Clinical narratives as a predictor for prognosticating functional outcomes after intracerebral hemorrhage.

BACKGROUND: Intracerebral hemorrhage (ICH) is a devastating stroke type that causes high mortality rates and severe disability among survivors. Many prognostic models are available for prognosticating patients with ICH. This study aimed to investigate whether clinical narratives can improve the performance for predicting functional outcomes after ICH. METHODS: This study used data from the hospital stroke registry and electronic health records. The study population (n = 1363) was randomly divided into a training set (75%, n = 1023) and a holdout test set (25%, n = 340). Five risk scores for ICH were used as baseline prognostic models. Using natural language processing (NLP), text-based markers were generated from the clinical narratives of the training set through machine learning (ML) and deep learning (DL) approaches. The primary outcome was a poor functional outcome (modified Rankin Scale score of 3 to 6) at hospital discharge. The predictive performance was compared between the baseline models and models enhanced by incorporating the text-based markers using the holdout test set. RESULTS: The enhanced prognostic models outperformed the baseline models, regardless of whether ML or DL approaches were used. The areas under the receiver operating characteristic curve (AUCs) of the baseline models were between 0.760 and 0.892. Adding the text-based marker to the baseline models significantly increased the model discrimination, with AUCs ranging from 0.861 to 0.914. The net reclassification improvement and integrated discrimination improvement indices also showed significant improvements. CONCLUSIONS: Using NLP to extract textual information from clinical narratives could improve the predictive performance of all baseline prognostic models for ICH.

A dorsal CA2 to ventral CA1 circuit contributes to oxytocinergic modulation of long-term social recognition memory.

BACKGROUND: Social recognition memory (SRM) is the ability to distinguish familiar from novel conspecifics and is crucial for survival and reproductive success across social species. We previously reported that oxytocin (OXT) receptor (OXTR) signaling in the CA2/CA3a of dorsal hippocampus is essential to promote the persistence of long-term SRM, yet how the endogenous OXT system influences CA2 outputs to regulate long-term SRM formation remains unclear. METHODS: To achieve a selective deletion of CA2 OXTRs, we crossed Amigo2-Cre mice with Oxtr-floxed mice to generate CA2-specific Oxtr conditional knockout (Oxtr-/-) mice. A three-chamber paradigm test was used for studying SRM in mice. Chemogenetic and optogenetic targeting strategies were employed to manipulate neuronal activity. RESULTS: We show that selective ablation of Oxtr in the CA2 suffices to impair the persistence of long-term SRM but has no effect on sociability and social novelty preference in the three-chamber paradigm test. We find that cell-type specific activation of OXT neurons within the hypothalamic paraventricular nucleus enhances long-term SRM and this enhancement is blocked by local application of OXTR antagonist L-368,899 into dorsal hippocampal CA2 (dCA2) region. In addition, chemogenetic neuronal silencing in dCA2 demonstrated that neuronal activity is essential for forming long-term SRM. Moreover, chemogenetic terminal-specific inactivation reveals a crucial role for dCA2 outputs to ventral CA1 (vCA1), but not dorsal lateral septum, in long-term SRM. Finally, targeted activation of the dCA2-to-vCA1 circuit effectively ameliorates long-term SRM deficit observed in Oxtr-/- mice. CONCLUSIONS: These findings highlight the importance of hippocampal CA2 OXTR signaling in governing the persistence of long-term SRM and identify a hippocampal circuit linking dCA2 to vCA1 necessary for controlling long-term SRM formation.

Developing a stroke alert trigger for clinical decision support at emergency triage using machine learning.

