Review of yeast culture concerning the interactions between gut microbiota and young ruminant animals.

Microorganisms inhabit the gastrointestinal tract of ruminants and regulate body metabolism by maintaining intestinal health. The state of gastrointestinal health is influenced not only by the macro-level factors of optimal development and the physiological structure integrity but also by the delicate equilibrium between the intestinal flora and immune status at the micro-level. Abrupt weaning in young ruminants causes incomplete development of the intestinal tract resulting in an unstable and unformed microbiota. Abrupt weaning also induced damages to the microecological homeostasis of the intestinal tract, resulting in the intestinal infections and diseases, such as diarrhea. Recently, nutritional and functional yeast culture has been researched to tackle these problems. Herein, we summarized current known interactions between intestinal microorganisms and the body of young ruminants, then we discussed the regulatory effects of using yeast culture as a feed supplement. Yeast culture is a microecological preparation that contains yeast, enriched with yeast metabolites and other nutrient-active components, including ß-glucan, mannan, digestive enzymes, amino acids, minerals, vitamins, and some other unknown growth factors. It stimulates the proliferation of intestinal mucosal epithelial cells and the reproduction of intestinal microorganisms by providing special nutrient substrates to support the intestinal function. Additionally, the ß-glucan and mannan effectively stimulate intestinal mucosal immunity, promote immune response, activate macrophages, and increase acid phosphatase levels, thereby improving the body's resistance to several disease. The incorporation of yeast culture into young ruminants' diet significantly alleviated the damage caused by weaning stress to the gastrointestinal tract which also acts an effective strategy to promote the balance of intestinal flora, development of intestinal tissue, and establishment of mucosal immune system. Our review provides a theoretical basis for the application of yeast culture in the diet of young ruminants.

Bone marrow mesenchymal stem cell-derived exosomes promote osteoblast proliferation, migration and inhibit apoptosis by regulating KLF3-AS1/miR-338-3p.

AIM: This study aimed to investigate the effect and mechanism of bone marrow mesenchymal stem cell-derived exosomes on osteoblast function. METHODS: The expression of KLF3-AS1 and miR-338-3p in serum of fracture patients was detected by qRT-PCR. Exosomes from BMSCs were isolated by ultrafast centrifugation. MC3T3-E1 cells were cultured in vitro as experimental cells. Intracellular gene expression was regulated by transfection of si-KLF3-AS1 or miR-338-3p inhibitors. MTT assay, Transwell assay and flow cytometry were used to evaluate cell viability, migration, and apoptosis. The luciferase reporter gene was used to verify the targeting relationship between KLF3-AS1 and miR-338-3p. Bioinformatics analysis was used to identify the basic functions and possible enrichment pathways of miR-338-3p target genes. RESULTS: The expressions of KLF3-AS1 and miR-338-3p in the serum of fracture patients were down-regulated and up-regulated, respectively. The expression of KLF3-AS1 was increased in MC3T3-E1 cells cultured with BMSCs-Exo, while the viability and migration ability of MC3T3-E1 cells were enhanced, and the apoptosis ability was weakened. Further analysis revealed miR-338-3p was the target gene of KLF3-AS1. The expression of miR-338-3p was downregulated in MC3T3-E1 cells cultured with BMSCs-Exo. Inhibition of miR-338-3p in MC3T3-E1 cells enhanced the viability and migration ability of MC3T3-E1 cells when cultured with BMSCs-Exo, while suppressing apoptosis. Bioinformatics analysis demonstrated that the target genes of miR-338-3p were predominantly localized at the axon's initiation site, involved in biological processes such as development and growth regulation, and mainly enriched in MAPK and ErbB signaling pathways. CONCLUSION: In vitro, BMSCs-Exo exhibits the capacity to enhance proliferation and migration while inhibiting apoptosis of MC3T3-E1 cells, potentially achieved through modulation of KLF3-AS1 and miR-338-3p expression in MC3T3-E1 cells.

Early versus delayed antihypertensive treatment in patients with acute ischaemic stroke: multicentre, open label, randomised, controlled trial.

