Intestinal epithelial Krüppel-like factor 4 alleviates endotoxemia and atherosclerosis through improving NF-κB/miR-34a-mediated intestinal permeability.

Maintenance of intestinal barrier function contributes to gastrointestinal homeostasis and therefore cardiovascular diseases. A number of studies show that intestinal permeability is affected by excessive inflammatory responses. Krüppel-like factor (KLF) 4 is one of the critical transcriptional factors, which controls multiple immune responses. In this study we investigated the role of KLF4 in regulating intestinal inflammation and permeability during the atherosclerotic process. Atherosclerotic model was established in ApoE-/- mice by feeding a high fat high cholesterol (HFHC) diet. We showed that colon expression levels of KLF4 and tight junction proteins were significantly decreased whereas inflammatory responses increased in atherosclerotic mice. Overexpression of colon epithelial Klf4 decreased atherosclerotic plaque formation and vascular inflammation in atherosclerotic mice, accompanied by remarkable suppression of intestinal NF-κB activation. We found that overexpression of epithelial Klf4 in atherosclerotic mice significantly increased intestinal tight junction expression and ameliorated endotoxemia, whereas replenishment of LPS abolished these benefits. Overexpression of Klf4 reversed LPS-induced permeability and downregulation of ZO-1 and Occludin in Caco-2 cells in vitro. HFHC diet stimulated the expression of epithelial microRNA-34a, whereas silence of epithelial Klf4 abolished the benefits of microRNA-34a sponge, a specific miR-34a inhibitor, on intestinal permeability and atherosclerotic development. A clinical cohort of 24 atherosclerotic patients supported colon KLF4/NF-κB/tight junction protein axis mediated intestine/cardiovascular interaction in patients with atherosclerosis. Taken together, intestinal epithelial KLF4 protects against intestinal inflammation and barrier dysfunction, ameliorating atherosclerotic plaque formation.

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).

A Single-Center Experience of Endovascular Treatment in Subtypes of Basilar Artery Occlusion: Embolization Caused by Tandem Vertebral Artery Stenosis May Be Associated with Better Outcomes.

OBJECTIVE: Basilar artery occlusion (BAO) is a severe condition with high mortality. However, surgical procedures and outcomes of BAO with different pathologic subtypes have not been fully clarified. This study compared the surgical procedures and clinical outcomes of mechanical thrombectomy in different subtypes of BAO. METHODS: Eighty-six patients with acute BAO receiving endovascular treatment between October 2015 and July 2019 were retrospectively analyzed and placed in 3 groups: pure embolism (group 1), arterial-arterial embolism from steno-occlusion of the tandem vertebral artery (group 2), and in situ atherosclerotic thrombosis (group 3). Recanalization rates, procedure times, surgical characteristics, and clinical outcomes were analyzed. RESULTS: Groups 1, 2, and 3 included 33 (38.4%), 17 (19.8%), and 36 (41.9%) patients, respectively. The overall successful recanalization rate was 95.3%, and the good outcome rate was 61.6%. The procedure time in group 1 was shorter than the time in groups 2 and 3 (P < 0.001). The clinical good outcome rate was higher in group 2 than in group 1 (88.2% vs. 54.5%; P = 0.017). Groups 1 and 3 had similar good outcome rates (54.5% vs. 55.6%; P = 0.933). Twenty-seven patients received stent angioplasty: 10 of 17 in group 2 (58.8%) and 17 of 36 in group 3 (47.2%). CONCLUSIONS: The outcome of endovascular treatment for BAO varies among patients with different pathologic mechanisms. Patients with embolism from tandem vertebral artery steno-occlusion achieved the best outcomes. Rescue treatment was more common in patients with embolic BAO with tandem vertebral artery steno-occlusion and BAO with in situ atherosclerotic thrombosis.

Mechanical Thrombectomy Outcome Predictors in Stroke Patients with M2 Occlusion: A Single-Center Retrospective Study.

BACKGROUND: Mechanical thrombectomy (MT) has demonstrated benefit in patients with acute ischemic stroke due to proximal large-vessel occlusion. However, it is unclear whether these results can be extrapolated to patients with an occlusion of the second segment (M2) of the middle cerebral artery (MCA). We sought to study outcomes in patients with M2 occlusion treated with MT and to better understand clinical predictors of these outcomes. METHODS: We performed a single-center retrospective analysis of consecutive patients with acute MCA M2 segment occlusion who underwent stent retriever MT. We correlated clinical and radiographic outcomes with demographic, clinical, and technical characteristics. RESULTS: Thirty-seven patients were included in the analysis (median admission National Institutes of Health Stroke Scale [NIHSS] score, 15 [12-19], mean age 74 [67-80] years, 48.6% women). Good clinical outcome at 3 months (modified Rankin Scale ≤2) was achieved in 48.6% of patients. Baseline NIHSS was a predictor of clinical outcomes, based on modified Rankin Scale distribution at 3 months after MT (P = 0.015, odds ratio 1.63, 95% confidence interval 1.01-2.43). CONCLUSIONS: The results of our single-institution experience suggest that MT-based endovascular therapy for M2 occlusions is safe and effective. Baseline NIHSS was a predictor of outcomes in patients treated with MT for M2 segment occlusion of the MCA.

