INTRODUCTION:Stroke remains a leading cause of disability and mortality worldwide, with an urgent need for novel therapeutic strategies to improve recovery. Bupropion hydrochloride, a norepinephrine-dopamine reuptake inhibitor, may promote motor and cognitive recovery due to its unique mechanism of action. To evaluate the efficacy and safety of early adjunctive treatment with bupropion hydrochloride versus placebo on functional recovery in patients with acute ischaemic stroke. METHODS AND ANALYSIS:BASE is an investigator-initiated, multicentre, randomised, double-blind, placebo-controlled trial. We plan to enrol 1054 eligible patients with acute ischaemic stroke (National Institutes of Health Stroke Scale (NIHSS) score 8-15, within 2-7 days after onset) from approximately 40 stroke centres across China. Participants will be randomly assigned (1:1) to receive either oral bupropion hydrochloride (75 mg two times per day) or matched placebo for 30 days, in addition to standard guideline-based care. The primary efficacy endpoint is the proportion of patients achieving a favourable functional outcome, defined as a modified Rankin Scale (mRS) score of 0-3 at 90 days. Key secondary endpoints include shifts in mRS scores, changes in NIHSS, Hamilton Depression Rating Scale (HAMD-17), Fugl-Meyer Motor Scale scores and quality of life (EQ-5D). Safety endpoints include mortality, vascular events and incidence of adverse events. Analyses will be performed on both the intention-to-treat and per-protocol populations ETHICS AND DISSEMINATION: The study protocol was approved by the Ethics Committee of the First Affiliated Hospital of Chongqing Medical University (ID ZZ2025-747-01), and all participants will provide written informed consent. Results will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRY NUMBER:ChiCTR2500105746 (www.chictr.org.cn).

INTRODUCTION:The hypoperfusion intensity ratio (HIR) was significantly correlated with the futile reperfusion (FR) and National Institutes of Health Stroke Scale (NIHSS) score. We aimed to quantify the direct and indirect effect of HIR on FR. METHODS:We analyzed acute ischemic stroke patients with large vessel occlusion who underwent endovascular treatment at seven comprehensive stroke centers between 2017 and 2022 in China. HIR was automatically calculated on baseline perfusion imaging as the ratio of brain volume with time-to-max (Tmax) delay >10 s over volume with Tmax >6 s. The established threshold HIR >0.4 was regarded as poor tissue-level collaterals (TLCs). FR was defined as the modified Rankin Scale score of 4-6 at 90 days despite successful recanalization. Mediation analysis using the "mediation" package in R 4.2.2 was performed to examine the potential causal chain. RESULTS:Among the 891 included patients, FR was observed in 320 (35.9%) patients. Inadequate TLC was significantly associated with a higher NIHSS score (adjusted common odds ratio [OR], 1.47; 95% confidence interval [CI], 1.12-1.93; p = 0.006) and higher rates of FR (aOR, 1.87; 95% CI, 1.31-2.68; p = 0.001) within 90 days. The baseline NIHSS score was a predictor of FR (aOR, 1.13; 95% CI, 1.10-1.16; p < 0.001). Causal mediation analyses revealed that 20.4% (95% CI, 5.5%-40.9%) of the relationship between HIR and FR was mediated by the baseline NIHSS score. CONCLUSION:Higher NIHSS score partially mediates the association between poorer HIR and FR at 90 days among patients after EVT. Our study provided primarily mechanistic and prognostic findings about the effect of HIR on FR.

BackgroundFunctional outcomes in patients with acute ischemic stroke (AIS) with large vessel occlusion (LVO) undergoing endovascular treatment (EVT) with successful reperfusion (expanded Thrombolysis In Cerebral Infarction (eTICI) 2b-3) complicated by symptomatic intracranial hemorrhage (sICH) were compared with patients with unsuccessful reperfusion (eTICI 0–2a) without sICH.MethodsPatients enrolled in this post hoc analysis were from two Chinese multicenter, randomized controlled trials: the DEVT and the RESCUE BT registries. Patients with AIS who underwent EVT were categorized into two groups according to the state of reperfusion: eTICI 2b-3 with sICH and eTICI 0–2a without sICH. The primary outcome was the modified Rankin Scale (mRS) scores at 90 days. The safety outcomes included early neurological deterioration and 90-day mortality.Results161 patients were included in this cohort analysis, among whom 71 experienced eTICI 2b-3 with sICH, and 90 had eTICI 0–2a without sICH. After adjusting for potential confounding factors, patients in the eTICI 2b-3 with sICH group had worse mRS at 90 days compared with those in the eTICI 0–2a without sICH group in the adjusted analysis (median 6 (IQR 4–6) vs median 4 (IQR 3–6); adjusted common OR 0.39, 95% CI 0.17 to 0.66). There were also higher rates of very poor outcome (mRS 5–6, 70.4% vs 42.2%; OR 2.90, 95% CI 1.38 to 6.11), mortality (66.2% vs 32.2%; OR 0.48, 95% CI 0.30 to 0.79), and early neurological deterioration (81.7% vs 40.0%; OR 0.16, 95% CI 0.07 to 0.35) in the eTICI 2b-3 with sICH group versus the eTICI 0–2a without sICH group.ConclusionsSuccessful reperfusion complicated by sICH after EVT was associated with worse outcomes and higher mortality than unsuccessful reperfusion without sICH. These findings emphasize the need for additional efforts in assessing and managing post-EVT-associated sICH to optimize treatment strategies and improve outcomes.Trial registration numberDirect Endovascular Treatment for Large Vessel Occlusion Stroke;https://www.chictr.org.cn; ChiCTR-IOR-17013568.Intravenous Tirofiban Before Endovascular Thrombectomy for Acute Ischemic Stroke;https://www.chictr.org.cn; ChiCTR-INR-17014167.

