Background: Concentrations of extracellular vesicles (EVs) and other particles are measured in plasma for biomarker exploration. A commonly used method, flow cytometry, requires plasma dilution to ensure single-particle detection. Since plasma EVs are outnumbered by variable concentrations of lipoproteins, dilution differs between the plasma samples. Dilution can result in misidentification of fluorescent background signals as labeled EVs. This phenomenon, called the dilution paradox, leads to overestimation of plasma EV concentrations, and likely impacts conclusions from earlier performed biomarker studies. Objectives: This study reevaluated earlier conclusions from our clinical biomarker studies Antiplatelet Therapy Effect on Extracellular Vesicles (AFFECT EV) and Circulating Nanotraces to Identify the Cause of Stroke (CINTICS), by taking the dilution paradox into account. Methods: We developed a model that quantifies the fluorescent background and estimates whether a flow cytometry measurement is dominated by fluorescent background, that is, if the measurement is unreliable. This model was applied to the original datasets of the AFFECT EV and CINTICS studies to identify and exclude unreliable measurements. We investigated whether exclusion of unreliable data affects the original conclusions. Results: Our model estimated that 47% (1156/2457) of the evaluated measurements are unreliable, and conclusions from both biomarker studies required adjustment. Conclusion: Our model improves reliability and reproducibility of EV concentration measurements using flow cytometry. We recommend to reanalyze earlier EV flow cytometry studies using our model and to use a fixed dilution factor in future EV flow cytometry studies to enable reliable EV concentration measurements.

Abstract Introduction Migraine increases the risk of ischemic stroke and cardiovascular disease in women, potentially due to systemic vascular dysfunction. We investigated whether migraine is associated with increased aortic stiffness and impaired cardiac function as markers of macrovascular dysfunction in middle-aged women with ischemic stroke. Methods This cross-sectional study included three groups of women aged 40–60 years with: (I) ischemic stroke, (II) ischemic stroke with migraine, and (III) no history of stroke or migraine. Aortic stiffness was measured by assessing aortic arch pulse wave velocity (arch PWV) using high-temporal 2D-phase contrast MRI. Cardiac function was evaluated through left ventricular measures, including stroke volume (SV), cardiac output (CO), and ejection fraction (EF), from two orthogonal cine biplane long-axis (2-/4-Chamber) acquisitions. Multivariable linear regression was used to estimate mean differences in arch PWV and left ventricular function, comparing groups 1 and 2 with group 3 as the reference. Results Among 118 included women (mean age 51 years [SD 5]), (I) 44 had ischemic stroke, (II) 44 had both ischemic stroke and migraine, and (III) 30 had no stroke or migraine. In the reference group (group III), mean (SD) values were 6.97 (1.05) m/s for arch PWV, 95.91 (15.82) mL for SV, 6.73 (1.61) L/min for CO, and 64.90 (5.96)% for EF. Comparisons of groups I and II with group III showed no statistically significant mean differences in arch PWV, SV, CO, or EF. Although mean arch PWV was slightly higher in group II (7.11 [1.53] m/s), the adjusted mean difference (-0.03 m/s; 95%CI: -0.60 to 0.54 m/s) was not statistically significant. Small, non-significant reductions in SV, CO, and EF were also observed in the ischemic stroke groups compared with the reference group. Conclusions The increased risk of ischemic stroke in middle-aged women with migraine was not associated with differences in arch PWV or left ventricular function in this cohort. We did not detect evidence that macrovascular dysfunction plays a key role in linking migraine and cardiovascular risk, supporting other studies that point to a potential role for microvascular dysfunction.

