Summary
Background
The sensitivity of current upper limit of normal (ULN) of serum alanine aminotransferase (ALT) levels for detecting chronic liver disease has been challenged recently.
Aim
To ...identify modulating factors for serum ALT levels and to refine its ULN threshold.
Methods
We enrolled 34 346 consecutive subjects who completed the health check‐up at Taipei Veterans General Hospital from 2002 to 2009. ULN was set for healthy ALT level to the 95th percentile of the reference healthy population.
Results
A group of 21 282 subjects were used as a training set to define an ULN with the highest sensitivity; afterwards, this ULN was validated in another set of 13 064 subjects. A reference healthy population was selected from the training set after excluding subjects with any abnormalities in independent risk factors associated with elevated serum ALT level (>40 IU/L) by multivariate analysis like body mass index, waist circumference, glucose, cholesterol, high‐density lipoprotein‐cholesterol, triglyceride, hepatitis B virus surface antigen, anti‐hepatitis C virus antibody and fatty liver. The new ULN of serum ALT level defined as the 95% percentile in the healthy population were 21 IU/L and 17 IU/L for men and women respectively. These cut‐off values had the highest Youden's index and areas under the corresponding receiver operating curves among four widely applied thresholds in both the training and validation sets.
Conclusions
The suggested threshold of upper limit of normal provides better discrimination between healthy and unhealthy status. Viral hepatitis, metabolic syndrome and fatty liver are the major risk factors of elevated serum alanine aminotransferase levels.
Malignant pleural effusion (MPE) is a poor prognostic sign for patients with non-small-cell lung cancer (NSCLC). The generation of MPE is largely regulated by vascular endothelial growth factor ...(VEGF), and upregulation of VEGF by Stat3 has been observed in several types of tumor cells. In this study, we demonstrate constitutively activated Stat3 in several human lung cancer cell lines and in tumor cells infiltrated in the pleurae of patients with adenocarcinoma cell lung cancer (ADCLC) and MPE. The observations suggest that activated Stat3 plays a role in the pathogenesis of ADCLC. In PC14PE6/AS2 cells, a Stat3-positive human ADCLC cell line, autocrine IL-6 activated Stat3 via JAKs, not via Src kinase. PC14PE6/AS2 cells express higher VEGF mRNA and protein than do Stat3-negative PC14PE6/AS2/dnStat3 cells. In an animal model, PC14P6/AS2/dnStat3 cells produced no MPE and less lung metastasis than did PC14P6/AS2 cells. PC14PE6/AS2 cells also expressed higher VEGF protein, microvessel density, and vascular permeability in tumors than did PC14P6/AS2/dnStat3 cells. Therefore, we hypothesize that autocrine IL-6 activation of Stat3 in ADCLC may be involved in the formation of malignant pleural effusion by upregulating VEGF. Higher levels of IL-6 and VEGF were also found in the pleural fluids of patients with ADCLC than in patients with congestive heart failure. The autocrine IL-6/Stat3/VEGF signaling pathway may also be activated in patients with ADCLC and MPE. These findings provide novel targets for the management of MPE.
Pulmonary vein isolation (PVI) is the cornerstone of catheter ablation to treat patients with symptomatic drug-refractory atrial fibrillation (AF).
The purpose of this study was to assess the safety ...and efficacy of PVI using the cryoballoon catheter to treat patients with persistent AF.
STOP Persistent AF (ClinicalTrials.gov Identifier: NCT03012841) was a prospective, multicenter, single-arm, Food and Drug Administration–regulated trial designed to evaluate the safety and efficacy of PVI-only cryoballoon ablation for drug-refractory persistent AF (continuous episodes <6 months). The primary efficacy endpoint was 12-month freedom from ≥30 seconds of AF, atrial flutter (AFL), or atrial tachycardia (AT) after a 90-day blanking period. The prespecified performance goals were set at >40% and <13% for the primary efficacy and safety endpoints, respectively. Secondary endpoints assessed quality of life using the AFEQT (Atrial Fibrillation Effect on Quality of Life) and SF (Short Form)-12 questionnaires.
Of 186 total enrollments, 165 subjects (70% male; age 65 ± 9 years; left atrial diameter 4.2 ± 0.6 cm; body mass index 31 ± 6) were treated at 25 sites in the United States, Canada, and Japan. Total procedural, left atrial dwell, and fluoroscopy times were 121 ± 46 minutes, 102 ± 41 minutes, and 19 ± 16 minutes, respectively. At 12 months, the primary efficacy endpoint was 54.8% (95% confidence CI 46.7%–62.1%) freedom from AF, AFL, or AT. There was 1 primary safety event, translating to a rate of 0.6% (95% CI 0.1%–4.4%). AFEQT and SF-12 assessments demonstrated significant improvements from baseline to 12 months postablation (P <.001).
