Outcome and Risk of Poststroke Pneumonia in Patients with Acute Ischemic Stroke After Endovascular Thrombectomy: A Post Hoc Analysis of the DIRECT-MT Trial.

BACKGROUND: In this study, we aimed to investigate the risk factors and impact of poststroke pneumonia (PSP) on mortality and functional outcome in patients with acute ischemic stroke (AIS) after endovascular thrombectomy (EVT). METHODS: This was a post hoc analysis of a prospective randomized trial (Direct intraarterial thrombectomy in order to revascularize AIS patients with large-vessel occlusion efficiently in Chinese tertiary hospitals: a multicenter randomized clinical trial). Patients with AIS who completed EVT were evaluated for the occurrence of PSP during the hospitalization period and their modified Rankin Scale (mRS) scores at 90 days after AIS. Logistic regression analysis was conducted to investigate the independent predictors of PSP. Propensity score matching was conducted for the PSP and non-PSP groups by using the covariates resulting from the logistic regression analysis. The associations between PSP and outcomes were analyzed. The outcomes included 90-day poor functional outcome (mRS scores > 2), 90-day mortality, and early 2-week mortality. RESULTS: A total of 639 patients were enrolled, of whom 29.58% (189) developed PSP. Logistic regression analysis revealed that history of chronic heart failure (unadjusted odds ratio [OR] 2.011, 95% confidence interval [CI] 1.026-3.941; P = 0.042), prethrombectomy reperfusion on initial digital subtraction angiography (OR 0.394, 95% CI 0.161-0.964; P = 0.041), creatinine levels at admission (OR 1.008, 95% CI 1.000-1.016; P = 0.049), and National Institutes of Health Stroke Scale at 24 h (OR 1.023, 95% CI 1.007-1.039; P = 0.004) were independent risk factors for PSP. With propensity scoring matching, poor functional outcome (mRS > 2) was more common in patients with PSP than in patients without PSP (81.03% vs. 71.83%, P = 0.043) at 90 days after EVT. The early 2-week mortality of patients with PSP was lower (5.74% vs. 12.07%, P = 0.038). But there was no statistically significant difference in 90-day mortality between the PSP group and non-PSP group (22.41% vs. 14.94%, P = 0.074). The survivorship curve also shows no statistical significance (P = 0.088) between the two groups. CONCLUSIONS: Nearly one third of patients with AIS and EVT developed PSP. Heart failure, higher creatinine levels, prethrombectomy reperfusion, and National Institutes of Health Stroke Scale at 24 h were associated with PSP in these patients. PSP was associated with poor 90-day functional outcomes in patients with AIS treated with EVT.

Intensive blood pressure control after endovascular thrombectomy for acute ischaemic stroke (ENCHANTED2/MT): a multicentre, open-label, blinded-endpoint, randomised controlled trial.