BACKGROUND:Malignant cerebral edema (MCE) following basilar artery occlusion (BAO) thrombectomy is a critical, yet understudied, complication. OBJECTIVE:To investigate the incidence, predictors, and clinical impact of MCE in patients with BAO after endovascular thrombectomy (EVT). METHODS:In this retrospective analysis of the national multicenter PERSIST Registry (2422 patients with BAO treated with EVT recruited from 65 Chinese centers, 2015-2022), MCE was defined as Jauss score ≥4 on follow-up imaging. Multivariable logistic regression identified predictors of MCE and its association with 90-day outcomes. A favorable outcome was defined as achieving a modified Rankin Scale score of 0-3 at 90 days. RESULTS:A total of 1883 patients who met the eligibility requirements were included. MCE occurred in 39.6% (746/1883) of patients. Independent predictors included admission systolic blood pressure ≥160 mm Hg (aOR=1.26, 95% CI 1.02 to 1.54), prolonged procedure time (aOR=1.01, 95% CI 1.01 to 1.01), BATMAN score ≥7 (aOR=0.68, 95% CI 0.55 to 0.84), and vertebral V4 occlusion (vs proximal BA: aOR=0.68, 95% CI 0.52 to 0.89). Successful reperfusion reduced MCE risk (aOR=0.57, 95% CI 0.42 to 0.75). Diabetes mellitus exhibited an inverse association (aOR=0.78, 95% CI 0.61 to 0.99). MCE predicted lower odds of favorable outcome (aOR=2.41, 95% CI 1.94 to 3.01; P<0.001) and higher mortality (aOR=1.85, 95% CI 1.51 to 2.27; P<0.001) at 90 days. CONCLUSIONS:MCE complicates 39.6% of patients with BAO after EVT and portends catastrophic outcomes despite successful recanalization. Shortening the procedure time, increasing the likelihood of first-pass success, and optimal admission blood pressure management might be targets to decrease MCE for patients with BAO undergoing EVT.

To investigate the combined predictive value of plasma trimethylamine N-oxide (TMAO) and white matter lesions (WMLs) burden for 90-day prognosis after endovascular thrombectomy (EVT) in acute ischemic stroke (AIS) with large vessel occlusion (AIS-LVO). This retrospective study included 202 AIS-LVO patients from six centers who achieved successful recanalization after EVT between February 2023 and October 2024. Patients were categorized into good (mRS ≤ 3, n = 89) and poor prognosis (mRS > 3, n = 113) groups based on 90-day modified Rankin Scale (mRS). Univariate and multivariable logistic regression analyses were performed to identify independent predictors of poor prognosis. Receiver operating characteristic (ROC) curves evaluated the predictive performance of combined TMAO and WML scores. DeLong's test confirmed that combining TMAO with the Aharon Peretz score improves the predictive value for poor outcomes over traditional risk factors (NIHSS score and age). The poor prognosis group exhibited significantly higher age, TMAO levels, creatinine, Aharon Peretz scores and NIHSS compared to the good prognosis group (p < 0.05). Multivariable analysis identified TMAO (OR = 2.854, 95%CI: 1.693-4.812), and Aharon Peretz score (OR = 1.881, 95%CI: 1.384-2.558) as new independent predictors (p < 0.05). The combination of TMAO and Aharon Peretz scores predicted poor prognosis with an AUC of 0.786 (95%CI: 0.723-0.848). TMAO and Aharon Peretz scores are independent risk factors for poor short-term prognosis after EVT in patients with AIS. The combination of TMAO and Aharon Peretz scores more accurately predicts the occurrence of short-term poor prognosis after EVT in patients with AIS.

