Wenting Guo

Introduction: The cerebroprotective effects of hypothermia via selective intra-arterial cooling infusion (SI-AC) as an adjunct to endovascular thrombectomy (EVT) for acute ischemic stroke (AIS) due to large vessel occlusion (LVO) are uncertain. This trial aimed to determine the efficacy and safety of SI-AC in patients with anterior circulation LVO-AIS undergoing EVT. Methods: A multicenter, national, investigator-initiated and -conducted, randomized, controlled, and subject- and assessor-blinded superiority clinical trial was conducted at 12 hospitals in China. Patients with anterior circulation LVO-AIS presenting within 24 h of symptom onset are randomized 1:1 to receive SI-AC plus EVT (intervention) or EVT (control) in addition to standard care and be followed up for 90 days. Using a two-sided significance level of 0.05 and assuming a 5% loss of patients at follow-up, we estimate 258 patients provides 80% power to detect a common odds ratio of 1.9 for improved functional recovery, evaluated using the modified Rankin Scale (mRS) at 90 days. The primary outcome is mRS score distribution at 90 days. Secondary outcomes include different cut points on the mRS (0–2 and 0–1) at 90 days, Barthel index scores at 90 days, infarct volume at 7 days, and early neurologic improvement at 24 h. Safety outcomes include the incidence of symptomatic intracranial hemorrhage and any intracranial hemorrhage at 24 h, procedure-related complications, and all-cause mortality at 90 days. Conclusion: This trial is designed to evaluate the efficacy and safety of SI-AC as a novel cerebroprotective strategy for patients with anterior circulation LVO-AIS undergoing EVT.

Objective: This study aimed to develop and validate a predictive model for differentiating central from peripheral etiologies in patients with isolated vestibular syndrome (VS). Methods: In this multicenter retrospective cohort study, 506 patients with isolated VS from five hospitals were divided into derivation ( n = 301) and validation ( n = 205) cohorts. Multivariable logistic regression was performed to determine independent predictors of central VS. These predictors were assigned weights to construct the SAV ₃ E score. The performance of the SAV ₃ E was assessed using the area under the curve (AUC), calibration, and decision curve analysis (DCA) and compared with that of the TriAGe+ and STANDING models. Results: The SAV ₃ E score incorporated five predictors: absence of vestibular vagal symptoms (OR, 0.233; 95% CI, 0.084–0.648; p = 0.005), prior stroke (OR, 15.204; 95% CI, 4.455–51.884; p < 0.001), ABCD ₂ score of 4–7 (OR, 1.903; 95% CI, 1.206–3.004; p = 0.006), central video oculography nystagmus (OR, 38.377; 95% CI, 8.631–170.644; p < 0.001), and positive video head impulse test (OR, 0.078; 95% CI, 0.033–0.188; p < 0.001). It displayed good discriminative performance with AUCs 0.910 and 0.886 in the derivation and validation cohorts, respectively. It outperformed TriAGe+ (AUC: 0.706) and STANDING (AUC: 0.779) models. Furthermore, calibration analysis revealed good model fit across cohorts (Hosmer‐Lemeshow test results: derivation cohort, p = 0.899; validation cohort, p = 0.789). DCA confirmed good clinical utility across a wide range of probability thresholds (derivation cohort: 0.01–0.86, validation cohort: 0.01–1.00). Conclusion: The SAV ₃ E score is a validated tool aimed at differentiating central versus peripheral VS, with the potential to improve diagnostic accuracy for urgent etiologies such as stroke.