BACKGROUND: The optimum systolic blood pressure after endovascular thrombectomy for acute ischaemic stroke is uncertain. We aimed to compare the safety and efficacy of blood pressure lowering treatment according to more intensive versus less intensive treatment targets in patients with elevated blood pressure after reperfusion with endovascular treatment. METHODS: We conducted an open-label, blinded-endpoint, randomised controlled trial at 44 tertiary-level hospitals in China. Eligible patients (aged ≥18 years) had persistently elevated systolic blood pressure (≥140 mm Hg for >10 min) following successful reperfusion with endovascular thrombectomy for acute ischaemic stroke from any intracranial large-vessel occlusion. Patients were randomly assigned (1:1, by a central, web-based program with a minimisation algorithm) to more intensive treatment (systolic blood pressure target <120 mm Hg) or less intensive treatment (target 140-180 mm Hg) to be achieved within 1 h and sustained for 72 h. The primary efficacy outcome was functional recovery, assessed according to the distribution in scores on the modified Rankin scale (range 0 [no symptoms] to 6 [death]) at 90 days. Analyses were done according to the modified intention-to-treat principle. Efficacy analyses were performed with proportional odds logistic regression with adjustment for treatment allocation as a fixed effect, site as a random effect, and baseline prognostic factors, and included all randomly assigned patients who provided consent and had available data for the primary outcome. The safety analysis included all randomly assigned patients. The treatment effects were expressed as odds ratios (ORs). This trial is registered at ClinicalTrials.gov, NCT04140110, and the Chinese Clinical Trial Registry, 1900027785; recruitment has stopped at all participating centres. FINDINGS: Between July 20, 2020, and March 7, 2022, 821 patients were randomly assigned. The trial was stopped after review of the outcome data on June 22, 2022, due to persistent efficacy and safety concerns. 407 participants were assigned to the more intensive treatment group and 409 to the less intensive treatment group, of whom 404 patients in the more intensive treatment group and 406 patients in the less intensive treatment group had primary outcome data available. The likelihood of poor functional outcome was greater in the more intensive treatment group than the less intensive treatment group (common OR 1·37 [95% CI 1·07-1·76]). Compared with the less intensive treatment group, the more intensive treatment group had more early neurological deterioration (common OR 1·53 [95% 1·18-1·97]) and major disability at 90 days (OR 2·07 [95% CI 1·47-2·93]) but there were no significant differences in symptomatic intracerebral haemorrhage. There were no significant differences in serious adverse events or mortality between groups. INTERPRETATION: Intensive control of systolic blood pressure to lower than 120 mm Hg should be avoided to prevent compromising the functional recovery of patients who have received endovascular thrombectomy for acute ischaemic stroke due to intracranial large-vessel occlusion. FUNDING: The Shanghai Hospital Development Center; National Health and Medical Research Council of Australia; Medical Research Futures Fund of Australia; China Stroke Prevention; Shanghai Changhai Hospital, Science and Technology Commission of Shanghai Municipality; Takeda China; Hasten Biopharmaceutic; Genesis Medtech; Penumbra.

Association of Hypertension With Both Occurrence and Outcome of Symptomatic Patients With Mild Intracranial Atherosclerotic Stenosis: A Prospective Higher Resolution Magnetic Resonance Imaging Study.

BACKGROUND: Intracranial atherosclerotic plaque causing mild luminal stenosis might lead to acute ischemic events. However, the difference between culprit and nonculprit lesions is unclear, as are the factors associated with favorable treatment outcomes. PURPOSE: To quantify characteristics of intracranial atherosclerosis with mild luminal stenosis and to identify factors associated with lesion type (culprit or nonculprit) and with clinical outcomes. STUDY TYPE: Prospective POPULATION: 293 patients who had acute stroke with mild luminal stenosis (<50%) in the middle cerebral or basilar artery. FIELD STRENGTH/SEQUENCE: 3.0 T higher resolution magnetic resonance imaging (hrMRI) of intracranial arteries and whole brain MR images. ASSESSMENT: Morphological and compositional analysis of plaques was performed. This included assessment of plaque volume, plaque burden, remodeling ratio, eccentricity, intraplaque hemorrhage, and enhancement ratio. Clinical outcomes were assessed according to the modified Rankin Scale (mRS) at day 90, with a favorable outcome being defined as a 90-day mRS ≤2. STATISTICAL TESTS: The odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by a logistic regression model. RESULTS: Hypertension (OR 5.2; 95% CI 2.6-10.3; P < 0.05) and hrMRI enhancement ratio (OR 2.7; 95% CI 1.4-5.1; P < 0.05) were independently associated with lesion type. Patients without hypertension had significantly more (P < 0.05) favorable outcomes (124/144) than patients with hypertension (97/149). Most hypertensive patients without any previous blood pressure control (54/63) had a favorable outcome. However, these patients were significantly younger (P < 0.05) than those with adequate blood pressure control. After adjusting for all significant characteristics, hypertension duration (OR 1.19; 95% CI 1.09-1.29; P < 0.05), hypertension management (OR 2.49; 95% CI 1.18-5.26; P < 0.05), and enhancement ratio (OR 0.01; 95% CI 0.001-0.157; P < 0.05) were found to be independent high-risk factors for outcome prediction. DATA CONCLUSION: hrMRI provided incremental value over traditional risk factors in identifying higher risk intracranial atherosclerosis with mild luminal stenosis. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Safety and Efficacy of Intravenous Thrombolytic Therapy in Patients With Acute Posterior Circulation Stroke: A Single-Center Study.

