Explainable machine learning model for identifying key gut microbes and metabolites biomarkers associated with myasthenia gravis.

Diagnostic markers for myasthenia gravis (MG) are limited; thus, innovative approaches are required for supportive diagnosis and personalized care. Gut microbes are associated with MG pathogenesis; however, few studies have adopted machine learning (ML) to identify the associations among MG, gut microbiota, and metabolites. In this study, we developed an explainable ML model to predict biomarkers for MG diagnosis. We enrolled 19 MG patients and 10 non-MG individuals. Stool samples were collected and microbiome assessment was performed using 16S rRNA sequencing. Untargeted metabolic profiling was conducted to identify fecal amplicon significant variants (ASVs) and metabolites. We developed an explainable ML model in which the top ASVs and metabolites are combined to identify the best predictive performance. This model uses the SHapley Additive exPlanations method to generate both global and personalized explanations. Fecal microbe-metabolite composition differed significantly between groups. The key bacterial families were Lachnospiraceae and Ruminococcaceae, and the top three features were Lachnospiraceae, inosine, and methylhistidine. An ML model trained with the top 1 % ASVs and top 15 % metabolites combined outperformed all other models. Personalized explanations revealed different patterns of microbe-metabolite contributions in patients with MG. The integration of the microbiota-metabolite features and the development of an explainable ML framework can accurately identify MG and provide personalized explanations, revealing the associations between gut microbiota, metabolites, and MG. An online calculator employing this algorithm was developed that provides a streamlined interface for MG diagnosis screening and conducting personalized evaluations.

A systematic-search-and-review of registered pharmacological therapies investigated to improve neuro-recovery after a stroke.

Background: Stroke burden is largely due to long-term impairments requiring prolonged care with loss of productivity. We aimed to identify and assess studies of different registered pharmacological therapies as treatments to improve post-stroke impairments and/or disabilities. Methods: We performed a systematic-search-and-review of treatments that have been investigated as recovery-enhancing or recovery-promoting therapies in adult patients with stroke. The treatment must have received registration or market authorization in any country regardless of primary indication. Outcomes included in the review were neurological impairments and functional/disability assessments. "The best available studies" based on study design, study size, and/or date of publication were selected and graded for level of evidence (LOE) by consensus. Results: Our systematic search yielded 7,801 citations, and we reviewed 665 full-text papers. Fifty-eight publications were selected as "the best studies" across 25 pharmacological classes: 31 on ischemic stroke, 21 on ischemic or hemorrhagic stroke, 4 on intracerebral hemorrhage, and 2 on subarachnoid hemorrhage (SAH). Twenty-six were systematic reviews/meta-analyses, 29 were randomized clinical trials (RCTs), and three were cohort studies. Only nimodipine for SAH had LOE A of benefit (systematic review and network meta-analysis). Many studies, some of which showed treatment effects, were assessed as LOE C-LD, mainly due to small sample sizes or poor quality. Seven interventions had LOE B-R (systematic review/meta-analysis or RCT) of treatment effects. Conclusion: Only one commercially available treatment has LOE A for routine use in stroke. Further studies of putative neuroprotective drugs as adjunctive treatment to revascularization procedures and more confirmatory trials on recovery-promoting therapies will enhance the certainty of their benefit. The decision on their use must be guided by the clinical profile, neurological impairments, and target outcomes based on the available evidence. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=376973, PROSPERO, CRD42022376973.

Assessing the length of hospital stay for patients with myasthenia gravis based on the data mining MARS approach.

Predicting the length of hospital stay for myasthenia gravis (MG) patients is challenging due to the complex pathogenesis, high clinical variability, and non-linear relationships between variables. Considering the management of MG during hospitalization, it is important to conduct a risk assessment to predict the length of hospital stay. The present study aimed to successfully predict the length of hospital stay for MG based on an expandable data mining technique, multivariate adaptive regression splines (MARS). Data from 196 MG patients' hospitalization were analyzed, and the MARS model was compared with classical multiple linear regression (MLR) and three other machine learning (ML) algorithms. The average hospital stay duration was 12.3 days. The MARS model, leveraging its ability to capture non-linearity, identified four significant factors: disease duration, age at admission, MGFA clinical classification, and daily prednisolone dose. Cut-off points and correlation curves were determined for these risk factors. The MARS model outperformed the MLR and the other ML methods (including least absolute shrinkage and selection operator MLR, classification and regression tree, and random forest) in assessing hospital stay length. This is the first study to utilize data mining methods to explore factors influencing hospital stay in patients with MG. The results highlight the effectiveness of the MARS model in identifying the cut-off points and correlation for risk factors associated with MG hospitalization. Furthermore, a MARS-based formula was developed as a practical tool to assist in the measurement of hospital stay, which can be feasibly supported as an extension of clinical risk assessment.