Background:The modified Geriatric Nutritional Risk Index (mGNRI) is a simple, objective tool for assessing malnutrition risk. Its potential utility in patients with urosepsis, however, remains insufficiently explored. Methods:We conducted a retrospective study of patients with sepsis secondary to urinary tract infections using data from the Medical Information Mart for Intensive Care (MIMIC-IV) database and a cohort from the Affiliated Hospital of Guizhou Medical University. The association between the mGNRI and short-term adverse outcomes was examined using restricted cubic spline (RCS) regression, multivariate Cox proportional hazards regression, Kaplan-Meier survival curves, and subgroup analyses. Furthermore, multivariate Cox regression was employed to evaluate the incremental predictive value of mGNRI when integrated with conventional critical illness scores. Results:This study included 1,875 patients with urosepsis. The 28-day ICU and in-hospital mortality rates were 15.5 and 14.3%, respectively. In fully adjusted models, both the continuous and categorical mGNRI were significantly associated with 28-day mortality. For each one-unit increase in the continuous mGNRI, the hazard ratios (HRs) for ICU and in-hospital mortality were 0.98 (95% CI: 0.97-0.99) and 0.98 (95% CI: 0.96-0.99), respectively. Similarly, for each one-standard deviation (SD) increase, the HRs were 0.83 (95% CI: 0.73-0.94) for ICU mortality and 0.81 (95% CI: 0.70-0.93) for in-hospital mortality. When using the no-risk group as a reference, the high-risk group exhibited significantly increased mortality, with HRs of 1.55 (95% CI: 1.07-2.24) for ICU death and 1.59 (95% CI: 1.08-2.32) for in-hospital death. RCS analysis revealed a negative linear relationship between the continuous mGNRI and mortality. Furthermore, subgroup and interaction analyses demonstrated that this association remained consistent across nearly all predefined subgroups. All findings were subsequently validated in an external, real-world cohort. Conclusion:Our findings indicate that the mGNRI serves as a significant inverse predictor of short-term mortality risk in patients with urosepsis. It demonstrates potential as a practical stratification tool to help clinicians identify high-risk patients early for targeted interventions.

BACKGROUND:Secondary platelet activation peaks ≈2 hours after intravenous thrombolysis with alteplase. This study evaluated the safety and efficacy of ultra-early tirofiban administration and compared different tirofiban regimens following intravenous thrombolysis in patients with noncardioembolic acute ischemic stroke. METHODS:This observational study enrolled patients with acute ischemic stroke who received tirofiban within 24 hours following intravenous thrombolysis. Patients were divided into ultra-early (within 2 hours) and early (2-24 hours) groups based on tirofiban initiation time. A secondary analysis was performed based on whether the tirofiban regimen included a bolus dose. The primary outcome was 90-day excellent functional outcome (modified Rankin Scale score 0-1). The safety outcomes included symptomatic intracranial hemorrhage, intracranial hemorrhage, and 3-month all-cause mortality. RESULTS:A total of 472 patients were enrolled, with 214 in the ultra-early tirofiban group and 258 in the early tirofiban group. The ultra-early tirofiban group was associated with 3-month excellent functional outcomes (67.5% versus 53.3%; adjusted odds ratio [aOR], 1.56 [95% CI, 1.01-2.42]). There were no significant differences in intracranial hemorrhage (3.7% versus 1.6%; P=0.18), symptomatic intracranial hemorrhage (0.5% versus 0.4%; P=0.99), or 3-month mortality (1.5% versus 2.5%; P=0.94). Propensity score matching analyses showed consistent outcomes. No significant differences in excellent functional outcomes (61.4% versus 71.0%; aOR, 0.68 [95% CI, 0.36-1.30]) or symptomatic intracranial hemorrhage (0.4% versus 0%; P=0.99) were observed between bolus and maintained groups for prophylactic tirofiban after intravenous thrombolysis. CONCLUSIONS:Ultra-early tirofiban administration following recombinant tissue plasminogen activator was associated with excellent functional outcomes without increasing the risk of symptomatic intracranial hemorrhage, intracranial hemorrhage, or mortality. The extra bolus dose did not show superiority over only maintained dose administration.

