In patients with coronary artery disease who are being evaluated for percutaneous coronary intervention (PCI), procedures can be guided by fractional flow reserve (FFR) or intravascular ...ultrasonography (IVUS) for decision making regarding revascularization and stent implantation. However, the differences in clinical outcomes when only one method is used for both purposes are unclear.
We randomly assigned 1682 patients who were being evaluated for PCI for the treatment of intermediate stenosis (40 to 70% occlusion by visual estimation on coronary angiography) in a 1:1 ratio to undergo either an FFR-guided or IVUS-guided procedure. FFR or IVUS was to be used to determine whether to perform PCI and to assess PCI success. In the FFR group, PCI was to be performed if the FFR was 0.80 or less. In the IVUS group, the criteria for PCI were a minimal lumen area measuring either 3 mm
or less or measuring 3 to 4 mm
with a plaque burden of more than 70%. The primary outcome was a composite of death, myocardial infarction, or revascularization at 24 months after randomization. We tested the noninferiority of the FFR group as compared with the IVUS group (noninferiority margin, 2.5 percentage points).
The frequency of PCI was 44.4% among patients in the FFR group and 65.3% among those in the IVUS group. At 24 months, a primary-outcome event had occurred in 8.1% of the patients in the FFR group and in 8.5% of those in the IVUS group (absolute difference, -0.4 percentage points; upper boundary of the one-sided 97.5% confidence interval, 2.2 percentage points; P = 0.01 for noninferiority). Patient-reported outcomes as reported on the Seattle Angina Questionnaire were similar in the two groups.
In patients with intermediate stenosis who were being evaluated for PCI, FFR guidance was noninferior to IVUS guidance with respect to the composite primary outcome of death, myocardial infarction, or revascularization at 24 months. (Funded by Boston Scientific; FLAVOUR ClinicalTrials.gov number, NCT02673424.).
To cite this article: Kim YH, Yang TY, Park C‐S, Ahn S‐H, Son BK, Kim JH, Lim DH, Jang TY. Anti‐IL‐33 antibody has a therapeutic effect in a murine model of allergic rhinitis. Allergy 2012; 67: ...183–190.
Background: Interleukin (IL)‐33 is involved in the Th2 immune response and could play an essential role in nasal allergy. Therefore, we aimed to investigate the therapeutic potential of anti‐IL‐33 for allergic rhinitis (AR).
Methods: Twenty‐four BALB/c mice were used. In group A (control group, n = 6), mice were sensitized and challenged with saline. Group B ovalbumin (OVA) group, n = 6 mice received intraperitoneal and intranasal OVA challenge. In group C (control IgG group, n = 6), mice were injected intraperitoneally with rabbit control IgG before OVA challenge. In group D (anti‐IL‐33 group, n = 6), anti‐IL‐33 was injected before challenge. We evaluated the number of nose‐scratching events and external morphology; serum total and OVA‐specific IgE; number of eosinophils, neutrophils, and lymphocytes in bronchoalveolar lavage (BAL) fluid; histopathologic examination of nasal cavity; and IL‐4, IL‐5, and IL‐13 in BAL fluid.
Results: Anti‐IL‐33 treatment significantly reduced the nose‐scratching events and ameliorated skin denudation. Serum total and OVA‐specific IgE was significantly decreased in group D. The number of eosinophils in BAL fluid was also significantly decreased. Eosinophilic infiltration in the nasal cavity was significantly decreased in group D. IL‐4, IL‐5, and IL‐13 in BAL fluid were also significantly decreased after treatment.
Conclusions: Anti‐IL‐33 antibody has a therapeutic potential for experimental AR.
