The code and trained models will be released on GitHub: SA-CycleGAN.

Background: Portable low-field MRI (pMRI) offers rapid, bedside neuroimaging in emergency stroke unit (ESU) but suffering from low signal-to-noise ratio and blurred anatomy. We developed a residual diffusion model conditioned on original low-field images to enhance DWI, T2-FLAIR and T1w for acute stroke evaluation. Methods: We retrospectively analyzed 1,325 consecutive patients with suspected acute ischemic stroke imaged within 24 hours of onset using both 0.23 T pMRI and 3.0 T reference MRI. The model employs a Swin-UNet backbone with conditional feature modulation from the corresponding low-field scans, progressively suppressing noise and restoring fine structures across diffusion timesteps. Image quality was quantified by peak signal-to-noise ratio (PSNR) and structural similarity index (SSIM) against 3.0 T references. Segmentation-based clinical relevance was assessed using modality-specific tools: pre-trained nnUNet for lesion segmentation on DWI, WMH-SynthSeg for white-matter hyperintensity (WMH) evaluation on T2-FLAIR, and FreeSurfer for tissue-specific volumetry (white matter, gray matter, cerebrospinal fluid) on T1w. Inference was performed on an NVIDIA RTX 3090 GPU. Results: The model consistently improved fidelity across modalities. For DWI, PSNR increased from 19.1 to 26.1 dB and SSIM from 0.69 to 0.83, with lesion-volume correlation rising from r = 0.72 to r = 0.80. For T2-FLAIR, PSNR improved from 20.8 to 26.4 dB and SSIM from 0.66 to 0.85, with WMH-volume correlation from r = 0.81 to r = 0.88. For T1w, PSNR rose from 21.9 to 28.7 dB and SSIM from 0.74 to 0.90; correlations with 3.0 T volumes strengthened for WM (r = 0.479→0.936), GM (r = 0.390→0.945), and CSF (r = 0.726→0.767). Mean processing time was 3.7 s per scan. Conclusions: Conditioning a residual diffusion model on the native low-field image substantially improves pMRI quality and volumetric agreement with 3.0 T references across DWI, T2-FLAIR, and T1w, supporting accurate and rapid bedside assessment in ESU and underscoring the clinical potential of portable low-field MRI in acute stroke workflows.

Background: Accurate and timely neuroimaging is essential for distinguishing hemorrhagic from ischemic strokes in emergency settings. While CT is effective in detecting cerebral hemorrhage, it has limited sensitivity for early ischemia. Low-field MRI technology presents a promising alternative. Recently, a new Hematoma Enhanced Inversion Recovery (HEIR) sequence based on 0.23-Tesla MRI was developed, enabling fast and accurate stroke diagnosis according to previous single-center cohorts. However, its accuracy against CT in larger-scale cohorts remains to be proven. Purpose: To compare the performance of 0.23-T MRI versus CT in diagnosing acute cerebral hemorrhage at Emergency Departments within 24 hours of symptom onset. Materials and Methods: A prospective, multicenter study was performed at 6 Emergency Departments between January and July 2024. Patients with suspected stroke symptoms who underwent both CT and 0.23-T MRI within 24 hours of symptom onset were included. The 0.23-T MRI protocol consisted of diffusion-weighted imaging (DWI), fluid-attenuated inversion recovery (FLAIR), and HEIR sequences, with a total scan time of 7.2 minutes (Figure 1). Four readers independently evaluated the CT and 0.23-T MRI images. Diagnostic accuracy for stroke was compared between CT and 0.23-T MRI, with the final diagnosis based on all clinical and imaging evidence available serving as the reference. Results: A total of 1,013 participants were included in the study. Among all patients, 0.23-T MRI correctly identified 101 of 102 hemorrhagic strokes, missing only one small lesion (1 mm in diameter). CT also identified 101 of 102 hemorrhagic strokes, missing one case of chronic hematoma detected on SWI of 3T MRI. Both CT and 0.23-T MRI demonstrated 99.0% sensitivity, 100.0% specificity, and 99.9% accuracy in detecting cerebral hemorrhage (Figure 2). Moreover, 0.23-T MRI demonstrated a 2.5-fold more acute ischemic lesion detection compared to CT (358 0.23-T MRI positive vs. 142 CT positive (Figure 3). Conclusion: With a 7.2-minute protocol, 0.23-T MRI may be as accurate as CT for detecting cerebral hemorrhage within 24 hours of symptom onset, and it identified more acute ischemic strokes than CT in emergency settings. These results highlight the value of 0.23-Tesla MRI as an expedited, reliable screening modality for reperfusion therapy in emergency stroke care.