OBJECTIVES: To compared the effect of early antihypertensive treatment started within 24-48 h of stroke onset versus delaying treatment until day eight on reducing dependency or death. DESIGN: Multicentre, randomised, open label trial. SETTING: 106 hospitals in China between 13 June 2018 and 10 July 2022. PARTICIPANTS: 4810 patients (≥40 years) were enrolled with acute ischaemic stroke within 24-48 h of symptom onset and elevated systolic blood pressure between 140 mm Hg and <220 mm Hg. INTERVENTIONS: Patients were randomly assigned to receive antihypertensive treatment immediately after randomisation (aimed at reducing systolic blood pressure by 10%-20% within the first 24 h and a mean blood pressure <140/90 mm Hg within seven days) or to discontinue antihypertensive medications for seven days if they were taking them, and then receive treatment on day 8 (aimed at achieving mean blood pressure <140/90 mm Hg). MAIN OUTCOME MEASURES: The primary outcome was the combination of functional dependency or death (modified Rankin scale score ≥3) at 90 days. Intention to treat analyses were conducted. RESULTS: 2413 patients were assigned to the early treatment group and 2397 were assigned to the delayed treatment group. Mean systolic blood pressure was reduced by 9.7% (from 162.9 mm Hg to 146.4 mm Hg) in the early treatment group and by 4.9% (from 162.8 mm Hg to 154.3 mm Hg) in the delayed treatment group within 24 h after randomisation (P for group difference <0.001). Mean systolic blood pressure was 139.1 mm Hg in the early treatment group and 150.9 mm Hg in the delayed treatment group on day seven (P for group difference <0.001). Additionally, 54.6% of patients in the early treatment group and 22.4% in the delayed treatment group had blood pressure of less than 140/90 mm Hg (P<0.001 for group difference) on day seven. At day 90, 289 trial participants (12.0%) in the early treatment group, compared with 250 (10.5%) in the delayed treatment group, had died or experienced a dependency (odds ratio 1.18 (95% confidence interval 0.98 to 1.41), P=0.08). No significant differences in recurrent stroke or adverse events were reported between the two groups. CONCLUSIONS: Among patients with mild-to-moderate acute ischaemic stroke and systolic blood pressure between 140 mm Hg and <220 mm Hg who did not receive intravenous thrombolytic treatment, early antihypertensive treatment did not reduce the odds of dependency or death at 90 days. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03479554.

Immunometabolism and immune response regulate macrophage function in atherosclerosis.

Macrophages are crucial in the progression of atherosclerotic cardiovascular disease (ASCVD). In the atherosclerotic lesions, macrophages play a central role in maintaining inflammatory response, promoting plaque development, and facilitating thrombosis. Increasing studies indicate that metabolic reprogramming and immune response mediate macrophage functional changes in all stages of atherosclerosis. In this review article, we explain how metabolic changes in glycolysis, oxidative phosphorylation, the tricarboxylic acid cycle, fatty acid synthesis, fatty acid oxidation, and cholesterol metabolism regulate macrophage function in atherosclerosis. We discuss how immune response to oxidized lipids regulate macrophage function in atherosclerosis. Additionally, we explore how abnormal metabolism leads to macrophage mitochondrial dysfunction in atherosclerosis.

A Scheduling Method of Using Multiple SAR Satellites to Observe a Large Area.

This paper presents a scheduling problem of using multiple synthetic aperture radar (SAR) satellites to observe a large irregular area (SMA). SMA is usually considered as a kind of nonlinear combinatorial optimized problem and its solution space strongly coupled with geometry grows exponentially with the increasing magnitude of SMA. It is assumed that each solution of SMA yields a profit associated with the acquired portion of the target area, and the objective of this paper is to find the optimal solution yielding the maximal profit. The SMA is solved by means of a new method composed of three successive phases, namely, grid space construction, candidate strip generation and strip selection. First, the grid space construction is proposed to discretize the irregular area into a set of points in a specific plane rectangular coordinate system and calculate the total profit of a solution of SMA. Then, the candidate strip generation is designed to produce numerous candidate strips based on the grid space of the first phase. At last, in the strip selection, the optimal schedule for all the SAR satellites is developed based on the result of the candidate strip generation. In addition, this paper proposes a normalized grid space construction algorithm, a candidate strip generation algorithm and a tabu search algorithm with variable neighborhoods for the three successive phases, respectively. To verify the effectiveness of the proposed method in this paper, we perform simulation experiments on several scenarios and compare our method with the other seven methods. Compared to the best of the other seven methods, our proposed method can improve profit by 6.38% using the same resources.

