Associations of diabetes status and glucose measures with outcomes after endovascular therapy in patients with acute ischemic stroke: an analysis of the nationwide TREAT-AIS registry.

Background: Hyperglycemia affects the outcomes of endovascular therapy (EVT) for acute ischemic stroke (AIS). This study compares the predictive ability of diabetes status and glucose measures on EVT outcomes using nationwide registry data. Methods: The study included 1,097 AIS patients who underwent EVT from the Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke. The variables analyzed included diabetes status, admission glucose, glycated hemoglobin (HbA1c), admission glucose-to-HbA1c ratio (GAR), and outcomes such as 90-day poor functional outcome (modified Rankin Scale score ≥ 2) and symptomatic intracranial hemorrhage (SICH). Multivariable analyses investigated the independent effects of diabetes status and glucose measures on outcomes. A receiver operating characteristic (ROC) analysis was performed to compare their predictive abilities. Results: The multivariable analysis showed that individuals with known diabetes had a higher likelihood of poor functional outcomes (odds ratios [ORs] 2.10 to 2.58) and SICH (ORs 3.28 to 4.30) compared to those without diabetes. Higher quartiles of admission glucose and GAR were associated with poor functional outcomes and SICH. Higher quartiles of HbA1c were significantly associated with poor functional outcomes. However, patients in the second HbA1c quartile (5.6-5.8%) showed a non-significant tendency toward good functional outcomes compared to those in the lowest quartile (<5.6%). The ROC analysis indicated that diabetes status and admission glucose had higher predictive abilities for poor functional outcomes, while admission glucose and GAR were better predictors for SICH. Conclusion: In AIS patients undergoing EVT, diabetes status, admission glucose, and GAR were associated with 90-day poor functional outcomes and SICH. Admission glucose was likely the most suitable glucose measure for predicting outcomes after EVT.

Characteristics and risk of stroke in emergency department patients with acute dizziness.

Background: Acute dizziness is a common symptom in the emergency department (ED), with strokes accounting for 3 %-5 % of cases. We investigated the risk of stroke in ED patients with acute dizziness and compared stroke characteristics diagnosed during and after the ED visit. Methods: We identified adult patients with acute dizziness, vertigo, or imbalance using a hospital research-based database. Patients with abdominal or flank pain were used as the comparison group. Patients with dizziness were 1:1 matched to comparison patients. Each patient was traced for up to one year until being hospitalized for a stroke. Results: Out of the 24,266 eligible patients, 589 (2.4 %) were hospitalized for stroke during the ED visit. For the remaining 23,677 patients, the risk of stroke at 7, 30, 90, and 365 days after ED discharge was 0.40 %, 0.52 %, 0.71 %, and 1.25 % respectively. Patients with dizziness had a higher risk of stroke compared to the comparison group at 7, 30, 90, and 365 days. The risk ratios decreased from 5.69 (95 % confidence interval [CI], 3.34-9.68) to 2.03 (95 % CI, 1.65-2.49). Compared to patients hospitalized for stroke during the ED visit, those hospitalized for stroke after the ED visit had greater stroke severity despite a lower initial triage acuity. Patients with early stroke (≤7 days) after ED discharge were less likely to have hypertension, diabetes, hyperlipidemia, and atrial fibrillation. They mostly experienced posterior circulation stroke. Patients with late stroke (>7 days) were older and less likely to have hypertension and hyperlipidemia but more likely to have a history of prior stroke and ischemic heart disease. Their strokes were mainly located in the anterior circulation territory. Conclusions: The risk of stroke after ED discharge was higher in patients with dizziness than in the comparison group, with gradually decreasing risk ratios in the following year. Patients hospitalized for stroke during and after the ED visit had different profiles of vascular risk factors and clinical characteristics.

Chronopharmacology of diuresis via metabolic profiling and key biomarker discovery of the traditional Chinese prescription Ji-Ming-San using tandem mass spectrometry in rat models.

