Predictors of outcome in large vessel occlusion stroke patients with intravenous tirofiban treatment: a post hoc analysis of the RESCUE BT clinical trial.

OBJECTIVE: The aim of this study was to investigate the factors influencing good outcomes in patients receiving only intravenous tirofiban with endovascular thrombectomy for large vessel occlusion stroke. METHODS: Post hoc exploratory analysis using the RESCUE BT trial identified consecutive patients who received intravenous tirofiban with endovascular thrombectomy for large vessel occlusion stroke in 55 comprehensive stroke centers from October 2018 to January 2022 in China. RESULTS: A total of 521 patients received intravenous tirofiban, 253 of whom achieved a good 90-day outcome (modified Rankin Scale [mRS] 0-2). Younger age (adjusted odds ratio [aOR]: 0.965, 95% confidence interval [CI]: 0.947-0.982; p < 0.001), lower serum glucose (aOR: 0.865, 95%CI: 0.807-0.928; p < 0.001), lower baseline National Institutes of Health Stroke Scale (NIHSS) score (aOR: 0.907, 95%CI: 0.869-0.947; p < 0.001), fewer total passes (aOR: 0.791, 95%CI: 0.665-0.939; p = 0.008), shorter punctures to recanalization time (aOR: 0.995, 95%CI:0.991-0.999; p = 0.017), and modified Thrombolysis in Cerebral Infarction (mTICI) score 2b to 3 (aOR: 8.330, 95%CI: 2.705-25.653; p < 0.001) were independent predictors of good outcomes after intravenous tirofiban with endovascular thrombectomy for large vessel occlusion stroke. CONCLUSION: Younger age, lower serum glucose level, lower baseline NIHSS score, fewer total passes, shorter punctures to recanalization time, and mTICI scores of 2b to 3 were independent predictors of good outcomes after intravenous tirofiban with endovascular thrombectomy for large vessel occlusion stroke. CHINESE CLINICAL TRIAL REGISTRY IDENTIFIER: ChiCTR-IOR-17014167.

Predictors of unexplained early neurological deterioration after thrombectomy for posterior circulation infarction: a reanalysis of the BASILAR study.

OBJECTIVE: The efficacy of endovascular thrombectomy in patients with posterior circulation ischemic stroke remains controversial. Early neurological deterioration (END) as an important predictor of poor outcome is poorly understood, except in cases of symptomatic intracranial hemorrhage, recanalization failure, and malignant cerebral edema. The objective of this study was to assess predictors of unexplained END (UnEND) after endovascular thrombectomy. METHODS: The BASILAR study is a multicenter prospective observational study in which 647 patients with vertebrobasilar occlusion on imaging within 24 hours of stroke onset and who underwent endovascular treatment were enrolled, of whom 477 who had undergone successful recanalization were included in this study. Multivariate analysis was used to identify the predictors of UnEND, defined as a ≥ 4-point increase in National Institutes of Health Stroke Scale (NIHSS) score at 24 hours after endovascular thrombectomy. RESULTS: Among the 477 eligible patients included, UnEND occurred in 86 (18%) patients. The predictors of UnEND were stress hyperglycemic ratio (SHR) (OR 2.2, 95% CI 1.1-4.6; p = 0.031), baseline NIHSS score (OR 0.9, 95% CI 0.83-0.95; p = 0.001), and asymptomatic intracerebral hemorrhage (aICH) (OR 5.9, 95% CI 1.7-20.0; p = 0.004). The occurrence rate of a favorable outcome, defined as a modified Rankin Scale score of 0-2 at 90 days, was lower in the UnEND group (5.8% vs 47.6%, p < 0.001) compared with the group without END, and the UnEND group had higher mortality at 90 days (66.3% vs 27.4%, p < 0.001). CONCLUSIONS: UnEND may be associated with poor outcome after endovascular thrombectomy in patients with acute vertebrobasilar occlusion. Some modifiable factors such as SHR and aICH could be targeted to improve the efficacy of endovascular thrombectomy.

Protective effects of butorphanol in oleic acid-endotoxin "two-hit" induced rat lung injury by suppression of inflammation and apoptosis.