Brain symmetry index predicts 3-month mortality in patients with acute large hemispheric infarction.

Quantitative electroencephalography data are helpful to predict outcomes of cerebral infarction patients. The study was performed to evaluate the value of brain symmetry index by quantitative electroencephalography in predicting 3-month mortality of large hemispheric infarction. We studied a prospective, consecutive series of patients with large supratentorial cerebral infarction confirmed within 3 days from the onset in 2 intensive care units from August 2017 to February 2020. The electroencephalography was recorded once admission. The brain symmetry index (BSI) which is divided into BSIfast and BSIslow were calculated for each electrodes pair. The outcome was mortality at 3 months after the onset. A total of 38 patients were included. The subjects were divided into the mortality group (15 patients) and survival group (23 patients). Of the BSIfast and BSIslow at each electrodes pair, higher BSIfastC3-C4, higher BSIslowC3-C4, and higher BSIslowO1-O2 were noticed in the mortality group than that in the survival group at 3 months (P = .001; P = .010; P = .009). Multivariable analysis indicated that BSIfastC3-C4 was an independent predictor of 3-month mortality (odds ratio = 1.059, 95%CI 1.003, 1.119, P = .039). BSIfastC3-C4 could significant predict 3-month mortality (area under curve = 0.805, P = .005). And when we combined BSIfastC3-C4, Glasgow Coma Scale and infarct volume together to predict the 3-month mortality, the predicted value increased (area under curve = 0.840, P = .002). BSIfastC3-C4 could independently predict the 3-month mortality of large hemispheric infarction. The combination marker which includes Glasgow Coma Scale, infarct volume, and BSIfastC3-C4 has a better diagnostic value. Further clinical trials with a large sample size are still needed.

BMP-2 promotes osteogenic differentiation of mesenchymal stem cells by enhancing mitochondrial activity.

OBJECTIVES: Mesenchymal stem cells (MSCs) have become seed cells and basic elements for bone regeneration and bone tissue engineering. The aim of the present study was to investigate the roles and mechanisms of bone morphogenetic protein 2 (BMP-2) on osteogenic differentiation of MSCs. METHODS: Primary MSCs were isolated from the femur and tibia bone of rats and then transfected with BMP-2 and PGC-1α adenovirus vectors. Alkaline phosphatase (ALP) activity and alizarin red staining were used to measure osteogenic differentiation of MSCs. Real-time PCR and western blot assays were performed to assess osteogenic differentiation-related proteins levels. The activities of mitochondrial respiratory chain complexes I and II and mitochondrial fluorescence intensity were used to explore mitochondria status during osteogenic differentiation of MSCs. RESULTS: We found that the ability of BMP-2 overexpressed (OE) group osteogenic differentiation was significantly improved, compared with the negative control (NC) group. The results also indicated that BMP-2 can promote the activity of mitochondria. We further used the gain- and loss-of-function approaches to demonstrate that BMP-2 promotes mitochondrial activity by up-regulating PGC-1α to promote osteogenic differentiation of MSCs. CONCLUSIONS: These results explored the important role of BMP-2 in the osteoblast differentiation of MSCs from a new perspective, providing a theoretical and experimental basis for bone defect and repair.

Endovascular treatment with or without intravenous alteplase for acute ischaemic stroke due to basilar artery occlusion.