BACKGROUND: Acute stroke is an urgent medical condition that requires immediate assessment and treatment. Prompt identification of patients with suspected stroke at emergency department (ED) triage followed by timely activation of code stroke systems is the key to successful management of stroke. While false negative detection of stroke may prevent patients from receiving optimal treatment, excessive false positive alarms will substantially burden stroke neurologists. This study aimed to develop a stroke-alert trigger to identify patients with suspected stroke at ED triage. METHODS: Patients who arrived at the ED within 12 h of symptom onset and were suspected of a stroke or transient ischemic attack or triaged with a stroke-related symptom were included. Clinical features at ED triage were collected, including the presenting complaint, triage level, self-reported medical history (hypertension, diabetes, hyperlipidemia, heart disease, and prior stroke), vital signs, and presence of atrial fibrillation. Three rule-based algorithms, ie, Face Arm Speech Test (FAST) and two flavors of Balance, Eyes, FAST (BE-FAST), and six machine learning (ML) techniques with various resampling methods were used to build classifiers for identification of patients with suspected stroke. Logistic regression (LR) was used to find important features. RESULTS: The study population consisted of 1361 patients. The values of area under the precision-recall curve (AUPRC) were 0.737, 0.710, and 0.562 for the FAST, BE-FAST-1, and BE-FAST-2 models, respectively. The values of AUPRC for the top three ML models were 0.787 for classification and regression tree with undersampling, 0.783 for LR with synthetic minority oversampling technique (SMOTE), and 0.782 for LR with class weighting. Among the ML models, logistic regression and random forest models in general achieved higher values of AUPRC, in particular in those with class weighting or SMOTE to handle class imbalance problem. In addition to the presenting complaint and triage level, age, diastolic blood pressure, body temperature, and pulse rate, were also important features for developing a stroke-alert trigger. CONCLUSIONS: ML techniques significantly improved the performance of prediction models for identification of patients with suspected stroke. Such ML models can be embedded in the electronic triage system for clinical decision support at ED triage.

Lipopolysaccharide-Induced Nitric Oxide and Prostaglandin E2 Production Is Inhibited by Tellimagrandin II in Mouse and Human Macrophages.

Sepsis develops from a serious microbial infection that causes the immune system to go into overdrive. The major microorganisms that induce sepsis are Gram-negative bacteria with lipopolysaccharide (LPS) in their cell walls. Nitric oxide (NO) and cyclooxygenase-2 (COX-2) are the key factors involved in the LPS-induced pro-inflammatory process. This study aimed to evaluate the effects of polyphenol Tellimagrandin II (TGII) on anti-inflammatory activity and its underlying basic mechanism in murine macrophage cell line RAW 264.7 and human monocyte-derived macrophages. Macrophages with more than 90% cell viability were found in the cytotoxicity assay under 50 µM TGII. Pre- or post-treatment with TGII significantly reduced LPS-induced inducible nitric oxide synthase (NOS2) protein and mRNA expression, reducing LPS-induced COX-2 protein. Downstream of NOS2 and COX-2, NO and prostaglandin E2 (PGE2) were significantly inhibited by TGII. Upstream of NOS2 and COX-2, phospho-p65, c-fos and phospho-c-jun were also reduced after pre-treatment with TGII. Mitogen-activated protein kinases (MAPKs) are also critical to nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) stimulation, and phospho-p38 expression was found to have been blocked by TGII. TGII efficiently reduces LPS-induced NO production and its upstream regulatory factors, suggesting that TGII may be a potential therapeutic agent for sepsis and other inflammatory diseases.

Mono-(2-ethylhexyl) phthalate Promotes Dengue Virus Infection by Decreasing IL-23-Mediated Antiviral Responses.

Exposure to environmental hormones such as di(2-ethylhexyl) phthalate (DEHP) has become a critical human health issue globally. This study aimed to investigate the correlations between DEHP/mono-(2-ethylhexyl) phthalate (MEHP) levels and macrophage-associated immune responses and clinical manifestations in dengue virus (DV)-infected patients. Among 89 DV-infected patients, those with DV infection-related gastrointestinal (GI) bleeding (n = 13, 15% of patients) had significantly higher DEHP exposure than those without GI bleeding (n = 76, 85% of patients), which were 114.2 ng/ml versus 52.5 ng/ml ΣDEHP in urine; p = 0.023). In an in vitro study using cultured human monocyte-derived macrophages (MDMs) to investigate the effects of MEHP, treatment increased IL-1ß and TNF-α release but decreased IL-23 release, with negative correlations observed between urine ΣDEHP and serum IL-23 levels in patients. MEHP-treated MDMs had lower antiviral Th17 response induction activity in mixed T-cell response tests. The in vitro data showed that MEHP increased DV viral load and decreased IL-23 release dose-dependently, and adding IL-23 to MEHP-exposed MDMs significantly reduced the DV viral load. MEHP also suppressed IL-23 expression via the peroxisome proliferator-activated receptor-gamma (PPAR-γ) pathway. Further, the PPAR-γ antagonist GW9662 significantly reversed MEHP-induced IL-23 suppression and reduced the DV viral load. These study findings help to explain the associations between high MEHP levels and the high global burden of dengue disease.

