Marqueurs non-invasifs de stéatose et fibrose hépatique

Les méthodes non invasives d'évaluation des lésions tissulaires hépatiques les plus utilisées et les mieux validées sont l'élastométrie et le FibroTest. La stéatopathie non-alcoolique (NAFLD) est devenue la forme la plus fréquente de maladie hépatique. Différentes études suggèrent que la NAFLD est associée à un risque accru de mortalité, en particulier d'origine cardiovasculaire. Les objectifs de cette thèse étaient 1) de mieux définir certaines limites des méthodes non invasives d'évaluation de la fibrose hépatique; 2) d'évaluer la valeur pronostique du FibroTest et d'un biomarqueur de stéatose, le SteatoTest chez les patients ayant un diabète et/ou une dyslipidémie. Le travail réalisé a permis de montrer une variabilité interobservateur notable de l'élastométrie entre deux opérateurs expérimentés dans l'hépatite chronique virale C. La stéatose du foie, estimée par le SteatoTest, a été identifiée comme un facteur indépendant associé à la surestimation de la fibrose du foie par l'élastométrie chez les sujets ayant un diabète de type 2. Nous avons également mis en évidence une variabilité du test APRI et l'impact de l'activité nécrotico-inflammatoire sur ce test dont la formule comprend l'aspartate transaminase exprimée en multiple de la normale dans l'hépatite chronique virale C. Chez des patients à haut risque de NAFLD, nous avons pu démontrer la valeur pronostique à 10 ans du FibroTest et du SteatoTest, pour prédire la mortalité globale indépendamment des facteurs métaboliques. Le FibroTest était également prédictif de la mortalité d'origine hépatique et de l'incidence des complications cardiovasculaires et le SteatoTest de la mortalité d'origine cardiovasculaireSeveral non-invasive methods have been proposed to replace liver biopsy. Transient elastography and FibroTest are the most widely used and best validated non-invasive methods to assess liver fibrosis. Subjects with metabolic disorders such as type-2 diabetes or dyslipidemia, have a high risk of non-alcoholic fatty liver disease (NAFLD). Evidence was previously provided to indicate that NAFLD is associated with an increased risk of cardiovascular disease and overall mortality. The aims of this thesis were. 1) to evaluate the main limitations of non-invasive methods to assess liver fibrosis. 2) to evaluate the prognostic value of liver biomarkers, such as FibroTest and SteatoTest, in patients with type-2 diabetes and/or dyslipidemia. We demonstrated a marked interobserver variability of transient elastography between two experienced operators in chronic hepatitis C. Hepatic steatosis, estimated by SteatoTest, was identified as an independent factor associated with an overestimation of liver fibrosis by transient elastography in patients with type-2 diabetes. We could also show the variability of the APRI test, based on the expression of aspartate aminotransferase relative to the upper limit of normal and the risk of overestimating fibrosis stage by this test due to necro-inflammatory activity in chronic hepatitis C. We reported that FibroTest and SteatoTest had a 10-year prognostic value for prediction of overall mortality independently of metabolic factors in patients at high risk of NAFLD. FibroTest was also predictive of liver-related death and incidence of cardiovascular events. In addition, SteatoTest had a prognostic value for cardiovascular-related death.PARIS-JUSSIEU-Bib.électronique (751059901) / SudocSudocFranceF