PurposeThis study aimed to investigate the associations between gut metabolites Trimethylamine N-Oxide (TMAO), the novel platelet-derived inflammatory ratio index neutrophil-to-platelet ratio (NPR), and the prognosis of patients with acute ischemic stroke (AIS) undergoing endovascular therapy (EVT).MethodsThis study was a retrospective case–control study. Data were collected from 213 AIS patients who underwent EVT at the Stroke Alliance of the Affiliated Hospital of Xuzhou Medical University between October 2022 and December 2024, including baseline characteristics, laboratory results, and gut-derived metabolite levels from the proximal culprit vessel. Functional outcome was assessed using the modified Rankin scale (mRS) at 3 months after EVT. Based on univariable analysis, a multivariable binary logistic regression model was employed to explore the association of gut-derived TMAO and the platelet-derived inflammatory biomarker NPR with poor functional outcomes. The predictive values of TMAO and NPR, both individually and in combination, were quantitatively compared using receiver operating characteristic (ROC) curves integrated with the DeLong test, continuous net reclassification improvement (cNRI), and integrated discrimination improvement (IDI). Finally, both multiplicative and additive interactions between TMAO and NPR regarding poor functional outcomes were evaluated.ResultsA total of 213 eligible patients were divided into the favorable group (mRS ≤ 3, N = 77) and the unfavorable group (mRS > 3, N = 136). After adjusting for confounding factors, multivariable logistic regression analysis revealed that age (OR: 1.065, 95% CI: 1.022–1.109, p = 0.002), baseline National Institutes of Health Stroke Scale (NIHSS) (OR: 1.069, 95% CI: 1.008–1.133, p = 0.025), TMAO (OR: 2.889, 95% CI: 1.563–5.338, p < 0.001), NPR (OR: 1.864, 95% CI: 1.122–3.096, p = 0.016), onset-to-reperfusion time (OTR) (OR: 1.004, 95% CI: 1.002–1.007, p = 0.002), complete recanalization (OR: 0.129, 95% CI: 0.032–0.530, p = 0.004), and hemorrhagic transformation(HT) (OR: 3.271, 95% CI: 1.351–7.918, p = 0.009) were independent predictors of poor functional outcomes. The areas under the curve (AUC) for TMAO, NPR and the combined value of TMAO and NPR in predicting unfavorable outcomes at 3 months after EVT were 0.698, 0.651 and 0.749, respectively. Furthermore, the DeLong test, along with cNRI and IDI analyses, confirmed the significant incremental predictive value of the combined model, and a significant additive interaction between TMAO and NPR was identified.ConclusionThis study revealed that elevated levels of TMAO and NPR are independently associated with poor functional outcomes in AIS patients after EVT. The combined assessment of TMAO and NPR provides incremental value in predicting the prognosis of these patients.

RATIONALE AND OBJECTIVES:Half of ischemic stroke patients are subject to futile reperfusion (FR) after endovascular treatment (EVT). The hypoperfusion intensity ratio (HIR) represents tissue-level collaterals (TLC). We aimed to evaluate the predictive performance of HIR in the assessment of FR. MATERIALS AND METHODS:Retrospective data were derived from a multicenter cohort study of patients with large vessel occlusion in the anterior circulation who underwent EVT in China. HIR was automatically calculated on baseline perfusion imaging as the ratio of brain volume with Tmax >10 s over volume with Tmax >6 s. Poor TLC was regarded as HIR >0.4. The primary outcome was FR, defined as modified Rankin Scale score of 4-6 at 90 days despite successful recanalization. Safety outcomes were symptomatic intracranial hemorrhage (sICH) within 36 h and all-cause mortality at 90 days. RESULTS:A total of 910 patients were included, and we observed FR in 325 (35.7%) patients after EVT. More frequent FR at 90 days was seen in patients with poor TLC (50.2% vs. 30.1%; odds ratio [OR], 2.34; 95% confidential interval [CI], 1.74-3.25; P<0.001). In multivariable regression, the higher HIR was independently associated with higher odds of FR (adjusted OR, 1.88; 95% CI, 1.31-2.68; P=0.001). The rates of sICH were not significantly different between the two groups. HIR>0.4 was correlated with higher rates of 90-day mortality even after adjusting covariates. CONCLUSION:Poorer HIR on admission perfusion imaging was strongly associated with FR occurrence after EVT. This automated and rapidly available perfusion parameter might help the identification of stroke patients at risk of FR.

Background and purpose Acute ischaemic strokes caused by posterior circulation large-vessel occlusions (pc-LVOs) are associated with particularly poor prognoses, including significant disability and mortality rates. This study sought to develop and validate a novel scoring system for predicting functional outcomes in pc-LVO cases following successful endovascular recanalisation. Methods We derived a predictive model from the DETECT-China cohort and externally validated it using the DETECT2-China dataset. Poor outcome was defined as a modified Rankin Scale score of 4-6 at 90 days. Cerebral circulation time (CCT), measured via digital subtraction angiography (DSA), served as a key predictor. Multivariable logistic regression was employed to construct the scoring system. Results The training cohort comprised 92 patients, of whom 52 (56.5%) experienced poor outcomes. Multivariate analysis identified prolonged CCT (adjusted OR (aOR) 1.365; 95% CI 1.105 to 1.686; p=0.004), elevated admission National Institutes of Health Stroke Scale (NIHSS) (aOR 1.235; 95% CI 1.120 to 1.363; p<0.001) and higher blood glucose levels (aOR 1.345; 95% CI 1.023 to 1.769; p=0.034) as independent predictors. These variables were integrated into the GNC score (Glucose-NIHSS-CCT). The GNC score demonstrated excellent predictive performance for clinical outcome, good discrimination and calibration in this cohort, as well as the bootstrap validation. Importantly, the excellent performance of this score was further validated in DETECT2-China. Conclusions This is the first report that CCT based on DSA is an independent prognostic marker in pc-LVO patients with successful recanalisation post-endovascular treatment. The GNC score, incorporating readily available clinical and angiographic parameters, offers a reliable tool for outcome prediction in this high-risk population.