Butorphanol is widely used as an anesthetic drug, whether butorphanol could reduce organ injury and protecting lung tissue is unknown. This study explored the effects of butorphanol on ALI and investigated its underlying mechanisms. We established a "two-hit" rat model and "two-hit" cell model to prove our hypothesis. Rats were divided into four groups [control, "two-hit" (OA + LPS), "two-hit" + butorphanol (4 mg/kg and 8 mg/kg) (OA + LPS + B1 and OA + LPS + B2)]. RPMVE cells were divided into four groups [control, "two-hit" (OA + LPS), "two-hit" + butorphanol (4 µM and 8 µM) (OA + LPS + 4 µM and OA + LPS + 8 µM)]. Inflammatory injury was assessed by the histopathology and W/D ratio, inflammatory cytokines, and arterial blood gas analysis. Apoptosis was assessed by Western blotting and flow cytometry. The effect of NF-κB p65 was detected by ELISA. Butorphanol could relieve the "two-hit" induced lung injury, the expression of TNF, IL-1ß, IL-6, and improve lung ventilation. In addition, butorphanol decreased Bax and cleaved caspase-3, increased an antiapoptotic protein (Bcl-2), and inhibited the "two-hit" cell apoptosis ratio. Moreover, butorphanol suppressed NF-κB p65 activity in rat lung injury. Our research showed that butorphanol may attenuate "two-hit"-induced lung injury by regulating the activity of NF-κB p65, which may supply more evidence for ALI treatment.

Endovascular Therapy and Outcomes Among Patients With Very Large Ischemic Core Stroke.

Importance: The association of endovascular therapy (EVT) with outcomes is unclear for patients with very low Alberta Stroke Program Early Computed Tomography Score (ASPECTS) within 24 hours of stroke onset. Objective: To explore the association of EVT with functional and safety outcomes among patients with ASPECTS of 0 to 2 scored with noncontrast computed tomography. Design, Setting, and Participants: This cohort study used data from an ongoing, prospective, observational, nationwide registry including all patients treated at 38 stroke centers in China with an occlusion in the internal carotid artery or M1 or M2 segment of the middle cerebral artery within 24 hours of witnessed symptom onset. Patients with ASPECTS of 0 to 2 between November 1, 2021, and February 8, 2023, were included in analysis. Data were analyzed October to November 2023. Exposures: EVT vs standard medical treatment (SMT). Main Outcomes and Measures: The primary outcome was favorable functional outcome, defined as modified Rankin Scale score (mRS) of 0 to 3, at 90 days. Safety outcomes included symptomatic intracerebral hemorrhage (sICH) within 48 hours and mortality at 90 days. Results: A total of 245 patients (median [IQR] age, 71 [63-78] years; 118 [48%] women) with ASPECTS of 0 to 2 were included, of whom 111 patients (45.1%) received SMT and 135 patients (54.9%) received EVT. The EVT group had significantly greater odds of favorable functional outcome at 90 days than the SMT group (30 patients [22.2%] vs 11 patients [9.9%]; P = .01; adjusted odds ratio [aOR], 3.07 [95% CI, 1.29-7.31]; P = .01). Patients in the EVT group, compared with the SMT group, had significantly greater odds of any ICH (56 patients [41.5%] vs 16 patients [11.4%]; P < .001; aOR, 4.27 [95% CI, 2.19-8.35]; P < .001) and sICH (24 patients [17.8%] vs 1 patient [0.9%]; P < .001; aOR, 23.07 [95% CI, 2.99-177.79]; P = .003) within 48 hours. There were no differences between groups for 90-day mortality (80 patients [59.3%] vs 59 patients [53.2%]; P = .34; aOR, 1.38 [95% CI, 0.77-2.47]; P = .28). The results remained robust in the propensity score-matched analysis. Conclusions and Relevance: In this cohort study of patients with very low ASPECTS based on NCCT within 24 hours of stroke onset, those treated with EVT had higher odds of a favorable functional outcome compared with those who received SMT. Randomized clinical trials are needed to assess these findings.

Endovascular treatment versus standard medical treatment in patients with established large infarct: a cohort study.