Mechanical Thrombectomy Using Solitaire in Acute Ischemic Stroke Patients with Vertebrobasilar Occlusion: A Prospective Observational Study.

BACKGROUND: The safety and effectiveness of endovascular mechanical thrombectomy in patients with acute vertebrobasilar occlusion (VBO) are debatable and undergoing evaluation. We report the clinical outcome and prognostic factors in a prospective cohort of acute ischemic stroke patients with VBO. METHODS: In total, 48 consecutive patients with acute VBO underwent mechanical thrombectomy using Solitaire. We analyzed clinical and imaging data and searched for predictors of good clinical outcome (modified Rankin scale score: 0-3). RESULTS: The median prethrombectomy National Institutes of Health Stroke Scale score was 22.0. The median duration from symptom onset to recanalization was 493.5 minutes. A total of 35.4% of the patients received rescue therapy. Recanalization (modified Thrombolysis In Cerebral Infarction: 2b-3) was successful in all patients. Clinically relevant intracranial hemorrhage was observed in 2 patients. After 90 days, good outcomes were obtained in 27 patients. The baseline National Institutes of Health Stroke Scale score, posterior circulation Acute Stroke Prognosis Early CT Score (pc-ASPECTS), anesthesia type, and posterior communicating artery (PComA) patency were significantly associated with outcomes at 90 days in univariate analysis. Multivariate logistic regression indicated that high pc-ASPECTS at admission and PComA patency were independent predictors of good outcome at 90 days. CONCLUSIONS: Up to 60.4% of the patients reached good outcomes after endovascular treatment and 35.4% of the patients received rescue therapy, suggesting that mechanical thrombectomy using Solitaire in patients with stroke with VBO is safe and effective and that rescue therapy is readily required and employed. High baseline pc-ASPECTS and PComA patency were associated with better outcomes after thrombectomy in these patients.

Plasma adrenomedullin levels are associated with long-term outcomes of acute ischemic stroke.

Plasma adrenomedullin concentration has been found to be enhanced in ischemic stroke. Up to now, little is known about the association of plasma adrenomedullin concentration with clinical outcomes of ischemic stroke. This study recruited 138 patients with ischemic stroke and 138 healthy volunteers. Unfavorable outcome was defined as modified Rankin Scale score >2 at 3 months. Plasma adrenomedullin concentrations were determined by enzyme-linked immunosorbent assay. Plasma adrenomedullin concentrations were statistically significantly higher in patients than in healthy individuals (79.9±27.3pg/mL vs. 36.8±10.4pg/mL; P<0.001). 3-Month mortality was 20.3% (28/138) and sixty-six patients (47.8%) had unfavorable outcome in 3 months. A logistic regression analysis identified plasma adrenomedullin concentration as an independent predictor of 3-month mortality (odds ratio, 1.211; 95% confidence interval, 1.101-1.582; P=0.004) and unfavorable outcome (odds ratio, 1.193; 95% confidence interval, 1.082-1.447; P=0.006). Receiver operating characteristic curve analysis showed that plasma adrenomedullin concentration predicted 3-month mortality (area under curve, 0.806; 95% confidence interval, 0.730-0.868) and unfavorable outcome (area under curve, 0.816; 95% confidence interval, 0.742-0.877) with the high predictive value. Its predictive performance was similar to that of National Institutes of Health Stroke Scale score (P=0.694 or 0.206). Its combined use with National Institutes of Health Stroke Scale score did not improve the predictive value (P=0.236 or 0.590). Thus, adrenomedullin may aid to predict long-term clinical outcomes of patients with ischemic stroke.

Prognostic significance of plasma visfatin levels in patients with ischemic stroke.

Plasma visfatin concentration has been enhanced in ischemic stroke. The aim of the current investigation was to test whether determination of visfatin in plasma is associated with 6-month clinical outcomes including mortality and unfavorable outcome (modified Rankin Scale score>2) in the patients with ischemic stroke. Between July 2009 and January 2012, plasma visfatin concentrations of 186 patients and 100 healthy individuals were quantified by enzyme-linked immunosorbent assay. Plasma visfatin concentrations were higher in patients than in healthy individuals (108.5±41.1 ng/mL vs. 13.8±3.9 ng/mL, P<0.001). A logistic regression analysis selected plasma visfatin concentration as an independent predictor for 6-month clinical outcomes (both P<0.01). Using receiver operating characteristic curve analysis, plasma visfatin concentration was found to predict 6-month clinical outcomes with the high predictive performance. The predictive value of visfatin was in the range of National Institutes of Health Stroke Scale score (both P>0.05). Combined use of visfatin and National Institutes of Health Stroke Scale score did not improve the predictive significance (both P>0.05). Thus, visfatin may help in the prediction of long-term clinical outcomes in patients with ischemic stroke.