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)

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