Clinical-pathological features and gene profile in colorectal cancer

El cáncer colorectal es el tercer cáncer más frecuente en hombres y el segundo más frecuente en mujeres, con una incidencia mundial aproximada de 1.2 millones de casos nuevos por año. El objetivo primario es estudiar la relación existente entre las características clínico-histológicas de individuos con cáncer colorectal y el estado mutacional de los codones 12 y 13 del gen KRAS (7 mutaciones validadas), con el fin de hallar un marcador histopatológico para los tumores mutados. El objetivo secundario es determinar cuantos pacientes tienen mutaciones adicionales en los codones 15 y 61 del gen KRAS y 600 del gen BRAF que podrían modificar el fenotipo tumoral. Fueron seleccionados 60 individuos con cáncer colorrectal (30 wild-type y 30 con mutaciones validadas en los codones 12 y 13 del gen KRAS). Se amplificaron y secuenciaron del gen KRAS los exones 2 y 3, y del gen BRAF el exón 15. La información recolectada se examinó mediante un análisis descriptivo, análisis univariado y/ó análisis multivariado según correspondiese. En conclusión, no se encontró relación entre las características clínico-histológicas de los tumores de individuos con diagnostico de cáncer colorectal y el estado mutacional de los codones 12 y 13 del gen KRAS. No hallamos un marcador histopatológico para los tumores mutados resulta interesante considerar el estudio del codón 600 del gen BRAF.Colorectal cancer is the third most frequent cancer in men and the second most frequent in women, with a worldwide incidence of approximately 1.2 million new cases per year. Our primary objective was to study the relationship between clinical and histological features of individuals with colorectal cancer and the mutational status of codons 12 and 13 of the KRAS gene (7 validated mutations), in order to find a histopathological marker to mutated tumors. The secondary objective was to determine how many patients had additional mutations in codons 15 and 61 of the KRAS gene, and codon 600 of the BRAF gene, which could modify the tumor phenotype. Sixty individuals with colorectal cancer (30 wild-type subjects and 30 with validated mutations in codons 12 and 13 of the KRAS gene) were selected. Exons 2 and 3 of the KRAS gene, and exon 15 of the BRAF gene were amplified and sequenced. The data collected were reviewed by a descriptive, univariate and/or multivariate analysis, as appropriate. In conclusion, no relation was found between clinical and histological features of individuals with colorectal cancer and their mutational status for codons 12 and 13 of the KRAS gene. This suggests that those easily available data do not allow predicting the response to anti-EGFR therapy. In patients with advanced colorectal adenocarcinomas and KRAS wild-type status, further study of codon 600 of the BRAF gene could be required.Fil: Perazzo, Florencia. Centro de Educación Médica e Investigaciones Clínicas; ArgentinaFil: Piaggio, Fernando. Centro de Educación Médica e Investigaciones Clínicas; ArgentinaFil: Krupitzki, Hugo Bernardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Centro de Educación Médica e Investigaciones Clínicas; ArgentinaFil: Garcia, Alejandro Javier. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Centro de Educación Médica e Investigaciones Clínicas; ArgentinaFil: Avagnina, Alejandra. Centro de Educación Médica e Investigaciones Clínicas; ArgentinaFil: Elsner, Boris. Centro de Educación Médica e Investigaciones Clínicas; ArgentinaFil: Denninghoff, Valeria Cecilia. Centro de Educación Médica e Investigaciones Clínicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

LOS COCHINOS [Material gráfico]

Acuarela de José Hurtado de Mendoza. Propiedad de Caridad Rodríguez Pérez-Galdós.Finca de cochinos en La Aldea de San Nicolás.Copia digital. Madrid : Ministerio de Educación, Cultura y Deporte. Subdirección General de Coordinación Bibliotecaria, 201

Estudo da Carbonatação Acelerada em Argamassas do CAA com Elevados Teores de Adições Minerais

Este artigo avalia a carbonatação, o índice de atividade pozolânica e a resistência à compressão em argamassas de concretos autoadensáveis (CAA), na substituição do cimento por adições minerais (Metacaulim, Cinza da casca de arroz e Cinza da biomassa da cana de açúcar), acrescendo a cal (hidróxido de cálcio) para reposição alcalina. O objetivo foi avaliar a influência das adições na carbonatação por meio DRX, TG e profundidade de carbonatação (em câmara acelerada). Observou-se uma pequena pozolanicidade das adições minerais pela redução dos picos de portlandita e maior frente de carbonatação. A cal não apresentou boa interação com a cinza da cana de açúcar elevando a profundidade de carbonatação. Contudo, os traços com as adições apresentaram profundidades menores a referência. Já na resistência à compressão os resultados foram inferiores, porém, com pequenas perdas, tornando viável a utilização das misturas

Estudo da Carbonatação Acelerada em Argamassas do CAA com Elevados Teores de Adições Minerais

