Asociación de fibrosis hepática mediante elastografía por shear wave 2D y score APRI

Introducción: Las hepatopatías son un problema prevalente a nivel mundial. La biopsia hepática ha sido hasta la fecha el gold standard para valorar el grado de fibrosis, sin embargo, con el advenimiento de nuevos métodos no invasivos, costo-efectivos para el sistema sanitario, cada vez recurrimos menos a esta. En nuestro medio se introdujo recientemente la elastografía por onda cizallamiento con imagen biplanar, lo que implica una curva de aprendizaje por parte de los técnicos. Objetivo: Valorar la asociación de los grados de fibrosis hepática determinado por la elastografía por onda de cizallamiento con imagen biplanar (2D-SWE) y el score APRI en pacientes portadores de enfermedad hepática asistidos en el servicio de hepatología del Hospital Pasteur.Médica 2. Metodología: Se incluyeron los pacientes con enfermedad hepática de cualquier etiología, asistidos entre el 01/10/21 al 31/08/22, mayores de 15 años, de ambos sexos y que han sido valorados con elastografía por onda de cizallamiento con imagen biplanar (2D-SWE) y analítica sanguínea realizado por el equipo médico del servicio mencionado en los últimos 6 meses. Resultados: Se incluyeron 158 pacientes. Se encontró mayor prevalencia de enfermedad hepática en mujeres, con predominio de la etiología de enfermedad por hígado graso no alcohólico (EHGNA) e infección por virus de hepatitis C (VHC). Se evidenció asociación positiva entre la elastografía (2D-SWE) y el score APRI para el diagnóstico o exclusión de enfermedad hepática avanzada, sin diferencia estadísticamente significativa entre los dos médicos hepatólogos. Conclusiones: Existe asociación entre la elastografía por SWE y el score APRI para el diagnóstico de enfermedad hepática avanzada en la población general y por etiología.

Introduction: Liver diseases are a prevalent problem worldwide. To date, liver biopsy has been the gold standard for assessing the degree of fibrosis; however, with the advent of new non-invasive, cost-effective methods for the healthcare system, we are resorting to it less and less. Shear wave elastography with biplanar imaging was recently introduced in our setting, which implies a learning curve for technicians. Objective: To assess the association of the degrees of liver fibrosis determined by shear wave elastography with biplanar imaging (2D-SWE) and the APRI score in patients with liver disease treated in the hepatology service of the Pasteur Hospital. Methodology: Patients with liver disease of any etiology, attended between 01/10/21 and 08/31/22, over 15 years of age, of both sexes and who have been evaluated with shear wave elastography with biplanar image were included. (2D-SWE) and blood analysis performed by the medical team of the aforementioned service in the last 6 months. Results: 158 patients were included. A higher prevalence of liver disease was found in women, with a predominance of the etiology of nonalcoholic fatty liver disease (NAFLD) and hepatitis C virus (HCV) infection. A positive association was evident between elastography (2D-SWE) and the APRI score for the diagnosis or exclusion of advanced liver disease, with no statistically significant difference between the two hepatologists. Conclusions: There is an association between SWE elastography and the APRI score for the diagnosis of advanced liver disease in the general population and by etiology.

Introdução: As doenças hepáticas são um problema prevalente em todo o mundo. Até o momento, a biópsia hepática tem sido o padrão ouro para avaliar o grau de fibrose, porém, com o advento de novos métodos não invasivos e de baixo custo para o sistema de saúde, recorremos cada vez menos a ela. A elastografia por onda de cisalhamento com imagem biplanar foi introduzida recentemente em nosso meio, o que implica uma curva de aprendizado para os técnicos. Objetivo: Avaliar a associação dos graus de fibrose hepática determinados pela elastografia por ondas de cisalhamento com imagem biplanar (2D-SWE) e o escore APRI em pacientes com hepatopatia atendidos no serviço de hepatologia do Hospital Pasteur. Metodologia: Foram incluídos pacientes portadores de doença hepática de qualquer etiologia, atendidos entre 10/01/21 e 31/08/22, maiores de 15 anos, de ambos os sexos e que foram avaliados com elastografia por onda de cisalhamento com imagem biplanar. ( 2D-SWE) e análises sanguíneas realizadas pela equipa médica do referido serviço nos últimos 6 meses. Resultados: foram incluídos 158 pacientes. Foi encontrada maior prevalência de doença hepática em mulheres, com predomínio da etiologia da doença hepática gordurosa não alcoólica (DHGNA) e da infecção pelo vírus da hepatite C (HCV). Foi evidente uma associação positiva entre a elastografia (2D-SWE) e o escore APRI para o diagnóstico ou exclusão de doença hepática avançada, sem diferença estatisticamente significativa entre os dois hepatologistas. Conclusões: Existe associação entre a elastografia SWE e o escore APRI para o diagnóstico de doença hepática avançada na população geral e por etiologia.

