Determination of reliability criteria for liver stiffness evaluation by transient elastography

UNLABELLED: Liver stiffness evaluation (LSE) is usually considered as reliable when it fulfills all the following criteria: ≥10 valid measurements, ≥60% success rate, and interquartile range / median ratio (IQR/M) ≤0.30. However, such reliable LSE have never been shown to be more accurate than unreliable LSE. Thus, we aimed to evaluate the relevance of the usual definition for LSE reliability, and to improve reliability by using diagnostic accuracy as a primary outcome in a large population. 1,165 patients with chronic liver disease from 19 French centers were included. All patients had liver biopsy and LSE. 75.7% of LSE were reliable according to the usual definition. However, these reliable LSE were not significantly more accurate than unreliable LSE with, respectively: 85.8% versus 81.5% well-classified patients for the diagnosis of cirrhosis (P = 0.082). In multivariate analyses with different diagnostic targets, LSE median and IQR/M were independent predictors of fibrosis staging, with no significant influence of ≥10 valid measurements or LSE success rate. These two reliability criteria determined three LSE groups: "very reliable" (IQR/M ≤0.10), "reliable" (0.10< IQR/M ≤0.30, or IQR/M >0.30 with LSE median <7.1 kPa), and "poorly reliable" (IQR/M >0.30 with LSE median ≥7.1 kPa). The rates of well-classified patients for the diagnosis of cirrhosis were, respectively: 90.4%, 85.8%, and 69.5% (P < 10(-3) ). According to these new reliability criteria, 9.1% of LSE were poorly reliable (versus 24.3% unreliable LSE with the usual definition, P < 10(-3) ), 74.3% were reliable, and 16.6% were very reliable. CONCLUSION: The usual definition for LSE reliability is not relevant. LSE reliability depends on IQR/M according to liver stiffness median level, defining thus three reliability categories: very reliable, reliable, and poorly reliable LSE. (HEPATOLOGY 2013)

Brain anomalies in maternally inherited diabetes and deafness syndrome

International audienc

Proteomic analysis identifies argininosuccinate synthase 1 as a useful biomarker for hepatocellular adenoma classification and patient management

International audienc

The complexity of lipoprotein (a) lowering by PCSK9 monoclonal antibodies

Since 2012, clinical trials dedicated to proprotein convertase subtilisin kexin type 9 (PCSK9) inhibition with monoclonal antibodies (mAbs) have unambiguously demonstrated robust reductions not only in low-density lipoprotein (LDL) cholesterol (LDL-C) but also in lipoprotein (a) [Lp(a)] levels. The scientific literature published prior to those studies did not provide any evidence for a link between PCSK9 and Lp(a) metabolism. More recent investigations, either in vitro or in vivo, have attempted to unravel the mechanism(s) by which PCSK9 mAbs reduce circulating Lp(a) levels, with some showing a specific implication of the LDL receptor (LDLR) in Lp(a) clearance whereas others found no significant role for the LDLR in that process. This elusive pathway appears clearly distinct from that of the widely prescribed statins that also enhance LDLR function but do not lower circulating Lp (a) levels in humans. So how does PCSK9 inhibition with mAbs reduce Lp(a)? This still remains to be established

Analysis of Curved-Cooling-Channel Flow and Heat Transfer in Rocket Engines

Coolant-flow modeling in regeneratively cooled rocket engines fed with turbomachinery is a challenging task because of the high wall-temperature gradient, the high Reynolds number, the high aspect ratio of the channel cross section, and the curved geometry. In the present study, to better comprehend the role of the thrust-chamber shape of a rocket engine on the heat exchange, computations of supercritical hydrogen flow in single- and double-curvature channels are carried out. In particular, a parametric numerical analysis of the flow in an asymmetrically heated rectangular channel with a high aspect ratio and various radii of curvature is performed by means of a Reynolds. averaged Navier Stokes solver for real fluids, which is validated against experimental data of heated and curved. channel flow taken from open literature. Results permit the effect of curvature on global heat transfer coefficient, pressure loss, and bulk temperature increase to be quantified

Cooling Channel Analysis of a LOX/LCH4 Rocket Engine Demonstrator

A computational procedure able to describe the coupled hot-gas/wall/coolant environment that occurs in most liquid rocket engines is presented and demonstrated. The coupled analysis is performed by loose coupling of the two-dimensional axisymmetric Reynolds-Averaged Navier-Stokes equations for the hot-gas flow and the conjugate three-dimensional model for the coolant flow and solid material heat transfer in the regenerative cooling circuit. The latter model is in turn based on the coupled Reynolds-Averaged Navier-Stokes equations for the coolant flow and Fourier equation for the thermal conduction in the solid material. In this study, the thermal behavior of a regeneratively cooled oxygen/methane engine demonstrator is analyzed in detail. Starting from a nominal operative condition of the engine, different levels of channel surface roughness and coolant mass flow rate are considered in order to understand their influence on the heat transfer capability of the cooling system. Results show that the heat transfer can be markedly impaired if the operating parameters undergo rather minor changes with respect to the nominal condition

Complex Formation between Heptakis(2,6-di-O-methyl)-β-cyclodextrin and Cyclopentadienyl Molybdenum(II) Dicarbonyl Complexes: Structural Studies and Cytotoxicity Evaluations

The inclusion compounds isolated from nonaqueous solutions of heptakis(2,6-di-O-methyl)-β-cyclodextrin (DIMEB) and the complexes [CpMoL2(CO)2](BF4) (L = MeCN, L2 = 2,2′-biimidazole) were characterized in the solid state by powder X-ray diffraction (XRD), thermogravimetric analysis (TGA), 13C{1H} CP/MAS NMR, and FTIR spectroscopy. Powder XRD showed that the compound with [CpMo(MeCN)2(CO)2](BF4) was amorphous, while that with [CpMo(H2biim)(CO)2](BF4) was microcrystalline. The powder XRD pattern of the microcrystalline product could be satisfactorily indexed in the orthorhombic crystal system with space group P212121 and final unit cell parameters of a = 28.489(3) Å, b = 19.198(2) Å, and c = 16.042(2) Å. A hypothetical structural model for the crystal packing was obtained through Monte Carlo optimizations using fixed DIMEB, [CpMo(H2biim)(CO)2]+, and BF4− geometries. In the final model the BF4− anions are housed inside the toroidal cavity of DIMEB and the organometallic complex cations are regularly distributed in between the DIMEB-tetrafluoroborate complexes, occupying the intermolecular void spaces. The cytotoxicity of the free complexes and the corresponding DIMEB adducts was tested against K1735-M2 mouse melanoma cells and H9c2 rat myoblast cells in aqueous solution. The MeCN complex and its corresponding DIMEB adduct showed no significant activity for use as chemotherapeutic agents. In contrast, the biimidazole complex exhibited significant cytotoxicity against K1735-M2 cells, especially for concentrations above 50 μM, and the cytotoxicity was even higher when the DIMEB adduct was used. Epifluorescence microscopy indicated that mitochondrial alterations took place at an earlier time point than major changes in cell morphology