BACKGROUND:Lp-PLA2 (lipoprotein-associated phospholipase A2) is a sensitive biomarker of vascular inflammation and atherosclerosis. This study evaluated the influence of Lp-PLA2 activity on the efficacy and safety of ticagrelor-aspirin versus clopidogrel-aspirin among patients with minor stroke or transient ischemic attack carrying CYP2C19 loss-of-function alleles. METHODS:The CHANCE-2 trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events-II) randomized 6412 patients with minor stroke or transient ischemic attack carrying CYP2C19 loss-of-function alleles to receive ticagrelor-aspirin or clopidogrel-aspirin. This subgroup study included patients with available baseline Lp-PLA2 activity measurements, stratified by the median value of 188.4 nmol/min per milliliter. The primary efficacy and safety outcomes were stroke recurrence and severe or moderate bleeding events within 90 days. Associations between treatment and outcomes were assessed using multivariable Cox proportional hazards models, adjusting for a history of hyperlipidemia. RESULTS:A total of 5919 patients were included (mean age, 64.4 years; 33.9% female). Among patients with low Lp-PLA2 activity, ticagrelor-aspirin reduced the 90-day risk of recurrent stroke compared with clopidogrel-aspirin (5.4% versus 7.4%; adjusted hazard ratio, 0.72 [95% CI, 0.54-0.97]). In patients with high Lp-PLA2 activity, no significant difference was observed (6.9% versus 8.2%; adjusted hazard ratio, 0.84 [95% CI, 0.65-1.09]). The P value was 0.45 for the treatment × Lp-PLA2 activity interaction effect on stroke recurrence. The risk of bleeding associated with ticagrelor-aspirin did not differ across Lp-PLA2 activity levels. CONCLUSIONS:In patients with minor stroke or transient ischemic attack carrying CYP2C19 loss-of-function alleles, elevated Lp-PLA2 activity did not significantly modify the efficacy or safety of dual antiplatelet therapy. Further research is needed to clarify the potential role of Lp-PLA2 in guiding individualized treatment decisions. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT04078737.

BACKGROUND:Thromboembolism is a common complication after interventional treatment of unruptured intracranial aneurysms. Glycoprotein IIb/IIIa inhibitor tirofiban may reduce thromboembolic complications during neurointerventional therapy for unruptured intracranial aneurysms. We aim to assess the efficacy and safety of prophylactic tirofiban in this clinical setting. METHODS:In this investigator-initiated, phase 2, prospective, randomized, open-label, blinded end point trial (TEAR [Thromboembolic Events in Endovascular Unruptured Aneurysm Repair]), adults aged 18 years to 80 years with unruptured intracranial aneurysms suitable for neurointerventional therapy were enrolled at 2 comprehensive stroke centers in China. Patients were randomly assigned (1:1) to receive intravenous tirofiban combined with dual antiplatelet therapy or dual antiplatelet therapy alone during endovascular aneurysm repair. The primary outcome was the number and volume of new ischemic lesions on diffusion-weighted imaging within 48 hours postprocedure. Key secondary outcomes included the incidence of symptomatic stroke and hemorrhagic events within 48 hours and at 30 days. RESULTS:Between March 2024 and October 2025, 228 patients were screened; we randomly allocated 192 patients to treatment-one individual did not receive magnetic resonance imaging because of intensive care unit hospitalization before imaging; 191 patients were enrolled (95 in the tirofiban group, 96 in the control group). Median age of the patients was 58 years; 22.0% were men, and 78.0% were women. Adjunctive tirofiban significantly reduced the median volume of new infarcts (48.6 versus 88.2 mm3, P=0.007) and showed a downward trend in the number of new infarction lesions (P=0.046). There were no significant differences between groups in symptomatic stroke, intracranial hemorrhage, or major bleeding rates at either 48 hours or 30 days (all P>0.05). CONCLUSIONS:In this randomized, phase 2 trial, prophylactic intravenous tirofiban combined with dual antiplatelet therapy significantly reduced the new postoperative infarct lesions, without increasing hemorrhagic complications and mortality. These findings warrant validation in a multicenter, large-sample trial. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT06238115.