BACKGROUND: Previous trials confirmed the benefit of endovascular treatment (EVT) in acute large core stroke, but the effect of EVT on outcomes in these patients based on non-contrast computed tomography (NCCT) in real-world clinical practice was unclear. The aim of this study was to explore the effect of EVT versus standard medical treatment (SMT) in patients with large ischemic core stroke defined as Alberta Stroke Program Early CT Score (ASPECTS)≤5 based on NCCT alone. MATERIALS AND METHODS: Patients with acute large core stroke at 38 Chinese centers between November 2021 and February 2023 were reviewed from prospectively maintained databases. The primary outcome was favorable functional outcome (modified Rankin Scale score [mRS], 0-3) at 90 days. Safety outcomes included 48-hour symptomatic intracerebral hemorrhage (sICH) and 90-day mortality. RESULTS: Of 745 eligible patients recruited at 38 stroke centers between November 2021 and February 2023, 490 were treated with EVT and 255 with SMT alone. One hundred and eighty-one (36.9%) in the EVT group achieved favorable functional independence versus 48 (18.8%) treated with SMT only (adjusted risk ratio [RR], 1.86; 95% CI, 1.43 to 2.42, P<0.001; adjusted risk difference [RD], 13.77; 95% CI, 7.40 to 20.15, P<0.001). The proportion of sICH was significantly higher in patients undergoing EVT (13.3% vs. 2.4%; adjusted RR, 5.17; 95% CI, 2.17 to 12.32, P<0.001; adjusted RD, 10.10; 95% CI, 6.12 to 14.09, P<0.001). No significant difference of mortality between the groups was observed (41.8% vs. 49.0%; adjusted RR, 0.91; 95% CI, 0.77 to 1.07, P=0.24; adjusted RD, -5.91; 95% CI, -12.91 to 1.09, P=0.1). CONCLUSION: Among patients with acute large core stroke based on NCCT in real world, EVT is associated with better functional outcomes at 90 days despite of higher risk of sICH. Rates of procedure-related complications were high in the EVT group.

The effectiveness and safety of human urinary kallidinogenase in acute ischemic stroke patients undergoing endovascular therapy.

The effectiveness and safety of human urinary kallidinogenase (HUK) in acute ischemic stroke (AIS) patients undergoing endovascular therapy (EVT) due to large vessel occlusion (LVO) was unclear. A pooled analysis was performed using individual data from the DEVT and RESCUE BT trials. Patients were divided into two groups based on HUK treatment. The primary outcome was the 90-day modified Rankin Scale (mRS) score. Safety outcomes included 90-day mortality and symptomatic intracranial hemorrhage (sICH) within 48 hours. A total of 1174 patients were included in the study. Of these, 150 (12.8%) patients received HUK. The adjusted common odds ratio (OR) of the mRS score was 1.458 (95% confidence interval [CI] = 1.072-1.983; p = 0.016) favoring HUK. The incidence of sICH (2.0% vs. 8.6%; adjusted OR: 0.198; 95% CI: 0.061-0.638; p = 0.007) and mortality (11.3% vs.18.5%; adjusted OR: 0.496; 95% CI: 0.286-0.862; p = 0.013) was lower in HUK group than non-HUK group. This association was consistent with propensity score-matching and the inverse probability of treatment weighting analysis. In conclusion, HUK was safe and associated with a preferable prognosis in AIS patients due to LVO in the anterior circulation.

The impact of stress hyperglycemia ratio on short-term and long-term outcomes for acute basilar artery occlusion underwent endovascular treatment.

BACKGROUND: Stress hyperglycemia ratio (SHR) reflects a true acute hyperglycemic state during acute basilar artery occlusion (ABAO). We aimed to investigate the association between SHR and short-term and long-term outcomes in patients with ABAO receiving endovascular treatment (EVT). METHODS: We selected patients treated with EVT from the BASILAR study, a nationwide prospective registry. A total 250 patients with documented glucose and glycated hemoglobin (HbA1C) values at admission were included. SHR was calculated as the ratio of glucose/HbA1C. All 250 patients completed 90 days of follow-up and 234 patients (93.6%) completed 1 year of follow-up. The primary outcome was the favorable outcome defined as modified Rankin Scale (mRS) score ≤ 3 at 90 days. Safety outcomes included mortality at 90 days and 1 year, and intracranial hemorrhage. RESULTS: Among the 250 patients included, patients with higher tertiles of SHR were associated with decreased odds of a favorable functional outcome at 90 days (adjusted OR, 0.26; 95% CI, 0.12-0.56; P = 0.001 and adjusted OR, 0.37; 95% CI, 0.18-0.80; P = 0.01; respectively) and 1 year (adjusted OR, 0.34; 95% CI, 0.16-0.73; P = 0.006 and adjusted OR, 0.38; 95% CI, 0.18-0.82; P = 0.01; respectively) after adjusting for confounding covariates. The mortality was comparable across tertiles of SHR groups at 90 days and 1 year. CONCLUSIONS: Our study showed that SHR was associated with a decreased probability of favorable functional outcome both at 90 days and 1 year after EVT in patients with ABAO. The relationship was more pronounced in non-diabetes patients. TRIAL REGISTRATION: Clinical Trial Registry Identifier: ChiCTR1800014759 (November 12, 2013).

Thrombectomy alone versus intravenous thrombolysis before thrombectomy for acute basilar artery occlusion.