BACKGROUND AND PURPOSE: The safety and efficacy of intravenous thrombolytic therapy (IVT) for posterior circulation stroke (PCS) in the real world are rarely studied. This study was designed to evaluate the prestroke and baseline characteristics, stroke sub-types, complications, and outcomes of PCS patients and compare them with anterior circulation stroke (ACS) after intravenous thrombolysis. METHODS: Data of consecutive patients with PCS and ACS treated with alteplase in a standard dose of 0.9 mg/kg in our stroke center were collected and analyzed retrospectively. Presenting characteristics, hemorrhage transformation, mortality, and favorable outcomes (modified Rankin scale 0 or 1) at 90 days were compared between PCS and ACS patients. RESULTS: A total of 462 patients were included in this study, including 350 (75.8%) in ACS group and 112 (24.2%) in PCS group. A history of coronary artery disease was significantly more common in ACS patients than that in PCS patients (15.1% versus 6.3%, P = .015). There was no significant difference in fast glucose and baseline NIHSS scores between PCS and ACS groups. In PCS group, 7 patients (6.3%) had hemorrhage transformation after IVT and 5 patients (4.5%) were symptomatic versus 32 (9.1%) and 22 (6.3%) in ACS group (P > .05). 75.5% PCS patients versus 72.2% ACS patients had excellent recovery outcomes (mRS 0-1) at 90 days (P = .507). For PCS patients, logistic regression analysis after adjusting the covariates identified age (P = .047, OR .920, 95% CI = .847-.999) and atrial fibrillation (P = .007, OR 12.149, 95% CI = 1.966-75.093) as independent significant predictors of hemorrhage transformation. In addition, atrial fibrillation was also an independent predictor of symptomatic intracranial hemorrhage (P = .008, OR 21.176, 95% CI = 2.228-201.273). Multivariate logistic analysis identified hemorrhage transformation (P = .012; OR .131, 95% CI = .027-.644) and onset to drug time (P = .026, OR 1.006, 95% CI = 1.001-1.011) as independent predictors of functional independence (mRS 0-2). Symptomatic intracranial hemorrhage (P = .007, OR 15.094, 95% CI = 2.097-108.661) and baseline NIHSS score (P = .050; OR 1.070, 95% CI = 1.000-1.145) were independent predictors of mortality. CONCLUSION: Our results suggest that IVT in PCS patients is safe and effective as that in ACS patients. In PCS patients, long onset to needle time and hemorrhage transformation were identified as independent predictors of unfavorable outcomes.

Serum Aldosterone Is Associated with Cerebral Artery Atherosclerosis and Calcification.

BACKGROUND AND PURPOSE: Elevated serum aldosterone concentration is known to be linked with elevated risk of cerebrovascular events as a result of vascular senescence. We studied the association between serum aldosterone concentration and cerebral arteriosclerosis status involving cerebral atherosclerosis burden and cerebral vascular calcification. METHODS: A total of 207 patients (mean age = 62.40 ± 10.54, 70 female patients) admitted with acute ischemic stroke from a single center-based stroke registry were included in the study. The participants were categorized into 4 groups in accordance to the serum aldosterone concentration. Cerebral atherosclerosis burden was derived as the stenosis degree of main intracranial arteries, and cerebral artery calcification was investigated from the cavernous portions of both internal carotid arteries from brain computed tomography angiography. RESULTS: The median aldosterone was 146.00 pg/mL; interquartile range was 133.18-172.10 pg/mL. Advanced intracranial atherosclerosis was present in 134 patients (64.7%) and advanced intracranial arterial calcification was present in 77 patients (37.2%). The prevalence of cerebral atherosclerosis burden and cerebral artery calcification showed increasing tendency through the aldosterone quartiles. Multivariable logistic regression analysis including age, sex, vascular risk factors, estimated glomerular filtration rate and aldosterone quartiles disclosed that the highest serum aldosterone quartile was an independent predictor of advanced intracranial atherosclerosis (odds ratio, 5.07; 95% confidence interval, 1.82-14.17; Ptrend = .001) and advanced intracranial arterial calcification (odds ratio, 6.24; 95% confidence interval, 2.03-19.22; Ptrend = .001). CONCLUSIONS: An increased serum aldosterone concentration was independently associated with intracranial atherosclerosis burden and arterial calcification. Future studies should investigate whether aldosterone antagonists prevent stroke in at risk population.