The ULTRA trial evaluated the impact of ultra-early and short-term tranexamic acid (TXA) treatment in patients with subarachnoid hemorrhage (SAH) and found no clinical benefit at six months. This post-hoc analysis examines whether TXA improves quality of life (QoL) at three and six months. The ULTRA trial was a randomized, controlled, multicenter study conducted from July 2013 to July 2019. Patients received either TXA or standard care. This analysis included patients who completed at least one QoL questionnaire. The primary endpoint was QoL, assessed using the EQ-5D-3L questionnaire at three and six months. Linear mixed models adjusted for confounders were used to analyze the association between TXA and QoL. Of the 955 ULTRA patients, approximately 25

Concentrations of extracellular vesicles (EVs) can be measured by flow cytometry, which detects fluorescence and light scattering signals from single particles. To ensure single particle detection, plasma samples are diluted based on their particle concentration, which can differ 100-fold between samples. Here we studied how sample dilution affects EV detection by flow cytometry. EVs were measured in human plasma (i) with different concentrations of spiked-in purified lipoproteins, (ii) at different dilutions, and (iii) using either scatter-triggering or fluorescence-triggering. In addition, the reliability of two published clinical EV studies was evaluated using an analytical model. Our results show that the minimum dilution factor to prevent swarm detection by the light scattering detector can exceed the maximum dilution factor that ensures labelled EVs outnumber fluorescent background events. This 'dilution paradox' precludes reliable detection of both fluorescence and light scattering signals of EVs for some samples. In the two clinical studies, 30% and 65% of the measurements were unreliable, depending on the label used. Therefore, results from previous studies should be re-evaluated. The dilution paradox might be overcome by using fluorescence-triggering at a fixed sample dilution, removing non-EV particles from the sample, removing fluorescent particulates from staining reagents, and setting stricter inclusion criteria.

Video-based telemedicine can improve prehospital triage. However, it is unclear which portable device enabling a real-time specialist consultation via two-way video and audio connection in dynamic emergency medical service environments should be used. This feasibility study identified the most suitable portable telemedicine device for prehospital triage. Four simulated stroke-like scenarios were conducted with ambulance professionals and remote vascular neurologists. Three portable telemedicine devices were tested: two head-mounted assisted-reality devices (RealWear Navigator ™ 520, Vuzix M400) and a smartphone using Siilo Messenger application. Feasibility was evaluated through structured surveys from both user groups and a patient actor. Quantitative data were analysed using Multi-Criteria Decision Analysis with stakeholder-derived criterion weights to generate overall value scores and device ranking. Out of 47 analysed surveys, the Vuzix head-mounted device achieved the highest overall value score (0.80), followed by Siilo Messenger smartphone application (0.77) and RealWear head-mounted device (0.73). Ambulance professionals prioritised usability, favouring the smartphone application, whereas neurologists emphasised video quality, favouring Vuzix head-mounted device. Qualitative feedback highlighted trade-offs: head-mounted devices offered hands-free use but required peripherals and hindered patient interaction, while smartphones were intuitive but limited by video quality and image stability. Device suitability for prehospital telemedicine depends on balancing technical performance with usability. The smartphone-based application provides practical solution for early implementation, while head-mounted devices may be preferable when hands-free operation and video quality are critical. Future research should assess their clinical and operational impact to enable safe and scalable implementation.

INTRODUCTION:It is unclear whether renal function is associated with outcome in patients with ischaemic stroke treated with EVT, as findings in existing literature have been inconsistent. We studied the association between renal function and outcomes in EVT-treated patients. PATIENTS AND METHODS:We used data from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) Registry. We assessed the association between renal function using estimated glomerular filtration rate (eGFR) and functional outcome measured with the mRS score, mortality and the occurrence of sICH in ischaemic stroke patients treated with EVT. We used ordinal regression modelling to estimate common odds ratios (cOR) per 10-unit decrease in eGFR, adjusted for known prognostic factors. RESULTS:We analysed 4466 patients included between March 2014 and December 2018. Patients with lower eGFR were older, had more severe strokes at baseline, more comorbidities and higher pre-stroke mRS scores (all P < .001). In unadjusted analyses, higher eGFR was associated with better 3-month functional outcome (cOR 1.18; 95% CI, 1.15-1.21) and lower mortality (cOR 0.81; 95% CI, 0.78-0.83). After adjusting for demographic factors, only the association between eGFR and mortality remained significant. After further adjustment for medical history and comorbidities, no association was found between eGFR and mRS (adjusted odds ratio [aOR] 0.99; 95% CI, 0.96-1.02) or mortality (aOR 0.96; 95% CI, 0.93-1.01). There was no association between eGFR and sICH (cOR 0.95; 95%CI, 0.89-1.01, aOR 0.99; 95% CI, 0.93-1.06). CONCLUSION:Renal function was not an independent modifier of outcome after EVT for ischaemic stroke although eGFR may serve as a predictor of increased risk of disability and mortality. Based on these results, renal function alone should not determine eligibility for EVT in ischaemic stroke patients.

