Different Approaches to Analyze Muscle Fat Replacement With Dixon MRI in Pompe Disease

Altres ajuts: Asociación Española de Enfermos de Glucogenosis (AEEG)Quantitative MRI is an increasingly used method to monitor disease progression in muscular disorders due to its ability to measure changes in muscle fat content (reported as fat fraction) over a short period. Being able to objectively measure such changes is crucial for the development of new treatments in clinical trials. However, the analysis of the images involved continues to be a daunting task because of the time needed. Whether a more specific analysis selecting individual muscles or a global one analyzing the whole thigh or compartments could be a suitable alternative has only been marginally studied. In our study we compare three methods of analysis of 2-point-dixon images in a cohort of 34 patients with late onset Pompe disease followed over a period of one year. We measured fat fraction on MRIs obtained at baseline and at year 1, and we calculated the increment of fat fraction. We correlated the results obtained with the results of muscle function tests to investigate whether the three methods of analysis were equivalent or not. We observed significant differences between the three methods in the estimation of the fat fraction at both baseline and year 1, but no difference was found in the increment in fat fraction between baseline and year 1. When we correlated the fat fraction obtained with each method and the muscle function tests, we found a significant correlation with most tests in all three methods, although in most comparisons the highest correlation coefficient was found with the analysis of individual muscles. We conclude that the fastest strategy of analysis assessing compartments or the whole thigh could be reliable for certain cohorts of patients where the variable to study is the fat increment. In other sorts of studies, an individual muscle approach seems the most reliable technique

Espacio de investigación, espacio de enseñanza

Comunicacion presentada en la IV Jornada Nacional sobre Estudios Universitarios, celebrada en la Universitat Jaume I (Castellón, España), los días 8 y 9 de Julio de 2013La investigación y la docencia son dos funciones inherentes al espacio universitario y tienen sentido en el aprendizaje de los estudiantes [1]. Newman [2] realizó una investigación en la que argumentaba la hipótesis de un efecto positivo en la dirección de la investigación hacia la docencia señalando tres modos en los que esta relación se manifiesta: (a) una conexión tangible que implica la transmisión de conocimientos avanzados y habilidades de investigación a los estudiantes; (b)Una conexión intangible que se relaciona con el desarrollo de actitudes y enfoques positivos hacia la investigación y el aprendizaje; y (c) Una conexión global referida a la interacción entre la docencia y la investigación a nivel departamental. El proyecto de “laboratorio de familia” es un proyecto continuo y progresivo en el que se pretende que confluyan intereses de mejora y crecimiento en el ámbito de la familia y de los profesionales expertos ampliando y mejorando el conocimiento y las destrezas del alumnado del Máster Universitario en Intervención y Mediación Familiar a través de la investigación y la asistencia a familias de casos seleccionados. Desde este “espacio de encuentro”, una de las acciones desarrolladas ha sido el área de Potenciación y desarrollo personal. El trabajo que se presenta pretende, a partir de la experiencia realizada, ofrecer las bases para una transferencia del espacio de investigación y asistencia familiar en la relación de ayuda al contexto de enseñanza en la docencia de asignaturas del Máster en Intervención y Mediación Familiar. Para ello se analizan los modelos generados e implantados en el área de potenciación y desarrollo familiar y se propone, a partir de la experiencia realizada, una redefinición de competencias y organización curricular en la docencia de las asignaturas: Terapia Familiar y Desarrollo Personal y Sentido Vital en Proyectos de Intervención Psicosocial. Esta transferencia ha mejorado la coordinación docente entre las dos asignaturas, generando una clasificación de competencias de aprendizaje integradas con la práctica profesional. Así mismo, las herramientas prácticas docentes se han restructurado en un sentido más coherente y fundamentado con la práctica profesional

Laboratorio de Familia: acción mediación

Comunicacion presentada en la IV Jornada Nacional sobre Estudios Universitarios, celebrada en la Universitat Jaume I (Castellón, España), los días 8 y 9 de Julio de 2013El Laboratorio de Familia tuvo su origen en el curso 2008-09 por iniciativa del Máster Universitario de Intervención y Mediación Familiar de la Universitat Jaume I y a la Unitat de Suport Educatiu de la misma universidad. El Laboratorio tiene dos acciones la de Potenciación que se explica en otro comunicado de este Congreso y la de Mediación que es la que nos ocupa. Inicialmente, los alumnos que asistían al Laboratorio cumplían el requisito de haber realizado el máster o estar realizándolo en el momento, posteriormente fueron integrándose licenciados y estudiantes de licenciatura o grado vinculados con la mediación como Psicología y Derecho, también participaron otros alumnos que habían realizado másters sobre mediación. El Laboratorio se diseñó con dos objetivos, de una parte, ofrecer a los alumnos la posibilidad de poder ejercitar su formación de forma práctica y supervisada por los profesores del máster. De otra, atender a familias a las cuales la mediación pudiera serles útil para gestionar o resolver algún conflicto, para cubrir este objetivo se han realizado diversas acciones de coordinación con diversos servicios, eventualmente, interesados en colaborar. En cada curso escolar han participado una media de 15 alumnos, las sesiones se han venido realizando con una periodicidad quincenal, con una elevada regularidad en la asistencia a las sesiones, lo que ha sido un indicador de la satisfacción percibida, esta información ha sido confirmada por las evaluaciones realizadas por los alumnos. A partir del curso 2011-12, en colaboración con la Fundación Universitat Empresa se formaliza el postgrado Curso de especialización Laboratorio de familia, entrenamiento y formación en potenciación y mediación familiar con una duración de 20 ECTS, como consecuencia la oferta se limita a licenciados y diplomados. En la formación se incluye la participación en las sesiones presenciales, preparación de las mismas, puesta en común acerca del diagnóstico, pronóstico y estrategias a implementar, así como visión de vídeos y valoración de los mismos, lecturas recomendadas, estudio y elaboración de un trabajo final

