Leukoaraiosis in patients with tirofiban before endovascular thrombectomy: A post hoc analysis of a multicentre randomized clinical trial.

BACKGROUND AND PURPOSE: To evaluate the effectiveness and safety of intravenous tirofiban before endovascular thrombectomy in subgroups of acute ischemic stroke patients with different degrees of leukoaraiosis (LA). METHODS: Patients of the RESCUE BT trial whose LA grade could be assessed were included. Eligible patients were dichotomized into two strata according to the van Swieten scale (VSS) score, absent-to-moderate LA (VSS score <3) and severe LA (VSS score ≥3). Furthermore, patients were divided into tirofiban and placebo groups in each stratum. The primary outcome was the 90-day modified Rankin Scale (mRS) score. Safety outcome was radiological intracranial hemorrhage within 48 h. RESULTS: 861 patients were included, 439 patients with absent-to-moderate LA and 422 patients with severe LA. There were no significant differences in 90-day mRS score between the tirofiban and placebo groups in either stratum (absent-to-moderate LA: adjusted OR 0.92 (95%CI, 0.66-1.28), P = 0.62; severe LA: adjusted OR 0.99 (95% CI, 0.69-1.42), P = 0.96). In the severe LA stratum, the occurrence of radiologic intracranial hemorrhage was greater in the tirofiban group compared to the placebo group. (35.7% vs 26.4%; adjusted OR, 1.72 (95% CI, 1.12-2.66); P = 0.014). However, no difference was observed in the absent-to-moderate LA stratum (33.2% vs 29.3%; adjusted OR, 1.15 (95% CI, 0.76-1.75); P = 0.51). CONCLUSION: There was no significant difference in disability severity at 90 days when treating AIS patients using intravenous tirofiban before endovascular therapy, in either absent-to-moderate or severe LA strata. It should be noted that intravenous tirofiban before endovascular therapy increases the incidence of radiologic intracranial hemorrhage in patients with severe LA.

Effect of Intravenous Tirofiban vs Placebo Before Endovascular Thrombectomy on Functional Outcomes in Large Vessel Occlusion Stroke: The RESCUE BT Randomized Clinical Trial.

Importance: Tirofiban is a highly selective nonpeptide antagonist of glycoprotein IIb/IIIa receptor, which reversibly inhibits platelet aggregation. It remains uncertain whether intravenous tirofiban is effective to improve functional outcomes for patients with large vessel occlusion ischemic stroke undergoing endovascular thrombectomy. Objective: To assess the efficacy and adverse events of intravenous tirofiban before endovascular thrombectomy for acute ischemic stroke secondary to large vessel occlusion. Design, Setting, and Participants: This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 55 hospitals in China, enrolling 948 patients with stroke and proximal intracranial large vessel occlusion presenting within 24 hours of time last known well. Recruitment took place between October 10, 2018, and October 31, 2021, with final follow-up on January 15, 2022. Interventions: Participants received intravenous tirofiban (n = 463) or placebo (n = 485) prior to endovascular thrombectomy. Main Outcomes and Measures: The primary outcome was disability level at 90 days as measured by overall distribution of the modified Rankin Scale scores from 0 (no symptoms) to 6 (death). The primary safety outcome was the incidence of symptomatic intracranial hemorrhage within 48 hours. Results: Among 948 patients randomized (mean age, 67 years; 391 [41.2%] women), 948 (100%) completed the trial. The median (IQR) 90-day modified Rankin Scale score in the tirofiban group vs placebo group was 3 (1-4) vs 3 (1-4). The adjusted common odds ratio for a lower level of disability with tirofiban vs placebo was 1.08 (95% CI, 0.86-1.36). Incidence of symptomatic intracranial hemorrhage was 9.7% in the tirofiban group vs 6.4% in the placebo group (difference, 3.3% [95% CI, -0.2% to 6.8%]). Conclusions and Relevance: Among patients with large vessel occlusion acute ischemic stroke undergoing endovascular thrombectomy, treatment with intravenous tirofiban, compared with placebo, before endovascular therapy resulted in no significant difference in disability severity at 90 days. The findings do not support use of intravenous tirofiban before endovascular thrombectomy for acute ischemic stroke. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR-IOR-17014167.

Single nucleotide polymorphisms in the ANGPTL4 gene and the SNP-SNP interactions on the risk of atherosclerotic Ischaemic stroke.