The ULTRA trial demonstrated no improvement in clinical outcome at 6 months in patients with subarachnoid hemorrhage (SAH) when treated with ultra-early and short-term tranexamic acid (TXA). In this post hoc analysis, we evaluated the effect of TXA in females and males on clinical outcome after aneurysmal SAH (aSAH). The ULTRA trial was a prospective, randomized, controlled, open-label trial, conducted between 2013 and 2020. Patients with spontaneous SAH were assigned to ultra-early, short-term TXA in addition to usual care, or usual care only. In this study, we only included ULTRA participants with radiologically proven aSAH. We analyzed the potential effect of sex on the association between treatment group and clinical outcome by assessing effect modification, and evaluated the effect of TXA separately in females and males. The primary endpoint was clinical outcome at 6 months, assessed by the distribution of the modified Rankin Scale (mRS). Odds ratios (OR) and adjusted OR (aOR) with 95

BACKGROUND:Long-term evidence for endovascular treatment in medium or distal vessel occlusion stroke is scarce. Three out of four randomised trials reported no benefit of endovascular treatment over best medical treatment at 90 days. We aimed to assess efficacy of endovascular treatment plus best medical treatment versus best medical treatment alone at 12 months in patients enrolled in the DISTAL trial, as well as overall survival. METHODS:DISTAL was an open-label, randomised trial with blinded endpoint assessment conducted at 55 hospitals in Europe and the Middle East. Adults (≥18 years) with acute ischaemic stroke due to medium or distal vessel occlusion (occlusion of co-dominant or non-dominant M2 or M3-M4 middle cerebral artery, A1-A3 anterior cerebral artery, or P1-P3 posterior cerebral artery) presenting from home within 6 h of last known well, or between 6 h and 24 h if neuroimaging demonstrated potentially salvageable tissue, were randomly assigned (1:1) through a centralised web-based system to endovascular treatment plus best medical treatment or best medical treatment alone. The prespecified primary outcome at 12 months was disability measured by use of the ordinal modified Rankin Scale (mRS; scores 5 and 6 combined) in the intention-to-treat population. The only safety outcome was overall survival. The trial is registered on ClinicalTrials.gov (NCT05029414) and is completed. FINDINGS:Between Dec 16, 2021, and July 10, 2024, we enrolled 553 patients. Ten patients declined post-hoc consent, leaving 543 participants in the analysis (239 [44%] females and 304 [56%] males; median age 77 years, IQR 68-84). 271 (50%) were assigned to endovascular treatment plus best medical treatment and 272 (50%) to best medical treatment alone. The median NIHSS score at admission was 6 (IQR 5-9); 355 (65%) participants received intravenous thrombolysis. Predominant occlusion locations were the M2 (239 [44%]), M3 (146 [27%]), P2 (73 [13%]), and P1 (30 [6%]) segments. 12-month data were available for 524 (97%) participants. The median mRS score was 2 (IQR 1-4) in the endovascular treatment plus best medical treatment group and 2 (1-4) in the best medical treatment alone group. There was no difference in 12-month mRS distribution between endovascular treatment plus best medical treatment and best medical treatment alone (adjusted common odds ratio for better functional outcome 0·81, 95% CI 0·59-1·12; p=0·20). Overall survival was similar between the two groups (hazard ratio 1·46, 95% CI 0·93-2·30; p=0·10). INTERPRETATION:In patients with a medium or distal vessel occlusion stroke, endovascular treatment plus best medical treatment was not associated with a reduction of disability or death at 12 months compared with best medical treatment. These results are consistent with the 90-day results. Routine endovascular treatment is therefore not supported for patients with mild-to-moderate medium or distal vessel occlusion stroke. FUNDING:Swiss National Science Foundation, Gottfried und Julia Bangerter-Rhyner-Foundation, Medtronic, Stryker Neurovascular, Phenox, Rapid Medical, and Penumbra.