Google Trends-based non-English language query data and epidemic diseases: a cross-sectional study of the popular search behaviour in Taiwan.

OBJECTIVE: This study developed a surveillance system suitable for monitoring epidemic outbreaks and assessing public opinion in non-English-speaking countries. We evaluated whether social media reflects social uneasiness and fear during epidemic outbreaks and natural catastrophes. DESIGN: Cross-sectional study. SETTING: Freely available epidemic data in Taiwan. MAIN OUTCOME MEASURE: We used weekly epidemic incidence data obtained from the Taiwan Centers for Disease Control and online search query data obtained from Google Trends between 4 October 2015 and 2 April 2016. To validate whether non-English query keywords were useful surveillance tools, we estimated the correlation between online query data and epidemic incidence in Taiwan. RESULTS: With our approach, we noted that keywords ('common cold'), ('fever') and ('cough') exhibited good to excellent correlation between Google Trends query data and influenza incidence (r=0.898, p<0.001; r=0.773, p<0.001; r=0.796, p<0.001, respectively). They also displayed high correlation with influenza-like illness emergencies (r=0.900, p<0.001; r=0.802, p<0.001; r=0.886, p<0.001, respectively) and outpatient visits (r=0.889, p<0.001; r=0.791, p<0.001; r=0.870, p<0.001, respectively). We noted that the query ('enterovirus') exhibited excellent correlation with the number of enterovirus-infected patients in emergency departments (r=0.914, p<0.001). CONCLUSIONS: These results suggested that Google Trends can be a good surveillance tool for epidemic outbreaks, even in Taiwan, the non-English-speaking country. Online search activity indicates that people are concerned about epidemic diseases, even if they do not visit hospitals. This prompted us to develop useful tools to monitor social media during an epidemic because such media usage reflects infectious disease trends more quickly than does traditional reporting.

The Impact of Loading Dose on Outcome in Stroke Patients Receiving Low-Dose Tissue Plasminogen Activator Thrombolytic Therapy.

BACKGROUND: Intravenous tissue plasminogen activator (tPA) (0.9 mg/kg, maximum 90 mg) with a bolus of 10% of the total dose given within 1-2 mins is the standard therapy for patients receiving thrombolytic therapy. Low-dose (0.6 mg/kg) tPA is also approved for thrombolytic therapy for ischemic stroke patients. Low-dose tPA is associated with a low bolus dose. It is unknown whether increasing the bolus dose in patients receiving low-dose tPA thrombolysis may improve outcomes or increase the risk of hemorrhagic transformation (HT). AIM: This study investigated the impact of the bolus dose on the outcome in ischemic stroke patients receiving low-dose tPA thrombolytic therapy. METHODS: In this retrospective, observational study, we enrolled 214 ischemic stroke patients receiving low-dose tPA thrombolytic therapy. Of these 214 patients, 107 patients received 10% of the total dose as a bolus dose, and 107 patients received 15% of the total dose as a bolus dose. The National Institutes of Health Stroke Score (NIHSS) were evaluated before tPA infusion, 24 h after thrombolytic therapy, and at discharge. Stroke severity was categorized as mild (0-5), moderate (6-14), severe (15-24), or very severe (≥25). Neurological improvement (NI) was defined as an improvement of 6 or more points in the NIHSS, and no response (NR) was defined as an increase in the NIHSS of ≤4 points or a decrease ≤6 points. Neurological deterioration (ND) was defined as an increase in the NIHSS >4 points. A good outcome was defined as a modified Ranking Score (mRS) of 0 or 1. We compared the NI, NR, and ND rates at 24 hrs after thrombolytic therapy and discharge between the 15% and 10% bolus dose groups. RESULTS: In patients with mild and moderate stroke, there was no significant difference in the NI, NR, ND, and HT rates and 6-month outcomes between the 15% and 10% bolus groups. In patients with severe and very severe stroke, outcomes at 6 months were significantly better in the 15% bolus group than in the 10% bolus group. The factors affecting the outcomes of severe and very severe stroke patients are hypertension and bolus dose. CONCLUSION: In severe and very severe stroke patients receiving low-dose tPA thrombolytic therapy, a bolus dose of 15% of the total dose can improve outcomes.