Aims: With the progress of thrombectomy technology, the vascular recanalization rate of patients with stroke has been continuously improved, but the proportion of futile recanalization (FR) is still quite a few. The long‐term prognosis and survival of patients with FR and its influencing factors remain unclear.Methods: Consecutive patients who received endovascular treatment (EVT) for ischemic stroke were enrolled between 2013 and 2021 from a single‐center prospectively registry study. We evaluated the long‐term outcome of these patients by Kaplan–Meier survival analysis, and the multivariable logistic regression curve was performed to analyze influencing factors.Results: Among 458 patients with FR, 56.4% of patients survived at 1 year, and 50.4% at 2 years. In the multivariate regression analysis, age, premorbid modified Rankin Scale (mRS), National Institutes of Health Stroke Scale (NIHSS), posterior circulation infarct, general anesthesia, symptomatic intracerebral hemorrhage (sICH), and decompressive craniectomy were found to be related to unfavorable outcomes in long‐term. Age, premorbid mRS, NIHSS, general anesthesia, and sICH were predictors of long‐term mortality.Conclusions: Futile recanalization accounts for a large proportion of stroke patients after thrombectomy. This study on the long‐term prognosis of such patients is beneficial to the formulation of treatment plans and the prediction of therapeutic effects.

Background and Objective. Approximately 50% of acute ischemic stroke (AIS) patients who achieve complete recanalization after endovascular therapy (EVT) experience unfavorable outcomes that are potentially partially attributed to incomplete microvascular reperfusion, which can possibly be improved by antiplatelet treatment. This study aimed to evaluate the effect of periprocedural tirofiban on AIS patients who achieved complete recanalization with EVT. Methods. Anterior circulation large‐vessel occlusion stroke patients who achieved complete recanalization after EVT were retrospectively analyzed. Patients were dichotomized into tirofiban and nontirofiban groups and compared. Propensity score matching (PSM) was used to balance baseline confounders. 3‐month functional independence (modified Rankin scale: 0–2), any intracranial hemorrhage (ICH), symptomatic ICH (sICH), arterial reocclusion, in‐hospital mortality, and 3‐month mortality were evaluated. Results. This study included 303 patients with 118 and 185 in the nontirofiban and tirofiban groups, respectively. After PSM, 85 couples with balanced baseline characteristics were generated. 49 (57.6%) and 36 patients (42.4%) in the tirofiban and nontirofiban groups achieved functional independence at 3 months with a significant difference (risk ratio: 1.361, 95% confidence interval: 1.001–1.852, P = 0.046). However, there was no significant difference between the tirofiban and nontirofiban groups in terms of the other outcomes (all P > 0.05). Conclusions. In anterior circulation, large‐vessel occlusion AIS patients who achieved complete recanalization with EVT, periprocedural tirofiban may improve the functional outcomes and does not appear to increase the rate of ICH and sICH.

Background: Exploratory studies have shown that remote ischemic conditioning (RIC) has the potential to lower blood pressure (BP). We investigated whether chronic RIC reduces BP for hypertension. Methods: This is a multicenter, randomized, double-blind, parallel-controlled trial. Patients with an office BP of 130/80 to 160/100 mm Hg and a 24-hour average BP ≥125/75 mm Hg not on antihypertensive medications were recruited. After a 1-week compliance screening phase, they were randomly assigned in a 1:1 ratio to receive RIC or sham RIC twice daily for 4 weeks. The primary efficacy outcome was the change in 24-hour average systolic BP from baseline to 4 weeks. Safety events were assessed over the study period. Results: Ninety-five participants were randomly allocated to the RIC (n=49) and sham RIC (n=46) groups. In the intention-to-treat analysis, the reduction in 24-hour average systolic BP was greater in the RIC group than the sham RIC group (−4.6±9.5 versus −0.9±6.8 mm Hg; baseline-adjusted between-group mean difference: −3.6 mm Hg [95% CI, −6.9 to −0.3 mm Hg]; adjusted P =0.035). The per-protocol analysis showed that 24-hour average systolic BP reduced −5.9±8.6 mm Hg in the RIC group and −0.7±6.7 mm Hg in the sham RIC group (baseline-adjusted between-group mean difference: −5.2 mm Hg [95% CI, −8.5 to −1.9 mm Hg]; adjusted P =0.002). No major adverse events were reported in both groups. Conclusions: RIC is safe in patients with mild hypertension and may lower BP in the absence of antihypertensive medications. However, the effects of RIC on clinical outcomes in these patients require further investigation. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04915313.