Rapid diagnosis, timely treatment, and continuous monitoring are essential for improving outcomes in neurovascular diseases (time=brain). Such point-of-care applications, however, require imaging to be conducted in dynamic and often confined spaces. While magnetic particle imaging (MPI) shows preclinical promise for fast (neuro)vascular imaging, it relies on complex and restricted imaging gantries. Here, we present a unique gantry-free robot-assisted MPI strategy (Robotic MPI) that is 'portable'. Using permanent magnets, Hall sensors and correction coils, we developed a single-sided detector with a detection threshold of ~ 5 µg iron-containing contrast agent at the detector surface. Robot-assisted positioning and pose tracking, combined with a dedicated maximum likelihood expectation-maximization-based reconstruction algorithm, translates detector signals into tomographic images with a spatial resolvability of 7 mm (visually evaluated at an imaging depth of ~ 5 mm). Surface imaging (SI) provided anatomical reference, delivering hybrid MPI/SI scans. Robotic-MPI's ability to visualize 3D (neuro)vasculature in a phantom model, highlights the system's potential for next-generation, portable vascular imaging solutions.

BACKGROUND:Patients with acute ischaemic stroke often present with elevated blood pressure. Evidence has emerged that challenges the longstanding recommendation across clinical guidelines that blood pressure should be controlled to a systolic pressure of less than 185 mm Hg before initiating reperfusion therapy in these patients. RECENT: developments Major clinical trials (INTERACT4, MR-ASAP, and RIGHT-2) and an observational study (TRUTH) indicate that intensively lowering blood pressure before initiating reperfusion therapy for acute ischaemic stroke is associated with increased risk of death and disability. Similar evidence has reshaped our approach to blood pressure management in patients who receive successful endovascular thrombectomy for acute ischaemic stroke from large-vessel occlusion. The underlying mechanisms of cerebral ischaemia are likely to involve alterations in cerebral blood flow through collateral vessels and the microcirculation. WHERE: next? Current evidence underscores the harms of more intensive lowering of blood pressure to a systolic target of less than 140 mm Hg both before and after reperfusion therapy for acute ischaemic stroke. Despite the challenges in obtaining the necessary randomised evidence, such efforts are now required to establish whether elevated blood pressure should be controlled at all with this disease or left to decrease naturally.

Importance:Imaging-based end points may enhance the understanding of endovascular treatment (EVT) outcomes in patients with medium- or distal-vessel occlusion stroke. Objective:To investigate the outcomes of endovascular treatment (EVT) in addition to best medical treatment (BMT) compared with BMT alone on the volume of brain tissue initially at risk preserved in patients with a medium or distal vessel occlusion stroke. Design, Setting, and Participants:Post hoc imaging analysis of the Endovascular Treatment for Stroke Due to Occlusion of Medium or Distal Vessels (DISTAL) trial, a multicenter randomized clinical trial with blinded end point assessment conducted at 55 hospitals in 11 countries from December 2021 through July 2024, with clinical follow-up at 90 days. Patients with baseline perfusion imaging and follow-up imaging at 24 hours were included. Interventions:EVT plus BMT compared with BMT alone. Main Outcomes and Measures:Primary outcome was calculated as the difference in volume of tissue at risk and the final infarct volume divided by the tissue at risk (change in Vrel). We defined a Vrel of 0.8 or greater as a good imaging outcome, meaning that at least 80% of the brain tissue initially at risk was not infarcted at 24 hours. Additionally, the association between brain tissue preserved and clinical outcome at 90 days was investigated. Results:From the 447 patients (252 [56.4%] male; median [IQR] age, 77.0 [68.0-84.0] years) included in this secondary analysis, 226 received EVT plus BMT and 221 received BMT alone. Median (IQR) time of the follow-up imaging was 22.9 (19.2-25.5) hours. Median (IQR) Time to maximum less than 6 seconds (Tmax6) volume was 34.0 (20.0-50.0) mL. Median follow-up infarct volume was 7.0 (1.0-22.9) mL. The median (IQR) change in absolute volume in the EVT plus BMT group was 23.6 (5.7-38.9) mL and 14.8 (0-30.3) mL in the BMT group. Median (IQR) change in Vrel was 0.8 (0.2-1.0) in the EVT plus BMT group and 0.6 (0-0.9) in the BMT group. Odds for reaching a change in Vrel of 0.8 or greater were higher in the EVT plus BMT group compared with BMT (adjusted odds ratio [aOR], 1.6; 95% CI, 1.1-2.3) and with successful reperfusion compared with no successful reperfusion (aOR, 2.5; 95% CI, 1.3-4.8). Patients with a change in Vrel of 0.8 or greater had a better clinical outcome at 90 days. Conclusions and Relevance:In this post hoc analysis of the DISTAL trial data, EVT plus BMT was associated with a higher likelihood of achieving a good imaging outcome compared with BMT alone. A good imaging outcome was associated with a better clinical outcome in both treatment groups.