OBJECTIVE:To determine whether an elevated head position (30-40°) improves functional outcomes compared with a flat head position (0-10°) in patients with acute ischaemic stroke caused by anterior circulation large vessel occlusion who have achieved successful reperfusion after endovascular thrombectomy. DESIGN:Multicentre, prospective, randomised, open label, blinded endpoint clinical trial. SETTING:67 comprehensive stroke centres in China, between 16 November 2023 and 23 January 2025. PARTICIPANTS:1368 adults (aged ≥18 years) with acute ischaemic stroke caused by anterior circulation large vessel occlusion who achieved successful endovascular reperfusion, defined as an expanded thrombolysis in cerebral infarction score ≥2b after endovascular thrombectomy. INTERVENTIONS:Participants were randomly assigned (1:1) to maintain either an elevated head position (30-40°, n=685) or a flat head position (0-10°, n=683) for 72 hours after endovascular thrombectomy. MAIN: outcome measures The primary outcome was functional status at 90 days after randomisation, assessed by shift analysis of scores on the modified Rankin scale (range 0-6). The primary safety outcome was all cause mortality at 90 days after randomisation. Efficacy analyses used the randomised, full analysis set, and safety analyses used the safety population (identical to the randomised population). Adjusted models included age, baseline National Institutes of Health Stroke Scale score (NIHSS), baseline Alberta Stroke Programme Early Computed Tomography Score, occlusion site, and time from last known well (ie, the last time when the patient was known to be at their usual neurological baseline before the current stroke event) to randomisation. RESULTS:In the population of 1368 randomised patients, the median age was 68 years, 565 participants (41.3%) were women, and 1358 (99.3%) completed the 90 day follow-up. The median baseline NIHSS score was 15, the median 90 day modified Rankin scale score was 3 (interquartile range (IQR) 1-5) in the head elevation group versus 3 (IQR 1-5) in the flat head position group (adjusted generalised odds ratio for a lower level of disability 1.12, 95% confidence interval (CI) 0.97 to 1.29, P=0.14). All cause mortality at 90 days occurred in 125 (18.3%) of 682 patients in the elevated head position group and 137 (20.3%) of 676 patients in the flat head position group (adjusted risk ratio 0.86, 95% CI 0.69 to 1.07, P=0.18). CONCLUSIONS:72 hours of head elevation did not significantly improve 90 day functional outcomes versus flat head positioning in patients who had acute ischaemic stroke from large vessel occlusion with successful reperfusion after thrombectomy. The smaller than expected difference in results between the two groups leaves open the possibility of a modest but clinically meaningful benefit of head elevation in these patients. TRIAL:registration ClinicalTrials.gov NCT06115707.

AIMS:To preliminarily characterize metabolic molecular subtypes of cerebral thromboemboli and evaluate their clinical significance in anterior circulation acute ischemic stroke due to large vessel occlusion (AIS-LVO). METHODS:Untargeted metabolomics was performed on thromboemboli retrieved from 36 patients with anterior circulation AIS-LVO using ultra-performance coupled liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Unsupervised hierarchical clustering was employed to identify distinct metabolic molecular subtypes, and their associations with stroke etiology, radiographic severity, and functional outcomes were analyzed. RESULTS:Two distinct thrombus metabolic molecular subtypes (C1 and C2) were identified based on 12 metabolites significantly associated with both short-term (7-day ∆NIHSS) and long-term (90-day mRS) functional outcomes. The C1 subtype, predominantly cardioembolic, exhibited enhanced lipid metabolism, whereas the C2 subtype, primarily atherothrombotic, demonstrated increased folate metabolism. Patients with C1 thromboemboli presented more severe admission ischemic lesions (as indicated by ASPECTS) and experienced poorer short-term and long-term outcomes. A six-metabolite signature derived from LASSO regression was identified for exploratory discrimination of thrombus metabolic subtypes, etiological subtypes, and 90-day outcomes. CONCLUSION:This preliminary exploratory study identifies two metabolically distinct thrombus molecular subtypes with clinical implications in anterior circulation AIS-LVO, providing a novel basis for risk stratification and personalized secondary prevention and warrants further investigation.