Follow-up of late-onset Pompe disease patients with muscle magnetic resonance imaging reveals increase in fat replacement in skeletal muscles

Altres ajuts: This investigation was sponsored by the following grants, one from Sanofi Genzyme and another from the Spanish Ministry of Health, Fondos FEDER-ISCIII. Isabel Illa has received speaker honorarium from Grifols and Sanofi-Genzyme. Jordi Díaz-Manera has received speaker honorarium from PTC Therapeutics and Sanofi-Genzyme. The authors of this manuscript certify that they comply with the ethical guidelines for authorship and publishing in the Journal of Cachexia, Sarcopenia, and Muscle.42Late-onset Pompe disease (LOPD) is a genetic disorder characterized by progressive degeneration of the skeletal muscles produced by a deficiency of the enzyme acid alpha-glucosidase. Enzymatic replacement therapy with recombinant human alpha-glucosidase seems to reduce the progression of the disease; although at the moment, it is not completely clear to what extent. Quantitative muscle magnetic resonance imaging (qMRI) is a good biomarker for the follow-up of fat replacement in neuromuscular disorders. The aim of this study was to describe the changes observed in fat replacement in skeletal muscles using qMRI in a cohort of LOPD patients followed prospectively. A total of 36 LOPD patients were seen once every year for 4 years. qMRI, several muscle function tests, spirometry, activities of daily living scales, and quality-of-life scales were performed on each visit. Muscle MRI consisted of two-point Dixon studies of the trunk and thigh muscles. Computer analysis of the images provided the percentage of muscle degenerated and replaced by fat in every muscle (known as fat fraction). Longitudinal analysis of the measures was performed using linear mixed models applying the Greenhouse-Geisser test. We detected a statistically significant and continuous increase in mean thigh fat fraction both in treated (+5.8% in 3 years) and in pre-symptomatic patients (+2.6% in 3years) (Greenhouse-Geisser p < 0.05). As an average, fat fraction increased by 1.9% per year in treated patients, compared with 0.8% in pre-symptomatic patients. Fat fraction significantly increased in every muscle of the thighs. We observed a significant correlation between changes observed in fat fraction in qMRI and changes observed in the results of the muscle function tests performed. Moreover, we identified that muscle performance and mean thigh fat fraction at baseline visit were independent parameters influencing fat fraction progression over 4 years (analysis of covariance, p < 0.05). Our study identifies that skeletal muscle fat fraction continues to increase in patients with LOPD despite the treatment with enzymatic replacement therapy. These results suggest that the process of muscle degeneration is not stopped by the treatment and could impact muscle function over the years. Hereby, we show that fat fraction along with muscle function tests can be considered a good outcome measures for clinical trials in LOPD patients

Platelet Derived Growth Factor-AA Correlates With Muscle Function Tests and Quantitative Muscle Magnetic Resonance in Dystrophinopathies

Introduction: Duchenne (DMD) and Becker (BMD) muscular dystrophy are X-linked muscular disorders produced by mutations in the DMD gene which encodes the protein dystrophin. Both diseases are characterized by progressive involvement of skeletal, cardiac, and respiratory muscles. As new treatment strategies become available, reliable biomarkers and outcome measures that can monitor disease progression are needed for clinical trials. Methods: We collected clinical and functional data and blood samples from 19 DMD patients, 13 BMD patients, and 66 healthy controls (8 pediatric and 58 adult controls), and blood samples from 15 patients with dysferlinopathy (DYSF) and studied the serum concentration of 4 growth factors involved in the process of muscle fibrosis. We correlated the serum concentration of these growth factors with several muscle function tests, spirometry results and fat fraction identified by quantitative Dixon muscle MRI. Results: We found significant differences in the serum concentration of Platelet Derived Growth Factor-AA (PDGF-AA) between DMD patients and pediatric controls, in Connective Tissue Growth Factor (CTGF) between BMD patients and adult controls, and in and Transforming Growth Factor- β1 (TGF-β1) between BMD and DYSF patients. PDGF-AA showed a good correlation with several muscle function tests for both DMD and BMD patients and with thigh fat fraction in BMD patients. Moreover, PDGF-AA levels were increased in muscle biopsies of patients with DMD and BMD as was demonstrated by immunohistochemistry and Real-Time PCR studies. Conclusion: Our study suggests that PDGF-AA should be further investigated in a larger cohort of DMD and BMD patients because it might be a good biomarker candidate to monitor the progression of these diseases