Este artigo avalia a carbonatação, o índice de atividade pozolânica e a resistência à compressão em argamassas de concretos autoadensáveis (CAA), na substituição do cimento por adições minerais (Metacaulim, Cinza da casca de arroz e Cinza da biomassa da cana de açúcar), acrescendo a cal (hidróxido de cálcio) para reposição alcalina. O objetivo foi avaliar a influência das adições na carbonatação por meio DRX, TG e profundidade de carbonatação (em câmara acelerada). Observou-se uma pequena pozolanicidade das adições minerais pela redução dos picos de portlandita e maior frente de carbonatação. A cal não apresentou boa interação com a cinza da cana de açúcar elevando a profundidade de carbonatação. Contudo, os traços com as adições apresentaram profundidades menores a referência. Já na resistência à compressão os resultados foram inferiores, porém, com pequenas perdas, tornando viável a utilização das misturas

Imunohistoquímica na avaliação das doenças inflamatórias intestinais (DII)

As doenças inflamatórias intestinais são desordens de etiologia idiopática cujo diagnóstico histopatológico é dado por meio de marcadores imunohistoquímicos. Portanto, o objetivo do presente estudo foi revisar os mais recentes ensaios clínicos publicados, que se utilizaram da imunohistoquímica para a avaliação de marcadores úteis no diagnóstico, no tratamento e no acompanhamento de tais doenças. Para isso, realizou-se uma revisão bibliográfica dos trabalhos publicados entre 2014 e 2017, presentes nas bases de dados Pubmed/medline e Cochrane Library, a partir da busca pelos descritores “Inflammatory bowel disease” AND “immunohistochemistry”. Os resultados evidenciaram que MMP-9 e calprotectina fecal são marcadores úteis para o diagnóstico das doenças inflamatórias intestinais. Além disso, as quantificações de TNF, IL-6 e Anti-TNF se mostraram úteis para o acompanhamento desses pacientes, principalmente na verificação de melhora ou piora do quadro clínico após a instituição da terapia farmacológica. Concluiu-se, então, que a imunohistoquímica é uma metodologia bastante promissora para a avaliação das DII e, por isso, mais pesquisas que visem a descobertas de outros marcadores e que contribuam para o cuidado desses pacientes devem ser estimuladas

Programa Conectar Igualdad -Seguimiento y evaluación

El presente documento tiene por propósito presentar los lineamientos de seguimiento y evaluación del Programa CONECTAR IGUALDAD, en particular el componente de estudios especiales

Non-invasive markers of steatosis and liver fibrosis.

Les méthodes non invasives d'évaluation des lésions tissulaires hépatiques les plus utilisées et les mieux validées sont l'élastométrie et le FibroTest. La stéatopathie non-alcoolique (NAFLD) est devenue la forme la plus fréquente de maladie hépatique. Différentes études suggèrent que la NAFLD est associée à un risque accru de mortalité, en particulier d'origine cardiovasculaire. Les objectifs de cette thèse étaient 1) de mieux définir certaines limites des méthodes non invasives d'évaluation de la fibrose hépatique; 2) d'évaluer la valeur pronostique du FibroTest et d'un biomarqueur de stéatose, le SteatoTest chez les patients ayant un diabète et/ou une dyslipidémie. Le travail réalisé a permis de montrer une variabilité interobservateur notable de l'élastométrie entre deux opérateurs expérimentés dans l'hépatite chronique virale C. La stéatose du foie, estimée par le SteatoTest, a été identifiée comme un facteur indépendant associé à la surestimation de la fibrose du foie par l'élastométrie chez les sujets ayant un diabète de type 2. Nous avons également mis en évidence une variabilité du test APRI et l'impact de l'activité nécrotico-inflammatoire sur ce test dont la formule comprend l'aspartate transaminase exprimée en multiple de la normale dans l'hépatite chronique virale C. Chez des patients à haut risque de NAFLD, nous avons pu démontrer la valeur pronostique à 10 ans du FibroTest et du SteatoTest, pour prédire la mortalité globale indépendamment des facteurs métaboliques. Le FibroTest était également prédictif de la mortalité d'origine hépatique et de l'incidence des complications cardiovasculaires et le SteatoTest de la mortalité d'origine cardiovasculaireSeveral non-invasive methods have been proposed to replace liver biopsy. Transient elastography and FibroTest are the most widely used and best validated non-invasive methods to assess liver fibrosis. Subjects with metabolic disorders such as type-2 diabetes or dyslipidemia, have a high risk of non-alcoholic fatty liver disease (NAFLD). Evidence was previously provided to indicate that NAFLD is associated with an increased risk of cardiovascular disease and overall mortality. The aims of this thesis were. 1) to evaluate the main limitations of non-invasive methods to assess liver fibrosis. 2) to evaluate the prognostic value of liver biomarkers, such as FibroTest and SteatoTest, in patients with type-2 diabetes and/or dyslipidemia. We demonstrated a marked interobserver variability of transient elastography between two experienced operators in chronic hepatitis C. Hepatic steatosis, estimated by SteatoTest, was identified as an independent factor associated with an overestimation of liver fibrosis by transient elastography in patients with type-2 diabetes. We could also show the variability of the APRI test, based on the expression of aspartate aminotransferase relative to the upper limit of normal and the risk of overestimating fibrosis stage by this test due to necro-inflammatory activity in chronic hepatitis C. We reported that FibroTest and SteatoTest had a 10-year prognostic value for prediction of overall mortality independently of metabolic factors in patients at high risk of NAFLD. FibroTest was also predictive of liver-related death and incidence of cardiovascular events. In addition, SteatoTest had a prognostic value for cardiovascular-related death