Prediction of phase equilibrium and hydration free energy of carboxylic acids by Monte Carlo simulations.

In this work, a new transferable united-atom force field has been developed to predict phase equilibrium and hydration free energy of carboxylic acids. To take advantage of the transferability of the AUA4 force field, all Lennard-Jones parameters of groups involved in the carboxylic acid chemical function are reused from previous parametrizations of this force field. Only a unique set of partial electrostatic charges is proposed to reproduce the experimental gas phase dipole moment, saturated liquid densities and vapor pressures. Phase equilibrium properties of various pure carboxylic acids (acetic acid, propanoic acid, butanoic acid, pentanoic acid, hexanoic acid) and one diacid (1,5-pentanedioic) are studied through Monte Carlo simulations in the Gibbs ensemble. A good accuracy is obtained for pure compound saturated liquid densities and vapor pressures (average deviation of 2% and 6%, respectively), as well as for critical points. The vaporization enthalpy is, however, poorly predicted for short acids, probably due to a limitation of the force field to correctly describe the significant dimerization in the vapor phase. Pressure-composition diagrams for two binary mixtures (acetic acid + n-butane and propanoic acid + pentanoic acid) are also computed with a good accuracy, showing the transferability of the proposed force field to mixtures. Hydration free energies are calculated for three carboxylic acids using thermodynamic integration. A systematic overestimation of around 10 kJ/mol is observed compared to experimental data. This new force field parametrized only on saturated equilibrium properties appears insufficient to reach an acceptable precision for this property, and only relative hydration free energies between two carboxylic acids can be correctly predicted. This highlights the limitation of the transferability feature of force fields to properties not included in the parametrization database.

Transferable force field for carboxylate esters: application to fatty acid methylic ester phase equilibria prediction.

In this work, a new transferable united-atoms force field for carboxylate esters is proposed. All Lennard-Jones parameters are reused from previous parametrizations of the AUA4 force field, and only a unique set of partial electrostatic charges is introduced for the ester chemical function. Various short alkyl-chain esters (methyl acetate, ethyl acetate, methyl propionate, ethyl propionate) and two fatty acid methylic esters (methyl oleate and methyl palmitate) are studied. Using this new force field in Monte Carlo simulations, we show that various pure compound properties are accurately predicted: saturated liquid densities, vapor pressures, vaporization enthalpies, critical properties, liquid-vapor surface tensions. Furthermore, a good accuracy is also obtained in the prediction of binary mixture pressure-composition diagrams, without introducing empirical binary interaction parameters. This highlights the transferability of the proposed force field and gives the opportunity to simulate mixtures of industrial interest: a demonstration is performed through the simulation of the methyl oleate + methanol mixture involved in the purification sections of biodiesel production processes.

Prediction of the PC-SAFT associating parameters by molecular simulation.

In this work, we propose a new methodology to determine association scheme and association parameters (energy and volume) of a SAFT-type EoS for hydrogen-bonding molecules. This paper focuses on 1-alkanol molecules, but the new methodology can also be applied for any other associating system. The idea is to use molecular simulation technique to determine independently monomer and free hydrogen fractions from which the association scheme can be deduced. The 3B scheme thus appeared to be the most appropriate for 1-alkanols. Once the association scheme is defined, the association strength can be back-calculated from molecular simulation results and used as an independent property for the equation of state parameters regression, in addition of the classical phase properties such as vapor pressure and liquid molar volume. A new set of parameters for 1-alkanol for the PPC-SAFT equation of state has been proposed following this methodology. Results are found in good agreement with experimental data for both phase properties and free hydrogen-bonding sites. Hence, this new methodology makes it possible to optimize parameters allowing an accurate reproduction of pure compounds data and yielding physically significant values for associating energy and associating volume.