The current study was carried out to define the involvement of Peroxiredoxin (Prx) II in progression of hepatocellular carcinoma (HCC) and the underlying molecular mechanism(s). Expression and ...function of Prx II in HCC was determined using H-ras(G12V)-transformed HCC cells (H-ras(G12V)-HCC cells) and the tumor livers from H-ras(G12V)-transgenic (Tg) mice and HCC patients. Prx II was upregulated in H-ras(G12V)-HCC cells and H-ras(G12V)-Tg mouse tumor livers, the expression pattern of which highly similar to that of forkhead Box M1 (FoxM1). Moreover, either knockdown of FoxM1 or site-directed mutagenesis of FoxM1-binding site of Prx II promoter significantly reduced Prx II levels in H-ras(G12V)-HCC cells, indicating FoxM1 as a direct transcription factor of Prx II in HCC. Interestingly, the null mutation of Prx II markedly decreased the number and size of tumors in H-ras(G12V)-Tg livers. Consistent with this, knockdown of Prx II in H-ras(G12V)-HCC cells reduced the expression of cyclin D1, cell proliferation, anchorage-independent growth and tumor formation in athymic nude mice, whereas overexpression of Prx II increased or aggravated the tumor phenotypes. Importantly, the expression of Prx II was correlated with that of FoxM1 in HCC patients. The activation of extracellular signal-related kinase (ERK) pathway and the expression of FoxM1 and cyclin D1 were highly dependent on Prx II in H-ras(G12V)-HCC cells and H-ras(G12V)-Tg livers. Prx II is FoxM1-dependently-expressed antioxidant in HCC and function as an enhancer of Ras(G12V) oncogenic potential in hepatic tumorigenesis through activation of ERK/FoxM1/cyclin D1 cascade.
Abstract
Background
We aimed to assess absolute risk and benefit from OAC therapies in individual AF patients with liver cirrhosis (LC), and to develop the optimal dose selecting risk calculator for ...each patient.
Methods
We derived and validated a prediction model for major bleeding (MB) and stroke/systemic thromboembolism (SSTE) in AF patients with LC from two-center observational cohort (n=420 in derivation cohort, n=180 in validation cohort) with 4 treatment options (standard-, low-dose NOACs, warfarin, and no OACs). Readily available clinical variables were included in machine learning-based ensembled risk calculation models.
Results
Model calibration and discrimination was adequate with c-statistics of 0.770.66-0.87 for MB and 0.740.74-0.84 for SSTE. Three-year absolute risk increases (ARIs) for MB with standard-dose NOACs ranged from <10% in 37% of patients to >30% in 18% of patients, with low-dose NOACs ranged from <10% in 47% of patients to >30% in 12% of patients compared without OACs. Three-year absolute risk reductions (ARRs) for SSTE with standard-dose NOACs ranged from <7% in 48% of patients to >15% in 22% of patients, with low-dose NOACs ranged from <7% in 57% of patients to >15% in 17% of patients compared without OACs. The ARI cutoff for MB and ARR cutoff for SSTE with OAC were shown as >2.4%/year and >1.2%/year (c-statistics 0.810.78-0.83, 0.750.72-0.79).
Conclusions
Artificial intelligence combining clinical variables was found to predict individual patient’s bleeding and stroke/systemic embolism risks well and it can also guide each patient’s appropriate OAC dose in AF patients with LC (web-calculator can be accessed as: https://riskcalc.shinyapps.io/AFLC/).
Summary
Background
A proportion of chronic hepatitis B (CHB) patients are diagnosed with advanced hepatocellular carcinoma (HCC) despite regular surveillance.
Aims
To determine predictors for HCC ...detection failure in CHB patients who underwent regular surveillance.
Methods
CHB patients with well‐preserved liver function, who underwent ultrasonography and alpha‐foetoprotein (AFP) analysis every 6 months, were enrolled. Cox regression analysis was used to identify predictors for detection failure, defined as HCC initially diagnosed at Barcelona Clinic Liver Cancer (BCLC) stage B or C.