Pentraxin-3 in Thrombolytic Therapy for Acute Ischemic Stroke: No Relation with Curative Effect and Prognosis.

BACKGROUND Pentraxin-3 (PTX3) is considered a high quality inflammatory marker of the severity and prognosis of several diseases, however, the value of PTX3 in thrombolytic therapy for acute ischemic stroke remains unclear and PTX3 is still controversial in evaluating the prognosis of stroke patients. In this study, we investigated the association of PTX3 with thrombolytic therapy in patients with acute ischemic stroke. MATERIAL AND METHODS Forty-seven stroke patients who received thrombolytic therapy within 4.5 hours after symptom onset were enrolled consecutively between July 2016 and June 2017. All the patients underwent multiphase CTA (computerized tomography angiography) or CT perfusion before thrombolysis with no indication for endovascular treatment. Initial and 24 hours of National Institute of Health Stroke Scale (NIHSS) scores and serum PTX3 level, stroke risk factors and predictors, and mRS (modified Rankin scale) at 3 months were collected prospectively. Predictors of thrombolytic therapy effect and long-term prognosis were investigated by univariate and multivariate logistic regression. RESULTS The 24 hour NIHSS score and the treatment time was associated with symptom improvement, while the PTX3 level had no association with neurological improvement and prognosis in stroke patients receiving thrombolytic therapy. CONCLUSIONS PTX3 is not suitable to serve as an indicator of thrombolytic efficacy and had no association with long-term prognosis in stroke patients receiving thrombolytic therapy.

Clinical Study of Intracranial and Extracranial Atherosclerotic Stenosis in Spontaneous Intracerebral Hemorrhage Patients.

BACKGROUND AND PURPOSE: Nowadays, researchers had begun to focus on the use of antiplatelet and statins in patients with spontaneous intracerebral hemorrhage (sICH), but atherosclerosis treatment remains uncertain in these patients. We aimed to investigate the incidence and characteristics of intracranial and extracranial atherosclerotic stenosis in these patients and analyze its related risk factors. METHODS: Intracranial and extracranial arteries of consecutive patients with sICH were studied retrospectively with computed tomography angiography of head and neck. The risk factors, severity, and distribution of atherosclerotic stenosis were examined and analyzed. RESULTS: We included 226 patients with sICH, of whom 110 patients (48.7%) had atherosclerotic stenosis. Of the patients, 57 (51.8%) had intracranial stenosis and 75 (68.2%) had multiple stenosis. A total of 1870 vessels were examined and 287 vessels (15.3%) had atherosclerotic stenosis, of which 217 cases (75.6%) were mild stenosis. Intracranial and extracranial atherosclerosis was more likely to be found in patients with advanced age (P < .001), diabetes mellitus (P = .008), non-deep hemorrhage (P = .011). CONCLUSIONS: Atherosclerotic stenosis is common in patients with sICH, and is characterized by mild stenosis and the involvement of multiple sites. The stenosis of the vertebrobasilar system is relatively severe. Advanced age, diabetes mellitus, and non-deep bleeding are its related risks.

A retrospective study of 23 cases with subacute combined degeneration.

PURPOSE: To study retrospectively the diverse presentations, ancillary tests and neuroimaging in patients with subacute combined degeneration (SCD). METHODS: Twenty-three Chinese patients with SCD were included in this study. The clinical presentations and laboratory data including comprehensive metabolic panel, serum folic acid, vitamin B12 levels, gastroscopy and images of spinal cord on magnetic resonance imaging (MRI) were evaluated. Rating scales for localizations of lesions and functional disabilities were used to define the severity of neurological impairment. RESULTS: No difference was found between men and women in the age of disease onset. For most of the patients, sensory symptoms, oftentimes as initial symptoms, occurred earlier than motor symptoms. The signs of the disease were more obvious than the symptoms. Six patients had sensory deficit levels mimicking transverse myelopathy. Anemia was not always detected in our patients with SCD. Normal or even elevated serum levels of vitamin B12 were found in seven patients. Spinal cord lesions on MRI were observed in six patients and the clinical and neuroimaging findings were not necessarily consistent. CONCLUSIONS: The sensory symptoms occur earlier than the motor symptoms in SCD patients. SCD patients may have sensory deficit level. Normal or even elevated serum levels of vitamin B12 may occur in patients with SCD.