BACKGROUND AND OBJECTIVES:A 2005 review identified smoking, hypertension, and excessive alcohol intake as the most important risk factors of aneurysmal subarachnoid hemorrhage (aSAH), but data on other factors remained inconclusive. While aSAH is more prevalent in female participants, evidence on sex differences and female-specific factors remains limited. Comprehensive identification of all risk factors, including potential sex differences and female-specific factors, is essential for improving prevention and accurately assessing aSAH risk. We aimed to determine whether there is now greater certainty around previously inconclusive risk factors, identify any new emerging factors, and explore sex differences in both established and emerging risk factors. METHODS:We conducted a systematic review and meta-analysis of cohort and case-control studies on prevalent lifestyle exposures, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. These exposures included smoking, hypertension, alcohol abuse, oral contraception, hormone replacement therapy, hypercholesterolemia, rigorous physical activity, lean body mass index, and diabetes. We calculated pooled sex-specific relative risks (RRs) and odds ratios (ORs) with 95% CIs for overall risk and female-to-male ratios of RRs (RRRs) and ORs (RORs) for sex comparisons. RESULTS:We included 67 studies (34 cohort [8 with sex-specific data], 33 case-control [6 with sex-specific data]; n = 5,743,262; 57% female). A sex-specific association was found for current smoking (RRR 1.53, 95% CI 1.05-2.23), but not for hypertension (RRR 1.50, 95% CI 0.78-2.89) or excessive alcohol intake (RRR 0.46, 95% CI 0.13-1.63). Regular rigorous exercise (RR 0.74, 95% CI 0.53-1.04; OR 0.69, 95% CI 0.57-0.83) and diabetes (RR 0.75, 95% CI 0.55-1.02; OR 0.52, 95% CI 0.41-0.65) were associated with reduced risk, without sex-specific associations. Data on hypercholesterolemia (RR 1.24, 95% CI 0.97-1.58; OR 0.52, 95% CI 0.37-0.74) and lean BMI (RR 1.31, 95% CI 1.15-1.50; OR 1.39, 95% CI 0.74-2.60) were inconsistent and showed no sex-specific associations. Hormone replacement therapy (RR 1.03, 95% CI 0.72-1.48) and oral contraceptive use (RR 5.40, 95% CI 0.68-42.57) were limited to female patients, with current users compared with never users. Most studies contained potential sources of bias. DISCUSSION:Current smoking, but not hypertension or excessive alcohol, has a stronger association with aSAH in female patients than in male patients. Regular exercise and diabetes are associated with a reduced risk, with no sex-specific associations. Data on female-specific factors remain inconsistent. Targeted smoking prevention may particularly benefit female patients. Large-scale studies are needed to clarify the role of female-specific factors in explaining the higher incidence of aSAH in female patients.