Tumor size combined with staging systems for thymoma recurrence prediction: A 28-year experience.

Background: We evaluated a new thymoma prognosis prediction model by combining current staging systems with tumor size. Methods: The clinical records of thymoma patients in a single center between January 1993 and December 2021 were collected, and data on tumor size and stage and recurrence-free survival (RFS) was obtained. The prediction model was designed by combining staging with tumor size. Results: During 28 years, 219 thymoma patients were enrolled. Twenty-seven patients had a median RFS of 8.2 years. Further, 153 patients were categorized into limited stage and 66 patients into advanced stage. The RFS was statistically different between these two groups (P = 0.022). The largest area under the curve (AUC) of receiver operating characteristic (ROC) was the dividing group as 5 cm (AUC: 0.804). Conclusions: Combining tumor staging and size improves thymoma recurrence prediction. Patients with advanced stage and tumor size >5 cm may show a poor prognosis.

Machine learning strategy for identifying altered gut microbiomes for diagnostic screening in myasthenia gravis.

Myasthenia gravis (MG) is a neuromuscular junction disease with a complex pathophysiology and clinical variation for which no clear biomarker has been discovered. We hypothesized that because changes in gut microbiome composition often occur in autoimmune diseases, the gut microbiome structures of patients with MG would differ from those without, and supervised machine learning (ML) analysis strategy could be trained using data from gut microbiota for diagnostic screening of MG. Genomic DNA from the stool samples of MG and those without were collected and established a sequencing library by constructing amplicon sequence variants (ASVs) and completing taxonomic classification of each representative DNA sequence. Four ML methods, namely least absolute shrinkage and selection operator, extreme gradient boosting (XGBoost), random forest, and classification and regression trees with nested leave-one-out cross-validation were trained using ASV taxon-based data and full ASV-based data to identify key ASVs in each data set. The results revealed XGBoost to have the best predicted performance. Overlapping key features extracted when XGBoost was trained using the full ASV-based and ASV taxon-based data were identified, and 31 high-importance ASVs (HIASVs) were obtained, assigned importance scores, and ranked. The most significant difference observed was in the abundance of bacteria in the Lachnospiraceae and Ruminococcaceae families. The 31 HIASVs were used to train the XGBoost algorithm to differentiate individuals with and without MG. The model had high diagnostic classification power and could accurately predict and identify patients with MG. In addition, the abundance of Lachnospiraceae was associated with limb weakness severity. In this study, we discovered that the composition of gut microbiomes differed between MG and non-MG subjects. In addition, the proposed XGBoost model trained using 31 HIASVs had the most favorable performance with respect to analyzing gut microbiomes. These HIASVs selected by the ML model may serve as biomarkers for clinical use and mechanistic study in the future. Our proposed ML model can identify several taxonomic markers and effectively discriminate patients with MG from those without with a high accuracy, the ML strategy can be applied as a benchmark to conduct noninvasive screening of MG.

Utilization of Decision Tree Algorithms for Supporting the Prediction of Intensive Care Unit Admission of Myasthenia Gravis: A Machine Learning-Based Approach.