Decreased levels and function of circulating endothelial progenitor cells in unruptured intracranial saccular aneurysm patients.

Circulating endothelial progenitor cells (EPCs) play a critical role in maintaining endothelial integrity and keeping vascular homeostasis. Previously, we reported that EPCs were involved in repair and remodeling of aneurismal wall. In the present study, we verified this hypothesis by investigating the proliferative ability and count of EPCs in peripheral blood of patients with unruptured intracranial aneurysms (UIAs). Twenty-four patients with UIAs (UIA group) and 24 negative controls (control group) were included in this study. Peripheral blood monocytes (PBMCs) were harvested and selectively cultured. The colony-forming ability of cultured cells was analyzed and the biological functions were examined by testing the adsorption of ulex europaeus agglutinin-1 labeled by fluorescein isothiocyanate and acetylated low-density lipoprotein internalization. The migratory and adhesive ability of cultured EPCs were assessed. In vitro cultured PBMCs were identified as EPCs by examining surface markers CD34, CD133 and vascular endothelial growth factor receptor 2 using flow cytometry. EPCs from UIA group possessed significantly decreased proliferative, migratory and adhesive capacities compared with EPCs from control group. Furthermore, EPCs count in UIA group was significantly decreased. Collectively, these results indicated that the circulating EPCs of UIA patients may be involved in intracranial aneurysm repair and remodeling.

Correlations of 2 Novel Inflammation Indexes With the Risk for Early Neurological Deterioration in Acute Ischemic Stroke Patients After Intravenous Thrombolytic Therapy.

OBJECTIVES: Elevation of the systemic immune inflammation (SII) index and system inflammation response index (SIRI) is known to be associated with higher risk of stroke and all-cause death. However, no study has reported their correlation with early neurological deterioration (END) following recombinant tissue-type plasminogen activator (IV-rtPA) in acute ischemic stroke patients. The aim of this study was to explore the correlation of SII and SIRI with the risk of END after IV-rtPA. METHODS: Included in this study were 466 consecutive patients treated with IV-rtPA. SII and SIRI were calculated according to blood cell counts before IV-rtPA. Patients were divided into 3 groups based on trisectional quantiles according to SII and SIRI values. The risk of END was assessed by multivariate regression. The overall discriminative ability of SII and SIRI in predicting END was assessed by receiver operating characteristic curve analysis. RESULTS: Of the 466 included patients, 62 (13.3%) were identified as having END. Compared with the first tertile of SII, multivariable regression analysis demonstrated that patients were more likely to have END (odds ratio 2.54; 95% CI: 1.23-5.23) and poor outcome at 90 days (odds ratio 2.02; 95% CI: 1.06-3.86) in third tertile after adjustment for potential confounders. In addition, a cutoff value of 591.63 for SII was detected in predicting post-thrombolysis END with a sensitivity of 58.1% and a specificity of 64.6% (area under the curve 0.61; 95% CI: 0.54-0.69). CONCLUSIONS: Higher SII but not SIRI may prove to be a predictor for high risk of END and a poor functional outcome at 90 days after IV-rtPA.

The role of the D-dimer to fibrinogen ratio in the classification of cardioembolism and atherosclerotic stroke.

BACKGROUND: The D-dimer-to-fibrinogen ratio (DFR) is a good indicator of thrombus activity in thrombotic diseases, but its clinical role in acute ischaemic stroke (AIS) patients with different etiologies has not been studied. We evaluated the diagnostic value of the DFR for different subtypes of AIS. METHODS: We conducted a single-center retrospective study of 269 patients with AIS who were referred to our stroke center within 4.5 h from Jan 2017 to Oct 2019. Coagulation data including DFRs were compared among the different stroke subtypes, and a separate retrospective validation sample was utilized to evaluate the prediction efficiency of the DFR for subtype diagnosis. RESULTS: A higher DFR was observed in patients with cardioembolism than in those with large artery atherosclerosis (LAA) (odds ratio (OR) per 0.1 increase of the DFR: 1.49 [1.01-2.18]) after we adjusted for vascular risk factors. The diagnostic value of the DFR for detecting cardioembolism (AUC = 0.722, 95 % CI = 0.623-0.820) exceeded that of isolated D-dimer or fibrinogen. The validation sample (n = 117) further supported the notion that a diagnosis of cardioembolism was more common in patients with a DFR > 0.11 (multivariable risk ratio = 3.11[1.33-7.31], P = 0.009). CONCLUSION: High DFRs were associated with cardioembolism in patients with AIS. The utilization of DFR can be beneficial for distinguishing a cardiac embolic source from atherosclerotic stroke.