BACKGROUND AND AIMS:Evidence supporting first-line cryoballoon ablation (CBA) in treatment-naive persistent atrial fibrillation (PersAF) is limited. Consequently, we compared CBA with guideline-directed antiarrhythmic drug (AAD) therapy in this advanced form of disease. METHODS:This multicenter, prospective, randomized, open-label trial assigned 320 symptomatic, treatment-naive patients with PersAF (1:1) to CBA or AAD therapy. The primary endpoint was the first documented atrial tachyarrhythmia recurrence lasting at least 30 seconds during days 91-365. Secondary endpoints included recurrence during days 1-90 and 1-365, time-to-first recurrence, quality of life, and safety. RESULTS:In the intention-to-treat population, recurrence during days 91-365 occurred in 30/160 (18.8%) patients assigned to CBA and 71/160 (44.4%) assigned to AAD therapy (absolute difference, -25.6 percentage points; 95% confidence interval, -35.4 to -15.8; P<0.001). Supportive time-to-event analysis favored CBA (hazard ratio for AAD vs. CBA, 2.29; 95% confidence interval, 1.48-3.56; log-rank P<0.001). In CBA vs AAD comparisons, overall recurrence during days 1-365 was 23.8% vs. 55.6%, and early recurrence was 11.2% vs. 28.1% (both P<0.001; respectively). Improvement in AFEQT score was greater with CBA (17.3 vs. 6.6 points; P<0.001); whereas SF-12 component scores did not differ significantly. Adverse events recorded on event forms were infrequent in both cohorts. CONCLUSION:In selected treatment-naive patients with PersAF, first-line CBA reduced atrial tachyarrhythmia recurrence and improved disease-specific quality of life compared with AAD therapy.

BACKGROUND:Current evidence on differential outcomes of endovascular therapy for the different pathological subtypes of vertebrobasilar artery occlusion is still limited. The study aimed to compare characteristics and clinical outcomes among distinct pathological subtypes of vertebrobasilar artery occlusion undergoing endovascular therapy. METHODS:This was a posthoc pooled analysis of 1320 patients from the BASILAR (Endovascular Treatment for Acute Basilar Artery Occlusion Study; 2014-2019) and the PERSIST (Posterior Circulation Ischemic Stroke Registries; 2015-2018) registries. This analysis included adults (≥18 years) with moderate to severe vertebrobasilar artery occlusion who underwent endovascular therapy within 24 hours of their last known well. Patients were stratified by stroke mechanism: group 1 (embolism without vertebral stenosis), group 2 (tandem embolism from vertebral stenosis/occlusion), and group 3 (in situ atherosclerotic thrombosis). Baseline characteristics, procedural details, and clinical outcomes were compared across these 3 groups. The primary outcome was a favorable functional outcome, defined as a modified Rankin Scale score of 0 to 3 at 90 days. Baseline characteristics, procedural details, and clinical outcomes were compared across these 3 groups. Because the primary independent variable was categorical with no single referent category, all comparisons among the 3 groups were conducted as exploratory analyses. RESULTS:A total of 1067 patients were included (group 1, n=257 [24.08%]; group 2, n=176 [16.49%]; group 3, n=634 [59.42%]). The overall successful recanalization rate was 84.72% (904/1067), and the favorable functional outcome (90-day modified Rankin Scale score of 0-3) rate was 33.40% (275/1063). The procedure time in group 1 was significantly shorter than that in groups 2 and 3 (median time, 90 versus 135 and 110 minutes, P<0.001). There was no significant difference in the primary outcome of a favorable functional outcome among the 3 groups. After adjusting for potential confounders, group 1 exhibited a significantly higher proportion of patients achieving excellent outcomes at 90 days (modified Rankin Scale score, 0-1) compared with groups 2 and 3 (21.9% versu 17.1%, adjusted odds ratio, 0.57 [95% CI, 0.32-0.99]; 21.9% versus 16.5%, adjusted odds ratio, 0.59 [95% CI, 0.37-0.95]). No significant differences were observed in recanalization rates, favorable functional outcome, symptomatic intracranial hemorrhage, or mortality among the 3 groups. CONCLUSIONS:The outcome of endovascular therapy for vertebrobasilar artery occlusion may vary based on the stroke mechanism; patients with embolism without vertebral artery steno-occlusion may achieve excellent outcomes compared with other causes. REGISTRATION:URL: http://www.chictr.org.cn; Unique identifier: CTR1800014759 and CTR2000033211.