Background Supracardiac atherosclerosis is a major cause of stroke. Although vessel wall MRI (vwMRI) can assess plaques, current techniques lack full head-neck-aortic arch coverage and efficiency. Purpose To develop and evaluate a head-neck-aortic vwMRI protocol for supracardiac atherosclerosis, compare its performance with that of supra-aortic CT angiography (CTA), and determine its feasibility in helping identify causes of embolic stroke of undetermined source (ESUS). Materials and Methods We developed a noncontrast head-neck-aortic vwMRI protocol integrated with neural network-based acceleration and multichannel coils, enabling a scan time of approximately 15 minutes. Then, participants with acute ischemic stroke or transient ischemic attack were recruited from October 2024 to March 2025. They received routine supra-aortic CTA and this new vwMRI protocol. Plaque vulnerabilities, vascular stenosis, and stroke etiologies were compared between the modalities. The accuracy of vwMRI for detecting calcification was evaluated using CTA as the reference standard, and the McNemar test was used to compare the findings between CTA and vwMRI. Results Among 108 participants who underwent imaging with both modalities (mean age, 56 years ± 14 [SD]; 89 male participants), the plaque detection rate was higher with vwMRI than CTA (88 of 108 participants [81.5%] vs 75 of 108 participants [69.4%]; P = .002). Moreover, vwMRI helped achieve 91% (98 of 108 participants) accuracy for calcification detection. vwMRI helped identify intraplaque hemorrhage in 27.8% (30 of 108) of participants and demonstrated an ulceration rate comparable with that of CTA (28 of 108 participants [25.9%] vs 25 of 108 participants [23.1%]; P = .51). CTA helped identify 49 participants with vascular stenosis, whereas vwMRI helped identify 47 participants with causes including atherosclerosis (n = 41), thrombus (n = 3), and dissection (n = 3). For 38 participants initially classified with ESUS via CTA, vwMRI enabled reclassification of 16, reducing the percentage of participants with ESUS from 35.2% (38 of 108 participants) to 20.4% (22 of 108 participants) (P < .001). Conclusion This head-neck-aortic vwMRI protocol was feasible and demonstrated a higher plaque detection rate than supra-aortic CTA. © RSNA, 2026 Supplemental material is available for this article. See also the editorial by von Kummer in this issue.

BACKGROUND:Headache may manifest as the sole or predominant presenting symptom of various types of acute stroke. While mobile low-field magnetic resonance imaging (mLF-MRI) shows promise for rapid and accurate diagnosis in the emergency department (ED), its diagnostic concordance using computed tomography (CT) as the reference standard requires clarification. METHODS:This prospective study included 199 patients who presented to the ED of Beijing Tiantan Hospital with headache within 72 h of onset, without Face-Arm-Speech Test (FAST) symptoms, and who underwent 0.23-T mLF-MRI between January and July 2024. This study evaluated the diagnostic utility of 0.23-T mLF-MRI in emergency patients presenting with an isolated acute headache. We specifically compared the consistency of mLF-MRI and CT in detecting subarachnoid hemorrhage (SAH) and other causes. RESULTS:Of the 199 patients with headache who did not have FAST symptoms, 71 (35.68%) were diagnosed with stroke, including 60 cases of SAH and 2 patients with intracerebral hemorrhage (ICH). Notably, 9 patients presenting with headaches but without FAST symptoms were diagnosed with acute ischemic stroke. The diagnostic concordance between the fluid-attenuated inversion recovery (FLAIR) sequence of mLF-MRI and CT for SAH was excellent (κ = 0.99). The mLF-MRI provided short scanning times and offered a portable, low-power diagnostic tool. CONCLUSION:For emergency patients with headaches as the initial and isolated clinical manifestation, mLF-MRI may serve as a supplementary diagnostic imaging modality that provides additional diagnostic information in selected ED settings. mLF-MRI, especially FLAIR sequences, demonstrated high CT-referenced diagnostic concordance for SAH and may also detect early ischemic lesions.