Marqueurs non-invasifs de stéatose et fibrose hépatique

Several non-invasive methods have been proposed to replace liver biopsy. Transient elastography and FibroTest are the most widely used and best validated non-invasive methods to assess liver fibrosis. Subjects with metabolic disorders such as type-2 diabetes or dyslipidemia, have a high risk of non-alcoholic fatty liver disease (NAFLD). Evidence was previously provided to indicate that NAFLD is associated with an increased risk of cardiovascular disease and overall mortality. The aims of this thesis were. 1) to evaluate the main limitations of non-invasive methods to assess liver fibrosis. 2) to evaluate the prognostic value of liver biomarkers, such as FibroTest and SteatoTest, in patients with type-2 diabetes and/or dyslipidemia. We demonstrated a marked interobserver variability of transient elastography between two experienced operators in chronic hepatitis C. Hepatic steatosis, estimated by SteatoTest, was identified as an independent factor associated with an overestimation of liver fibrosis by transient elastography in patients with type-2 diabetes. We could also show the variability of the APRI test, based on the expression of aspartate aminotransferase relative to the upper limit of normal and the risk of overestimating fibrosis stage by this test due to necro-inflammatory activity in chronic hepatitis C. We reported that FibroTest and SteatoTest had a 10-year prognostic value for prediction of overall mortality independently of metabolic factors in patients at high risk of NAFLD. FibroTest was also predictive of liver-related death and incidence of cardiovascular events. In addition, SteatoTest had a prognostic value for cardiovascular-related death.Les méthodes non invasives d'évaluation des lésions tissulaires hépatiques les plus utilisées et les mieux validées sont l'élastométrie et le FibroTest. La stéatopathie non-alcoolique (NAFLD) est devenue la forme la plus fréquente de maladie hépatique. Différentes études suggèrent que la NAFLD est associée à un risque accru de mortalité, en particulier d'origine cardiovasculaire. Les objectifs de cette thèse étaient 1) de mieux définir certaines limites des méthodes non invasives d'évaluation de la fibrose hépatique; 2) d'évaluer la valeur pronostique du FibroTest et d'un biomarqueur de stéatose, le SteatoTest chez les patients ayant un diabète et/ou une dyslipidémie. Le travail réalisé a permis de montrer une variabilité interobservateur notable de l'élastométrie entre deux opérateurs expérimentés dans l'hépatite chronique virale C. La stéatose du foie, estimée par le SteatoTest, a été identifiée comme un facteur indépendant associé à la surestimation de la fibrose du foie par l'élastométrie chez les sujets ayant un diabète de type 2. Nous avons également mis en évidence une variabilité du test APRI et l'impact de l'activité nécrotico-inflammatoire sur ce test dont la formule comprend l'aspartate transaminase exprimée en multiple de la normale dans l'hépatite chronique virale C. Chez des patients à haut risque de NAFLD, nous avons pu démontrer la valeur pronostique à 10 ans du FibroTest et du SteatoTest, pour prédire la mortalité globale indépendamment des facteurs métaboliques. Le FibroTest était également prédictif de la mortalité d'origine hépatique et de l'incidence des complications cardiovasculaires et le SteatoTest de la mortalité d'origine cardiovasculair