BACKGROUND AND PURPOSE: It remains controversial if endovascular treatment (EVT) can improve the outcome of patients with acute basilar artery occlusion (BAO). This study aims to compare the functional outcomes between EVT with and without intravenous thrombolysis (IVT) first in patients who had acute ischaemic stroke (AIS) due to BAO. METHODS: Patients who had AIS with BAO who underwent EVT within 24 hours of onset were enrolled in this multicentre cohort study, and the efficacy and safety were compared between IVT+EVT and direct EVT. The primary outcome was 90-day functional independence. All outcomes were assessed with adjusted OR (aOR) from the multivariable logistic regression. In addition, a meta-analysis was performed on all recently published pivotal studies on functional independence after EVT in patients with BAO. RESULTS: Of 310 enrolled patients with BAO, 241 (78%) were treated with direct EVT and 69 (22%) with IVT+EVT. Direct EVT was associated with a worse functional outcome (aOR, 0.46 (95% CI 0.24 to 0.85), p=0.01). IVT+EVT was associated with a lower percentage of patients who needed ≥3 passes of stent retriever (10.14% vs 20.75%). The meta-analysis regression revealed a potential positive correlation between bridging with IVT first and functional independence (r=0.14 (95% CI 0.05 to 0.24), p<0.01). CONCLUSIONS: This study showed that compared with direct EVT, EVT with IVT first was associated with better functional outcomes in patients with BAO treated within 24 hours of onset. The meta-analysis demonstrated similar favourable efficacy of IVT first followed by EVT in patients with BAO.

Quantitative EEG provides early prediction of poor outcome in acute ischemic stroke after endovascular treatment: a preliminary study.

Background and Purpose: Quantitative electroencephalogram (QEEG) parameters have been previously utilized in prognosis following acute ischemic stroke (AIS). However, the use and interpretation of QEEG parameters remain scarce following endovascular treatment (EVT) of AIS.Methods: AIS patients were prospectively enrolled following EVT, and 24-hour EEG monitoring was conducted. Global delta/alpha ratio (DAR), (delta + theta)/(alpha + beta) ratio (DTABR), and relative band power were analyzed. Primary outcome was a poor outcome (modified Rankin Scale ≥4 at 90-day follow-up). Multivariate logistic regression and diagnostic analyses were performed.Results: Poor outcome was seen in 35.5% (11/31) of enrolled patients. Multivariable logistic regression identified that higher DAR (OR 1.10, 95% CI 1.02-1.18, p = 0.02) and higher DTABR (OR 1.13, 95% CI 1.01-1.27, p = 0.02) were associated with poor outcome. DAR ≥14.3 demonstrated high sensitivity (90.9%), specificity (90.0%) and accuracy (90.3%) for poor outcome.Conclusions: Early evidence of elevated DAR and DTABR on quantitative EEG was associated with poor outcome at 90 days following EVT for AIS.

Prior Antithrombotic Therapy is Associated with Increased Risk of Death in Patients with Intracerebral Hemorrhage: Findings from the Chinese Stroke Center Alliance (CSCA) Study.

The association of preceding antithrombotic therapy with outcomes of patients with intracerebral hemorrhage (ICH) has not been well clarified. We investigated the characteristics and associations of prior antithrombotic therapy (oral anticoagulants, antiplatelet therapy or both) in outcomes of in-hospital patients with ICH. Data were derived from the Chinese Stroke Center Alliance (CSCA) database. Enrolled patients were categorized by the different types of preceding antithrombotic therapy: antiplatelet therapy (APT), oral coagulants (OAs), both OAs and APT use and no-antithrombotic therapy (no-ATT). Among 85705 patients enrolled, 4969 (5.8%), 720 (0.8%), 905 (1.1%) and 79111 (92.3%) patients were on APT, OAs, both OAs and APT, and non-ATT respectively prior to their admission. Crude in-hospital death was 149(3.0%), 41(5.7%), 46(5.1%) and 1781(2.3%) in APT, OAs, both OAs and APT, and non-ATT groups, respectively (P<0.0001). Multivariate analysis revealed that patients in prior OAs (adjusted odds ratio [aOR], 1.95; 95% confidence interval [CI], 1.18-3.21; P=0.0091) and both OAs and APT groups (aOR 1.92, 95% CI 1.17-3.15, P=0.0094) were associated with an increased risk of in-hospital mortality compared with the non-ATT group, but not in those who were on APT (aOR 1.12, 95% 0.93-1.36, P=0.2372). In the subgroup analysis, a stronger association between prior OAs and in-hospital death was found among patients who were older ≥ 65 years (P for interaction is 0.0382). In this nationwide prospective study, prior OAs and concomitant use of OAs and APT but not prior ATP were associated with increased odds of in-hospital mortality compared with ICH patients who were on no-ATT.