Background The role of renal function in patients with acute ischaemic stroke (AIS) receiving blood pressure (BP) lowering therapy remains incompletely understood. In this prespecified subgroup analysis of the CATIS-2 trial, we tested the hypothesis that baseline estimated glomerular filtration rate (eGFR) affects the relationship between early antihypertensive therapy and outcomes in AIS.Methods In the CATIS-2 trial, AIS patients were randomly assigned to early treatment (initiating BP-lowering agents within 24–48 hours of stroke onset) or delayed treatment (withholding such agents until day 8). The composite of functional dependence or death (modified Rankin Scale score ≥3) at day 90 was defined as the primary outcome. The treatment effect was analysed between different baseline eGFR values (<90 versus ≥90 mL/min per 1.73 m²).Results 4685 patients were finally enrolled. Among 1061 patients with eGFR<90, the risk of the primary outcome was higher in early treatment compared with delayed treatment (15.3% vs 10.5%; OR (OR) 1.55, 95% CI 1.07–2.23; p=0.02). In 3624 patients with eGFR≥90, no such difference was observed (10.7% vs 10.2%; OR 1.05, 95% CI 0.85 to 1.30; p=0.63). The interaction was marginally significant (p=0.07).Conclusions The modification effect of renal function on different antihypertensive timing for AIS was not observed. Further, adequately powered studies were warranted.Trial registration number NCT03479554.

Over the past three decades, thrombolytic therapy for acute ischaemic stroke has evolved dramatically since the landmark National Institute of Neurological Disorders and Stroke (NINDS) trial in 1995, which formally established recombinant tissue plasminogen activator as an effective treatment for stroke. This evolution has occurred along three key dimensions: (1) an expanding repertoire of thrombolytic agents, (2) a progressive broadening of the therapeutic window and (3) organisational and technological innovations aimed at minimizing prehospital and in-hospital treatment delays.In this review, we summarise the major milestones in the clinical evidence supporting thrombolytic therapy over the past 30 years, with particular emphasis on large phase III randomised clinical trials. Our goal is to delineate the trajectory of progress in stroke thrombolysis and to provide clinicians and researchers with a clear and coherent framework for understanding the field’s past achievements and future directions.

OBJECTIVE:Whether initial systolic blood pressure (SBP) influences blood pressure management in acute ischemic stroke (AIS) and its association with outcome remains inconclusive. We conducted a subgroup analysis of CATIS-2 trial (China Antihypertensive Trial in Acute Ischemic Stroke II) to assess the impact of early vs. delayed antihypertensive treatment in AIS, stratified by baseline SBP. METHODS:CATIS-2 was a multicenter, randomized trial enrolling AIS patients within 24-48 h after onset, presenting with SBP 140-219 mmHg and without reperfusion therapy. Participants were randomized to receive immediate antihypertensive treatment or delayed treatment initiated on day 8. The primary outcome was functional dependency or death (modified Rankin Scale score ≥3) at 90-day. Three prespecified baseline SBP subgroups (<160, 160-179, and ≥180 mm Hg) were analyzed. RESULTS:4802 patients (mean age 63.7 years, 65.0% male) were included, with baseline SBP < 160 mmHg ( n  = 2233), 160-179 mmHg ( n  = 1849), and ≥180 mmHg ( n  = 720). Among patients with baseline SBP 160-179 mmHg, early antihypertensive treatment was associated with increased risk of primary outcome compared to delayed treatment [13.3% vs. 10.4%; odds ratio (OR) 1.32, 95% confidence interval (CI) 1.00-1.76]. This finding was not observed in the baseline SBP < 160 mmHg subgroup (OR 1.12, 95% CI 0.84-1.50) or ≥180 mmHg subgroup (OR 0.98, 95% CI 0.66-1.46). No significant differences were found in stroke recurrence or major vascular events between treatment strategies across SBP subgroups. CONCLUSION:Early antihypertensive treatment may increase the risk of functional dependency or death in AIS patients with moderately elevated baseline SBP. These findings provide valuable insights into clinical practice regarding individualized blood pressure management in AIS. Further research is warranted. REGISTRATION:ClinicalTrials.gov (NCT03479554).