OBJECTIVE:To evaluate the cost-effectiveness and cost-utility of adding ultra-early and short-term administration of tranexamic acid (TXA) to standard care in patients with subarachnoid hemorrhage (SAH). MATERIALS AND METHODS:An economic evaluation was performed alongside the ultra-early tranexamic acid after subarachnoid hemorrhage (ULTRA) trial. The main outcomes were the incremental cost-effectiveness ratio (ICER), expressed as costs per one-point increase in modified Rankin scale (mRS) score, and the incremental cost-utility ratio (ICUR), expressed as costs per quality-adjusted life-year (QALY). Cost-effectiveness acceptability curves (CEACs) were visualized with varying ICER cut-offs. Bootstrapping techniques and sensitivity analyses were performed to account for uncertainty. RESULTS:The ULTRA trial included 955 patients, with 480 assigned to the TXA group and 475 to the control group. The mean mRS score was 3.4 (95% CI: 3.2-3.5) in the TXA group and 3.2 (95% CI: 3.0-3.4) in the control group. The mean QALY was 0.26 (95% CI: 0.24-0.28) in the TXA group and 0.28 (95% CI: 0.26-0.30) in the control group. Mean costs were €62,180 (95% CI: 57,589-66,913) in the TXA group and €58,624 (95% CI: 53,693-63,955) in the control group. The probability of treatment with TXA being cost-effective ranged from 4% to 16% for mRS and from 8% to 16% for QALYs. CONCLUSIONS:Ultra-early and short-term administration of TXA to patients with SAH is not cost-effective. Therefore, we recommend against using TXA for this patient group. TRIAL REGISTRATION:Netherlands Trial Register: NTR3272. CLINICALTRIALS:gov identifier: NCT02684812.

BACKGROUND AND OBJECTIVES:Various prehospital scales have been developed to detect patients with anterior-circulation large-vessel occlusion (aLVO) ischemic stroke to enable direct transportation to a thrombectomy-capable stroke center. To guide implementation, a head-to-head comparison of aLVO stroke detection scales is needed to determine which scale is most useful for prehospital triage in different regional contexts. We aimed to systematically identify and compare these scales. METHODS:Published prehospital aLVO stroke scales were identified with a systematic literature search. Scales were reconstructed from individual patient data of 2 large prospective observational cohort studies conducted between 2018 and 2019, the Leiden Prehospital Stroke Study and PREhospital triage of patients with suspected STrOke symptoms study. Both studies included consecutive adult patients suspected by paramedics of having a stroke within 6 hours of symptom onset, from 4 Dutch ambulance regions, encompassing 15 stroke centers and serving 3.7 million people. All data used for the reconstruction of scales were acquired by paramedics in the field before hospital arrival. Scales' diagnostic performance to detect aLVO stroke was compared with the area under the receiver operating characteristic curve (AUROC) of the full scale and sensitivity and specificity at the scales' original cut-point. Decision curve analysis was used to evaluate harm-benefit trade-offs between delaying IV thrombolysis and expediting endovascular thrombectomy with direct transportation of patients to a thrombectomy-capable center. RESULTS:We identified 63 aLVO scales, of which 14 could be reconstructed. Of 2,358 included patients (mean age 70 years; 47% female), 231 (9.8%) had aLVO stroke. The AUROC was highest for Rapid Arterial oCclusion Evaluation (RACE) (0.81, 95% CI 0.78-0.84), Los Angeles Motor Scale (LAMS) (0.80, 95% CI 0.77-0.83), Gaze-Face-Arm-Speech-Time (G-FAST) (0.80, 95% CI 0.77-0.83), and modified Gaze-Face-Arm-Speech-Time (mG-FAST) (0.79, 95% CI 0.76-0.82). The Emergency Medical Stroke Assessment had highest sensitivity (85%, 95% CI 80%-90%) but lowest specificity (58%, 95% CI 56%-61%) while Cincinnati Prehospital Stroke Scale with an adjusted cut-point of 3 + gaze had highest specificity (94%, 95% CI 93%-95%) but lowest sensitivity (35%, 95% CI 29%-41%). In decision curve analysis, RACE had the highest benefit across a clinically reasonable range of harm-benefit trade-offs. DISCUSSION:RACE, LAMS, G-FAST, and mG-FAST are the best-performing scales, with RACE being preferred in most triage settings. Our findings may support policymakers with implementing a scale suitable for their region.