The change index of quantitative electroencephalography for evaluating the prognosis of large hemispheric infarction.

A growing number of studies have demonstrated the role of quantitative electroencephalography in assessing brain function in neuro-intensive care units. Still, few studies have examined patients with large hemisphere infarction. Thirty patients with large hemisphere infarction were included in this preliminary study, and the patients were divided into the death group (twelve patients) and survival group (eighteen patients). Electroencephalography monitored the patients, and a computerized tomography inspection was performed. The quantitative electroencephalography of the alpha-beta/delta-theta ratio change index was calculated and used to predict the prognosis of early large hemisphere infarction patients. The relationship between three months modified Rankin Scale, and alpha-beta/delta-theta ratio change index was analyzed. The death group had negative changes for alpha-beta/delta-theta ratio change index (-0.0140 ± 0.0193), while there was an opposite trend in the survival group, the median is 0.004 (-0.0067, 0.0137). The death group's brain function decreased more severely and rapidly than the survival group (P = 0.004). The highest diagnostic value (AUC value 0.815, P < 0.001) was observed when the alpha-beta/delta-theta ratio change index dropped and exceeded -0.008. The area under the GCS curve was 0.674, but its predictive ability was low (P = 0.094). The correlation analysis result showed that the 3-month modified Rankin Scale was negatively correlated with the alpha-beta/delta-theta ratio change index (r = -0.489, P = 0.006). The alpha-beta/delta-theta ratio change index is considered an indicator for predicting the prognosis of large hemisphere infarction. Therefore, the alpha-beta/delta-theta ratio change index may be a reliable quantitative EEG parameter that predicts the early prognosis of patients with acute large hemispheric infarction.

ß-Glucan from Saccharomyces cerevisiae alleviates oxidative stress in LPS-stimulated RAW264.7 cells via Dectin-1/Nrf2/HO-1 signaling pathway.

ß-Glucan from Saccharomyces cerevisiae has been described to be effective antioxidants, but the specific antioxidation mechanism of ß-glucan is unclear. The objectives of this research were to determine whether the ß-glucan from Saccharomyces cerevisiae could regulate oxidative stress through the Dectin-1/Nrf2/HO-1 signaling pathway in lipopolysaccharides (LPS)-stimulated RAW264.7 cells. In this study, we examined the effects of ß-glucan on the enzyme activity or production of oxidative stress indicators in LPS-stimulated RAW264.7 cells by biochemical analysis and the protein expression of key factors of Dectin-1/Nrf2/HO-1 signaling pathway by immunofluorescence and western blot. The biochemical analysis results showed that ß-glucan increased the LPS-induced downregulation of enzyme activity of intracellular heme oxygenase (HO), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) while decreasing the production of reactive oxygen species (ROS) and malondialdehyde (MDA). Furthermore, immunofluorescence results showed that ß-glucan can activate the nuclear factor erythroid 2-related factor 2 (Nrf2). The antioxidant mechanism study indicated that ß-glucan activated dendritic-cell-associated C-type lectin 1 (Dectin-1) receptors mediated Nrf2/HO-1 signaling pathway, thereby downregulating the production of ROS and thus produced the antioxidant effects in LPS-stimulated RAW 264.7 cells. In conclusion, these results indicate that ß-glucan potently alleviated oxidative stress via Dectin-1/Nrf2/HO-1 in LPS-stimulated RAW 264.7 cells.

Tranexamic acid for acute intracerebral haemorrhage growth based on imaging assessment (TRAIGE): a multicentre, randomised, placebo-controlled trial.