Background:This study sought to characterize sex-specific treatment effects by comparing clinical outcomes between men and women undergoing EVT. Methods:Analyses were based on the DEVT, RESCUE BT, and MARVEL databases. Men and women were matched using propensity score matching (PSM). The primary outcome was defined as the 90-day ordinal modified Rankin Scale score (mRS) distribution. Secondary outcomes included the favorite outcome (mRS 0 to 3), functional independence (mRS 0 to 2), and excellent outcome (mRS 0 to 1). Safety outcomes were symptomatic intracranial hemorrhage (sICH) and mortality. Results:Of 2,862 patients, 1,221 (42.7%) were women and 1,641 (57.3%) were men. After adjusting for covariates, there were no sex differences in 90-day ordinal mRS distribution (median [interquartile range], 3 [1-6] versus 3 [1-5], common odds ratio [OR], 1.02 [0.89-1.18], p = 0.741). The secondary outcomes demonstrated consistency with the primary findings, and the safety outcomes remained stable across men and women. After 1:1 PSM, the results remained consistent with the adjusted outcomes described above. Conclusion:This pooled analysis demonstrated that no statistically significant differences were observed between men and women in clinical or safety outcomes following EVT for anterior circulation LVO. Furthermore, there was no evidence of interaction between sex and predefined subgroups in terms of treatment effect modification for EVT outcomes.

To explore how neutrophil extracellular traps (NETs) mediate neuropathic pain in primary Sjögren's syndrome-associated peripheral neuropathy (pSS-PN). We analyzed clinical features in pSS-PN (n = 6) by DN4 Questions, Electromyography examination and sural nerve biopsies from six pSS-PN patients and six traumatic amputees using histology, immunohistochemistry (IHC), transmission electron microscopy (TEM), and immunofluorescence (IF) for NETs markers (cit-H3/MPO). And we created a model of pSS-PN. Pain behaviors were assessed, plasma cit-H3 was measured by ELISA, and hindlimb perfusion was quantified via laser speckle imaging. To inhibit NETosis, DNase I was administered intravenously. PSS-PN patients exhibited neuropathic pain, nerve conduction deficits, reduced nerve fiber density, and inflammatory vasa nervorum injury with significant cit-H3/MPO accumulation. NOD. Aire⁻/⁻ mice developed mechanical allodynia (1.885 vs. 2.497, P < 0.001 vs. C57BL/6 J; 1.885 vs. 2.367 P < 0.01 vs. NOD WT) and thermal hyperalgesia (6.993 vs. 8.585, P < 0.05 vs. C57BL/6 J; 6.93 vs. 8.815 P < 0.05 vs. NOD WT), accompanied by elevated plasma cit-H3 (44.61 vs. 27.49, P < 0.0001 vs. C57BL/6 J; 44.61 vs. 30.96 P < 0.0001 vs. NOD WT), sciatic nerve NETs deposition (44.61 vs. 35.60, P < 0.0001 24 vs. 18 weeks, NOD. Aire⁻/⁻), and increased hindlimb perfusion. DNase I treatment effectively reduced plasma cit-H3, alleviated pain behaviors, mitigated microvascular damage, and normalized perfusion. NETs drive peripheral neuropathy in pSS by inducing vasa nervorum inflammation and microcirculatory dysfunction, leading to neuropathic pain. These findings identify NETs as a key mechanistic link, biomarker, and promising therapeutic target in pSS-PN.

Importance Persisting or new thrombi in the distal arteries and the microcirculation have been reported to limit the benefits of successful endovascular thrombectomy for patients with acute ischemic stroke. It remains uncertain whether intra-arterial thrombolysis by urokinase following near-complete to complete reperfusion by thrombectomy improves outcomes among patients with ischemic stroke due to large vessel occlusion. Objective To assess the efficacy and adverse events of intra-arterial urokinase after near-complete to complete reperfusion by thrombectomy for acute ischemic stroke due to large vessel occlusion. Design, Setting, and Participants This investigator-initiated, randomized, open-label, blinded–end point trial was implemented at 35 hospitals in China, enrolling 535 patients with proximal intracranial large vessel occlusion presenting within 24 hours of time last known well, who achieved near-complete or complete reperfusion by endovascular thrombectomy and did not receive intravenous thrombolysis prior to the procedure. Recruitment took place between November 15, 2022, and March 29, 2024, with final follow-up on July 4, 2024. Interventions Eligible patients were randomly assigned to the intra-arterial urokinase group (a single dose of intra-arterial 100 000 IU urokinase injected in the initial target territory; n = 267) or control group (without intra-arterial thrombolysis; n = 267). Main Outcomes and Measures The primary efficacy outcome was the percentage of patients achieving survival without disability (modified Rankin Scale score of 0 or 1) at 90 days. The primary safety outcomes were mortality at 90 days and incidence of symptomatic intracranial hemorrhage within 48 hours. Results A total of 535 patients were enrolled (median age, 69 years; 223 [41.8%] female) and 532 (99.6%) completed the trial. The percentage of patients with survival without disability at 90 days was 45.1% (120/266) in the intra-arterial urokinase group and 40.2% (107/266) in the control group (adjusted risk ratio, 1.13 [95% CI, 0.94-1.36]; P = .19). Mortality at 90 days (18.4% vs 17.3%, respectively; adjusted hazard ratio, 1.06 [95% CI, 0.71-1.59]; P = .77) and incidence of symptomatic intracranial hemorrhage (4.1% vs 4.1%, respectively; adjusted risk ratio, 1.05 [95% CI, 0.45-2.44]; P = .91) were not significantly different between groups. Conclusions and Relevance Among patients with acute ischemic stroke due to large vessel occlusion, adjunct intra-arterial urokinase after near-complete to complete reperfusion by endovascular thrombectomy did not significantly increase the likelihood of survival without disability at 90 days. Trial Registration ChiCTR.org.cn Identifier: ChiCTR2200065617