Insulin Reduces Inflammation by Regulating the Activation of the NLRP3 Inflammasome.

The NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome is the platform for IL-1ß maturation, aimed at mediating a rapid immune response against danger signals which must be tightly regulated. Insulin is well known as the critical hormone in the maintenance of glucose in physiologic response. Previous studies have proved insulin has the anti-inflammatory effect but the molecular mechanism of immunomodulation provided by insulin is not clear so far. Here we investigated whether insulin reduces inflammation by regulating the NLRP3 inflammasome. In the present study, we used LPS and ATP to induce the intracellular formation of the NLRP3 inflammasome. Insulin inhibited the secretion of IL-1ß by preventing the assembly of the ASC in THP-1 cells and human CD14+ monocyte-derived macrophages. The phosphorylation status of Syk, p38 mitogen-activated protein kinase (MAPK) and ASC were altered by insulin. These effects were attenuated in THP-1 cells transfected with small interfering RNA targeting insulin receptors. In vivo, administration of glucose-insulin-potassium reduced serum IL-1ß level, intestinal ASC speck formation, local macrophage infiltration and alleviated intestinal injury in mice exposed to LPS. Insulin may play an immunomodulatory role in anti-inflammation by regulating the NLRP3 inflammasome.

Tellimagrandin II, A Type of Plant Polyphenol Extracted from Trapa bispinosa Inhibits Antibiotic Resistance of Drug-Resistant Staphylococcus aureus.

The emergence of methicillin-resistant Staphylococcus aureus (MRSA) has become a critical global concern. Identifying new candidates of anti-S. aureus agents is urgently required because the therapeutic strategies for infected patients are limited currently. Therefore, the present study investigated whether Tellimagrandin II (TGII), a pure compound extracted from the shells of Trapa bispinosa, exhibits antibacterial effects against MRSA. We first showed that TGII exerted potent inhibitory activity against MRSA with a minimum inhibitory concentration of 128 µg/mL. The obtained fractional inhibitory concentration suggested that TGII could alone exert antistaphylococcal activity, and TGII combined with low doses of antibiotics displayed synergistic effects against MRSA. Moreover, we found that TGII exerted bactericidal activity by reducing the expression of mecA followed by the negative regulation of the penicillin-binding protein 2a (PBP2a) of MRSA. Transmission electron microscopy (TEM) images further confirmed that TGII destroyed the integrity of the cell wall of MRSA and caused the loss of cytoplasm content. In conclusion, we evidenced the antibacterial effects of TGII against MRSA, which enables the effective dose of current antibiotics to be reduced and the predicament of drug-resistant S. aureus isolates to be overcome.

Progression of Mild to Moderate Stenosis in the Internal Carotid Arteries of Patients With Ischemic Stroke.