Risk factors for and outcomes of poststroke pneumonia in patients with acute ischemic stroke treated with mechanical thrombectomy.

Objective: The purpose of the study was to assess the risk factors for poststroke pneumonia (PSP) and its association with the outcomes in patients with acute ischemic stroke (AIS) due to large artery occlusion treated with mechanical thrombectomy (MT). Methods: Consecutive patients with AIS who underwent MT from January 2019 to December 2019 in the stroke center of Changhai Hospital were identified retrospectively. All of the patients were evaluated for the occurrence of PSP while in the hospital, and their modified Rankin scale (mRS) scores were assessed 90 days after having a stroke. Logistic regression analysis was conducted to determine the independent predictors of PSP, and the associations between PSP and clinical outcomes were analyzed. Results: A total of 248 patients were enrolled, of whom 33.47% (83) developed PSP. Logistic regression analysis revealed that body mass index (BMI) [unadjusted odds ratio (OR) 1.200, 95% confidence interval (CI) 1.038-1.387; p = 0.014], systemic immune-inflammation index (SII) (OR 1.001, 95% CI 1.000-1.002; p = 0.003), dysphagia (OR 9.498, 95% CI 3.217-28.041; p < 0.001), and intubation after MT (OR 4.262, 95% CI 1.166-15.581; p = 0.028) were independent risk factors for PSP. PSP was a strong predictor of clinical outcomes: it was associated with functional independence (mRS score ≤ 2) (OR 0.104, 95% CI 0.041-0.260; p < 0.001) and mortality at 90 days (OR 3.010, 95% CI 1.068-8.489; p = 0.037). Conclusion: More than one in three patients with AIS treated with MT developed PSP. Dysphagia, intubation, higher BMI, and SII were associated with PSP in these patients. Patients with AIS who develop PSP are more likely to experience negative outcomes. The prevention and identification of PSP are necessary to reduce mortality and improve clinical outcomes.

A Cryptogenic Stroke Associated With Infective Endocarditis and Antiphospholipid Antibody Syndrome: Case Report and Literature Review.

Introduction: Accurate definition of stroke etiology is crucial, as this will guide effective targets for treatment. Both antiphospholipid antibody syndrome (APS) and infective endocarditis (IE) can be independent risk factors for ischemic stroke in young adults. When an embolic stroke occurs with IE and APS simultaneously, the origin of the embolic source is difficult to identify. Case Report: A 19-year-old man was admitted to the hospital for the onset of stroke. A diagnosis of APS accompanied by IE was made after a series of examinations. We identified aortic valve vegetation as the embolic source. Although both APS and IE can induce valve vegetation, we considered IE to be the primary cause according to the infective clues. Despite treatment with ampicillin, the patient's fever persisted, and surgical aortic valve replacement was performed urgently. The patient recovered without recurrence of stroke during the 1-year follow-up. Conclusion: A considerable challenge for physicians is evaluating all the signs suggestive of embolic sources in acute stroke and identifying the primary etiology when there are multiple causes. Early diagnosis and surgical intervention for bicuspid aortic valve (BAV) vegetation complicated by acute stroke may yield favorable clinical results.

Fine-tuning of microglia polarization prevents diabetes-associated cerebral atherosclerosis.