Background: Remote ischemic conditioning (RIC) has shown an impressive neuroprotective effect on acute ischemic stroke (AIS) in animal experiments. But whether chronic RIC improves long-term functional outcomes remains unclear. Materials and Methods: We performed a non-randomized controlled trial. Eligible patients (aged 18 –80 y) with hemiplegia caused by AIS were allocated to the RIC group and the control group. All participants received normal protocol rehabilitation therapy. Patients in the RIC group underwent RIC twice daily for 90 days. The outcome included the 90-day Fugl-Meyer Assessment (FMA) scores and modified Rankin’s scale (mRS) scores, as well as changes in angiogenesis-related factors in serum from baseline to 90 days. Results: Twenty-seven patients were included in the analysis (13 in the RIC group and 14 in the control group). There was no significant difference in 90-day total FMA scores between the two groups. Lower limb FMA scores at day 90 were significantly higher in the RIC group (32.8±8.7 vs. 24.8±5.4, adjusted P=0.042). The proportion of favorable outcome (mRSP=0.705). A significant increase has been found in the level of epidermal growth factor (EGF) in serum (9.4 [1.1 to 25.7] vs. −8.7 [−15.1 to 4.7], P=0.036) after chronic RIC procedure. Conclusion: This study investigated the role that RIC plays in AIS recovery, especially in motor function. RIC may have beneficial effects on lower limbs recovery by enhancing the EGF level. The effect of RIC on motor recovery should be further validated in future studies.

Evidence on joint association of a phthalate mixture with thyroid function among children and its underlying mechanism is largely unknown. We aimed to explore the associations of 10 urinary phthalate metabolites (mPAEs), either as individuals or as a mixture, with thyroid function indicators [free thyroxine, free triiodothyronine (FT3), and thyroid-stimulating hormone (TSH)] in 144 children aged 4-12 years with up to 3 repeated visits across 3 seasons. Significant and positive associations were observed for mono-(2-ethylhexyl) phthalate (MEHP), mono-iso-butyl phthalate (MiBP), and mono-n-butyl phthalate (MnBP) with TSH, as well as monobenzyl phthalate (MBzP) with FT3 in dose-response manners. The relationship between MEHP and TSH remained robust in multiple-phthalate models. Bayesian kernel machine regression (BKMR) models revealed overall linear associations of the 10 mPAE mixture with higher TSH and FT3 levels, and MEHP and MBzP were major contributors. Meanwhile, MEHP, MiBP, and MnBP were linked to the elevation of multiple cytokines including CCL 27, CCL3, CXCL1, and IL-16. Among them, IL-16 mediated the relationships of MEHP and MiBP with TSH, and the mediated proportions were 24.16% and 24.27%, respectively. Our findings suggested that mPAEs dominated by MEHP were dose-responsively associated with elevated TSH among healthy children and mediated by IL-16.

Objective: This study aimed to explore the effect of different administration routes of a low dose of tirofiban on acute ischemic stroke (AIS) patients with successful recanalization after endovascular treatment (EVT).Methods: This is a cohort study that retrospectively analyzed data of patients with AIS who underwent EVT and achieved successful recanalization from a prospective registry. Eligible patients were divided into three groups according to their use of tirofiban. Propensity score matching (PSM) was used to balance baseline bias. Safety outcomes included any intracranial hemorrhage (ICH) and symptomatic ICH (sICH). Efficacy outcomes included arterial reocclusion, in‐hospital mortality, 3‐month mortality, and 3‐month functional outcomes.Results: We included 821 patients with 306 in the no tirofiban group, 202 in the IA + IV tirofiban group, and 313 in the IV tirofiban group. After PSM, each group included 101 patients with balanced baseline characteristics. There was no difference between the IV tirofiban group and the no tirofiban group in terms of safety and efficacy outcomes (all p > 0.05). Compared with no tirofiban, IA + IV tirofiban group did not increase ICH (30.7% vs. 37.6%, p > 0.05) and sICH (6.9% vs. 17.8%, p > 0.05) whereas reduced 3‐month mortality (14.3% vs. 28.7%, p < 0.05) and improved 3‐month modified Rankin Scale (median 3 vs. 4, p < 0.05).Conclusions: A low dose of tirofiban, regardless of their administration routes, was safe for AIS patients who achieved successful recanalization with EVT, whereas only IA + IV tirofiban improved clinical outcomes.