BACKGROUND: Ji-Ming-Shan (JMS) is a traditional prescription used for patients with rheumatism, tendons swelling, relief of foot pain, athlete's foot, diuresis, gout. Although many studies have investigated the active compounds in each herb, the functional mechanism behind its therapeutic effect remains unclear. STUDY DESIGN: Metabolic cages for sample collection. The serum components obtained from the experimental animals were analyzed using LC-MS/MS. Furthermore, cross-analysis using the software MetaboAnalyst and Venn diagrams were used to investigate chronopharmacology of JMS in the animal models. PURPOSE: The aim of this study is to analyze the diuretic effects of JMS and to explore their chronopharmacology involved in organ regulation through four-quarter periods from serum samples of rat models. METHODS: Metabolic cages were used for collecting the urine samples and PocketChem UA PU-4010, Fuji DRI-CHEM 800 were used to examine the urine biochemical parameters. The serum components were identified through ultra-performance liquid chromatography-quadrupole time-of-flight (UPLC-Q-TOF) with a new developed method. Cross analysis, Venn diagram, MetaboAnalyst were used to investigate the key biomarker and major metabolism route with the oral administration of the drug. RESULT: JMS significantly changed the 6 h urine volume with no observed kidney toxicity. Urine pH value ranges from 7.0 to 7.5. The chronopharmacology of JMS diuresis activity were 0-6 and 6-12 groups. UPLC-Q-TOF analyses identified 243 metabolites which were determined in positive mode and negative mode respectively. With cross analysis in the Venn diagram, one key biomarker naringenin-7-O-glucoside has been identified. Major metabolic pathways such as 1: Glycerophospholipid metabolism, 2: Primary bile acid biosynthesis, 3: Sphingolipid metabolism, 4: Riboflavin metabolism, 5: Linoleic acid metabolism, 6: Butanoate metabolism. CONCLUSION: JMS significantly changed the urine output of animals in the 0-6 and 6-12 groups. No change in urine pH was observed and also kidney toxicity. A new UPLC-Q-TOF method was developed for the detection of the metabolites of JMS after oral administration. The cross analysis with Venn diagram and identified the key biomarker of JMS namely naringenin-7-O-glucoside. The results showed that six major pathways are involved in the gastrointestinal system and the liver. This study demonstrated the capability of JMS prescription in the regulation of diuresis and identified a key biomarker that is responsible for its therapeutic effect.

Sesamin: A Promising Therapeutic Agent for Ameliorating Symptoms of Diabetes.

Diabetes is a chronic metabolic disease characterized by improperly regulating proteins, carbohydrates, and lipids due to insulin deficiency or resistance. The increasing prevalence of diabetes poses a tremendous socioeconomic burden worldwide, resulting in the rise of many studies on Chinese herbal medicines to discover the most effective cure for diabetes. Sesame seeds are among these Chinese herbal medicines that were found to contain various pharmacological activities, including antioxidant and anti-inflammatory properties, lowering cholesterol, improving liver function, blood pressure and sugar lowering, regulating lipid synthesis, and anticancer activities. These medicinal benefits are attributed to sesamin, which is the main lignan found in sesame seeds and oil. In this study, Wistar rat models were induced with type 2 diabetes using streptozotocin (STZ) and nicotinamide, and the effect of sesamin on the changes in body weight, blood sugar level, glycosylated hemoglobin (HbA1c), insulin levels, and the states of the pancreas and liver of the rats were evaluated. The results indicate a reduced blood glucose level, HbA1c, TG, and ALT and AST enzymes after sesamin treatment, while increased insulin level, SOD, CAT, and GPx activities were also observed. These findings prove sesamin's efficacy in ameliorating the symptoms of diabetes through its potent pharmacological activities.

Anti-COVID-19, Anti-Inflammatory, and Anti-Osteoarthritis Activities of Sesamin from Sesamum indicum L.

During the COVID-19 (coronavirus disease 2019) outbreak, many people were infected, and the symptoms may persist for several weeks or months for recovering patients. This is also known as "long COVID" and includes symptoms such as fatigue, joint pain, muscle pain, et cetera. The COVID-19 virus may trigger hyper-inflammation associated with cytokine levels in the body. COVID-19 can trigger inflammation in the joints, which can lead to osteoarthritis (OA), while long-term COVID-19 symptoms may lead to joint damage and other inflammation problems. According to several studies, sesame has potent anti-inflammatory properties due to its major constituent, sesamin. This study examined sesamin's anti-inflammatory, anti-osteoarthritis, and anti-COVID-19 effects. Moreover, in vivo and in vitro assays were used to determine sesamin's anti-inflammatory activity against the RAW264.7 and SW1353 cell lines. Sesamin had a dose-dependent effect (20 mg/kg) in a monoiodoacetic acid (MIA)-induced osteoarthritis rat model. Sesamin reduced paw swelling and joint discomfort. In addition, the findings indicated that sesamin suppressed the expression of iNOS (inducible nitric oxide synthase) and COX-2 (cyclooxygenase-2) in the RAW264.7 cell line within the concentration range of 6.25-50 µM. Furthermore, sesamin also had a suppressive effect on MMP (matrix metalloproteinase) expression in chondrocytes and the SW1353 cell line within the same concentration range of 6.25-50 µM. To examine the anti-viral activity, an in silico analysis was performed to evaluate sesamin's binding affinity with SARS-CoV-2 RdRp (severe acute respiratory syndrome coronavirus 2 RNA-dependent RNA polymerase) and human ACE2 (angiotensin-converting enzyme 2). Compared to the controls, sesamin exhibited strong binding affinities towards SARS-CoV-2 RdRp and human ACE2. Furthermore, sesamin had a higher binding affinity for the ACE2 target protein. This study suggests that sesamin shows potential anti-SARS-CoV-2 activity for drug development.