Background and purpose: Severe stenosis in the internal carotid artery may increase the risk of ischemic stroke. The factors that affect the progression of carotid artery stenosis in patients with ischemic stroke are poorly studied. No guidelines for the duration of follow-up of patients with ischemic stroke through carotid ultrasonography exist. Methods: In this retrospective study, 179 patients (108 men; mean age, 68 years) with ischemic stroke and mild to moderate stenosis in the internal carotid artery (ICA) were recruited. Carotid artery ultrasonography was performed over the period of January 2013 to June 2016 with a median follow-up of 36 months (mean 36.5 ± 3.5 months). The severity of carotid artery stenosis was estimated with the following equation: 1- (narrowest ICA diameter/total lumen diameter at the narrowest site). The severity of stenosis was categorized into grades I (0-29%), II (30-49%), III (50-59%), and IV (60-69%). The patient's stenosis grade was defined on the basis of the stenosis rate of the ICA side with most severe stenosis. Results: Stenosis progressed in 17.9% (64/358) of the vessels in 30.7% (55/179) of patients. The risk of stenosis progression increased as the severity of ICA stenosis increased. Patients with stenosis rates of above 50% are at a higher risk of stenosis progression than those with stenosis rate of < 50%. Relative to the patient group with an ICA stenosis rate of 0-29%, the adjusted odds ratios of stenosis progression were 2.33 (p = 0.03; 95% CI: 1.05~5.17), 3.50 (p = 0.09; 95% CI: 0.81~15.84), and 6.61 (p = 0.03; 95% CI: 1.01~39.61) in patient groups with ICA stenosis rates of 30-49%, 50-59%, and 60-69%, respectively. Hyper-LDL-cholesterolemia (Hyper-LDL-c) also increased the risk of stenosis progression, with an adjusted odds ratio of 2.22 (p = 0.03; 95% CI: 1.05~4.71). Conclusion: The rate of ICA stenosis progression increases with stenosis grade. Patients with ICA stenosis severity >50% and Hyper-LDL-c have high rates of stenosis progression. For the patients with stroke and ICA stenosis severity >50%, annual follow up through carotid artery ultrasonography may be necessary.

Applying natural language processing techniques to develop a task-specific EMR interface for timely stroke thrombolysis: A feasibility study.

OBJECTIVE: To reduce errors in determining eligibility for intravenous thrombolytic therapy (IVT) in stroke patients through use of an enhanced task-specific electronic medical record (EMR) interface powered by natural language processing (NLP) techniques. MATERIALS AND METHODS: The information processing algorithm utilized MetaMap to extract medical concepts from IVT eligibility criteria and expanded the concepts using the Unified Medical Language System Metathesaurus. Concepts identified from clinical notes by MetaMap were compared to those from IVT eligibility criteria. The task-specific EMR interface displays IVT-relevant information by highlighting phrases that contain matched concepts. Clinical usability was assessed with clinicians staffing the acute stroke team by comparing user performance while using the task-specific and the current EMR interfaces. RESULTS: The algorithm identified IVT-relevant concepts with micro-averaged precisions, recalls, and F1 measures of 0.998, 0.812, and 0.895 at the phrase level and of 1, 0.972, and 0.986 at the document level. Users using the task-specific interface achieved a higher accuracy score than those using the current interface (91% versus 80%, p = 0.016) in assessing the IVT eligibility criteria. The completion time between the interfaces was statistically similar (2.46 min versus 1.70 min, p = 0.754). DISCUSSION: Although the information processing algorithm had room for improvement, the task-specific EMR interface significantly reduced errors in assessing IVT eligibility criteria. CONCLUSION: The study findings provide evidence to support an NLP enhanced EMR system to facilitate IVT decision-making by presenting meaningful and timely information to clinicians, thereby offering a new avenue for improvements in acute stroke care.

Lucidone suppresses dengue viral replication through the induction of heme oxygenase-1.

Dengue virus (DENV) infection causes life-threatening diseases such as dengue hemorrhagic fever and dengue shock syndrome. Currently, there is no effective therapeutic agent or vaccine against DENV infection; hence, there is an urgent need to discover anti-DENV agents. The potential therapeutic efficacy of lucidone was first evaluated in vivo using a DENV-infected Institute of Cancer Research (ICR) suckling mouse model by monitoring body weight, clinical score, survival rate, and viral titer. We found that lucidone effectively protected mice from DENV infection by sustaining survival rate and reducing viral titers in DENV-infected ICR suckling mice. Then, the anti-DENV activity of lucidone was confirmed by western blotting and quantitative-reverse-transcription-polymerase chain reaction analysis, with an EC50 value of 25 ± 3 µM. Lucidone significantly induced heme oxygenase-1 (HO-1) production against DENV replication by inhibiting DENV NS2B/3 protease activity to induce the DENV-suppressed antiviral interferon response. The inhibitory effect of lucidone on DENV replication was attenuated by silencing of HO-1 gene expression or blocking HO-1 activity. In addition, lucidone-stimulated nuclear factor erythroid 2-related factor 2 (Nrf2), which is involved in transactivation of HO-1 expression for its anti-DENV activity. Taken together, the mechanistic investigations revealed that lucidone exhibits significant anti-DENV activity in in vivo and in vitro by inducing Nrf2-mediated HO-1 expression, leading to blockage of viral protease activity to induce the anti-viral interferon (IFN) response. These results suggest that lucidone is a promising candidate for drug development.