Results
Of the 4590 CHB patients (mean age, 52.1 years; men, 61.6%), 169 patients were diagnosed with HCC (3.68%) and 35 (20.7%) HCC patients were initially diagnosed with HCC BCLC stage B or C. The cumulative incidence of HCC detection failure was 0.2% at year 1 and 1.3% at year 5. Multivariate analyses indicated that cirrhosis (hazard ratio HR, 3.078; 95% CI, 1.389‐6.821; P = 0.006), AFP levels ≥9 ng/mL (HR, 5.235; 95% CI, 2.307‐11.957; P = 0.010), and diabetes mellitus (HR, 3.336; 95% CI, 1.341‐8.296; P = 0.010) were independent predictors of HCC detection failure. Another model that incorporated liver stiffness (LS) values identified LS values ≥11.7 kPa (HR, 11.045; 95% CI, 2.066‐59.037; P = 0.005) and AFP levels ≥9 ng/mL (HR, 4.802; 95% CI, 1.613‐14.297; P = 0.005) as predictors of detection failure.
Conclusions
In CHB patients undergoing regular surveillance with ultrasonography and alpha‐foetoprotein (AFP) analysis every 6 months, the HCC detection failure rate was not high (0.8% per person; 0.1% per test). However, careful attention should be paid in patients with advanced liver fibrosis (clinical cirrhosis or LS value >11.7 kPa), high AFP levels, or diabetes mellitus, who are prone to surveillance failure.
Background
Both vertebrobasilar dolichoectasia (VBD) and cerebral microbleeds (CMBs) are related with the risk of intracerebral hemorrhage. We aimed to examine the relationship between the VBD and ...CMB in ischaemic stroke patients.
Methods
A consecutive series of 182 patients hospitalized because of ischaemic stroke or transient ischaemic attack (TIA), and who underwent gradient echo brain magnetic resonance imaging were retrospectively recruited from a prospective stroke registry. CMB locations were categorized into anterior and posterior circulation. Ectasia was defined as basilar artery (BA) diameter > 4.5 mm, and dolichosis, as either BA bifurcation above the suprasellar cistern or lateral to the margin of the clivus or dorsum sellae. Whether VBD is associated with CMB anywhere in the brain or in anterior or posterior circulation territories was analysed using binary and multinomial logistic regression models.
Results
Twenty‐four subjects (13.2%) had VBD and 48 (26.4%) had CMBs. CMBs were more frequently observed in patients with VBD than without (66.7% vs. 20.3%, P < 0.001). VBD was significantly associated with CMBs in any location (crude odds ratio, 7.88; 95% confidence interval, 3.10–20.02), in the posterior circulation territory only (9.63; 2.60–34.94), and in both territories (9.25; 3.40–26.29), but not in the anterior circulation only (1.14; 0.009–11.20). These associations remained unchanged after adjusting for age, gender, hypertension, leukoaraiosis and stroke subtype.
Conclusions
VBD in patients with ischaemic stroke or TIA is independently associated with CMBs, especially in the posterior circulation territory.
Key insights in materials at extreme temperatures and pressures can be gained by accurate measurements that determine the electrical conductivity. Free-electron laser pulses can ionize and excite ...matter out of equilibrium on femtosecond time scales, modifying the electronic and ionic structures and enhancing electronic scattering properties. The transient evolution of the conductivity manifests the energy coupling from high temperature electrons to low temperature ions. Here we combine accelerator-based, high-brightness multi-cycle terahertz radiation with a single-shot electro-optic sampling technique to probe the evolution of DC electrical conductivity using terahertz transmission measurements on sub-picosecond time scales with a multi-undulator free electron laser. Our results allow the direct determination of the electron-electron and electron-ion scattering frequencies that are the major contributors of the electrical resistivity.
Objective
In this study, we isolated the milk sphingolipid‐enriched fraction (MSEF) of sweet buttermilk powder and conducted a clinical trial for evaluating its efficacy in skin barrier recovery.
...Methods
Milk sphingolipid‐enriched fraction was isolated via solvent extraction of buttermilk powder, and further concentrated by removing the phospholipids and neutral lipids. A cream containing 1% MSEF was used during clinical trials to assess for water holding and skin barrier recovery capacities.