Approximately 16% of stroke-related deaths can be attributed to PM2.5, and extensive evidence has consistently linked short-term exposure to PM2.5 to an increased risk of ischemic stroke onset. However, most previous studies rely on the assumption of a constant impact of PM2.5 over time, despite emerging evidence on the time-variant nature of PM2.5-associated health effects. This study aims to assess the temporal changes in the association between PM2.5 and its components and the risk of ischemic stroke. We employed the case-crossover design and included 1,625,763 participants from the Chinese Stroke Center Alliance (CSCA) program. Conditional logistic models were used to estimate the acute effect of PM2.5 and its components on the ischemic stroke onset. Temporal changes in PM2.5 and its components were evaluated across two periods (2015-2017 and 2018-2022) and annually. A 10 μg/m3 increase in PM2.5 at lag 0 day demonstrated a stronger association with ischemic stroke during Period 1 (percent change in risk: 0.54% [0.42 to 0.65%]) compared to Period 2 (0.29% [0.19 to 0.38%]), indicating a significant decline of -0.25% (-0.40 to -0.10%). This decreasing trend was consistent across five PM2.5 components, particularly for black carbon (BC), which exhibited the largest reduction (-4.47% [-7.47, -1.38%]). Nonlinear exposure-response curves for PM2.5 and its components also exhibited a steeper trend in Period 1. By integrating individual ischemic stroke onset data from over 2,600 hospitals across China, our study demonstrates a declining trend in the health effects of PM2.5 and its chemical components on ischemic stroke onset. These findings highlight the importance of accounting for temporal variations in PM2.5-related health effects when estimating disease burden, designing and evaluating air pollution control policies, and informing public health decision-making.

OBJECTIVE:To evaluate the efficacy of a clinical decision support system (CDSS) on stroke care quality and clinical outcomes among patients with acute ischaemic stroke. DESIGN:Multicentre, cluster randomised clinical trial. SETTING:77 hospitals across China. PARTICIPANTS:77 hospitals (38 randomised to intervention group, 39 to control group) enrolled 21 603 patients with acute ischaemic stroke admitted to hospital within seven days after symptom onset. INTERVENTIONS:Hospitals in the intervention group received stroke CDSS support including artificial intelligence assisted imaging analysis, classification of stroke causes, and evidence based treatment recommendations. Hospitals in the control group provided usual care. MAIN OUTCOMES MEASURES:The primary outcome was a new vascular event (composite of ischaemic stroke, haemorrhagic stroke, myocardial infarction, and vascular death) within three months after initial symptom onset. Secondary outcomes included the composite measure and all-or-none measure of evidence based performance measures for acute ischaemic stroke care quality, a new vascular event at six and 12 months, and disability (modified Rankin Scale score 3-6) and all cause mortality at three, six, and 12 months. Safety outcomes were moderate or severe bleeding events and all bleeding events at three, six, and 12 months. RESULTS:11 054 patients in the intervention group and 10 549 patients in the control group were enrolled from January 2021 to June 2023. New vascular events at three months occurred in 2.9% (320/11 054) in the intervention group compared with 3.9% (416/10 549) in the control group (adjusted hazard ratio 0.74, 95% confidence interval (CI) 0.58 to 0.93, P=0.01). The CDSS intervention effect remained significant in the cluster level analysis (-0.01, -0.02 to -0.004, P=0.003). Patients in the intervention group were more likely to have a higher composite measure (91.4% (77 049/84 276) v 89.8% (70 794/78 834), adjusted odds ratio 1.21, 95% CI 1.17 to 1.26, P<0.001). New vascular events were significantly lower in the intervention group at 12 months (4.0% (440/11 054) v 5.5% (576/10 549), adjusted hazard ratio 0.73, 95% CI 0.56 to 0.95, P=0.02). No significant differences were found in disability and all cause mortality. Moderate or severe bleeding, and all bleeding did not differ significantly between the two groups. CONCLUSIONS:Use of the stroke CDSS in patients with acute ischaemic stroke in China led to a significant decrease in new vascular events at three months. The stroke CDSS intervention was also effective in improving stroke care quality and decreasing long term vascular events. TRIAL REGISTRATION:ClinicalTrials.gov NCT04524624.