BACKGROUND: Endovascular treatment (EVT) is a well-established approach for acute ischemic stroke. Whether bridging intravenous thrombolysis (IVT) before EVT confers any benefits remains uncertain. The objective of the study was to compare the efficacy and safety of direct EVT with or without bridging IVT in patients with acute basilar artery occlusion (BAO). METHODS: This multicenter cohort study enrolled 647 patients with acute BAO who underwent either bridging IVT before EVT or direct EVT from the BASILAR registry. The primary outcome was an independent functional outcome measured by the modified Rankin Scale (mRS) score of 0-2. Secondary outcomes included excellent functional outcome (mRS 0-1), favorable functional outcome (mRS 0-3), and mortality rate at 90 days, as well as symptomatic intracranial hemorrhage (sICH), and successful reperfusion between the two treatment groups. RESULTS: Direct EVT and bridging IVT before EVT exhibited similar primary outcomes (27.3% vs 27.7%, respectively) and distributions of mRS scores at 90 days. Moreover, rates of sICH and 90-day mortality were not significantly different between the two groups (7.3% vs 6.0%, adjusted OR (aOR) 0.79, 95% CI 0.34 to 1.86, P=0.84 for sICH; 46.8% vs 43.7%, aOR 0.86, 95% CI 0.54 to 1.38, P=0.53 for mortality). CONCLUSIONS: Among patients with acute BAO, functional outcomes were similar between those treated with bridging IVT before EVT and those treated with direct EVT, and there was no difference between the two groups in terms of sICH and mortality rates.

Intravenous tirofiban following successful reperfusion in intracranial large artery atherosclerotic stroke: A secondary analysis of a randomized clinical trial.

OBJECTIVE: This study aimed to investigate whether treatment with adjunct intravenous tirofiban is associated with improved outcomes following successful reperfusion in patients with intracranial atherosclerotic stroke. METHODS: Patients with intracranial large artery atherosclerotic (LAA) stroke and an expanded Treatment in Cerebral Ischemia angiographic score of 2b50 to 3 from the Effect of Intravenous Tirofiban versus Placebo Before Endovascular Thrombectomy on Functional Outcomes in Large Vessel Occlusion Stroke (RESCUE BT) trial were included. The primary outcome was the difference in proportion of independent functional outcome (modified Rankin score of 0-2 at 90 days). Safety outcomes included the rates of symptomatic intracranial hemorrhage (sICH) and 90-day mortality. RESULTS: Among the 382 patients with intracranial LAA stroke and successful reperfusion, 175 patients (45.8%) were treated with intravenous tirofiban and 207 (54.2%) with placebo. The proportion of patients with independent functional outcome at 90 days was 54.3% (95 out of 175) with tirofiban and 44.0% (91 out of 207) with placebo (adjusted odds ratio [aOR], 1.58; 95% CI, 1.02-2.44; p = 0.04). Intravenous tirofiban was not significantly associated with an increased risk of sICH (12/175 [6.9%] vs. 11/207 [5.3%]; aOR, 1.41; 95% CI, 0.59-3.34; p = 0.44) or 90-day mortality (21/175 [12.0%] vs. 34/207 [16.4%]; aOR, 0.71; 95% CI, 0.38-1.31; p = 0.27). INTERPRETATION: Among patients with acute intracranial LAA stroke and successful reperfusion following endovascular thrombectomy, adjunct intravenous tirofiban was associated with a higher rate of independent functional outcome, without higher rates of sICH or mortality. Confirmatory randomized trials in these patients are desirable.

Design, synthesis, and evaluation of novel pleuromutilin aryl acrylate derivatives as promising broad-spectrum antibiotics especially for combatting multi-drug resistant gram-negative bacteria.

The emergence of drug-resistant strains presents a grave challenge for traditional antibiotics, underscoring the exigency of exploring novel antibacterial drugs. To address this, the present study endeavors to design and synthesize a collection of pleuromutilin aromatic acrylate derivatives, guided by combination principles. The antibacterial activity and structure-activity relationship of these derivatives were evaluated, and most of the derivatives displayed moderate to excellent antibacterial activity against both Gram-positive bacteria and Gram-negative bacteria. Among these derivatives, 5g exhibited the strongest antibacterial activity, with MIC (minimum inhibitory concentration) values ranging from 1-32 µg/mL, and a MIC value against clinically isolated drug-resistant strains of 4-64 µg/mL. Additionally, 5g exhibited negligible cytotoxicity, superior anti-mycoplasma activity, and a greater propensity to perturb bacterial cell membranes. Notably, the administration of 5g resulted in an increased survival rate of MRSA (Methicillin-resistant Staphylococcus aureus)-infected mice, with an ED50 (median effective dose) value of 9.04 mg/kg. These results indicated the potential of 5g to be further developed as an antibacterial drug for the clinical treatment of drug-resistant bacterial infections.