Platelet Derived Growth Factor-AA Correlates With Muscle Function Tests and Quantitative Muscle Magnetic Resonance in Dystrophinopathies

Introduction: Duchenne (DMD) and Becker (BMD) muscular dystrophy are X-linked muscular disorders produced by mutations in the DMD gene which encodes the protein dystrophin. Both diseases are characterized by progressive involvement of skeletal, cardiac, and respiratory muscles. As new treatment strategies become available, reliable biomarkers and outcome measures that can monitor disease progression are needed for clinical trials.Methods: We collected clinical and functional data and blood samples from 19 DMD patients, 13 BMD patients, and 66 healthy controls (8 pediatric and 58 adult controls), and blood samples from 15 patients with dysferlinopathy (DYSF) and studied the serum concentration of 4 growth factors involved in the process of muscle fibrosis. We correlated the serum concentration of these growth factors with several muscle function tests, spirometry results and fat fraction identified by quantitative Dixon muscle MRI.Results: We found significant differences in the serum concentration of Platelet Derived Growth Factor-AA (PDGF-AA) between DMD patients and pediatric controls, in Connective Tissue Growth Factor (CTGF) between BMD patients and adult controls, and in and Transforming Growth Factor- β1 (TGF-β1) between BMD and DYSF patients. PDGF-AA showed a good correlation with several muscle function tests for both DMD and BMD patients and with thigh fat fraction in BMD patients. Moreover, PDGF-AA levels were increased in muscle biopsies of patients with DMD and BMD as was demonstrated by immunohistochemistry and Real-Time PCR studies.Conclusion: Our study suggests that PDGF-AA should be further investigated in a larger cohort of DMD and BMD patients because it might be a good biomarker candidate to monitor the progression of these diseases

Effectiveness and Safety of the Sequential Use of a Second and Third Anti-TNF Agent in Patients With Inflammatory Bowel Disease: Results From the Eneida Registry

Background: The effectiveness of the switch to another anti-tumor necrosis factor (anti-TNF) agent is not known. The aim of this study was to analyze the effectiveness and safety of treatment with a second and third anti-TNF drug after intolerance to or failure of a previous anti-TNF agent in inflammatory bowel disease (IBD) patients. Methods: We included patients diagnosed with IBD from the ENEIDA registry who received another anti-TNF after intolerance to or failure of a prior anti-TNF agent. Results: A total of 1122 patients were included. In the short term, remission was achieved in 55% of the patients with the second anti-TNF. The incidence of loss of response was 19% per patient-year with the second anti-TNF. Combination therapy (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.8-3; P < 0.0001) and ulcerative colitis vs Crohn's disease (HR, 1.6; 95% CI, 1.1-2.1; P = 0.005) were associated with a higher probability of loss of response. Fifteen percent of the patients had adverse events, and 10% had to discontinue the second anti-TNF. Of the 71 patients who received a third anti-TNF, 55% achieved remission. The incidence of loss of response was 22% per patient-year with a third anti-TNF. Adverse events occurred in 7 patients (11%), but only 1 stopped the drug. Conclusions: Approximately half of the patients who received a second anti-TNF achieved remission; nevertheless, a significant proportion of them subsequently lost response. Combination therapy and type of IBD were associated with loss of response. Remission was achieved in almost 50% of patients who received a third anti-TNF; nevertheless, a significant proportion of them subsequently lost response

PDGF-BB serum levels are decreased in adult onset Pompe patients

Adult onset Pompe disease is a genetic disorder characterized by slowly progressive skeletal and respiratory muscle weakness. Symptomatic patients are treated with enzymatic replacement therapy with human recombinant alfa glucosidase. Motor functional tests and spirometry are commonly used to follow patients up. However, a serological biomarker that correlates with the progression of the disease could improve follow-up. We studied serum concentrations of TGFβ, PDGF-BB, PDGF-AA and CTGF growth factors in 37 adult onset Pompe patients and 45 controls. Moreover, all patients performed several muscle function tests, conventional spirometry, and quantitative muscle MRI using 3-point Dixon. We observed a statistically significant change in the serum concentration of each growth factor in patients compared to controls. However, only PDGF-BB levels were able to differentiate between asymptomatic and symptomatic patients, suggesting its potential role in the follow-up of asymptomatic patients. Moreover, our results point to a dysregulation of muscle regeneration as an additional pathomechanism of Pompe disease