The STOP Persistent AF trial demonstrated cryoballoon ablation to be safe and effective in treating patients with drug-refractory persistent AF characterized by continuous AF episodes <6 months.
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The top-of-atmosphere (TOA) radiative fluxes are critical components to advancing our understanding of the Earth's radiative energy balance, radiative effects of clouds and aerosols, and climate ...feedback. The Clouds and the Earth's Radiant Energy System (CERES) instruments provide broadband shortwave and longwave radiance measurements. These radiances are converted to fluxes by using scene-type-dependent angular distribution models (ADMs). This paper describes the next-generation ADMs that are developed for Terra and Aqua using all available CERES rotating azimuth plane radiance measurements. Coincident cloud and aerosol retrievals, and radiance measurements from the Moderate Resolution Imaging Spectroradiometer (MODIS), and meteorological parameters from Goddard Earth Observing System (GEOS) data assimilation version 5.4.1 are used to define scene type. CERES radiance measurements are stratified by scene type and by other parameters that are important for determining the anisotropy of the given scene type. Anisotropic factors are then defined either for discrete intervals of relevant parameters or as a continuous functions of combined parameters, depending on the scene type. Significant differences between the ADMs described in this paper and the existing ADMs are over clear-sky scene types and polar scene types. Over clear ocean, we developed a set of shortwave (SW) ADMs that explicitly account for aerosols. Over clear land, the SW ADMs are developed for every 1 degree latitude x 1 degree longitude region for every calendar month using a kernel-based bidirectional reflectance model. Over clear Antarctic scenes, SW ADMs are developed by accounting the effects of sastrugi on anisotropy. Over sea ice, a sea-ice brightness index is used to classify the scene type. Under cloudy conditions over all surface types, the longwave (LW) and window (WN) ADMs are developed by combining surface and cloud-top temperature, surface and cloud emissivity, cloud fraction, and precipitable water. Compared to the existing ADMs, the new ADMs change the monthly mean instantaneous fluxes by up to 5 W m super(-2) on a regional scale of 1 degree latitude x 1 degree longitude, but the flux changes are less than 0.5 W m super(-2) on a global scale.
Background
Childhood asthma comprises different phenotypes with complex pathophysiology. Different asthma phenotypes evoke various clinical symptoms and vary in their responses to treatments.
Methods
...We applied k‐means clustering algorithm of twelve objective laboratory tests among 351 asthmatic children enrolled in the Taiwanese Consortium of Childhood Asthma Study (TCCAS). We constructed gene expression profiles of peripheral blood mononuclear cells (PBMC) from children with different asthma phenotypes.
Results
Five distinct phenotypes of childhood asthma were identified and can be characterized by either eosinophil‐predominant or neutrophil‐predominant inflammatory characteristics. In the gene expression profile analysis, significant differences were noted for neutrophil‐predominant asthma, compared with samples from all the other asthma phenotypes. The vast majority of the differentially expressed genes in neutrophil‐predominant asthma was associated with corticosteroid response. From an independent inhaled corticosteroid (ICS) response cohort, we also found neutrophils could be activated in this severe asthma phenotype and neutrophil‐predominant asthma may be associated with corticosteroid nonresponsiveness.
Conclusion
Phenotype clustering of childhood asthma can be helpful to identify clinically relevant patients and reveal different inflammatory characteristics in asthmatic children. Neutrophil‐predominant asthma is the most severe asthma phenotype with poor corticosteroid response. Gene expression profile of different asthma phenotypes not only improve our knowledge of childhood asthma, but also can guide asthma precision medicine.
Neutrophil‐predominant asthma is the most severe asthma phenotype with poor corticosteroid response. Five distinct phenotypes of childhood asthma identified in this study with differences in lung function, symptom frequency, healthcare utilization, percentages of eosinophils and neutrophils in peripheral blood, and serum IgE. Gene expression signature in PBMC constitutes an easier way to objectively identify corticosteroid‐resistant asthma in clinical settings.
Elderly individuals with tuberculosis (TB) are more likely to have a non-specific clinical presentation of TB and high mortality. However, factors associated with mortality in elderly TB patients ...have not been extensively studied. This retrospective cohort study aimed to identify factors associated with death among elderly Taiwanese with TB. All elderly patients with TB from 2006 to 2014 in Taipei, Taiwan, were included in a study. Multiple logistic regression was used to identify the factors associated with death in elderly TB patients. The mean age of the 5011 patients was 79·7 years; 74·1% were men; 32·7% had mortality during the study follow-up period. After controlling for potential confounders, age ⩾75 years (reference: 65–74 years), male sex, end-stage renal disease (ESRD), malignancy, acid-fast bacilli-smear positivity, TB-culture positivity, pleural effusion on chest radiograph and notification by an ordinary ward or intensive care unit were associated with a higher risk of all-cause death; while high school, and university or higher education, cavity on chest radiograph and directly observed therapy were associated with a lower risk of all-cause death. This study found that the proportion of death among elderly patients with TB in Taipei, Taiwan, was high. To improve TB treatment outcomes, future control programmes should particularly target individuals with comorbidities (e.g. ESRD and malignancy) and those with a lower socio-economic status (e.g. not educated).