Risk of Thrombosis Following the First Dose of ChAdOx1 nCoV-19 Vaccine in Patients Undergoing Maintenance Hemodialysis: A Self-Controlled Case Series Study.

Background: The ChAdOx1 nCoV-19 vaccine is associated with vaccine-induced thrombosis and thrombocytopenia (VITT). Patients with end-stage renal disease (ESRD) under hemodialysis are at elevated risk of heparin-induced thrombocytopenia, which shares similar mechanisms with VITT. We aimed to examine the risk of VITT after the first dose of ChAdOx1 nCoV-19 vaccine using a self-controlled case series analysis (SCCS) in the hemodialyzed ESRD population. Methods: Drawing from the largest multi-center electronic medical records database in Taiwan, we identified adult patients, with or without hemodialysis, between 1st December, 2020, and 31st December, 2021, who received a first dose of ChAdOx1 nCoV-19 vaccine and had an outcome of thrombocytopenia, venous thrombosis, or arterial thrombosis. We calculated the incident rate ratios (IRRs) of outcomes in different periods at risk, compared to periods not at risk. Results:  We identified 59 hemodialysis patients and 41 non-dialysis patients with an outcome. The SCCS analyses showed, for the hemodialysis group, a significantly increased risk of outcomes during the period 31 to 60 days post-exposure to ChAdOx1 nCoV-19 vaccine (IRR: 2.823; 95% CI: 1.423-5.600). However, in non-dialysis patients there was no increase in risks during any of the post-exposure risk periods. Conclusion: For ESRD patients under hemodialysis, the first dose of ChAdOx1 nCoV-19 vaccine was associated with a 2.8-fold increase in risk of thrombosis.

Herpes zoster associated with stroke incidence in people living with human immunodeficiency virus: a nested case-control study.

BACKGROUND: The incidence of stroke is increasing among younger people with human immunodeficiency virus (HIV). The burden of stroke has shifted toward the young people living with HIV, particularly in low- and middle-income countries. People infected with herpes zoster (HZ) were more likely to suffer stroke than the general population. However, the association of HZ infection with the incidence of stroke among patients with HIV remains unclear. METHODS: A nested case-control study was conducted with patients with HIV registered in the Taiwan National Health Insurance Research Database in 2000-2017. A total of 509 stroke cases were 1:10 matched to 5090 non-stroke controls on age, sex, and date of first stroke diagnosis. Logistic regression models were used to estimate the odds ratio and 95% confidence intervals (CI) of stroke incidence. RESULTS: The odds ratio of stroke was significantly higher in the HIV-infected population with HZ (adjusted odds ratio [AOR]: 1.85, 95% CI: 1.42-2.41). A significantly increased AOR of stroke was associated with hypertension (AOR: 3.53, 95% CI: 2.86-4.34), heart disease (AOR: 2.32, 95% CI: 1.54-3.48), chronic kidney disease (AOR: 1.82, 95% CI: 1.16-2.85), hepatitis C virus infection (AOR: 1.49, 95% CI: 1.22-1.83), hyperlipidemia (OR: 1.41, 95% CI: 1.12-1.78), and treatment with protease inhibitors (AOR: 1.33, 95% CI: 1.05-1.69). CONCLUSIONS: Our findings suggest that HZ concurrent with HIV may increase the risk of stroke. The incidence rates of stroke were independent of common risk factors, suggesting strategies for early prevention of HZ infection among people living with HIV.

In Silico Analysis of Anti-Inflammatory and Antioxidant Properties of Bioactive Compounds from Crescentia cujete L.