Importance:Persisting or new thrombi in the distal arteries and the microcirculation have been reported to limit the benefits of successful endovascular thrombectomy for patients with acute ischemic stroke. It remains uncertain whether intra-arterial thrombolysis by urokinase following near-complete to complete reperfusion by thrombectomy improves outcomes among patients with ischemic stroke due to large vessel occlusion. Objective:To assess the efficacy and adverse events of intra-arterial urokinase after near-complete to complete reperfusion by thrombectomy for acute ischemic stroke due to large vessel occlusion. Design, Setting, and Participants:This investigator-initiated, randomized, open-label, blinded-end point trial was implemented at 35 hospitals in China, enrolling 535 patients with proximal intracranial large vessel occlusion presenting within 24 hours of time last known well, who achieved near-complete or complete reperfusion by endovascular thrombectomy and did not receive intravenous thrombolysis prior to the procedure. Recruitment took place between November 15, 2022, and March 29, 2024, with final follow-up on July 4, 2024. Interventions:Eligible patients were randomly assigned to the intra-arterial urokinase group (a single dose of intra-arterial 100 000 IU urokinase injected in the initial target territory; n = 267) or control group (without intra-arterial thrombolysis; n = 267). Main Outcomes and Measures:The primary efficacy outcome was the percentage of patients achieving survival without disability (modified Rankin Scale score of 0 or 1) at 90 days. The primary safety outcomes were mortality at 90 days and incidence of symptomatic intracranial hemorrhage within 48 hours. Results:A total of 535 patients were enrolled (median age, 69 years; 223 [41.8%] female) and 532 (99.6%) completed the trial. The percentage of patients with survival without disability at 90 days was 45.1% (120/266) in the intra-arterial urokinase group and 40.2% (107/266) in the control group (adjusted risk ratio, 1.13 [95% CI, 0.94-1.36]; P = .19). Mortality at 90 days (18.4% vs 17.3%, respectively; adjusted hazard ratio, 1.06 [95% CI, 0.71-1.59]; P = .77) and incidence of symptomatic intracranial hemorrhage (4.1% vs 4.1%, respectively; adjusted risk ratio, 1.05 [95% CI, 0.45-2.44]; P = .91) were not significantly different between groups. Conclusions and Relevance:Among patients with acute ischemic stroke due to large vessel occlusion, adjunct intra-arterial urokinase after near-complete to complete reperfusion by endovascular thrombectomy did not significantly increase the likelihood of survival without disability at 90 days. Trial Registration:ChiCTR.org.cn Identifier: ChiCTR2200065617.

Background:A20 is an endogenous protective protein. We quantified serum A20 levels following acute intracerebral hemorrhage (ICH) and assessed their association with the severity of illness and clinical outcomes of patients. Methods:In total, 243 patients with acute supratentorial ICH and 76 controls were included in this prospective cohort study. Serum A20 levels were measured at admission in all patients, at study entry in all controls, and on post-ICH days 1, 3, 5, 7, 10, and 14 in 76 patients. The National Institutes of Health Stroke Scale (NIHSS) scores and hematoma volume were used to estimate the severity. Stroke-associated pneumonia (SAP), early neurological deterioration (END), and post-ICH 6-month poor prognosis (modified Rankin Scale scores: 3-6) were considered as the three outcome variables of interest. Results:Patients, as opposed to controls, exhibited significantly heightened serum A20 levels from admission until 14 days following ICH, with a peak value at day 3. Serum A20 levels at all-time points after ICH, which were significantly correlated with NIHSS scores and hematoma volume, were significantly higher in patients with END, SAP, or poor prognosis than in those without the corresponding one. Serum A20 levels at admission possessed similar predictive ability of these clinical outcomes to those at other time points. Serum A20 levels at admission, along with initial NIHSS scores and hematoma volume, remained independent predictors of clinical outcomes among patients. As confirmed by numerous statistical approaches, their conjunctions comprised three prediction models: satisfactory stability, clinical validity, and discrimination efficiency. Conclusion:Serum A20 levels were significantly increased following ICH and may accurately reflect hemorrhagic severity and effectively predict END, SAP, and poor neurological prognosis, suggesting that serum A20 may be a promising prognostic biomarker for ICH.