Diabetes increases the occurrence and severity of atherosclerosis. When plaques form in brain vessels, cerebral atherosclerosis causes thickness, rigidity, and unstableness of cerebral artery walls, leading to severe complications like stroke and contributing to cognitive impairment. So far, the molecular mechanism underlying cerebral atherosclerosis is not determined. Moreover, effective intervention strategies are lacking. In this study, we showed that polarization of microglia, the resident macrophage in the central nervous system, appeared to play a critical role in the pathological progression of cerebral atherosclerosis. Microglia likely underwent an M2c-like polarization in an environment long exposed to high glucose. Experimental suppression of microglia M2c polarization was achieved through transduction of microglia with an adeno-associated virus (serotype AAV-PHP.B) carrying siRNA for interleukin-10 (IL-10) under the control of a microglia-specific TMEM119 promoter, which significantly attenuated diabetes-associated cerebral atherosclerosis in a mouse model. Thus, our study suggests a novel translational strategy to prevent diabetes-associated cerebral atherosclerosis through in vivo control of microglia polarization.

Patient-Reported Anxiety/Depression After Endovascular Thrombectomy: A post-hoc Analysis of Direct-MT Trial.

OBJECTIVE: To analyze the effect of endovascular thrombectomy (EVT) alone vs. EVT after an intravenous (IV) alteplase of ischemic stroke on a patient-reported anxiety/depression, and to identify predictors of patient-reported anxiety/depression by analyzing data from Direct Intraarterial Thrombectomy in Order to Revascularize the patients with Acute Ischemic Stroke with a Large Vessel Occlusion Efficiently in Chinese Tertiary Hospitals: a Multicenter Randomized Clinical Trial (DIRECT-MT). METHODS: Patients with acute ischemic stroke (AIS), triggered by a large-vessel occlusion in the anterior circulation, were randomly allocated to undergo an EVT after IV alteplase (combination-therapy group) or an EVT alone (EVT-alone group) at a 1:1 ratio in DIRECT-MT. Patients in both groups were followed up for 90 days (±14 days) after stroke using a structured modified Ranking Scale (mRS), a Barthel Index (BI), and a 5-Dimensional European Quality of Life Scale (EQ-5D-5L). Patients who returned EQ-5D-5L were included. The EQ-5D-5L anxiety/depression dimension was used to analyze the patient-reported anxiety/depression. First, differences in patient-reported anxiety/depression were compared between the combination-therapy group and the EVT-alone group. Then, the baseline and influencing factors between the anxiety/depression group and no anxiety/depression group were analyzed using univariate regression analysis. Finally, variables with p < 0.1 in univariate regression were subjected to multivariable binary regression analysis to screen independent predictors for patient-reported anxiety /depression after ischemic stroke. RESULTS: : Five hundred fifteen patients returned the EQ-5D-5L in Direct-MT. Of these patients, 226 (43.88%) reported a level of anxiety/depression, and about 7% reported a severe or extremely severe anxiety/depression. The patient-reported anxiety/depression in the EVT-alone group was significantly higher than that in the combination-therapy group (48.26% vs. 39.45%, p = 0.04). The clinical outcomes were significantly different between the no Anxiety/Depression Group and the anxiety/depression group (mRS at 90 days:2 vs 3, p < 0.001; BI of 95 or 100 at 90 days: 73.36% vs 42.04%, p < 0.001; EQ-5D-5l utility indexes at 90 days:0.96 vs.57, p < 0.001). Logistic regression analysis showed that allocation to thrombolysis before EVT strategy was inversely associated with anxiety/depression [0.61(0.40, 0.94), p = 0.03], an insular cortex ischemia, and National Institute of Health Strocke Scale (NIHSS) at 7 days were positively associated with anxiety/depression [2.04(1.07, 3.90), p = 0.03; 1.07(1.03, 1.12), p < 0.001]. CONCLUSIONS: Patient-reported anxiety/depression may suggest that there is a benefit to administering intravenous alteplase before EVT. It may also indicate that it is better to provide IV alteplase before EVT, rather than EVT alone according to patient-reported anxiety/depression. Future research should consider not only the motor function impairments but also the patient-reported mental problems as measures of treatment efficacy in patients with stroke (DIRECT-MT ClinicalTrials.gov number, NCT03469206).

Naoxintong Capsule for Secondary Prevention of Ischemic Stroke: A Multicenter, Randomized, and Placebo-Controlled Trial.