Crescentia cujete is widely known as a medical plant with broad indigenous ethnomedicinal uses, including anti-inflammatory, and antioxidant. Despite being used for remedies and ethnomedicinal purposes, the benefits obtained from C. cujete still need to be fully utilized. The underwhelming studies on its pharmacological potential, bioactive compounds, and mechanism of action keep the pharmacological and new drug discovery progress of this plant slow. This study focuses on the incorporation of in silico analyses such as ADME prediction and molecular docking simulations on the bioactive compounds identified in the plant to assess their potential for antioxidant and anti-inflammatory applications. A comparison of the ADME properties and molecular docking scores showed that naringenin, pinocembrin, and eriodictyol had the most potential to act as inhibitors of the target proteins involved in inflammation and oxidation pathways against the positive controls.

High Neutrophil-to-Lymphocyte Ratio Predicts One-Year Risk of Pneumonia Post-Stroke Discharge.

INTRODUCTION: The neutrophil-to-lymphocyte ratio (NLR) may predict stroke-associated pneumonia, which is generally defined as pneumonia occurring in the first week after stroke. However, little is known whether the initial NLR is associated with pneumonia risk during the long-term follow-up in stroke survivors. We aimed to determine the relationship between admission NLR and the risk of post-stroke pneumonia within 1 year after discharge from acute stroke care. METHODS: Hospital databases were searched to identify adult patients hospitalized for acute stroke. Admission NLR was extracted using differential leukocyte counts. The outcome of interest was hospitalized pneumonia occurring within 1 year after discharge from hospitalization for stroke. Multivariable Cox proportional-hazards models were used to determine the independent effects of the NLR on the risk of pneumonia. RESULTS: In this study, 5,741 patients with acute stroke (mean age, 68 years; men, 62.1%) were analyzed. The median NLR was 2.72 (interquartile range, 1.78-4.49). Of the patients, 342 (6.0%) developed pneumonia within 1 year after discharge. In the multivariable models, the NLR was a significant predictor of pneumonia after discharge whether it was analyzed as a continuous or dichotomized variable. The corresponding adjusted hazard ratios were 1.037 (95% confidence interval [CI], 1.013-1.061) and 1.361 (95% CI, 1.087-1.704), respectively. CONCLUSION: The NLR could predict the risk of post-stroke pneumonia up to 1 year after discharge from acute stroke care. It may help identify high-risk stroke survivors, for whom appropriate interventions can be targeted.

Incidence, prescription patterns and risk factors of antipsychotic initiation in elderly stroke survivors.

OBJECTIVES: Epidemiological data regarding antipsychotic initiation in elderly patients with stroke are limited. We aimed to investigate the incidence, prescription patterns and determinants of antipsychotic initiation in elderly patients with stroke. METHODS: We conducted a retrospective cohort study to identify patients aged above 65 years who had been admitted for stroke from the National Health Insurance Database (NHID). The index date was defined as the discharge date. The incidence and prescription pattern of antipsychotics were estimated using the NHID. To evaluate the determinants of antipsychotic initiation, the cohort identified from the NHID was linked to the Multicenter Stroke Registry (MSR). Demographics, comorbidities and concomitant medications were obtained from the NHID. Information including smoking status, body mass index, stroke severity and disability was retrieved by linking to the MSR. The outcome was antipsychotic initiation after the index date. Hazard ratios for antipsychotic initiation were estimated using the multivariable Cox model. RESULTS: In terms of prognosis, the first 2 months after a stroke was the highest-risk period for antipsychotic use. A high burden of coexisting diseases carried an increased risk of antipsychotic use; in particular, chronic kidney disease (CKD) had the highest adjusted hazard ratio (aHR = 1.73; 95% CI 1.29-2.31) as compared with other risk factors. Furthermore, stroke severity and disability were significant risk factors for antipsychotic initiation. CONCLUSIONS: Our study indicated that elderly stroke patients with chronic medical conditions, particularly CKD, and a higher stroke severity and disability were at greater risk of psychiatric disorders during the first 2 months after a stroke. CLINICAL TRIAL REGISTRATION: NA.

Interactive deciphering electron-shuttling characteristics of Coffea arabica leaves and potential bioenergy-steered anti-SARS-CoV-2 RdRp inhibitor via microbial fuel cells.