OBJECTIVES: The purpose of this study was to investigate the impact of single nucleotide polymorphisms (SNPs) in the ANGPTL4 gene and the SNP-SNP interactions on atherosclerotic ischemic stroke (IS) risk. PATIENTS AND METHODS: A case-control study was conducted. A total of 360 patients with atherosclerotic IS and 342 controls between December 2018 and December 2019 from Longyan First Hospital affiliated to Fujian Medical University were included. A logistic regression model was used to examine the association between SNPs and atherosclerotic IS risk. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. Generalized multifactor dimensionality reduction was employed to analyze the SNP-SNP interaction. RESULTS: Logistic regression analysis showed that atherosclerotic IS risk was significantly lower in carriers with the rs11672433-T allele than those with the CC genotype (CT+ TT vs. CC); adjusted OR, 0.005; 95% CI, 0.02-0.11. We found a significant 2-locus model (P = 0.0010) involving rs11672433 and rs4076317; the cross-validation consistency of this model was 10 of 10, and the testing accuracy was 57.96%. Participants with the CT or TT of rs11672433 and CC of rs4076317 genotype have the lowest atherosclerotic IS risk, compared to subjects with CC of rs11672433 and the CC of rs4076317 genotype, OR (95%CI) was 0.06(0.02-0.22), after covariates adjustment for gender, age, smoking and alcohol status, hypertension, Diabetes mellitus, TG, TC, HDL-C, LDL-C, Uric acid. CONCLUSIONS: We found that rs11672433 was associated with decreased atherosclerotic IS risk; we also found that gene-gene interaction between rs11672433 and rs4076317 was associated with decreased atherosclerotic IS risk.

Endovascular Therapy for Basilar Artery Occlusion in Sudden Onset to Maximal Deficit Ischemic Events.

BACKGROUND: The presence of sudden onset to maximal deficit (SOTMD) in patients with acute basilar artery occlusion often results in more severe outcomes. However, the effect of endovascular therapy on SOTMD and whether the outcome is affected by onset-to-puncture time remain unclear. METHODS AND RESULTS: This retrospective analysis was conducted using data from the prospective BASILAR (Endovascular Treatment for Acute Basilar Artery Occlusion Study Registry). Consecutive patients with basilar artery occlusion receiving endovascular therapy were dichotomized into SOTMD and non-SOTMD cohorts. The primary outcomes included a favorable outcome (modified Rankin scale 0-3), recanalization, and mortality at 90 days. The outcomes of patients with SOTMD were analyzed using multivariable logistic regression. In the multivariate analysis, a favorable outcome was similar between the two cohorts (odds ratio [OR], 0.88 [95% CI, 0.58-1.34]; P=0.5), although the mortality of patients with SOTMD was higher than that of patients with non-SOTMD (OR, 1.67 [95% CI, 1.14-2.44]; P=0.008). The probability of mortality increased from 40.0% at 1 hour to 70.0% at 6 hours in the SOTMD cohort, and favorable outcomes of patients with non-SOTMD declined from 38.0% at 1 hour to 18.0% at 8 hours. CONCLUSIONS: No significant difference was observed in favorable outcomes between the SOTMD and non-SOTMD groups, although mortality was higher in the SOTMD cohort. The patients with SOTMD had a stronger time dependence for endovascular therapy in terms of mortality, while the time dependency regarding favorable outcome in the NSOTMD group was even higher. REGISTRATION: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR1800014759.

Effects of edaravone dexborneol on neurological function and serum inflammatory factor levels in patients with acute anterior circulation large vessel occlusion stroke.

The goal of this study is to evaluate and analyze the effects of edaravone (EDV) dexborneol on neurological function and serum inflammatory factor levels among patients with acute anterior circulation big artery blockage stroke. A total of 142 patients with acute anterior circulation large vessel occlusion (LVO) were randomly allocated to the study group (69 patients) or the control group (73 patients). In the study group, patients were treated with 37.5 mg EDV dexborneol twice a day for 10-14 days, based on the control group. The primary efficacy outcome was the National Institutes of Health Stroke Scale score change from baseline to 90 days and the proportion of modified Rankin Scale (mRS)score ≤1 at 90 days after randomization. The secondary outcome included the decrease in inflammatory factors at 14 days. The primary safety outcome was the incidence of hemorrhagic transformation assessed according to Heidelberg bleeding classification within 7 days. A higher percentage of patients with HIHSS score ≤5 at 90 days in the EDV dexcamphorol group was observed than in the control group (75.36% vs 64.38%; P = 0.015). A higher percentage of patients with mRS score ≤1 at 90 days in the EDV dexcamphorol group was observed than in the control group (63.77% vs 50.68%; P = 0.012). After treatment, the levels of IL-6 and hs-CRP were significantly lower following treatment and compared to the control group (P < 0.05). In patients receiving the EDV dexborneol group, a significantly decreased risk of radiographic intracranial hemorrhage was found compared with the control group (20.29% vs 39.73%; P = 0.0006). In conclusion, EDV dexborneol can improve the clinical outcomes of patients with acute anterior circulation LVO stroke, which can be used as an effective supplement to thrombectomy therapy.