Myasthenia gravis (MG), an acquired autoimmune-related neuromuscular disorder that causes muscle weakness, presents with varying severity, including myasthenic crisis (MC). Although MC can cause significant morbidity and mortality, specialized neuro-intensive care can produce a good long-term prognosis. Considering the outcomes of MG during hospitalization, it is critical to conduct risk assessments to predict the need for intensive care. Evidence and valid tools for the screening of critical patients with MG are lacking. We used three machine learning-based decision tree algorithms, including a classification and regression tree, C4.5, and C5.0, for predicting intensive care unit (ICU) admission of patients with MG. We included 228 MG patients admitted between 2015 and 2018. Among them, 88.2% were anti-acetylcholine receptors antibody positive and 4.7% were anti-muscle-specific kinase antibody positive. Twenty clinical variables were used as predictive variables. The C5.0 decision tree outperformed the other two decision tree and logistic regression models. The decision rules constructed by the best C5.0 model showed that the Myasthenia Gravis Foundation of America clinical classification at admission, thymoma history, azathioprine treatment history, disease duration, sex, and onset age were significant risk factors for the development of decision rules for ICU admission prediction. The developed machine learning-based decision tree can be a supportive tool for alerting clinicians regarding patients with MG who require intensive care, thereby improving the quality of care.

Assessment of Sarcopenia and Obesity in Patients with Myasthenia Gravis Using Dual-Energy X-ray Absorptiometry: A Cross-Sectional Study.

Sarcopenia and obesity can negatively impact quality of life and cause chronic fragility, and are associated with neuromuscular diseases, including myasthenia gravis (MG). The long-term consequences of body composition changes in chronic MG remain unknown; we therefore evaluated changes in body composition, including sarcopenia, obesity, lean body mass, and the prevalence of sarcopenic obesity in patients. In this cross-sectional study, 35 patients with MG (mean age: 56.1 years) and 175 matched controls were enrolled. Body fat mass and skeletal muscle mass were measured using whole body dual-energy X-ray absorptiometry. Patients with MG exhibited a higher prevalence of obesity and higher android adiposity and total body fat percentage than those of controls. Although the prevalence of sarcopenia and sarcopenic obesity did not increase with age, there was a decrease in arm and android muscle mass in patients with MG compared with controls. Lower muscle mass percentages were correlated with increased age and MG severity, but not with corticosteroid use. Thus, MG is associated with increased risk for obesity and decreased muscle mass with aging, regardless of corticosteroid use. Therefore, accurate diagnosis of body composition changes in MG could facilitate the application of appropriate therapies to promote health, improve quality of life, and prevent fragility.

Changes in Physical Fitness and Body Composition Associated with Physical Exercise in Patients with Myasthenia Gravis: A Longitudinal Prospective Study.

There is a lack of guidelines for physical exercise in patients with myasthenia gravis (MG). A few pilot studies have shown that exercise can be safely applied to patients with MG. However, how physical exercise affects body composition, disease function, and disease severity remains unknown. In this prospective study, we enrolled 34 patients with MG with stable condition and evaluated the disease severity, physical fitness parameters, and body composition (measured using whole-body dual-energy X-ray absorptiometry (DXA)), before and after conducting a 24-week physical exercise regimen of aerobic and resistance strength training. The outcomes were measured by DXA, quantitative MG (QMG) score, quality of life score, handgrip strength and walking speed. During the training regimen, participants were free to decide how many exercise sessions per week and regularly reported their weekly exercise time. The physical exercise program was well tolerated by the participants, the parameters of the QMG score and handgrip strength improved, and participants' body composition did not change significantly. The high exercise group experienced greater deterioration in muscle mass in the arms, but exhibited a greater improvement in forced vital capacity, walking speed, and symptom severity. The group with low QMG scores improved more in terms of physical fitness, including walking speed. These findings indicate that physical exercise is well tolerated by patients with MG, and is accompanied by improved muscular and physical functions. We propose that physical exercise is safe, effective, and appropriate for patients with well-regulated MG.

Progressive encephalomyelitis with rigidity: A Taiwanese case and review of literature.

INTRODUCTION: Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a rare disorder. However, the outcome is still variable with different serological and tumor associations, and the elements to good response with less relapse is yet to be elucidated. METHOD: We present a case and obtain a literature review of patients with PERM and make comparisons based on different serological groups. We also analyze patients with idiopathic PERM that had detailed medical records. RESULTS: 81 patients were collected and analyzed. The largest group were glycine receptor-antibody (GlyR-Ab)-positive (70%), and the seropositive-GlyR-Ab-negative group had better response to immunotherapy. Malignancy can occur up to 2 years from the presentation of PERM. Among the 18 cases with detailed records, the patients who had good outcome initiate immunotherapy within 2 months from presentation. 9 of the 12 patients who experienced no relapse had non-steroid immunotherapy. The maximal interval time of relapse was 24 months. CONCLUSION: We recommend tumor surveillance up to 2 years in patients with PERM and early administration of immunotherapies and maintain with non-steroid immunotherapy with or without oral corticosteroid for a minimum of 2 years to reduce the risk of relapse in GlyR-Ab-positive patients.