Background:Revascularization for acute ischemic stroke (AIS) can salvage at-risk brain tissue, but reperfusion injury may reduce their benefits. This study aims to evaluate the efficacy and safety of Dengzhanxixin (DZXX) injection in AIS patients receiving reperfusion therapy. Methods:The DAISY (Dengzhanxixin Injection for Acute Ischemic Stroke Receiving Reperfusion TherapY) is a multicenter, randomized, double-blind, placebo-controlled, dose-exploration clinical trial. AIS patients who received reperfusion therapy were randomly assigned in a 1:1:1 ratio: high-dose (80 mg per day) DZXX injection, low-dose (40 mg per day) DZXX injection, and placebo, for 10-14 consecutive days. The primary efficacy outcome was the proportion of participants with modified Rankin Scale (mRS) score (0-1) at 90 days. The safety outcome was any adverse event within 90 days after treatment. Results:Between September 2022 and August 2023, a total of 246 patients from 17 centers were enrolled, with 78 assigned to high-dose group, 89 to low-dose group, and 79 to placebo group. At 90-days, the proportion of participants with a mRS score of 0 or 1 was 78.21 % in high-dose, 77.53 % in low-dose, and 65.82 % in placebo (high-dose vs. placebo, OR, 1.85, 95 % CI, 0.91-3.77, P = 0.11; low-dose vs. placebo, OR, 1.75; 95 % CI, 0.88-3.48, P = 0.09). No significant differences observed in adverse events among three groups (P = 0.154). Conclusion:DZXX injection demonstrated a trend toward improved functional outcomes at 90-days, but the differences were not statistically significant. It would be safe for patients with AIS undergoing reperfusion therapy without increasing the risk of bleeding.

BACKGROUND:Insulin resistance is associated with increased platelet reactivity. We sought to investigate the effects of insulin resistance on dual antiplatelet therapy in CYP2C19 loss-of-function carriers with minor stroke or transient ischemic attack (TIA). METHODS:We conducted a post hoc analysis of the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events II (CHANCE-2) trial, in which we randomized patients with minor stroke or TIA who carried CYP2C19 loss-of-function mutations to receive ticagrelor-acetylsalicylic acid (ASA) or clopidogrel-ASA. We categorized patients by insulin resistance status using a cut-off of 8 mg/kg/min in the estimated glucose disposal rate. The primary efficacy outcome was recurrent stroke. The primary safety outcome was severe or moderate bleeding within 90 days of starting the intervention. RESULTS:Among 4954 patients included, 3122 (63.0%) had high insulin resistance and 1832 (37.0%) had low insulin resistance. Compared with clopidogrel-ASA, ticagrelor-ASA reduced the risk of recurrent stroke in the low-insulin resistance group (71 [7.8%] v. 36 [3.9%]; hazard ratio [HR] 0.52, 95% confidence interval [CI] 0.34 to 0.79), but not in the high-insulin resistance group (120 [7.7%] v. 120 [7.7%]; HR 0.96, 95% CI 0.74 to 1.24) (p = 0.01 for interaction). Results were similar among patients with and without diabetes (p for interaction = 0.3). The benefit of ticagrelor-ASA versus clopidogrel-ASA for recurrent stroke increased continuously as insulin resistance decreased (p for interaction = 0.03). Rates of severe or moderate bleeding were similar regardless of treatment or insulin resistance group (p for interaction = 0.8). INTERPRETATION:In CYP2C19 loss-of-function carriers with minor stroke or TIA, ticagrelor-ASA use was associated with reduced future stroke risk compared with clopidogrel-ASA among patients with low insulin resistance. Insulin resistance biomarkers have a potential role in optimal selection of antiplatelet therapy. TRIAL REGISTRATION:ClinicalTrials.gov, NCT04078737.

Despite successful thrombectomy, many patients with large-vessel occlusion stroke remain functionally dependent. The ATTRACTION trial evaluated low-dose tirofiban after successful endovascular reperfusion and showed a modest improvement in 90 day functional independence without a statistically significant increase in symptomatic intracranial haemorrhage. The benefit appeared greater in patients with large-artery atherosclerosis and possibly those with incomplete reperfusion, whereas patients with cardioembolic stroke showed less favourable profiles. Compared with previous negative adjunctive antithrombotic trials, ATTRACTION highlights the importance of timing, dose, and delivery route. Further studies are needed to refine patient selection and balance functional benefit against haemorrhagic risk.