Lipopolysaccharide-Induced Nitric Oxide, Prostaglandin E2, and Cytokine Production of Mouse and Human Macrophages Are Suppressed by Pheophytin-b.

Sepsis is an overwhelming systemic response to infection that frequently results in tissue damage, organ failure, and even death. Nitric oxide (NO), prostaglandin E2 (PGE2), and cytokine overproduction are thought to be associated with the immunostimulatory cascade in sepsis. In the present study, we analyzed the anti-inflammatory efficacy of the pheophytin-b on both RAW 264.7 murine macrophage and purified human CD14⁺ monocytes stimulated with lipopolysaccharide (LPS) and elucidated the mechanisms by analyzing the cell signaling pathways known to be activated in sepsis. Pheophytin-b suppressed the overexpression of NO, PGE2, and cytokines in LPS-stimulated macrophages without inducing cytotoxicity. It also reduced NOS2 and COX-2 mRNA and protein levels. The inhibitory effects on NO, PGE2, and cytokine overproduction arose from the suppression of STAT-1 and PI3K/Akt pathways; no changes in NF-κB, MAPK, and AP-1 signaling were detected. Thus, pheophytin-b may represent a potential candidate to beneficially modulate the inflammatory response in sepsis.

Sex-related differences in the risk factors for in-hospital mortality and outcomes of ischemic stroke patients in rural areas of Taiwan.

BACKGROUND AND PURPOSE: Sex-related differences in the clinical presentation and outcomes of stroke patients are issues that have attracted increased interest from the scientific community. The present study aimed to investigate sex-related differences in the risk factors for in-hospital mortality and outcome in ischemic stroke patients. METHODS: A total of 4278 acute ischemic stroke patients admitted to a stroke unit between January 1, 2007 and December 31, 2014 were included in the study. We considered demographic characteristics, clinical characteristics, co-morbidities, and complications, among others, as factors that may affect clinical presentation and in-hospital mortality. Good and poor outcomes were defined as modified Ranking Score (mRS)≦2 and mRS>2. Neurological deterioration (ND) was defined as an increase of National Institutes of Health Stroke Score (NIHSS) ≥ 4 points. Hemorrhagic transformation (HT) was defined as signs of hemorrhage in cranial CT or MRI scans. Transtentorial herniation was defined by brain edema, as seen in cranial CT or MRI scans, associated with the onset of acute unilateral or bilateral papillary dilation, loss of reactivity to light, and decline of ≥ 2 points in the Glasgow coma scale score. RESULTS: Of 4278 ischemic stroke patients (women 1757, 41.1%), 269 (6.3%) received thrombolytic therapy. The in hospital mortality rate was 3.35% (139/4278) [4.45% (80/1757) for women and 2.34% (59/2521) for men, p < 0.01]. At discharge, 41.2% (1761/4278) of the patients showed good outcomes [35.4% (622/1757) for women and 45.2% (1139/2521) for men]. Six months after stroke, 56.1% (1813/3231) showed good outcomes [47.4% (629/1328) for women and 62.2% (1184/1903) for men, p < 0.01]. Atrial fibrillation (AF), diabetes mellitus, stroke history, and old age were factors contributing to poor outcomes in men and women. Hypertension was associated with poor outcomes in women but not in men in comparison with patients without hypertension. Stroke severity and increased intracranial pressure were associated with increased in-hospital mortality in men and women. AF was associated with increased in-hospital mortality in women but not in men compared with patients without AF. CONCLUSION: The in-hospital mortality rate was not significantly different between women and men. Functional outcomes at discharge and six months after stroke were poorer in women than in men. Hypertension is an independent factor causing poorer outcomes in women than in men. AF is an independent factor affecting sex differences in hospital mortality in women.