Association of Tirofiban With Functional Outcomes After Thrombectomy in Acute Ischemic Stroke Due to Intracranial Atherosclerotic Disease.

BACKGROUND AND OBJECTIVE: To investigate the efficacy and safety of IV infusion of tirofiban before endovascular thrombectomy for patients with large vessel occlusion due to intracranial atherosclerotic disease. The secondary objective was to identify potential mediators for the clinical effect of tirofiban. METHODS: Post hoc exploratory analysis of the Endovascular Treatment With versus Without Tirofiban for Patients with Large Vessel Occlusion Stroke (RESCUE BT) trial, which was a randomized, double-blinded, placebo-controlled trial at 55 centers in China from October 2018 to October 2021. Patients with occlusion of the internal carotid artery or middle cerebral artery due to intracranial atherosclerosis were included. The primary efficacy outcome was the proportion of patients achieving functional independence (defined as modified Rankin scale 0-2) at 90 days. Binary logistic regression and causal mediation analyses were used to estimate the treatment effect of tirofiban and the potential mediators. RESULTS: This study included 435 patients, of whom 71.5% were men. The median age was 65 (interquartile range [IQR] 56-72) years, with a median NIH Stroke Scale of 14 (IQR 10-19). Patients in the tirofiban group had higher rates of functional independence at 90 days than patients in the placebo group (adjusted odds ratio 1.68; 95% CI 1.11-2.56, p = 0.02) without an increased risk of mortality or symptomatic intracranial hemorrhage. Tirofiban was associated with fewer thrombectomy passes (median [IQR] 1 [1-2] vs 1 [1-2], p = 0.004), which was an independent predictor of functional independence. Mediation analysis showed tirofiban-reduced thrombectomy passes explained 20.0% (95% CI 4.1%-76.0%) of the effect of tirofiban on functional independence. DISCUSSION: In this post hoc analysis of the RESCUE BT trial, tirofiban was an effective and well-tolerated adjuvant medication of endovascular thrombectomy for patients with large vessel occlusion due to intracranial atherosclerosis. These findings need to be confirmed in future trials. TRIAL REGISTRATION INFORMATION: The RESCUE BT trial was registered on the Chinese Clinical Trial Registry: chictr.org.cn, ChiCTR-INR-17014167. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that tirofiban plus endovascular therapy improves 90-day outcome for patients with large vessel occlusion due to intracranial atherosclerosis.

High Serum Levels of Otolin-1 in Patients With Benign Paroxysmal Positional Vertigo Predict Recurrence.

Background: Otolin-1 is an inner ear-specific protein that is exclusively expressed in otoconia and vestibule and cochlea cells. Recent investigations reported that otolin-1 can cross the blood-labyrinthine barrier and that the levels in serum well-reflected otolith status. Serum otolin-1 levels in patients with benign paroxysmal positional vertigo (BPPV) are significantly elevated compared with healthy controls. We aimed to explore whether otolin-1 can also serve as a biomarker for predicting BPPV recurrence. Method: Patients at our institution with new-onset of idiopathic BPPV between May, 2017 and May, 2018 were recruited and followed up for 2 years. All demographic data of the patients were collected, and serum levels of otolin-1 and other laboratory indicators were measured and compared according to the recurrence status. Results: A total of 74 patients, who met the inclusion criteria were enrolled in this study, of which 27 (36.5%) patients had suffered one or more episodes of recurrence after undergoing canal repositioning treatments during the study. The serum levels of otolin-1 in patients with recurrent BPPV were significantly higher than those in patients without recurrent BPPV (363.9 vs. 309.8 pg/ml, p = 0.001). In multivariate analysis comparing the second to fourth quartiles (Q2-Q4) against the first quartile (Q1) of otolin-1, the level of otolin-1 in Q4 could significantly predict BPPV recurrence, and the odds ratio (OR) was elevated by approximately 812% (OR = 9.12; 95% confidence interval [CI]: 1.44-57.9; p = 0.019). Conclusion: High serum levels of otolin-1 were associated with an increased risk of BPPV recurrence, and further investigation is required to confirm this association and clarify the exact mechanism.