Prognostic value and prevalence of complete right bundle branch block in an elderly population: a community-based 10-year prospective study.

Complete right bundle branch block (CRBBB) occurs in 0.2% to 1.3% of the general population, but its prognostic significance in the geriatric population is unknown. We prospectively investigated the prevalence and prognostic value of CRBBB in individuals aged ≥65 years in a community-based population in Taiwan. A total of 5,830 community-dwelling individuals were prospectively recruited from 7 regions across Taiwan starting in December 2008 through March 2013. Those aged ≥65 years were included in the analysis (N=3,383). All subjects underwent a home visit and standardized medical exams and were followed up annually until the end of April 2019; cause of death was documented by citizen death records. The mean age of the study cohort was 73.5±5.9 years (65-104), and 47.21% were men. Among these individuals, 171 (5.05%) had CRBBB; the prevalence was higher in men (7.08%) than in women (3.25%). Subjects with CRBBB were older than those without CRBBB (75.4±6.5 vs. 73.4±5.9), and the frequency of CRBBB increased with age. Survival analysis revealed that all-cause mortality and cardiac mortality were similar in individuals with and without CRBBB during a mean follow-up of 92.6±23.6 months. CRBBB is not associated with increased risk of mortality in the geriatric population.

The 10-Year Prognosis and Prevalence of Brugada-Type Electrocardiograms in Elderly Women: A Longitudinal Nationwide Community-Based Prospective Study.

BACKGROUND: Brugada syndrome is a disorder associated with sudden cardiac death and characterized by an abnormal electrocardiogram (ECG). Previous studies were predominantly conducted in men, and the data on long-term prognosis are limited. Information about women, especially elderly women, is lacking. OBJECTIVE: The aim of this study was to investigate the long-term prognosis of the Brugada ECG pattern in elderly women. METHOD: We investigated the 10-year prognosis of the Brugada ECG pattern in elderly women in a nationwide community-based population in Taiwan. Community-dwelling women older than 55 years were prospectively recruited from December 2008 to March 2013 by a stratified random sampling method. All enrolled individuals were followed up annually until April 2019, and the cause of death was documented by citizen death records. RESULTS: Among 2597 women, 60 (2.31%) had a Brugada-type ECG, and this prevalence was higher than the mean global prevalence of 0.23%. One woman had a type 1 ECG (0.04%), whereas 15 (0.58%) and 44 (1.70%) women had type 2 and type 3 ECG patterns, respectively. Cox survival analysis revealed that all-cause mortality and cardiac mortality were similar in the individuals with and without a Brugada-type ECG during a mean follow-up of 96.1 ± 20.5 months. CONCLUSIONS: Our findings suggest that Brugada ECG patterns are not infrequent in elderly women but are not associated with increased risk of mortality in long-term follow-up; these findings may help reduce unnecessary anxiety for physicians, nurses, allied health caregivers, and patients.

A Case of Occlusive Radiation Vasculopathy Presenting as Bilateral Internal Carotid Artery, Left Middle Cerebral Artery Occlusion and Literature Review.

Radiation vasculopathy is one of the rare causes of ischemic stroke. Carotid stenosis with large volume infarction may occur years after radiation therapy for head or neck cancer. We report a case of a patient with bilateral internal carotid artery occlusion presenting with left middle cerebral artery infarct 10 years after receiving treatment for tongue cancer. A literature review and discussion of treatment for such patients are presented.

Mechanical Thrombectomy and Stenting for Radiation-Induced Carotid Stenosis-Related Stroke: A Case Report.

