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

Evaluación física y clínica de sementales bovinos en dos municipios de la costa chica de Guerrero, México

Objective: To evaluate the reproductive physical characteristics and general health of stallions in two municipalities of Costa Chica of Guerrero, Mexico. Design/methodology/approach: The study was carried out in the municipalities of Ometepec and Cuajinicuilapa. Thirty bulls between 2 and 10 years of age were evaluated. In the physical reproductive and clinical examination were performed by direct observation, using ultrasound to evaluate attached reproductive glands and testicular parenchyma. Blood samples were taken to determine the blood profile. Descriptive statistics was used to present the results. Results: The 86% of the bulls had adequate legs and feet as well as preputial length. Scrotal circumference was according to the age and breed of the animals. Testicular defects were showed for 30% of the bulls, the most common was hypoplasia and unilateral tumors of testicular parenchyma and epididymis, as well as calcifications of the testicular parenchyma. The 93% of the bulls had normal accessory genital glands. Clinically 24% of the bulls with signs suggestive of anaplasmosis were found. The 76% of the bulls, apparently healthy, presented monocytosis, thrombocytopenia and anemia. Limitations on study/implications: the lack of knowledge of the producers about the need for a comprehensive evaluation of the bulls allows them to suffer from diseases without receiving any type of treatment, decreasing their reproductive efficiency. Findings/conclusions: Most of the bulls evaluated had the minimum physical characteristics required, although the presence of anemia and respiratory diseases may have an indirect negative impact on the reproductive efficiency of the bulls.Objetivo: Evaluar las características físicas reproductivas y la salud general de los sementales en dos municipios de Costa Chica de Guerrero, México. Diseño/metodología/aproximación: Se evaluaron reproductiva y clínicamente 30 sementales, de entre 2 y 10 años. El examen reproductivo, se realizó por observación directa, empleándose ecografía para evaluar glándulas reproductivas anexas y el parénquima testicular. La evaluación clínica se realizó por medio del examen físico y perfil hemático. Se empleó estadística descriptiva para la presentación de los resultados. Resultados: El 86% de los sementales tuvieron aplomos y largo prepucial adecuado, así como circunferencia escrotal acorde a la edad y raza de los animales. El 30% de los sementales presentaron defectos testiculares, siendo los más comunes, hipoplasia y tumores unilaterales de parénquima testicular y epidídimos, así como calcificaciones del parénquima testicular. El 93% de las glándulas anexas fueron normales. Clínicamente se encontró un 24% de los sementales con signos sugerentes a anaplasmosis. El 76% de los toros, aparentemente sanos, presentaron monocitosis, trombocitopenia y anemia. Limitaciones del estudio/implicaciones: El desconocimiento de los productores sobre la necesidad de una evaluación integral de los sementales permite que éstos padezcan enfermedades que no son tratadas, disminuyendo su eficiencia reproductiva. Hallazgos/conclusiones: La mayoría de los sementales evaluados tuvieron las características físicas mínimas requeridas, aunque la presencia de anemia y enfermedades respiratorias pueden tener incidencia negativa indirecta sobre la eficiencia reproductiva de los sementales

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

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Evolution of the use of corticosteroids for the treatment of hospitalised COVID-19 patients in Spain between March and November 2020: SEMI-COVID national registry

Objectives: Since the results of the RECOVERY trial, WHO recommendations about the use of corticosteroids (CTs) in COVID-19 have changed. The aim of the study is to analyse the evolutive use of CTs in Spain during the pandemic to assess the potential influence of new recommendations. Material and methods: A retrospective, descriptive, and observational study was conducted on adults hospitalised due to COVID-19 in Spain who were included in the SEMI-COVID- 19 Registry from March to November 2020. Results: CTs were used in 6053 (36.21%) of the included patients. The patients were older (mean (SD)) (69.6 (14.6) vs. 66.0 (16.8) years; p < 0.001), with hypertension (57.0% vs. 47.7%; p < 0.001), obesity (26.4% vs. 19.3%; p < 0.0001), and multimorbidity prevalence (20.6% vs. 16.1%; p < 0.001). These patients had higher values (mean (95% CI)) of C-reactive protein (CRP) (86 (32.7-160) vs. 49.3 (16-109) mg/dL; p < 0.001), ferritin (791 (393-1534) vs. 470 (236- 996) µg/dL; p < 0.001), D dimer (750 (430-1400) vs. 617 (345-1180) µg/dL; p < 0.001), and lower Sp02/Fi02 (266 (91.1) vs. 301 (101); p < 0.001). Since June 2020, there was an increment in the use of CTs (March vs. September; p < 0.001). Overall, 20% did not receive steroids, and 40% received less than 200 mg accumulated prednisone equivalent dose (APED). Severe patients are treated with higher doses. The mortality benefit was observed in patients with oxygen saturation </=90%. Conclusions: Patients with greater comorbidity, severity, and inflammatory markers were those treated with CTs. In severe patients, there is a trend towards the use of higher doses. The mortality benefit was observed in patients with oxygen saturation </=90%

Different approaches to analyze muscle fat replacement with Dixon MRI in Pompe disease

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

H2A.Z overexpression suppresses senescence and chemosensitivity in pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is one of the most intractable and devastating malignant tumors. Epigenetic modifications such as DNA methylation and histone modification regulate tumor initiation and progression. However, the contribution of histone variants in PDAC is unknown. Here, we demonstrated that the histone variant H2A.Z is highly expressed in PDAC cell lines and PDAC patients and that its overexpression correlates with poor prognosis. Moreover, all three H2A.Z isoforms (H2A.Z.1, H2A.Z.2.1, and H2A.Z.2.2) are highly expressed in PDAC cell lines and PDAC patients. Knockdown of these H2A.Z isoforms in PDAC cell lines induces a senescent phenotype, cell cycle arrest in phase G2/M, increased expression of cyclin-dependent kinase inhibitor CDKN2A/p16, SA-β-galactosidase activity and interleukin 8 production. Transcriptome analysis of H2A.Z-depleted PDAC cells showed altered gene expression in fatty acid biosynthesis pathways and those that regulate cell cycle and DNA damage repair. Importantly, depletion of H2A.Z isoforms reduces the tumor size in a mouse xenograft model in vivo and sensitizes PDAC cells to gemcitabine. Overexpression of H2A.Z.1 and H2A.Z.2.1 more than H2A.Z.2.2 partially restores the oncogenic phenotype. Therefore, our data suggest that overexpression of H2A.Z isoforms enables cells to overcome the oncoprotective barrier associated with senescence, favoring PDAC tumor grow and chemoresistance. These results make H2A.Z a potential candidate as a diagnostic biomarker and therapeutic target for PDAC