Neutrophil-to-lymphocyte ratio predicts parenchymal hematoma after mechanical thrombectomy in basilar artery occlusion.

Background: parenchymal hematoma (PH) is a severe complication of endovascular treatment (EVT) for acute basilar artery occlusion (ABAO). This study aimed to evaluate the incidence and predictors of PH after EVT for ABAO. Methods: Using data from the Endovascular Treatment for Acute Basilar Artery Occlusion Study, we enrolled patients treated with mechanical thrombectomy from the BASILAR registry. PH was assessed in accordance with the Heidelberg Bleeding Classification. Logistic regression was used to identify predictors of PH. Results: A total of 639 patients were included. Forty-eight patients (7.5%) were diagnosed with PH within 48 h of EVT. Ninety-day mortality was higher in patients with PH compared with those without (81.3 vs. 42.8%, P < 0.001). Favorable neurological outcomes (modified Rankin scale score, 0-3) rates was lower in patients with PH compared with those without (6.3 vs. 34.5%, P < 0.001). With a multivariate analysis, hypertension [odds ratio (OR) = 2.30, 95% confidence interval (CI) 1.04-5.08], pre-treatment National Institutes of Health Stroke Score (NIHSS, >25; OR = 3.04, 95% CI 1.43-6.45), and Neutrophil-to-lymphocyte ratio (NLR, >10; OR = 1.88, 95% CI 1.02-3.48) were associated with PH after EVT. Conclusions: PH occurred at a rate of 7.5% after EVT in patients with ABAO. Hypertension, higher baseline NIHSS, and higher NLR value increase the risk of PH after EVT for ABAO.

Impact of Body Temperature in Patients With Acute Basilar Artery Occlusion: Analysis of the BASILAR Database.

Background: A link between body temperature and stroke outcomes has been established but not for acute basilar artery occlusion. We aimed to determine the association between body temperature and clinical outcomes in patients with acute basilar artery occlusion and temperature management range. Methods: We included patients from the Endovascular Treatment for Acute Basilar Artery Occlusion Study (BASILAR) database with records of both admission body temperature (ABT) and peak body temperature (PBT). ABT was defined as the body temperature first measured at the hospital visit, PBT was defined as the highest temperature within 24 h of treatment, and minus body temperature (MBT) was defined as PBT-ABT. The primary clinical outcome was favorable functional outcome, defined as the proportion of patients with a modified Rankin Scale score of 0-3 at 3 months. Secondary outcomes included 3-month mortality, in-hospital mortality, and symptomatic cerebral hemorrhage. Results: A total of 664 patients were enrolled in the study; 74.7% were men, with a median age of 65 (interquartile range, 57.25-74) years. In all patients, multivariate analysis indicated that PBT and MBT were independent predictors of favorable functional outcome [odds ratio (OR), 0.57 (95% CI, 0.43-0.77); OR, 0.68 (95% CI, 0.52-0.88), respectively], and higher ABT, PBT, and MBT were associated with an increased 3-month mortality [OR, 1.47 (95% CI, 1.03-2.10), OR, 1.58 (95% CI, 1.28-1.96), OR, 1.35 (95% CI, 1.11-1.65), respectively]. Proportional odds models demonstrated that when ABT, PBT, MBT were in the range of <37.5, <38.9, and -0.6-2.7°C, respectively, the benefit of the endovascular treatment is clearly greater than that of standard medical treatment in terms of favorable functional outcome. Conclusions: Body temperature is an independent predictor of clinical outcome in patients with acute basilar artery occlusion. It is necessary to control the patient body temperature within the appropriate range in clinical settings. Trial Registration: Chinese Clinical Trial Registry ChiCTR1800014759. Registered 03 February 2018. Retrospectively registered.

Accumulation and transformation of heavy metals in surface sediments from the Yangtze River estuary to the East China Sea shelf.