Effect of collateral status on the outcomes of endovascular treatment of acute basilar artery occlusion due to large-artery atherosclerosis.

OBJECTIVE: Authors of this study aimed to evaluate the effects of collateral status on the prognostic value of endovascular treatment (EVT) in patients with basilar artery occlusion (BAO) due to large-artery atherosclerosis (LAA). METHODS: The study included 312 patients from the BASILAR (Endovascular Treatment for Acute Basilar Artery Occlusion Study) registry who had undergone EVT for acute BAO due to LAA and whose composite collateral scores were available. The effects of collateral status on EVT were assessed based on the composite collateral score (0-2 vs 3-5). The primary outcome was a favorable outcome (modified Rankin Scale score of 0-3) at 90 days. RESULTS: The composite collateral score was 0-2 in 130 patients and 3-5 in 182. A good collateral status (composite collateral score 3-5) was associated with a favorable outcome (66/182 [36.3%] vs 31/130 [23.8%], adjusted odds ratio [aOR] 2.21, 95% CI 1.18-4.14, p = 0.014). A lower baseline National Institutes of Health Stroke Scale (NIHSS) score was an independent predictor of a favorable outcome in the poor collateral status group (aOR 0.91, 95% CI 0.87-0.96, p = 0.001). In the good collateral status group, there was a significant correlation between favorable outcomes and a younger age (aOR 0.96, 95% CI 0.92-0.99, p = 0.016), lower baseline NIHSS score (aOR 0.89, 95% CI 0.85-0.93, p < 0.001), lower proportion of diabetes mellitus (aOR 0.31, 95% CI 0.13-0.75, p = 0.009), and shorter procedure time (aOR 0.99, 95% CI 0.98-1.00, p = 0.003). CONCLUSIONS: A good collateral status was a strong prognostic factor after EVT in patients with BAO underlying LAA. A shorter procedure time was associated with favorable outcomes in patients with a good collateral status.

SiC/Graphene Film by Laser CVD as an Implantable Sensor Material for Dopamine Detection.

Implantable electrochemical sensor holds great promise in the real-time monitoring of dopamine (DA) to regulate body function. However, the real application of these sensors is limited by the weak current signal of DA in the human body and the poor compatibility of the on-chip microelectronic devices. In this work, a SiC/graphene composite film was fabricated using laser chemical vapor deposition (LCVD) and employed as a DA sensor. The graphene in the porous nanoforest-like SiC framework offered efficient channels for electronic transmission, leading to an enhanced electron transfer rate and consequently an increased current response for DA detection. The three-dimensional (3D) porous network also facilitated the exposure of more catalytic active sites toward DA oxidation. Besides, the wide distribution of graphene in the nanoforest-like SiC films reduced the interfacial resistance of the charge transfer. The SiC/graphene composite film exhibited excellent electrocatalytic activity toward DA oxidation with a low detection limit of 0.11 µM and a high sensitivity of 0.86 µA·µM-1·cm-2. The film electrode also showed a wide linear response for DA in 0.5-78 µM, along with good selectivity, repeatability, and reproducibility. Furthermore, the cell counting kit-8 (CCK-8) and live-dead assays revealed that the film is also biocompatible for biomedical applications. Therefore, the nanoforest-like SiC/graphene composite film via the CVD process enables a promising candidate for an integrated miniature DA biosensor with high detection performance.

Effect of Imaging Selection Paradigms on Endovascular Thrombectomy Outcomes in Patients With Acute Ischemic Stroke.