Results
The main components of the MSEF were sphingomyelin, glucosylceramide and lactosylceramide, confirmed by TLC, HPLC, MS and NMR. The MSEF cream‐treated group had a significantly higher (P < 0.05) water holding capacity, compared with the base cream (vehicle) group. Compared with that in the base cream group, transepidermal water loss (TEWL) recovery increased in the presence of the sphingolipid‐containing MSEF cream (MSEF group), with a significant difference (P < 0.05) recorded on day 14.
Conclusion
The MSEF cream contributed to improving the water holding capacity and skin barrier recovery of damaged skin. Therefore, sphingolipid‐containing MSEF can be useful for strengthening or repairing skin barrier function.
Résumé
Objectif
Dans la présente étude, nous avons isolé la fraction enrichie en sphingolipides du lait (milk sphingolipid‐enriched fraction, MSEF) du lait de baratte doux en poudre et mené un essai clinique pour évaluer l’efficacité de la récupération de la barrière cutanée.
Méthodes
La fraction enrichie en sphingolipides du lait est isolée par l'extraction de solvant du lait de baratte en poudre, et ensuite concentrée en enlevant les phospholipides et les lipides neutres. Une crème contenant un pourcent (1%) de la fraction enrichie en sphingolipides du lait (MSEF) est utilisée pendant des essais cliniques visant à évaluer les capacités de la rétention d’eau et de la récupération de la barrière cutanée.
Résultats
Les principales composantes de la fraction enrichie en sphingolipides du lait (MSEF) étaient la sphingomyéline, la glucosylcéramide, et le lactosylcéramide, confirmées par la chromatographie sur couche mince (TLC), la chromatographie liquide à haute performance (CLHP), la spectrométrie de masse (MS) et la RMN(NMR). La groupe traitée par la crème enrichie en sphingolipides du lait (MSEF) avait une capacité de la rétention d’eau beaucoup plus élevée (P < 0.05), par rapport au groupe utilisant la crème de base (véhicule). Comparé au groupe utilisant la crème de base, la récupération de la perte d'eau transépidermique (TEWL) a augmenté en présence de la fraction enrichie en sphingolipides du lait (MSEF), avec une différence significative (P < 0.05) enregistrée au 14ème jour.
Conclusion
La crème enrichie en sphingolipides du lait (MSEF) a contribué à améliorer les capacités de la rétention d’eau et de la récupération de la barrière cutanée de la peau endommagée. Par conséquent, la fraction enrichie en sphingolipides du lait (MSEF) peut être utile pour renforcer ou réparer la fonction de barrière cutanée.
This study evaluated the ability of sphingolipids enriched fraction (MSEF) prepared from sweet butter milk to recovery skin barrier function. The main components of MSEF were sphingomyelin, galactosylceramide and lactosylceramide. In clinical tests, the application of MSEF‐cream showed an increase in water holding capacity and recovery of trans epidermal water loss (TEWL). MSEF containing sphingolipids has been found to help strengthen or restore skin barrier function.
Although acute exacerbations of idiopathic pulmonary fibrosis are well recognised, there are no studies documenting their prevalence or identifying pre-existing risk factors. This study analysed the ...clinical, radiological and pathological data of 11 patients who satisfied the criteria for acute exacerbation among 147 patients with biopsy-proven idiopathic pulmonary fibrosis. There were five additional patients who had similar demographics, radiology and surgical lung biopsy pathology, but had clinically less severe disease, and so were not included. The 2-yr frequency of acute exacerbation was 9.6% after the diagnosis. Most exacerbations were idiopathic, although two cases presented after surgical lung biopsy and one after bronchoalveolar lavage. No significant risk factor was found by univariate proportional hazard analysis. Imaging revealed diffuse bilateral ground-glass opacification superimposed on subpleural reticular and honeycombing densities. The biopsies of four patients taken during acute exacerbation exhibited diffuse alveolar damage superimposed upon usual interstitial pneumonia. The findings of this study demonstrate that acute exacerbation of idiopathic pulmonary fibrosis is rather common and this exacerbation is likely to have a spectrum of severity.
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