A transferable force field to predict phase equilibria and surface tension of ethers and glycol ethers.

We propose a new transferable force field to simulate phase equilibrium and interfacial properties of systems involving ethers and glycol ethers. On the basis of the anisotropic united-atom force field, only one new group is introduced: the ether oxygen atom. The optimized Lennard-Jones (LJ) parameters of this atom are identical whatever the molecule simulated (linear ether, branched ether, cyclic ether, aromatic ether, diether, or glycol ether). Accurate predictions are achieved for pure compound saturated properties, critical properties, and surface tensions of the liquid-vapor interface, as well as for pressure-composition binary mixture diagrams. Multifunctional molecules (1,2-dimethoxyethane, 2-methoxyethanol, diethylene glycol) have also been studied using a recently proposed methodology for the calculation of the intramolecular electrostatic energy avoiding the use of additional empirical parameters. This new force field appears transferable for a wide variety of molecules and properties. It is furthermore worth noticing that binary mixtures have been simulated without introducing empirical binary parameters, highlighting also the transferability to mixtures. Hence, this new force field gives future opportunities to simulate complex systems of industrial interest involving molecules with ether functions.

Monte Carlo simulations of mixtures involving ketones and aldehydes by a direct bubble pressure calculation.

Ketone and aldehyde molecules are involved in a large variety of industrial applications. Because they are mainly present mixed with other compounds, the prediction of phase equilibrium of mixtures involving these classes of molecules is of first interest particularly to design and optimize separation processes. The main goal of this work is to propose a transferable force field for ketones and aldehydes that allows accurate molecular simulations of not only pure compounds but also complex mixtures. The proposed force field is based on the anisotropic united-atoms AUA4 potential developed for hydrocarbons, and it introduces only one new atom, the carbonyl oxygen. The Lennard-Jones parameters of this oxygen atom have been adjusted on saturated thermodynamic properties of both acetone and acetaldehyde. To simulate mixtures, Monte Carlo simulations are carried out in a specific pseudoensemble which allows a direct calculation of the bubble pressure. For polar mixtures involved in this study, we show that this approach is an interesting alternative to classical calculations in the isothermal-isobaric Gibbs ensemble. The pressure-composition diagrams of polar + polar and polar + nonpolar binary mixtures are well reproduced. Mutual solubilities as well as azeotrope location, if present, are accurately predicted without any empirical binary interaction parameters or readjustment. Such result highlights the transferability of the proposed force field, which is an essential feature toward the simulation of complex oxygenated mixtures of industrial interest.

Transferable force field for alcohols and polyalcohols.

A new force field has been developed for alcohol and polyalcohol molecules. Based on the anisotropic united-atom force field AUA4 developed for hydrocarbons, it only introduces one new anisotropic united atom corresponding to the hydroxyl group OH. In the case of polyalcohols and complex molecules, the calculation of the intramolecular electrostatic energy is revisited. These interactions are calculated between charges belonging to the different local dipoles of the molecule, one dipole being defined as a group of consecutive charges globally neutral. This new method allows avoiding the use of empirical scaling parameters commonly introduced to calculate 1-4 electrostatic interactions. The transferability of the proposed potential is demonstrated through the simulation of a wide variety of alcohol families: primary alcohols (methanol, ethanol, propan-1-ol, hexan-1-ol, octan-1-ol), secondary alcohols (propan-2-ol), tertiary alcohols (2-methylpropan-2-ol), phenol, and diols (1,2-ethanediol, 1,3-propanediol, 1,5-pentanediol). Monte Carlo simulations carried out in the Gibbs ensemble lead to a good agreement between calculated and experimental data for the thermodynamic properties along the liquid/vapor saturation curve, for the critical point coordinates and for the liquid structure at room temperature. Additional simulations were performed on the methanol + n-butane system showing the capability of the proposed potential to reproduce the azeotropic behavior of such mixtures with a good agreement.