Due to the pandemics of COVID-19, herbal medicine has recently been explored for possible antiviral treatment and prevention via novel platform of microbial fuel cells. It was revealed that Coffea arabica leaves was very appropriate for anti-COVID-19 drug development. Antioxidant and anti-inflammatory tests exhibited the most promising activities for C. arabica ethanol extracts and drying approaches were implemented on the leaf samples prior to ethanol extraction. Ethanol extracts of C. arabica leaves were applied to bioenergy evaluation via DC-MFCs, clearly revealing that air-dried leaves (CA-A-EtOH) exhibited the highest bioenergy-stimulating capabilities (ca. 2.72 fold of power amplification to the blank). Furthermore, molecular docking analysis was implemented to decipher the potential of C. arabica leaves metabolites. Chlorogenic acid (-6.5 kcal/mol) owned the highest binding affinity with RdRp of SARS-CoV-2, showing a much lower average RMSF value than an apoprotein. This study suggested C. arabica leaves as an encouraging medicinal herb against SARS-CoV-2.

In vitro and in vivo anti-osteoarthritis effects of tradition Chinese prescription Ji-Ming-San.

ETHNOPHARMACOLOGICAL RELEVANCE: Ji-Ming-Shan (JMS) is a traditional herbal prescription consisting of seven herbs including Areca cathechu Burm.f., Citrus reticulata Blanco, Chaenomeles speciosa (Sweet) Nakai, Euodia ruticarpa (A. Juss.) Benth., Perilla frutescens (L.) Britton, Zingiber officinale Roscoe, Platycodon grandiflorus (Jacq.). It was first recorded during the Song dynasty and has been used extensively for protection against rheumatism, treatment of swelling of tendons, relief from foot pain, gout and diuresis and other forms of inflammation. AIM OF THE STUDY: The aim of this study is to evaluate the anti-inflammatory and anti-osteoarthritis activity of JMS extracts with the use of different cell lines (RAW 264.7 cells, SW1353 cells and primary cultured rat chondrocytes). MIA-induced rat animal models were used to assess the anti-osteoarthritis activity of the extract. MATERIALS AND METHODS: This study investigated the anti-inflammatory activity of JMS-95E on LPS-induced RAW 264.7 macrophages and IL-1ß-stimulated chondrocytes. For the in vivo study, male Wistar rats were used and they were randomly assigned in different groups: blank, control, positive control and three different JMS-95E treatment groups (200, 400, 800 mg/kg/d). Paw edema, hind-limb weight bearing, serum inflammatory cytokines including hematoxylin and eosin (HE) staining experiments were used to assess the efficacy of the extract in the rat model. RESULT: JMS 95% ethanol extract (JMS-95E, marker substance: narirutin (5.10 mg/g) and hesperidin (11.33 mg/g) has been identified in the extract using high pressure liquid chromatography. For in vitro assays, JMS-95E did not exhibit cytotoxicity and was able to downregulate the protein expression of iNOS, COX-2 and MMP-13. The production of inflammatory mediators such as NO and PGE2 were also reduced with an increase in dose-dependent manner in various cell lines. Inhibitory activity on the key enzyme xanthine oxidase was also observed in this study. In rat animal models, JMS-95E reduced the inflammatory responses such as acute swelling, chondrocyte degradation and pain section of paw edema in rat model. Molecular marker studies of inflammation demonstrated that JMS-95E significantly decrease PGE2 expression in MIA model. CONCLUSION: JMS-95E inhibited the inflammatory pathway leading to the production or expression levels of NO, iNOS, COX-2 and PGE2 in macrophage cells. In primary cultured rat chondrocytes iNOS and SW1353 MMP-13 expression were downregulated after JMS-95E treatment. For the in vivo study JMS-95E significantly reduced the paw volume of carrageenan-induced rat paw edema through each dose and significantly inhibited paw volume, counterweight the distribution of hind-paw weight bearing through the MIA model which means JMS-95E could promote recovery of the acute swelling and chondrocyte degradation of the ankle joints. The above results provided the multiple mechanism of JMS-95E in OA treatment of the scientific founding which supported the description of JMS in traditional use.

Utilization of screening and treatment for osteoporosis among stroke survivors.