Radiation-induced stenosis of the carotid artery is a significant risk factor for large-vessel ischemic stroke, which usually leads to significant impairment of neurological function. We performed intra-arterial thrombectomy on a 63-year-old male patient who had laryngeal cancer and postradiation carotid stenosis. He presented with acute-onset dysarthria and left hemiplegia. Brain computed tomography perfusion scan showed right middle cerebral artery ischemic change. Angiography confirmed total occlusion of the right internal carotid artery. Intra-arterial mechanical thrombectomy with carotid stenting was performed immediately, and recanalization was achieved. The patient fully recovered and was discharged after a 1-week hospitalization. Our experience suggests that early intervention for radiation-related carotid stenosis might be essential and beneficial for the outcome of large-vessel ischemic stroke.

Renal dysfunction increases the risk of recurrent stroke in patients with acute ischemic stroke.

BACKGROUND AND AIMS: This study investigated risks of short-term (1 and 3 months) and long-term (1-year) recurrent stroke associated with glomerular filtration rate (eGFR) in patients with acute ischemic stroke. METHODS: From the Taiwan Stroke Registry data, we identified 45,876 acute ischemic stroke patients from April 2006 to April 2014 and classified them into 4 groups based on the eGFR at admission: ≥ 90, 60-89, 30-59, and <30 mL/min/1.73 m2 or on dialysis. The risks of 1-month, 3-month and 1-year recurrent stroke related to the eGFR levels were investigated. RESULTS: Both the risks of short-term and long-term recurrent stroke increased as the eGFR levels declined. The 1-month recurrent incidence rates increased steadily from 0.54 to 0.59, 0.84 and 0.89 per 1000 person-days, as the eGFR declined from ≥90 to 60-89, 30-59, and <30 mL/min/1.73 m2 or on dialysis, respectively. Compared to patients with eGFR ≥90 mL/min/1.73 m2, the adjusted subhazard ratio of 1-month recurrent stroke decreased from 1.69 (95% confidence interval (CI) = 1.24-2.31) for patients with eGFR < 30 mL/min/1.73 m2 or on dialysis to 1.14 (95% CI = 0.91-1.43) for patients with eGFRs of 60-89 mL/min/1.73 m2, considering the competing risk of deaths. Similar patterns were also observed for the adjusted HRs of 3-month and 1-year recurrent stroke, but with reduced hazard values, by the corresponding eGFR levels. CONCLUSIONS: There is an independent graded association between an increased risk of recurrent stroke and declining eGFR levels in patients with acute ischemic stroke.

Licochalcone A Prevents Platelet Activation and Thrombus Formation through the Inhibition of PLCγ2-PKC, Akt, and MAPK Pathways.

Platelet activation is involved in cardiovascular diseases, such as atherosclerosis and ischemic stroke. Licochalcone A (LA), an active ingredient of licorice, exhibits multiple biological activities such as anti-oxidation and anti-inflammation. However, its role in platelet activation remains unclear. Therefore, the study investigated the antiplatelet mechanism of LA. Our data revealed that LA (2-10 µM) concentration dependently inhibited platelet aggregation induced by collagen, but not thrombin and U46619. LA markedly attenuated collagen-stimulated ATP release, P-selectin secretion, calcium mobilization, and GPIIbIIIa activation, but did not interfere with the collagen binding to platelets. Moreover, LA significantly reduced the activation of PLCγ2, PKC, Akt and MAPKs. Thus, LA attenuates platelet activation, possibly by inhibiting collagen receptor downstream signaling but not by blocking the collagen receptors. In addition, LA prevented adenosine diphosphate (ADP)-induced acute pulmonary thrombosis, fluorescein sodium-induced platelet thrombus formation, and middle cerebral artery occlusion/reperfusion-induced brain injury in mice, but did not affect normal hemostasis. This study demonstrated that LA effectively reduced platelet activation and thrombus formation, in part, through the inhibition of PLCγ2-PKC, Akt, and MAPK pathways, without the side effect of bleeding. These findings also indicate that LA may provide a safe and alternative therapeutic approach for preventing thromboembolic disorders such as stroke.

Impact of MCA stenosis on the early outcome in acute ischemic stroke patients.