BACKGROUND: The effect of imaging selection paradigms on endovascular thrombectomy outcomes in patients with acute ischemic stroke with large vessel occlusion remains uncertain. The study aimed to assess the effect of basic imaging (noncontrast computed tomography with or without computed tomographic angiography) versus advanced imaging (magnetic resonance imaging or computed tomography perfusion) on clinical outcomes following thrombectomy in patients with stroke with large vessel occlusion in the early and extended windows using a pooled analysis of patient-level data from 2 pivotal randomized clinical trials done in China. METHODS: This post hoc analysis used data from 1182 patients included in 2 multicenter, randomized controlled trials in China that evaluated adjunct therapies to endovascular treatment for acute ischemic stroke (Direct Endovascular Treatment for Large Artery Anterior Circulation Stroke performed from May 20, 2018, through May 2, 2020, and Intravenous Tirofiban Before Endovascular Treatment in Stroke from October 10, 2018, through October 31, 2021). Patients with occlusion of the intracranial internal carotid artery or proximal middle cerebral artery (M1/M2 segments) were categorized according to baseline imaging modality (basic versus advanced) as well as treatment time window (early, 0-6 hours versus extended, 6-24 hours from last known well to puncture). The primary outcome was the proportion of patients with functional independence (modified Rankin Scale score of 0-2) at 90 days. Multivariable Poisson regression analysis was performed to determine the association between imaging selection modality and outcomes after endovascular treatment at each time windows. RESULTS: A total of 1182 patients were included in this cohort analysis, with 648 in the early (471 with basic imaging versus 177 advanced imaging) and 534 in the extended (222 basic imaging versus 312 advanced imaging) time window. There were no differences in 90-day functional independence between the advanced and basic imaging groups in either time windows (early window: adjusted relative risk, 0.99 [95% CI, 0.84-1.16]; P=0.91; extended window: adjusted relative risk, 1.00 [95% CI, 0.84-1.20]; P=0.97). CONCLUSIONS: In this post hoc analysis of 2 randomized clinical trial pooled data involving patients with large vessel occlusion stroke, an association between imaging selection modality and clinical or safety outcomes for patients undergoing thrombectomy in either the early or extended windows was not detected. Our study adds to the growing body of literature on simpler imaging paradigms to assess thrombectomy eligibility across both the early and extended time windows. REGISTRATION: URL: http://www.chictr.org.cn; Unique identifiers: ChiCTR-IOR-17013568 and ChiCTR-INR-17014167.

Optimizing Electromagnetic Interference Shielding of Ultrathin Nanoheterostructure Textiles through Interfacial Engineering.

Strong electromagnetic wave reflection loss concomitant with second emission pollution limits the wide applications of electromagnetic interference (EMI) shielding textiles. Decoration of textiles by using various dielectric materials has been found efficient for the development of highly efficient EMI shielding textiles, but it is still a challenge to obtain EMI shielding composites with thin thickness. A route of interfacial engineering may offer a twist to overcome these obstacles. Here, we fabricated a Ni nanoparticle/SiC nanowhisker/carbon cloth nanoheterostructure, where SiC nanowhiskers were deposited by a simple manufacturing method, namely, laser chemical vapor deposition (LCVD), directly grown on carbon cloth. Through directly constructing a Ni/SiC interface, we find that the formation of Schottky contact can influence the interfacial polarization associated with the generation of dipole electric fields, leading to an enhancement of dielectric loss. A striking feature of this interfacial engineering strategy is able to enhance the absorption of the incident electromagnetic wave while suppressing the reflection. As a result, our Ni/SiC/carbon cloth exhibits an excellent EMI shielding effectiveness of 68.6 dB with a thickness of only 0.39 mm, as well as high flexibility and long-term duration stability benefited from the outstanding mechanical properties of SiC nanowiskers, showing potential for EMI shielding applications.

Association between stress hyperglycemia and outcomes in patients with acute ischemic stroke due to large vessel occlusion.

AIMS: This study aimed to evaluate the association between stress hyperglycemia ratio (SHR) and clinical outcomes at 90 days in acute ischemic stroke due to large vessel occlusion receiving endovascular treatment. METHODS: The RESCUE BT trial was a multicenter, randomized, double-blind, placebo-controlled clinical trial, consisting of 948 stroke patients from 55 centers in China. A total of 542 patients with glucose and glycated hemoglobin (HbA1C) values at admission were included in this analysis. SHR, measured by glucose/HbA1C, was evaluated as both a tri-categorical variable (≤1.07 vs. 1.08-1.29 vs. ≥1.30) and a continuous variable. The primary outcome was a favorable functional outcome (modified Rankin Scale [mRS] score ≤2) at 90 days. The secondary outcome included excellent functional outcome (mRS score ≤1) and safety outcomes, such as 90-day mortality and intracranial hemorrhage. The study was registered with Chictr.org.cn (ChiCTR-INR-17014167). RESULTS: Compared with patients in the lowest tertile of SHR, the highest tertile group had significantly lower odds of achieving favorable functional outcome of mRS score of 0-2 (adjusted odds ratio, 0.44; 95% confidence interval, 0.28-0.69; p < 0.001) and excellent clinical outcome of mRS score of 0-1 (adjusted odds ratio, 0.48; 95% confidence interval, 0.29-0.79; p = 0.004) at 90 days after adjusting for potential covariates. Similar results were observed after further adjustment for preexisting diabetes and Alberta Stroke Program Early Computed Tomography Score (ASPECTS). CONCLUSION: Stress hyperglycemia ratio, as measured by the glucose/HbA1C, was associated with a decreased odds of achieving a favorable functional outcome in patients with acute large vessel occlusion stroke at 90 days.