BACKGROUND: Studies show tranexamic acid can reduce the risk of death and early neurological deterioration after intracranial haemorrhage. We aimed to assess whether tranexamic acid reduces haematoma expansion and improves outcome in intracerebral haemorrhage patients susceptible to haemorrhage expansion. METHODS: We did a prospective, double-blind, randomised, placebo-controlled trial at 10 stroke centres in China. Acute supratentorial intracerebral haemorrhage patients were eligible if they had indication of haemorrhage expansion on admission imaging (eg, spot sign, black hole sign or blend sign), and were treatable within 8 hours of symptom onset. Patients were randomly assigned (1:1) to receive either tranexamic acid or a matching placebo. The primary outcome was intracerebral haematoma growth (>33% relative or >6 mL absolute) at 24 hours. Clinical outcomes were assessed at 90 days. RESULTS: Of the 171 included patients, 124 (72.5%) were male, and the mean age was 55.9±11.6 years. 89 patients received tranexamic acid and 82 received placebo. The primary outcome did not differ significantly between the groups: 36 (40.4%) patients in the tranexamic acid group and 34 (41.5%) patients in the placebo group had intracranial haemorrhage growth (OR 0.96, 95% CI 0.52 to 1.77, p=0.89). The proportion of death was lower in the tranexamic acid treatment group than placebo group (8.1% vs 10.0%), but there were no significant differences in secondary outcomes including absolute intracranial haemorrhage growth, death and dependency. CONCLUSIONS: Among patients susceptible to haemorrhage expansion treated within 8 hours of stroke onset, tranexamic acid did not significantly prevent intracerebral haemorrhage growth. Larger studies are needed to assess safety and efficacy of tranexamic acid in intracerebral haemorrhage patients.

Haemostatic therapy in spontaneous intracerebral haemorrhage patients with high-risk of haematoma expansion by CT marker: a systematic review and meta-analysis of randomised trials.

BACKGROUND AND PURPOSE: Current randomised controlled trials (RCTs) showed an uncertain benefit of haemostatic therapy on preventing haematoma expansion and improving the outcome in patients with intracerebral haemorrhage (ICH). This meta-analysis aims to systematically evaluate the effect of haemostatic agents on the prevention of haemorrhage growth in patients with high-risk spontaneous ICH predicted by CT signs in RCTs. METHODS: A comprehensive search of PubMed, EMBASE and Cochrane library from 1 January 2005 to 30 June 2021 was conducted. RCTs that compared haemostatic agents with placebo for the treatment of spontaneous patients with ICH with high-risk haemorrhage growth were included. The primary endpoint was haematoma expansion at 24 hours. Other major endpoints of interest included 90-day functional outcome and mortality. RESULTS: The meta-analysis included four RCTs that randomised 2666 patients with ICH with high-risk haemorrhage growth. Haemostatic therapy reduced the rate of haematoma expansion at a marginally statistically significant level when compared with placebo (OR 0.84; 95% CI 0.70 to 1.00; p=0.051). Subgroup analysis for patients with black hole sign on CT revealed a significant reduction of haematoma expansion with haemostatic therapy (OR 0.61; 95% CI 0.39 to 0.94; p=0.03). However, both the primary analysis and subgroup analyses showed that haemostatic therapy could not reduce the rate of poor functional outcome (modified Rankin Scale >3) or death. CONCLUSIONS: Haemostatic therapy showed a marginally significant benefit in reducing early haematoma expansion in patients with high-risk spontaneous ICH predicted by markers on CT scan. However, no significant improvement in functional outcome or reduction of mortality was observed.

Intraluminal Thrombus and Outcomes of Patients With Acute Large Vessel Occlusive Stroke Undergoing Endovascular Treatment.