Validation of a novel claims-based stroke severity index in patients with intracerebral hemorrhage.

BACKGROUND: Stroke severity is an important outcome predictor for intracerebral hemorrhage (ICH) but is typically unavailable in administrative claims data. We validated a claims-based stroke severity index (SSI) in patients with ICH in Taiwan. METHODS: Consecutive ICH patients from hospital-based stroke registries were linked with a nationwide claims database. Stroke severity, assessed using the National Institutes of Health Stroke Scale (NIHSS), and functional outcomes, assessed using the modified Rankin Scale (mRS), were obtained from the registries. The SSI was calculated based on billing codes in each patient's claims. We assessed two types of criterion-related validity (concurrent validity and predictive validity) by correlating the SSI with the NIHSS and the mRS. Logistic regression models with or without stroke severity as a continuous covariate were fitted to predict mortality at 3, 6, and 12 months. RESULTS: The concurrent validity of the SSI was established by its significant correlation with the admission NIHSS (r = 0.731; 95% confidence interval [CI], 0.705-0.755), and the predictive validity was verified by its significant correlations with the 3-month (r = 0.696; 95% CI, 0.665-0.724), 6-month (r = 0.685; 95% CI, 0.653-0.715) and 1-year (r = 0.664; 95% CI, 0.622-0.702) mRS. Mortality models with NIHSS had the highest area under the receiver operating characteristic curve, followed by models with SSI and models without any marker of stroke severity. CONCLUSIONS: The SSI appears to be a valid proxy for the NIHSS and an effective adjustment for stroke severity in studies of ICH outcome with administrative claims data.

Clinical Profile and Outcome of Myasthenic Crisis In Central Taiwan.

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disease caused by antibodies to acetylcholine receptors of the skeletal muscle. Myasthenic crisis (MC) is a complication observed during both early and late stage MG cases. In this study, we examined current treatments and three years outcomes in patients with MG and MC. We also investigated the impact of thymectomy and systemic lupus erythematosus (SLE) in patients with MG and MC. METHODS: In this retrospective study, we reviewed the medical records of all patients admitted to one teaching hospital between January 2006 and December 2014 and identified those for whom discharge diagnosis included the International Classification of Diseases, ninth revision (ICD-9) codes corresponding to MG (358.X, all extensions and all positions). RESULTS: We identified 29 patients and 49 hospitalizations. Among these patients, the cause for initial hospitalization was MG in 16 cases and MC in 13 cases. Six out of the 16 MG patients were readmitted within 3 years; with 2 of the cases due to MC. Eight of the initial 13 MC patients were readmitted within 3 years, and 6 of the cases due to MC. Among these 15 MC patients, 14 were admitted to the intensive care unit (ICU), and 8 were intubation and put on mechanical ventilators. The median ICU stay was 7 days (3-45). Both MG patients who were also diagnosed with SLE experienced MC. One patient died during the first-time hospitalization, and one patient died during re-hospitalization within 2 years. CONCLUSION: Plasma exchange (PE) is the main treatment modality of MC, and most patients in our cohort had a good response. Infection is the most common trigger of MC and a significant cause of death. Despite significant morbidity and mortality in patients with MC, a favorable long-term outcome is possible with intensive treatment. Key Words: myathenia gravis, myasthenic crisis, systemic lupus erythematosus, outcome.

Preliminary results of a non-invasive method to measure tumor size and distribution in vivo.