OBJECTIVE: To examine whether the combination of Naoxintong Capsule with standard care could further reduce the recurrence of ischemic stroke without increasing the risk of severe bleeding. METHODS: A total of 23 Chinese medical centers participated in this trial. Adult patients with a history of ischemic stroke were randomly assigned in a 1:1 ratio using a block design to receive either Naoxintong Capsule (1.2 g orally, twice a day) or placebo in addition to standard care. The primary endpoint was recurrence of ischemic stroke within 2 years. Secondary outcomes included myocardial infarction, death due to recurrent ischemic stroke, and all-cause mortality. The safety of drugs was monitored. Results were analyzed using the intention-to-treat principle. RESULTS: A total of 2,200 patients were enrolled from March 2015 to March 2016, of whom 143 and 158 in the Naoxintong and placebo groups were lost to follow-up, respectively. Compared with the placebo group, the recurrence rate of ischemic stroke within 2 years was significantly lower in the Naoxintong group [6.5% vs. 9.5%, hazard ratio (HR): 0.665, 95% confidence interval (CI): 0.492-0.899, P=0.008]. The two groups showed no significant differences in the secondary outcomes and safety, including rates of severe hemorrhage, cerebral hemorrhage and subarachnoid hemorrhage (P>0.05). CONCLUSION: The combination of Naoxintong Capsule with standard care reduced the 2-year stroke recurrence rate in patients with ischemic stroke without increasing the risk of severe hemorrhage in high-risk patients. (Trial registration No. NCT02334969).

[Flavonoids of puerarin versus tanshinone II A for ischemic stroke: a randomized controlled trial].

BACKGROUND: Flavonoids are widely used today in the treatment of ischemic stroke. The therapeutic effects and functions of flavonoids are, therefore, generating more and more interest. OBJECTIVE: To investigate the therapeutic effects and functions of flavonoids of puerarin in treating patients with ischemic stroke. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A total of 67 inpatients suffering from ischemic stroke from the Department of Neurology, Changhai Hospital in China were divided into two groups randomly, the treatment group, which was treated with flavonoids of puerarin, and the control group, administered with tanshinone II A sulfate instead. MAIN OUTCOME MEASURES: Defects in neurological function were evaluated according to the National Institutes of Health Stroke Scale (NIHSS) on the first day of onset. Lactate dehydrogenase (LDH), serum interleukin-6 (IL-6) and brain-derived neurotrophic factor (BDNF) levels were determined by radioimmunoassay on the second trial day. After a 14-day treatment, LDH, serum IL-6 and BDNF levels and NIHSS score were also detected, and CT perfusion imaging was used to measure and analyze the regional cerebral blood flow (rCBF), regional cerebral blood volume (rCBV) and mean transit time (MTT). RESULTS: On the first day, NIHSS scores of the two groups were similar. On the second day there was no significant difference in LDH and IL-6 levels between the treatment group and the control group. After a 14-day treatment, LDH and IL-6 levels and the NIHSS score in the treatment group were lower than those in the control group (P<0.05). There was no significant difference in BDNF levels in the two groups. After 14 d, the CT perfusion imaging demonstrated that the treatment group showed more effective blood perfusion than the control group. CONCLUSION: Flavonoids of puerarin can restrain the increase of IL-6 after acute ischemic stroke, and depress the LDH raised by reperfusion after cerebral ischemia. It can also enhance blood perfusion of the ischemic region.

Pinocembrin Promotes OPC Differentiation and Remyelination via the mTOR Signaling Pathway.

The exacerbation of progressive multiple sclerosis (MS) is closely associated with obstruction of the differentiation of oligodendrocyte progenitor cells (OPCs). To discover novel therapeutic compounds for enhancing remyelination by endogenous OPCs, we screened for myelin basic protein expression using cultured rat OPCs and a library of small-molecule compounds. One of the most effective drugs was pinocembrin, which remarkably promoted OPC differentiation and maturation without affecting cell proliferation and survival. Based on these in vitro effects, we further assessed the therapeutic effects of pinocembrin in animal models of demyelinating diseases. We demonstrated that pinocembrin significantly ameliorated the progression of experimental autoimmune encephalomyelitis (EAE) and enhanced the repair of demyelination in lysolectin-induced lesions. Further studies indicated that pinocembrin increased the phosphorylation level of mammalian target of rapamycin (mTOR). Taken together, our results demonstrated that pinocembrin promotes OPC differentiation and remyelination through the phosphorylated mTOR pathway, and suggest a novel therapeutic prospect for this natural flavonoid product in treating demyelinating diseases.