BACKGROUND AND PURPOSE: Intraluminal thrombus (ILT) is an emerging imaging marker in acute ischemic stroke. We aimed to investigate the association of ILT with outcomes of acute large vessel occlusion (LVO) patients receiving endovascular treatment. METHODS: Acute LVO stroke patients who underwent endovascular treatment within 24 hours, in a prospective, nationwide registry were enrolled. Pretreatment digital subtraction angiography was reviewed for the presence of ILT. The primary outcome was 90-day functional dependence (modified Rankin Scale scores, 3-6). Secondary outcomes included 24-hour LVO, 90-day death, and symptomatic intracranial hemorrhage. RESULTS: Among 711 patients enrolled, 75 (10.5%) with ILT were less likely to have 90-day functional dependence compared with those without ILT (adjusted odds ratio, 0.53 [95% CI, 0.31-0.90]; P=0.021). The same trend was found among those with successful reperfusion (modified Thrombolysis in Cerebral Infarction 2b-3; P=0.008) but not in those without successful reperfusion (P=0.107). Presence of ILT was also independently associated with a lower rate of 24-hour LVO (adjusted odds ratio 0.34 [95% CI, 0.13-0.89]; P=0.028). However, those with or without ILT had similar risks of symptomatic intracranial hemorrhage and 90-day death. CONCLUSIONS: Among acute LVO patients receiving endovascular treatment, pretreatment ILT-positive patients may have a better 90-day functional outcome (versus ILT-negative) but similar risk of death and symptomatic intracranial hemorrhage. The possibly favorable effect of ILT patients remained in those with successful reperfusion. Registration: URL: http://www.chictr.org.cn; Unique identifier: ChiCTR1900022154.

China Antihypertensive Trial in Acute Ischemic Stroke II (CATIS-2): rationale and design.

BACKGROUNDS: Increased blood pressure (BP) for patients who had an acute ischaemic stroke is associated with poor functional outcome, however the optimal timing of antihypertensive therapy is unknown. AIMS: We aim to compare early antihypertensive treatment to delayed antihypertensive treatment for reducing the risk of composite major disability and mortality at 3 months in acute ischaemic stroke. DESIGN: The China Antihypertensive Trial in Acute Ischemic Stroke II (CATIS-2) trial is a multicentre, randomised, open-label, blinded-endpoints trial that will be conducted in 100 hospitals in China. The primary outcome is the composite of death and major disability (modified Rankin Scale score ≥3) at 3 months of randomisation. Antihypertensive treatment will be received immediately after randomisation in the early treatment group, aimed at average systolic BP by 10%-20% reduction within the first 24 hours, and achieving an average BP level of <140/90 mm Hg within 5 days. Patients in the delayed treatment group will discontinue any antihypertension medications for the first 7 days of randomisation, and will receive antihypertensive therapy achieving a BP goal of <140/90 mm Hg after 7 days. CONCLUSION: The CATIS-2 trial will be testing the hypotheses that early BP lowering leads to improved functional outcome without any other harms, and developing clinical guidelines of the BP management for patients who had an acute ischaemic stroke. TRIAL REGISTRATION NUMBER: NCT03479554.

Adverse Outcomes Associated With Higher Mean Blood Pressure and Greater Blood Pressure Variability Immediately After Successful Embolectomy in Those With Acute Ischemic Stroke, and the Influence of Pretreatment Collateral Circulation Status.

Background To investigate whether collateral status could modify the associations between post-thrombectomy blood pressure (BP) measures and outcomes. Methods and Results Patients with anterior-circulation large-vessel-occlusion successfully recanalized in a multicenter endovascular thrombectomy registry were enrolled. Pretreatment collateral status was graded and dichotomized (good/poor) in angiography. Maximum, minimum, and mean systolic BP (SBP) and BP variability (assessed by the SD, coefficient of variation) during the initial 24 hours after endovascular thrombectomy were obtained. The primary outcome was unfavorable 90-day outcome (modified Rankin Scale score 3-6). Secondary outcomes included symptomatic intracranial hemorrhage and 90-day mortality. Adjusted odds ratios (aOR) of BP parameters over the outcomes were obtained in all patients and in patients with good/poor collaterals. Among 596 patients (mean age 66 years; 59.9% males), 302 (50.7%) patients had unfavorable 90-day outcome. In multivariable analyses, higher mean SBP (aOR, 1.59 per 10 mm Hg increment; 95% CI, 1.26-2.02; P<0.001), mean SBP >140 mm Hg (versus ≤120 mm Hg; aOR, 4.27; 95% CI, 1.66-10.97; P=0.002), and higher SBP SD (aOR, 1.08 per 1-SD increment; 95% CI, 1.01-1.16; P=0.02) were respectively associated with unfavorable 90-day outcome in patients with poor collateral but not in those with good collateral. A marginal interaction between SBP coefficient of variation tertiles and collaterals on 90-day functional outcome (P for interaction, 0.09) was observed. A significant interaction between SBP coefficient of variation tertiles and collaterals on 90-day mortality (P for interaction, 0.03) was observed. Conclusions Higher postprocedural BP is associated with 90-day unfavorable outcomes after successful endovascular thrombectomy in patients with poor collateral. Registration URL: https://www.chictr.org.cn; Unique identifier: ChiCTR1900022154.