Actin polymerisation and crosslinking drive left-right asymmetry in single cell and cell collectives.

Deviations from mirror symmetry in the development of bilateral organisms are common but the mechanisms of initial symmetry breaking are insufficiently understood. The actin cytoskeleton of individual cells self-organises in a chiral manner, but the molecular players involved remain essentially unidentified and the relationship between chirality of an individual cell and cell collectives is unclear. Here, we analysed self-organisation of the chiral actin cytoskeleton in individual cells on circular or elliptical patterns, and collective cell alignment in confined microcultures. Screening based on deep-learning analysis of actin patterns identified actin polymerisation regulators, depletion of which suppresses chirality (mDia1) or reverses chirality direction (profilin1 and CapZß). The reversed chirality  is mDia1-independent but requires the function of actin-crosslinker α-actinin1. A robust correlation between the effects of a variety of actin assembly regulators on chirality of individual cells and cell collectives is revealed. Thus, actin-driven cell chirality may underlie tissue and organ asymmetry.

Association between intravenous tirofiban and intracranial hemorrhage in acute large vessel occlusion stroke: insight from the RESCUE BT randomized placebo-controlled trial.

BACKGROUND: The aim of this study is to investigate the association between intravenous tirofiban and symptomatic intracranial hemorrhage (SICH) in patients with acute ischemic stroke (AIS) secondary to large vessel occlusion (LVO) receiving endovascular thrombectomy (EVT) within 24 h of time last known well (LKW). METHODS: Patients with AIS-LVO who were randomly assigned to receive intravenous tirofiban or placebo before EVT within 24 h of time LKW and had follow-up brain non-contrast computed tomography within 24 h after stopping tirofiban treatment were derived from "RESCUE BT": a multicenter, randomized, placebo-controlled, double-blind trial. All eligible patients were divided into SICH and NO-SICH groups. Subgroup analyses were performed to explore for heterogeneity. RESULTS: Of 945 patients included in this cohort, there were 76 (8.0%) in the SICH group and 869 (92.0%) in the NO-SICH group. The incidence of SICH was not higher in patients receiving intravenous tirofiban compared with placebo (adjusted risk ratio (RR), 1.51; 95% confidence interval (CI), 0.97-2.36; P = 0.07). Subgroup analyses showed that age greater than 67-year-old (adjusted RR, 2.18; 95% CI 1.18-4.00), NIHSS greater than 16 (adjusted RR, 1.88; 95% CI 1.06-3.34), and cardioembolism (adjusted RR, 3.73; 95% CI 1.66-8.35) were associated with increased SICH risk. CONCLUSIONS: In patients with acute large vessel occlusion stroke, intravenous tirofiban before EVT within 24 h of time from last known well is not associated with increased risk of SICH. Patients who are older, have more severe neurological deficits, or with cardioembolism are at higher risk of SICH with intravenous tirofiban. TRIAL REGISTRATION NUMBER: URL: http://www.chictr.org.cn ; Unique identifier: ChiCTR-INR-17014167.

Futile Recanalization After Endovascular Treatment in Patients With Acute Basilar Artery Occlusion.

BACKGROUND: It is estimated that >50% of acute basilar artery occlusion (ABAO) patients with successful reperfusion after endovascular treatment (EVT) have futile recanalization. However, few studies investigated the reasons behind this. OBJECTIVE: To identify the factors associated with futile recanalization in ABAO after successful reperfusion. METHODS: We recruited patients with successful reperfusion (expanded Thrombolysis In Cerebral Infarction score of ≥2b) after EVT from the Basilar Artery Occlusion Study registry. Patients were divided into meaningful recanalization (90-day modified Rankin Scale 0-3) and futile recanalization (90-day modified Rankin Scale 4-6) groups. Multivariable logistic regression analyses were used to identify the predictors of futile recanalization. RESULTS: A total of 522 patients with successful reperfusion were selected. Of these, 328 patients had futile recanalization and 194 had meaningful recanalization. Multivariable logistic regression shows that higher neutrophil-to-lymphocyte ratio ( P = .01), higher baseline National Institutes of Health Stroke Scale score ( P < .001), longer puncture to recanalization time ( P = .02), lower baseline posterior circulation Alberta Stroke Program Early CT score ( P < .001), lower posterior circulation collateral score ( P = .02), incomplete reperfusion ( P < .001), and diabetes mellitus ( P < .001) were predictors of futile recanalization. CONCLUSION: Higher neutrophil-to-lymphocyte ratio, longer puncture to recanalization time, incomplete reperfusion, stroke severity, lower baseline posterior circulation Alberta Stroke Program Early CT score, poor collaterals, and diabetes mellitus were independent predictors of futile recanalization in patients with ABAO with successful reperfusion after EVT. Moreover, multiple stent retriever passes were associated with a high proportion of futile recanalization in patients with late time windows.