Summary
Recent studies found that hepatitis C virus (HCV) may invade the central nervous system, and both HCV and Parkinson's disease (PD) have in common the overexpression of inflammatory ...biomarkers. We analysed data from a community‐based integrated screening programme based on a total of 62 276 subjects. We used logistic regression models to investigate association between HCV infection and PD. The neurotoxicity of HCV was evaluated in the midbrain neuron–glia coculture system in rats. The cytokine/chemokine array was performed to measure the differences of amounts of cytokines released from midbrain in the presence and absence of HCV. The crude odds ratios (ORs) for having PD were 0.62 95% confidence interval (CI), 0.48–0.81 and 1.91 (95% CI, 1.48–2.47) for hepatitis B virus (HBV) and HCV. After controlling for potential confounders, the association between HCV and PD remained statistically significant (adjusted OR = 1.39; 95% CI, 1.07–1.80), but not significantly different between HBV and PD. The HCV induced 60% dopaminergic neuron death in the midbrain neuron–glia coculture system in rats, similar to that of 1‐methyl‐4‐phenylpyridinium (MPP+) but not caused by HBV. This link was further supported by the finding that HCV infection may release the inflammatory cytokines, which may play a role in the pathogenesis of PD. In conclusion, our study demonstrated a significantly positive epidemiological association between HCV infection and PD and corroborated the dopaminergic toxicity of HCV similar to that of MPP+.
We describe a novel surgical technique in 31 women with histopathologically confirmed placenta accreta spectrum (PAS) disorders managed by a multidisciplinary team using a prophylactic infrarenal ...abdominal aortic cross‐clamping technique during caesarean hysterectomy. We conclude that this new surgical procedure is a relatively safe technique to potentially control operative blood loss. Our work may stimulate others to develop protocols assessing this innovative technique to improve the surgical outcome of PAS disorders.
Summary
Background
Previous studies have defined transcriptomic subtypes of adult asthma using samples of induced sputum and bronchial epithelium; however, those procedures are not readily applicable ...in the clinic, especially for childhood asthma.
Objective
We aim to dissect the transcriptomic clusters of childhood asthma using highly variably expressed genes of peripheral blood mononuclear cells (PBMC) among patients.
Methods
Gene expression of PBMC from 133 asthmatic children and 11 healthy controls was measured with Illumina microarrays. We applied the k‐means clustering algorithm of 2048 genes to assign asthmatic children into clusters. Genes with differential expression between asthma clusters and healthy controls were used to investigate whether they could identify severe asthma of children and adults.
Results
We identified 3 asthma clusters with distinct inflammatory profiles in peripheral blood. Cluster 1 had the highest eosinophil count. Cluster 2 showed lower counts of both eosinophils and neutrophils. Cluster 3 had the highest neutrophil count and the poorest treatment control. Compared with other patients, Cluster 3 exhibited a unique gene expression pattern which was associated with changes in the glucocorticoid signalling and activation of the T helper 1/T helper 17 (TH1/TH17) immune pathways. In the validation studies, an 84‐gene signature could identify severe asthma in children on leucocytes, as well as severe asthma in adults on CD8+ T cells.
Conclusions and Clinical Relevance
Gene expression profiling of PBMC is useful for the identification of TH1/TH17‐mediated asthma with poor treatment control. PBMC and CD8+ T cells could be important targets for the investigation and identification of severe asthma.
Coronal loops exist ubiquitously in the solar atmosphere. These loops puzzle astronomers over half a century. Solar magneto-seismology (SMS) provides a unique way to constrain the physical parameters ...of coronal loops. Here, we study the evolution of oscillations of a coronal loop observed by the Atmospheric Imaging Assembly (AIA). We measure geometric and physical parameters of the loop oscillations. In particular, we find that the mean period of the oscillations increased from 1048 to 1264 s during three oscillatory cycles. We employ the differential emission measure method and apply the tools of SMS. The evolution of densities inside and outside the loop is analyzed. We found that an increase of density inside the loop and decrease of the magnetic field strength along the loop are the main reasons for the increase in the period during the oscillations. Besides, we also found that the amplitude profile of the loop is different from a profile would it be a homogeneous loop. It is proposed that the distribution of magnetic strength along the loop rather than density stratification is responsible for this deviation. The variation in period and distribution of amplitude provide, in terms of SMS, a new and unprecedented insight into coronal loop diagnostics.
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