BACKGROUND:Migraine increases the risk of ischemic stroke and white matter hyperintensities (WMH), especially in women. Underlying shared mechanisms may include endothelial activation and hypercoagulability. We assessed these markers in middle-aged women with and without migraine and ischemic stroke to explore their role in WMH development. METHODS:We cross-sectionally measured fibrinogen and von Willebrand factor antigen (VWF:Ag) levels as markers of endothelial activation, and factor (F)IX and FXI activity (FXI:C) as markers of hypercoagulability in four groups of women aged 40-60 years with (1)ischemic stroke, (2)migraine, (3)both ischemic stroke and migraine, and (4)no stroke or migraine. Multivariable linear regression estimated mean differences in coagulation factor levels between groups 1 and 3, with group 4 as the reference. RESULTS:Among 166 women (mean age:51 years), (1) 45 had ischemic stroke, (2) 38 had migraine, (3) 48 had both, and (4) 35 had no stroke or migraine. Mean fibrinogen, FIX, and FXI:C levels were similar in all groups compared with group 4. VWF:Ag levels were higher in the ischemic stroke with migraine group (170 [57]%; adjusted β = 31%; 95% CI = 6%-56%) compared with group 4, but not in the other groups. There was no association between coagulation factors and WMH volume in any group. CONCLUSIONS:In women with both stroke and migraine, VWF:Ag levels were increased, while fibrinogen, FIX, and FXI:C were not. This suggests that endothelial activation might be more relevant than a procoagulant state alone in the pathophysiology of ischemic stroke in women with migraine. Coagulation factors did not seem to be related to WMH volume, suggesting other mechanisms may be involved in their development.

Background and ObjectivesVarious prehospital scales have been developed to detect patients with anterior-circulation large-vessel occlusion (aLVO) ischemic stroke to enable direct transportation to a thrombectomy-capable stroke center. To guide implementation, a head-to-head comparison of aLVO stroke detection scales is needed to determine which scale is most useful for prehospital triage in different regional contexts. We aimed to systematically identify and compare these scales.MethodsPublished prehospital aLVO stroke scales were identified with a systematic literature search. Scales were reconstructed from individual patient data of 2 large prospective observational cohort studies conducted between 2018 and 2019, the Leiden Prehospital Stroke Study and PREhospital triage of patients with suspected STrOke symptoms study. Both studies included consecutive adult patients suspected by paramedics of having a stroke within 6 hours of symptom onset, from 4 Dutch ambulance regions, encompassing 15 stroke centers and serving 3.7 million people. All data used for the reconstruction of scales were acquired by paramedics in the field before hospital arrival. Scales' diagnostic performance to detect aLVO stroke was compared with the area under the receiver operating characteristic curve (AUROC) of the full scale and sensitivity and specificity at the scales' original cut-point. Decision curve analysis was used to evaluate harm-benefit trade-offs between delaying IV thrombolysis and expediting endovascular thrombectomy with direct transportation of patients to a thrombectomy-capable center.ResultsWe identified 63 aLVO scales, of which 14 could be reconstructed. Of 2,358 included patients (mean age 70 years; 47% female), 231 (9.8%) had aLVO stroke. The AUROC was highest for Rapid Arterial oCclusion Evaluation (RACE) (0.81, 95% CI 0.78-0.84), Los Angeles Motor Scale (LAMS) (0.80, 95% CI 0.77-0.83), Gaze-Face-Arm-Speech-Time (G-FAST) (0.80, 95% CI 0.77-0.83), and modified Gaze-Face-Arm-Speech-Time (mG-FAST) (0.79, 95% CI 0.76-0.82). The Emergency Medical Stroke Assessment had highest sensitivity (85%, 95% CI 80%-90%) but lowest specificity (58%, 95% CI 56%-61%) while Cincinnati Prehospital Stroke Scale with an adjusted cut-point of 3 + gaze had highest specificity (94%, 95% CI 93%-95%) but lowest sensitivity (35%, 95% CI 29%-41%). In decision curve analysis, RACE had the highest benefit across a clinically reasonable range of harm-benefit trade-offs.DiscussionRACE, LAMS, G-FAST, and mG-FAST are the best-performing scales, with RACE being preferred in most triage settings. Our findings may support policymakers with implementing a scale suitable for their region.