Association of Intravenous Tirofiban with Functional Outcomes in Acute Ischemic Stroke Patients with Acute Basilar Artery Occlusion Receiving Endovascular Thrombectomy.

INTRODUCTION: The aim of this study was to test the hypothesis that intravenous tirofiban improves functional outcomes without promoting the risk of intracranial hemorrhage (ICH) in stroke secondary to basilar artery occlusion (BAO) receiving endovascular thrombectomy. METHODS: Patients with acute BAO stroke who were treated with endovascular thrombectomy and had tirofiban treatment information were derived from "BASILAR": a nationwide, prospective registry. All eligible patients were divided into tirofiban and no-tirofiban groups according to whether tirofiban was used intravenously. The primary endpoint was the 90-day severity of disability as assessed by the modified Rankin scale score. Safety outcomes were the frequency of ICH and mortality. RESULTS: Of 645 patients included in this cohort, 363 were in the tirofiban group and 282 were in the no-tirofiban group. Thrombectomy with intravenous tirofiban reduced the 90-day disability level over the range of the modified Rankin scale (adjusted common odds ratio, 2.08; 95% confidence interval (CI), 1.45-2.97; p < 0.001). The 90-day mortality of patients in the tirofiban group was lower than that in the no-tirofiban group (41.6% vs. 52.1%; adjusted hazard ratio, 0.60; 95% CI, 0.47-0.77; p < 0.001). The frequency of any ICH (6.7% vs. 13.7%; p = 0.004) and symptomatic ICH (4.8% vs. 10.1%; p = 0.01) in the tirofiban group was significantly lower than that in the no-tirofiban group. CONCLUSIONS: In patients with acute BAO stroke who underwent endovascular treatment, intravenous tirofiban might be associated with favorable outcome, reduced mortality, and a decreased frequency of ICH.

Clinical Predictors for Early Mortality of Patients with Acute Basilar Artery Occlusion.

BACKGROUND: Acute ischemic stroke due to basilar artery occlusion (BAO) is associated with the highest mortality in patients with large vessel occlusion. This study aimed to identify modifiable risk factors of early mortality in patients with BAO. METHODS AND RESULTS: This was a cohort study of consecutive patients with BAO admitted to 47 stroke centers in China between January 2014 and May 2019. The primary outcome was all-cause mortality within 7 days after hospitalization. Of 829 patients, 164 died (0-3 days: 115; 4-7 days: 49) within 7 days after hospitalization. Among pre- and periprocedural variables, higher admission National Institutes of Health Stroke Scale (NIHSS, adjusted OR, 1.06, 95% CI: 1.04-1.09; p < 0.001), lower admission posterior circulation-Alberta Stroke Program Early Computed Tomography Score (pc-ASPECTS, adjusted OR, 0.88, 95% CI: 0.79-0.98; p = 0.02), lower Basilar Artery on Computed Tomography Angiography score (BATMAN, adjusted OR, 0.84, 95% CI: 0.76-0.93; p = 0.001), and recanalization failure (adjusted OR, 2.99, 95% CI: 2.04-4.38; p < 0.001) were independently associated with a higher risk of early mortality. Herniation (adjusted OR, 2.84, 95% CI: 1.52-5.30; p = 0.001) is an independent postprocedural predictor of early mortality. In patients dying ≤3 days, higher NIHSS (p < 0.001), lower pc-ASPECTS (p = 0.01), lower BATMAN (p = 0.004), recanalization failure (p < 0.001), herniation (p = 0.001), gastrointestinal hemorrhage (p = 0.046), and absence of pneumonia (p < 0.001) were independent predictors of early mortality. Higher NIHSS (p = 0.01), recanalization failure (p < 0.001), and pneumonia (p = 0.03) were independently associated with early mortality between 4 and 7 days. CONCLUSIONS: Recanalization failure, herniation, gastrointestinal hemorrhage, and pneumonia are potentially modifiable risk factors for early mortality in basilar artery occlusion.