Background: Stroke survivors are prone to osteoporosis and fractures. However, bone mineral density (BMD) testing and osteoporosis treatment were underutilized in patients with recent stroke. We aimed to examine whether stroke has an impact on the utilization of BMD testing and osteoporosis treatment as well as the determinants of their utilization in stroke patients using nationwide population-based data in Taiwan. Methods: We identified patients aged 55 years and older who were hospitalized for hemorrhagic or ischemic stroke as the stroke cohort, and age- and sex-matched patients hospitalized for reasons other than stroke, fracture, or fall as the non-stroke cohort. We used the Fine-Gray sub-distribution hazard competing risk regression model to determine the predictors for BMD testing and osteoporosis treatment. Results: A total of 32997 stroke patients and 32997 age- and sex-matched controls comprised the stroke and non-stroke cohorts, respectively. BMD testing and osteoporosis treatment were performed in 1.0% and 5.2% of the stroke patients, respectively, within one year after hospitalization while these measures were performed in 0.8% and 4.7% of the controls. Stroke patients were more likely to receive BMD testing (adjusted hazard ratio [HR] 1.33; 95% confidence interval [CI] 1.11-1.58) and osteoporosis treatment (adjusted HR 1.19; 95% CI 1.11-1.29). Female sex, osteoporosis, prior BMD testing, and low-trauma fractures after stroke increased the likelihood of using BMD testing and osteoporosis treatment whereas greater stroke severity reduced the likelihood of receiving both measures. Conclusions: Both BMD testing and osteoporosis treatment were underutilized among stroke survivors even though they had a higher chance of receiving both measures than non-stroke patients.

Application of machine learning and natural language processing for predicting stroke-associated pneumonia.

Background: Identifying patients at high risk of stroke-associated pneumonia (SAP) may permit targeting potential interventions to reduce its incidence. We aimed to explore the functionality of machine learning (ML) and natural language processing techniques on structured data and unstructured clinical text to predict SAP by comparing it to conventional risk scores. Methods: Linked data between a hospital stroke registry and a deidentified research-based database including electronic health records and administrative claims data was used. Natural language processing was applied to extract textual features from clinical notes. The random forest algorithm was used to build ML models. The predictive performance of ML models was compared with the A2DS2, ISAN, PNA, and ACDD4 scores using the area under the receiver operating characteristic curve (AUC). Results: Among 5,913 acute stroke patients hospitalized between Oct 2010 and Sep 2021, 450 (7.6%) developed SAP within the first 7 days after stroke onset. The ML model based on both textual features and structured variables had the highest AUC [0.840, 95% confidence interval (CI) 0.806-0.875], significantly higher than those of the ML model based on structured variables alone (0.828, 95% CI 0.793-0.863, P = 0.040), ACDD4 (0.807, 95% CI 0.766-0.849, P = 0.041), A2DS2 (0.803, 95% CI 0.762-0.845, P = 0.013), ISAN (0.795, 95% CI 0.752-0.837, P = 0.009), and PNA (0.778, 95% CI 0.735-0.822, P < 0.001). All models demonstrated adequate calibration except for the A2DS2 score. Conclusions: The ML model based on both textural features and structured variables performed better than conventional risk scores in predicting SAP. The workflow used to generate ML prediction models can be disseminated for local adaptation by individual healthcare organizations.

Oral anticoagulant decreases stroke recurrence in patients with atrial fibrillation detected after stroke.

Background: Atrial fibrillation detected after stroke (AFDAS) has a lower risk of ischemic stroke recurrence than known atrial fibrillation (KAF). While the benefit of oral anticoagulants (OAC) for preventing ischemic stroke recurrence in KAF is well established, their role in patients with AFDAS is more controversial. This study aimed to evaluate the association between OAC use and the risk of recurrent ischemic stroke in patients with AFDAS in a real-world setting. Methods: This nationwide retrospective cohort study was conducted using the Taiwan National Health Insurance Research Database. Patients hospitalized with a first-ever ischemic stroke and AFDAS confirmed within 30 days after hospitalization were assigned to OAC and non-OAC cohorts. Inverse probability of treatment weighting was applied to balance the baseline characteristics of the cohorts. The primary outcome was ischemic stroke recurrence. Secondary outcomes were intracranial hemorrhage (ICH), death, and the composite outcome of "ischemic stroke recurrence, ICH, or death." Multivariate Cox proportional hazard models were used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI). Results: A total of 4,508 hospitalized patients with stroke and AFDAS were identified. Based on OAC use, 2,856 and 1,652 patients were assigned to the OAC and non-OAC groups, respectively. During the follow-up period (median duration, 2.76 years), the OAC cohort exhibited a lower risk of ischemic stroke recurrence (aHR, 0.84; 95% CI, 0.70-0.99), death (aHR, 0.65; 95% CI, 0.58-0.73), and composite outcome (aHR, 0.70; 95% CI, 0.63-0.78) than did the non-OAC cohort. The risk of ICH (aHR, 0.96; 95% CI, 0.62-1.50) was not significantly different between the two cohorts. Conclusion: OAC use in patients with AFDAS was associated with reduced risk of ischemic stroke recurrence, without an increased risk of ICH. This supports current guidelines recommending OACs for secondary stroke prevention in patients with AF, regardless of the time of diagnosis.