BACKGROUND: Asians have higher frequency of intracranial arterial stenosis. The present study aimed to compare the clinical features and outcomes of ischemic stroke patients with and without middle cerebral artery (MCA) stenosis, assessed by transcranial sonography (TCS), based on the Taiwan Stroke Registry (TSR). METHODS: Patients with acute ischemic stroke or transient ischemic attack registered in the TSR, and received both carotid duplex and TCS assessment were categorized into those with stenosis (≥50%) and without (<50%) in the extracranial internal carotid artery (ICA) and MCA, respectively. Logistic regression analysis, Kaplan-Meier method and Cox proportional hazard model were applied to assess relevant variables between groups. RESULTS: Of 6003 patients, 23.3% had MCA stenosis, 10.1% ICA stenosis, and 3.9% both MCA and ICA stenosis. Patients with MCA stenosis had greater initial NIHSS, higher likelihood of stroke-in-evolution, and more severe disability than those without (all p<0.001). Patients with MCA stenosis had higher prevalence of hypertension, diabetes and hypercholesterolemia. Patients with combined MCA and extracranial ICA stenosis had even higher NIHSS, worse functional outcome, higher risk of stroke recurrence or death (hazard ratio, 2.204; 95% confidence intervals, 1.440-3.374; p<0.001) at 3 months after stroke than those without MCA stenosis. CONCLUSIONS: In conclusion, MCA stenosis was more prevalent than extracranial ICA stenosis in ischemic stroke patients in Taiwan. Patients with MCA stenosis, especially combined extracranial ICA stenosis, had more severe neurological deficit and worse outcome.

Healthy lifestyle and normal waist circumference are associated with a lower 5-year risk of type 2 diabetes in middle-aged and elderly individuals: Results from the healthy aging longitudinal study in Taiwan (HALST).

Type 2 diabetes mellitus (DM) is known to be closely associated with lifestyle and obesity and has a prevalence that increases with age. This study aimed to assess the short-term composite effect of diet, physical activity, psychosocial health, and waist circumference (WC) on the incidence of DM in the elderly and to provide a lifestyle-based predictive index.We used baseline measurements (2009-2013) of 5349 community-dwelling participants (aged 55 years and older, 52% female) of the Healthy Aging Longitudinal Study in Taiwan (HALST) for fasting plasma glucose, HbA1C, serum cholesterol, triglycerides, blood pressures, WC, and outcomes of home-visit questionnaire. Principal component analysis (PCA) was used to identify participants with a healthy lifestyle (HLF: higher diet, physical activity, and psychosocial scores) and a lower WC, with cutoffs determined by the receiver-operating characteristics. A Cox regression model was applied to 3424 participants without DM at baseline by linking to their National Health Insurance records (median follow-up of 3.1 years).In total, 247 new DM cases (7.2%) were identified. The HLF and lower WC group had a relative risk (RR) of DM of 0.54 (95% CI 0.35-0.82) compared to the non-HLF and higher WC group. When stratified by the presence of impaired glucose tolerance (IGT) or metabolic syndrome (MS), only participants with IGT/MS showed significant risks (RR 0.55; 95% CI 0.33-0.92). However, except for WC, the individual lifestyle factors were nonsignificant in the overall model without PCA.A composite protective effect of HLF and normal WC on DM within 5 years was observed, especially in those with IGT or MS. Psychosocial health constituted an important lifestyle factor in the elderly. The cutoffs identified could be used as a lifestyle-based risk index for DM. Maintaining an HLF to prevent DM is especially important for the elderly.

Beneficial effects of prolonged blood pressure control after carotid artery stenting.

OBJECTIVES: The main purpose of this study was to investigate whether carotid artery stenting (CAS) plus medicine in patients with severe carotid artery stenosis provide a better long-term blood pressure (BP) control compared to other medical treatments alone. The other aim was to explore the correlation between post-CAS hypotension within 6 h and long-term BP reductions after CAS. MATERIALS AND METHODS: Patients with severe carotid stenosis were recruited either in the CAS group or in the medication group. BPs and the number of classes of antihypertensive agents were recorded at baseline, 6, and 12 months. Extra BP information was collected at 6 h, 3 days, and 1 month after CAS. Univariate and multivariate linear regressions were performed to test the relationship of BP changes among CAS and medication groups after 6 and 12 months of follow-up. Univariate linear regressions were also used to determine the correlations between the mean or maximal systolic BP (SBP) reductions at 6 h and 1 year post-CAS. RESULTS: In total, 72 members in the CAS group and 82 members in the medication group were recruited. Compared with the medication group, patients in the CAS group had greater BP reductions at 6 and 12 months of follow-up after adjusting for confounding factors (13.56 mmHg at 6 months, P=0.0002; 16.98 mmHg at 12 months, P<0.0001). This study also shows significant positive correlations between the mean or maximal SBP reductions 6 h post-CAS and SBP reductions 1 year post-CAS (ß =0.20±0.07, P=0.0067 and ß =0.47±0.10, P<0.0001, respectively). CONCLUSION: As compared to medical treatment alone, CAS may provide significant beneficial effect on long-term BP control 1 year post-CAS. Furthermore, SBP reductions 6 h post-CAS may predict the SBP reductions 1 year post-CAS.