Multiplicity issues for platform trials with a shared control arm.

This paper provides in-depth discussion about different types of error generated in platform trials with a common control arm, and how they compare to the ones arisen from standard independent trials. We provide our views on some of the popular "myths" associated with such design, under the frequentist framework. It is found that platform trial generally performs quite well in terms of type I error rate, false discovery rate, and power. In most cases, these operating characteristics of a platform trial are comparable to or even better than running individual trials.

Cortical Microinfarcts Associated With Worse Outcomes in Patients With Acute Ischemic Stroke Receiving Endovascular Treatment.

BACKGROUND AND PURPOSE: We aimed to evaluate the impact of cortical microinfarcts (CMIs) on functional outcome after endovascular treatment in patients with acute ischemic stroke. METHODS: In a multicenter registration study for RESCUE-RE (a registration study for Critical Care of Acute Ischemic Stroke After Recanalization), eligible patients with large vessel occlusion stroke receiving endovascular treatment, who had undergone 3T magnetic resonance imaging on admission or within 24 hours after endovascular treatment were analyzed. We evaluated the presence and numbers of CMIs with assessment of axial T1, T2-weighted images, and fluid-attenuated inversion recovery images. The primary outcome was functional dependence or death defined as modified Rankin Scale scores of 3 to 6 at 90 days. Secondary outcomes included early neurological improvement, any intracranial hemorrhage, symptomatic intracranial hemorrhage, and mortality. We investigated the independent associations of CMIs with the outcomes using multivariable logistic regression in overall patients and in subgroups. RESULTS: Among 414 patients (enrolled from July 2018 to May 2019) included in the analyses, 96 (23.2%) patients had at least one CMI (maximum 6). Patients with CMI(s) were more likely to be functionally dependent or dead at 90 days, compared with those without (55.2% versus 37.4%; P<0.01). In multivariable logistic regression analyses, presence of CMI(s) (adjusted odds ratio, 1.78 [95% CI, 1.04-3.07]; P=0.04) and multiple CMIs (CMIs ≥2; adjusted odds ratio, 7.41 [95% CI, 2.48-22.17]; P<0.001) were independently, significantly associated with the primary outcome. There was no significant difference between subgroups in the associations between CMI presence and the primary outcome. CONCLUSIONS: Acute large vessel occlusion stroke patients receiving endovascular treatment with CMI(s) were more likely to have a poor functional outcome at 90 days, independent of patients' characteristics. Such associations may be dose-dependent. Registration: URL: http://www.chictr.org.cn; Unique identifier: ChiCTR1900022154.

Implementation of a Phase Synchronization Scheme Based on Pulsed Signal at Carrier Frequency for Bistatic SAR.

Phase synchronization is one of the key technical challenges and prerequisites for the bistatic synthetic aperture radar (SAR) system, which can form a single-pass interferometry system to perform topographic mapping. In this paper, an advanced phase synchronization scheme based on a pulsed signal at carrier frequency is proposed for a bistatic SAR system and it is verified by a ground validation system. In the proposed phase synchronization scheme, the pulsed signal at carrier frequency is used for phase synchronization link, and it is exchanged by virtue of a time slot between radar signals. The feasibility of the scheme is proven by theoretical analysis of various factors affecting the performance of phase synchronization, and the reliability of the scheme is verified by the test results of the ground validation system.