Association between implantable loop recorder use and secondary stroke prevention: a meta-analysis.

OBJECTIVE: To conduct a meta-analysis of randomised controlled trials (RCTs) to evaluate the impact of ILR use on occurrence of recurrent stroke. METHODS: PubMed, EMBASE, CENTRAL and ClinicalTrials.gov were searched from 1966 to November 2021 to identify RCTs comparing ILR versus non-ILR in patients with ischaemic stroke. Relative risk (RR) with 95% CI was used as a measure of the effect of ILR versus non-ILR on recurrent stroke, recurrent ischaemic stroke, AF detection and oral anticoagulant (OAC) initiation. A fixed-effect estimate based on the Mantel-Haenszel method was computed. RESULTS: We identified three RCTs with 1233 patients with ischaemic stroke. Among three included RCTs, 54 recurrent stroke events were reported in two RCTs and 84 recurrent ischaemic stroke events were reported in three RCTs. Pooled results showed that patients who received ILR versus no ILR was not associated with a significantly reduced risk of recurrent stroke (5.6% vs 8.0%; RR 0.70; 95% CI 0.42 to 1.19) or recurrent ischaemic stroke (5.7% vs 7.9%; RR 0.72; 95% CI 0.48 to 1.10). Compared to non-ILR patients, ILR patients had higher rates of AF detection (12.9% vs 2.4%; RR 5.31; 95% CI, 3.10 to 9.11) and OAC initiation (15.2% vs 5.5%; RR 2.77; 95% CI 1.90 to 4.03). CONCLUSIONS: Patients assigned to ILR vs non-ILR did not have a significantly reduced risk of recurrent stroke or recurrent ischaemic stroke despite higher rates of AF detection and OAC initiation. Sufficiently powered RCTs of ILR to assess the risk of recurrent stroke are warranted.

Validation of Risk Scores for Predicting Atrial Fibrillation Detected After Stroke Based on an Electronic Medical Record Algorithm: A Registry-Claims-Electronic Medical Record Linked Data Study.

Background: Poststroke atrial fibrillation (AF) screening aids decisions regarding the optimal secondary prevention strategies in patients with acute ischemic stroke (AIS). We used an electronic medical record (EMR) algorithm to identify AF in a cohort of AIS patients, which were used to validate eight risk scores for predicting AF detected after stroke (AFDAS). Methods: We used linked data between a hospital stroke registry and a deidentified database including EMRs and administrative claims data. EMR algorithms were constructed to identify AF using diagnostic and medication codes as well as free clinical text. Based on the optimal EMR algorithm, the incidence rate of AFDAS was estimated. The predictive performance of 8 risk scores including AS5F, C2HEST, CHADS2, CHA2DS2-VASc, CHASE-LESS, HATCH, HAVOC, and Re-CHARGE-AF scores, were compared using the C-index, net reclassification improvement, integrated discrimination improvement, calibration curve, and decision curve analysis. Results: The algorithm that defines AF as any positive mention of AF-related keywords in electrocardiography or echocardiography reports, or presence of diagnostic codes of AF was used to identify AF. Among the 5,412 AIS patients without known AF at stroke admission, the incidence rate of AFDAS was 84.5 per 1,000 person-year. The CHASE-LESS and AS5F scores were well calibrated and showed comparable C-indices (0.741 versus 0.730, p = 0.223), which were significantly higher than the other risk scores. Conclusion: The CHASE-LESS and AS5F scores demonstrated adequate discrimination and calibration for predicting AFDAS. Both simple risk scores may help select patients for intensive AF monitoring.

Synergistic deciphering of bioenergy production and electron transport characteristics to screen traditional Chinese medicine (TCM) for COVID-19 drug development.