Quality Improvement in Acute Ischemic Stroke Care in Taiwan: The Breakthrough Collaborative in Stroke.

In the management of acute ischemic stroke, guideline adherence is often suboptimal, particularly for intravenous thrombolysis or anticoagulation for atrial fibrillation. We sought to improve stroke care quality via a collaborative model, the Breakthrough Series (BTS)-Stroke activity, in a nationwide, multi-center activity in Taiwan. A BTS Collaborative, a short-term learning system for a large number of multidisciplinary teams from hospitals, was applied to enhance acute ischemic stroke care quality. Twenty-four hospitals participated in and submitted data for this stroke quality improvement campaign in 2010-2011. Totally, 14 stroke quality measures, adopted from the Get With The Guideline (GWTG)-Stroke program, were used to evaluate the performance and outcome of the ischemic stroke patients. Data for a one-year period from 24 hospitals with 13,181 acute ischemic stroke patients were analyzed. In 14 hospitals, most stroke quality measures improved significantly during the BTS-activity compared with a pre-BTS-Stroke activity period (2006-08). The rate of intravenous thrombolysis increased from 1.2% to 4.6%, door-to-needle time ≤60 minutes improved from 7.1% to 50.8%, symptomatic hemorrhage after intravenous thrombolysis decreased from 11.0% to 5.6%, and anticoagulation therapy for atrial fibrillation increased from 32.1% to 64.1%. The yearly composite measures of five stroke quality measures revealed significant improvements from 2006 to 2011 (75% to 86.3%, p<0.001). The quarterly composite measures also improved significantly during the BTS-Stroke activity. In conclusion, a BTS collaborative model is associated with improved guideline adherence for patients with acute ischemic stroke. GWTG-Stroke recommendations can be successfully applied in countries besides the United States.

Nobiletin, a Polymethoxylated Flavone, Inhibits Glioma Cell Growth and Migration via Arresting Cell Cycle and Suppressing MAPK and Akt Pathways.

Nobiletin, a bioactive polymethoxylated flavone (5,6,7,8,3(') ,4(') -hexamethoxyflavone), is abundant in citrus fruit peel. Although nobiletin exhibits antitumor activity against various cancer cells, the effect of nobiletin on glioma cells remains unclear. The aim of this study was to determine the effects of nobiletin on the human U87 and Hs683 glioma cell lines. Treating glioma cells with nobiletin (20-100 µm) reduced cell viability and arrested the cell cycle in the G0/G1 phase, as detected using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and propidium iodide (PI) staining, respectively; however, nobiletin did not induce cell apoptosis according to PI-annexin V double staining. Data from western blotting showed that nobiletin significantly attenuated the expression of cyclin D1, cyclin-dependent kinase 2, cyclin-dependent kinase 4, and E2 promoter-binding factor 1 (E2F1) and the phosphorylation of Akt/protein kinase B and mitogen-activated protein kinases, including p38, extracellular signal-regulated kinase, and c-Jun N-terminal kinase. Our data also showed that nobiletin inhibited glioma cell migration, as detected by both functional wound healing and transwell migration assays. Altogether, the present results suggest that nobiletin inhibits mitogen-activated protein kinase and Akt/protein kinase B pathways and downregulates positive regulators of the cell cycle, leading to subsequent suppression of glioma cell proliferation and migration. Our findings evidence that nobiletin may have potential for treating glioblastoma multiforme.