The concentration and speciation of heavy metals (Cu, Co, Ni, Zn, Cr, Pb and Cd) were studied in surface sediment from the Yangtze River(YR)to the East China Sea (ECS) shelf. The results showed that high contents of metals were found in the YR estuary (YRE) and in the nearshore muddy area, while lower concentrations were found in the YR channel and the ECS shelf. However, after standardization, the total content of most heavy metals from the YR showed little change or slightly increased during the transport process from the river to the estuary but decreased significantly outside the estuary, especially in the sediments of the ECS shelf. The residual fraction is the dominant fraction for all the metals, while the oxidizable and reducible fractions are the most important forms of the nonlithogenic fractions. The total amount of heavy metals from the YR to the continental shelf is mainly affected by the filtration of the estuary and the barrier impacts of the coastal current in the ECS. The environmental physicochemical conditions that vary significantly in the turbidity zone greatly influence the associated forms of metals. The metals in the acid-soluble fraction are mostly affected by the pH change in the sediment and the discharge of human activities, while the reducible fraction is significantly affected by the bottom water DO. The oxidizable fraction was affected by oxidation-reduction potential (ORP), primary productivity, as well as OM content. Therefore, with changes in the physicochemical conditions of the environment, the metals have undergone significant changes in their speciation from the YR to the ECS shelf. Various complex effects in the estuary area have not only a large filtration effect on the total amount of metals but also a major impact on the geochemical forms of the metals.

Decreased 25-Hydroxyvitamin D Levels in Patients With Vestibular Neuritis.

Objective: Vestibular neuritis (VN) is characterized by acute onset of vertigo, nausea, and vomiting, without auditory or other neurological symptoms. Although the pathogenesis of VN is not yet clear, many studies have shown that a pro-inflammatory environment can lead to the induction and progression of the disease. Considering the importance of vitamin D in modulating the activation, proliferation, and differentiation of inflammatory physiological processes, we hypothesized that decreased serum vitamin D may be associated with the development of VN. In this study, we evaluated serum levels of 25-hydroxyvitamin D [25(OH)D] in patients presenting acutely with VN and healthy controls and investigated the possible correlation of serum 25(OH)D levels with VN. Methods: A total of 59 consecutive patients diagnosed with VN within 7 days of symptom onset and 112 age- and sex-matched healthy controls referred to Hwa Mei Hospital, University of Chinese Academy of Science, between March 2017 and March 2019 were recruited. Demographic and clinical data, such as age, sex, height, weight, living habits, ongoing health problems, and medication history, for all subjects were recorded, and levels of 25(OH)D were measured and compared. Results: Serum levels of 25(OH)D were lower in patients with VN than in controls (19.01 ± 6.53 vs. 22.94 ± 6.74 ng/ml, p < 0.001). Patients with VN had a higher frequency of vitamin D deficiency (61.0 vs. 34.8%, P = 0.001) than did controls. Regression analyses demonstrated that vitamin D deficiency was associated with VN, with an odds ratio of 4.53 (95% CI = 1.342-15.279, P = 0.015). Conclusion: This prospective study is the first to evaluate serum 25(OH)D levels in patients with VN and found that decreased serum 25(OH)D may be associated with VN occurrence.

De Novo Genome and Transcriptome Assembly of the Canadian Beaver (Castor canadensis).

The Canadian beaver (Castor canadensis) is the largest indigenous rodent in North America. We report a draft annotated assembly of the beaver genome, the first for a large rodent and the first mammalian genome assembled directly from uncorrected and moderate coverage (< 30 ×) long reads generated by single-molecule sequencing. The genome size is 2.7 Gb estimated by k-mer analysis. We assembled the beaver genome using the new Canu assembler optimized for noisy reads. The resulting assembly was refined using Pilon supported by short reads (80 ×) and checked for accuracy by congruency against an independent short read assembly. We scaffolded the assembly using the exon-gene models derived from 9805 full-length open reading frames (FL-ORFs) constructed from the beaver leukocyte and muscle transcriptomes. The final assembly comprised 22,515 contigs with an N50 of 278,680 bp and an N50-scaffold of 317,558 bp. Maximum contig and scaffold lengths were 3.3 and 4.2 Mb, respectively, with a combined scaffold length representing 92% of the estimated genome size. The completeness and accuracy of the scaffold assembly was demonstrated by the precise exon placement for 91.1% of the 9805 assembled FL-ORFs and 83.1% of the BUSCO (Benchmarking Universal Single-Copy Orthologs) gene set used to assess the quality of genome assemblies. Well-represented were genes involved in dentition and enamel deposition, defining characteristics of rodents with which the beaver is well-endowed. The study provides insights for genome assembly and an important genomics resource for Castoridae and rodent evolutionary biology.