Background: Traditional Chinese medicine (TCM) has been used as an "immune booster" for disease prevention and clinical treatment since ancient China. However, many studies were focused on the organic herbal extract rather than aqueous herbal extract (AHE; decoction). Due to the COVID-19 pandemics, this study tended to decipher phytochemical contents in the decoction of herbs and derived bioactivities (e.g., anti-oxidant and anti-inflammatory properties). As prior works revealed, the efficacy of Parkinson's medicines and antiviral flavonoid herbs was strongly governed by their bioenergy-stimulating proficiency. Methods: Herbal extracts were prepared by using a traditional Chinese decoction pot. After filtration and evaporation, crude extracts were used to prepare sample solutions for various bioassays. The phytochemical content and bioactivities of AHEs were determined via ELISA microplate reader. Microbial fuel cells (MFCs) were used as a novel platform to evaluate bioenergy contents with electron-transfer characteristics for antiviral drug development. Significant findings: Regarding 18 TCM herbal extracts for the prevention of SARS and H1N1 influenza, comparison on total polyphenol, flavonoid, condensed tannins and polysaccharides were conducted. Moreover, considerable total flavonoid contents were detected for 11 herb extracts. These AEHs were not only rich in phytonutrient contents but also plentiful in anti-oxidant and anti-inflammatory activities. Herbs with high polyphenol content had higher antioxidant activity. Forsythia suspensa extract expressed the highest inhibition against nitric oxide production for anti-inflammation. MFC bioenergy-stimulating studies also revealed that top ranking COVID-19 efficacious herbs were both bioenergy driven and electron mediated. That is, electron transfer-controlled bioenergy extraction was significant to antiviral characteristics for anti-COVID-19 drug development.

Effectiveness of Standard-Dose vs. Low-Dose Alteplase for Acute Ischemic Stroke Within 3-4.5 h.

BACKGROUND: The efficacy and safety of intravenous alteplase administered 3-4.5 h after acute ischemic stroke have been demonstrated. However, whether responses differ between low-dose and standard-dose alteplase during this time window and whether certain subgroups benefit more remain unknown. PATIENTS AND METHODS: The current analysis was based on a multicenter matched-cohort study conducted in Taiwan. The treatment group comprised 378 patients receiving intravenous alteplase 3-4.5 h after stroke onset, and the control group comprised 378 age- and sex-matched patients who did not receive alteplase treatment during the same period. Standard- and low-dose alteplase was administered to patients at the physician's discretion. RESULTS: Overall, patients receiving alteplase exhibited more favorable outcomes than did controls [34.0 vs. 22.7%; odds ratio (OR): 1.75, 95% confidence interval (CI): 1.27-1.42], and the effectiveness was consistent in all subgroups. Although patients in the standard-dose group (n = 182) were younger than those in the low-dose (n = 192) group, the proportions of patients with favorable outcomes (36.3 vs. 31.8%; OR: 1.22, 95% CI: 0.80-1.88) and symptomatic hemorrhage (2.8 vs 4.2%; OR: 0.65, 95% CI: 0.21-2.02) were consistently comparable in a covariate-adjusted model and an age-matched cohort. In the subgroup analysis, patients with cardioembolism, atrial fibrillation, and hypercholesterolemia were more likely to achieve favorable outcomes after receiving standard-dose than low-dose alteplase. CONCLUSION: In the 3-4.5 h time window, the effectiveness and safety of standard-dose and low-dose alteplase may be comparable. A standard dose may be selected for patients with cardioembolism, atrial fibrillation, or hypercholesterolemia.

Risk of Incident Epilepsy After a Middle Cerebral Artery Territory Infarction.

Background: Among poststroke morbidities, poststroke epilepsy (PSE) has been identified as a significant clinical issue. Although middle cerebral artery (MCA) infarct is the most common type of stroke among all vascular territories, very few studies specifically focused on the risk factors leading to PSE in patients with MCA infarct. Methods: A population study in Taiwan has been conducted, linking the National Health Insurance Research Database and Hospital Stroke Registry, from 2001 to 2015 and 2006 to 2010, respectively. Patients were divided into MCA and non-MCA groups, and the diagnosis of incident epilepsy between the groups has been compared. The multivariable Cox proportional hazard model was used to identify the risk factors for developing PSE. The distribution of time to PSE was estimated using the Kaplan-Meier method. Results: In total, 1,838 patients were recruited, with 774 and 1,064 in the MCA and non-MCA groups, respectively. PSE incidence in the MCA group was 15.5% vs. 6.2% in the non-MCA group, with a hazard ratio of (95% CI) 2.06 (1.33-3.19). Factors significantly associated with PSE included atrial fibrillation, depression, National Institutes of Health Stroke Scale (NIHSS) scores of ≥ 16, and alert on arrival. For patients with MCA infarct, higher NIHSS and Glasgow coma scale scores, the presence of visual field defects and weakness, urination control impairment, and complications during hospitalization were associated with a higher risk for PSE development. Conclusions: This study established the conditions leading to a higher risk of PSE and identified the important clinical risk factors in patients experiencing MCA infarct. Efforts to manage these risk factors may be important in preventing PSE in patients with MCA infarct.