[This corrects the article DOI: 10.1016/j.rpth.2025.103183.].

Importance Efficient care processes are crucial to minimize treatment delays and improve outcome after endovascular thrombectomy (EVT) in patients with ischemic stroke. A potential means to improve care processes is performance feedback. Objective To evaluate the effect of performance feedback to hospitals on treatment times for EVT. Design, Setting, and Participants This cluster randomized clinical trial was conducted from January 1, 2020, to June 30, 2022. Participants were consecutive adult patients with ischemic stroke who underwent EVT in 13 Dutch hospitals. No patients were excluded. Data analysis took place from March to May 2023. Intervention The intervention consisted of feedback on hospital performance using structure, process, and outcome indicators. Indicator scores were based on data from a national quality registry and compared with a benchmark. Performance feedback was provided through a dashboard for local quality improvement teams who developed and implemented improvement plans based on the feedback. Every 6 months, 3 to 4 randomly selected hospitals switched to the intervention condition. Main Outcome and Measures The primary outcome was time from door to groin puncture for all patients treated with EVT. Secondary outcomes included door-to-needle time, National Institutes of Health Stroke Scale (NIHSS) score at day 2, expanded Treatment in Cerebral Infarction (eTICI) score, and modified Rankin Scale (mRS) score at 3 months. The effect of the intervention was estimated with multivariable linear mixed models. Results A total of 4747 patients were included (intervention: 2431; control: 2316). Their mean (SD) age was 72 (13) years; 2337 (49.2%) were female and 2410 (50.8%) were male. The median (IQR) baseline NIHSS score was 14 (8-19). Median (IQR) door-to-groin puncture time under the intervention condition was 47 (25-71) minutes, compared with 52 (29-75) minutes under the control condition. The adjusted absolute reduction was 5 minutes (beta = -4.8; 95% CI, -9.5 to -0.1; P = .04), corresponding to a relative reduction of 9.2% (95% CI, -18.3% to -0.2%). Conclusion and Relevance This study found that performance feedback provided through a dashboard used by local quality improvement teams reduced door-to-groin puncture time for EVT. Implementation of performance feedback in hospitals providing EVT can improve the quality of care for ischemic stroke. Trial Registration The Netherlands Trial Register: NL9090

In acute stroke, timely diagnosis is essential to prevent extensive neuronal damage and improve patient outcomes. However, differentiating between ischemic stroke, intracerebral hemorrhage, and stroke mimics remains challenging. Transfer RNA-derived fragments (tRFs) have emerged as potential biomarkers for distinguishing between these stroke subtypes. Here we used reverse transcription-quantitative PCR (RT-qPCR) to investigate the expression of specific tRFs that we previously identified in small RNA sequencing data as potential biomarkers. Out of 12 measured tRFs, only the fragments ArgTCG53-67 and TyrGTA1-19 showed a trend for differential expression between stroke subtypes, but with insufficient predictive value to be of use in clinical practice. Combining expression data of specific tRFs into a joint model did not improve the predictive ability. Technical and computational challenges may compromise the reliability of tRF expression data from RNA sequencing, possibly explaining our inability to validate the specific tRFs as potential stroke biomarkers. Moreover, the limitations of RT-qPCR challenge a reliable quantification of these fragments even further. Our findings highlight the need for improved quantitative methods for tRF analysis to fully exploit their potential as clinically meaningful biomarkers. Addressing these technical barriers could unlock the diagnostic potential of tRFs, facilitating faster, more accurate stroke subtype identification in an acute setting.