Molecular imaging of reporter gene expression in cancer cells can provide rapid, sensitive and non-invasive monitoring of tumor behavior. The aim of the present study was to establish a non-invasive method to measure tumor size and distribution in vivo. Briefly, H-Ras-transformed cells were stably transfected with a plasmid containing the luciferase gene (Luc), designated as Ras/Luc. Ras/Luc cells were injected into the back or tail vein of nude BALB/cAnN-Foxn1nu/CrlNarl mice (age, 6-8 weeks). Mice were subsequently administered D-luciferin via intra-peritoneal injection, prior to image acquisition. Photons emitted from the mice were detected via an imaging system. Tumor size and distribution in vivo were quantified as photons/second. Andrographolide has demonstrated radiosensitization in previous in vitro and in vivo studies. In the present study, the potential effects of andrographolide cancer metastasis were investigated further, using an imaging system. Preliminary results of andrographolide combined with radiation indicated the inhibition of cancer metastasis. The present mechanistic study of andrographolide-mediated effects demonstrated that activated extracellular signal regulated kinase protein and H2O2 production levels were significantly increased by andrographolide. In summary, the present study established a non-invasive method to measure tumor size and distribution in vivo and indicated that andrographolide may be a potential therapeutic strategy in cancer therapy.

Exploring the impact of intravenous thrombolysis on length of stay for acute ischemic stroke: a retrospective cohort study.

BACKGROUND: Understanding the factors that influence the hospital length of stay (LOS) for patients with stroke will help in discharge planning and stroke unit management. We explored how intravenous thrombolysis (IVT) affects LOS in an acute-care hospital setting. METHODS: We analyzed adult patients with ischemic stroke who presented within 48 h of onset from a hospital-based stroke registry. The relationship between IVT and prolonged LOS (LOS ≥ 7 days) was studied by both multivariate logistic regression and the classification and regression tree (CART) analyses. RESULTS: Among the study population of 3054 patients, 1110 presented within 4.5 h. The median LOS (interquartile range) was 7 (4 to 11) days, and 1619 patients had prolonged LOS. Multivariate logistic regression revealed that IVT (odds ratio, 0.53; 95 % confidence interval 0.38-0.74) was an independent factor that reduced the risk of prolonged LOS, whereas age, National Institutes of Health Stroke Scale (NIHSS) score, diabetes mellitus, and leukocytosis at admission predicted prolonged LOS. CART analysis identified 4 variables (NIHSS score, IVT, leukocytosis at admission, and age) as important factors to partition the patients into six subgroups. The patient subgroup that had an NIHSS score of 5 to 7 and received IVT had the lowest probability (19 %) of prolonged LOS. CONCLUSIONS: IVT reduced the risk of prolonged LOS in patients with acute ischemic stroke. Measures to increase the rate of IVT are encouraged.

Underestimated Rate of Status Epilepticus according to the Traditional Definition of Status Epilepticus.

PURPOSE: Status epilepticus (SE) is an important neurological emergency. Early diagnosis could improve outcomes. Traditionally, SE is defined as seizures lasting at least 30 min or repeated seizures over 30 min without recovery of consciousness. Some specialists argued that the duration of seizures qualifying as SE should be shorter and the operational definition of SE was suggested. It is unclear whether physicians follow the operational definition. The objective of this study was to investigate whether the incidence of SE was underestimated and to investigate the underestimate rate. METHODS: This retrospective study evaluates the difference in diagnosis of SE between operational definition and traditional definition of status epilepticus. Between July 1, 2012, and June 30, 2014, patients discharged with ICD-9 codes for epilepsy (345.X) in Chia-Yi Christian Hospital were included in the study. A seizure lasting at least 30 min or repeated seizures over 30 min without recovery of consciousness were considered SE according to the traditional definition of SE (TDSE). A seizure lasting between 5 and 30 min was considered SE according to the operational definition of SE (ODSE); it was defined as underestimated status epilepticus (UESE). RESULTS: During a 2-year period, there were 256 episodes of seizures requiring hospital admission. Among the 256 episodes, 99 episodes lasted longer than 5 min, out of which 61 (61.6%) episodes persisted over 30 min (TDSE) and 38 (38.4%) episodes continued between 5 and 30 min (UESE). In the 38 episodes of seizure lasting 5 to 30 minutes, only one episode was previously discharged as SE (ICD-9-CM 345.3). Conclusion. We underestimated 37.4% of SE. Continuing education regarding the diagnosis and treatment of epilepsy is important for physicians.