Assessment by Patients of a Connected System for Telerehabilitation: Lessons Learned from a Randomized Qualitative Study.

International audienceThis poster presents the design of a connected system for telerehabilitation for patients with obesity and the assessment of the system through a randomized qualitative study on a sample of 15 patients. The patients expressed positive motivation but negatively assessed (as a deficiency) the system operation. All patients found that the system was neither intuitive nor easy to use

Response to Electrostimulation Is Impaired in Muscle Cells from Patients with Chronic Obstructive Pulmonary Disease

International audienceAmong the comorbidities associated with chronic obstructive pulmonary disease (COPD), skeletal muscle weakness and atrophy are known to affect patient survival rate. In addition to muscle deconditioning, various systemic and intrinsic factors have been implicated in COPD muscle dysfunction but an impaired COPD muscle adaptation to contraction has never been extensively studied. We submitted cultured myotubes from nine healthy subjects and nine patients with COPD to an endurance-type protocol of electrical pulse stimulation (EPS). EPS induced a decrease in the diameter, covered surface and expression of MHC1 in COPD myotubes. Although the expression of protein degradation markers was not affected, expression of the protein synthesis marker mTOR was not induced in COPD compared to healthy myotubes after EPS. The expression of the differentiation markers p16INK4a and p21 was impaired, while expression of Myf5 and MyoD tended to be affected in COPD muscle cells in response to EPS. The expression of mitochondrial biogenesis markers PGC1α and MFN2 was affected and expression of TFAM and COX1 tended to be reduced in COPD compared to healthy myotubes upon EPS. Lipid peroxidation was increased and the expression of the antioxidant enzymes SOD2 and GPx4 was affected in COPD compared to healthy myotubes in response to EPS. Thus, we provide evidence of an impaired response of COPD muscle cells to contraction, which might be involved in the muscle weakness observed in patients with COPD

Prognostic Impact of Sleep Patterns and Related-Drugs in Patients with Heart Failure

International audienceSleep disturbances are frequent among patients with heart failure (HF). We hypothesized that self-reported sleep disturbances are associated with a poor prognosis in patients with HF. A longitudinal study of 119 patients with HF was carried out to assess the association between sleep disturbances and the occurrence of major cardiovascular events (MACE). All patients with HF completed self-administered questionnaires on sleepiness, fatigue, insomnia, quality of sleep, sleep patterns, anxiety and depressive symptoms, and central nervous system (CNS) drugs intake. Patients were followed for a median of 888 days. Cox models were used to estimate the risk of MACE associated with baseline sleep characteristics. After adjustment for age, the risk of a future MACE increased with CNS drugs intake, sleep quality and insomnia scores as well with increased sleep latency, decreased sleep efficiency and total sleep time. However, after adjustment for left ventricular ejection fraction and hypercholesterolemia the HR failed to be significant except for CNS drugs and total sleep time. CNS drugs intake and decreased total sleep time were independently associated with an increased risk of MACE in patients with HF. Routine assessment of self-reported sleep disturbances should be considered to prevent the natural progression of HF

Impaired training-induced adaptation of blood pressure in COPD patients: implication of the muscle capillary bed

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Oxidative stress regulates autophagy in cultured muscle cells of patients with chronic obstructive pulmonary disease

International audienceThe proteolytic autophagy pathway is enhanced in the lower limb muscles of patients with chronic obstructive pulmonary disease (COPD). Reactive oxygen species (ROS) have been shown to regulate autophagy in the skeletal muscles, but the role of oxidative stress in the muscle autophagy of patients with COPD is unknown. We used cultured myoblasts and myotubes from the quadriceps of eight healthy subjects and twelve patients with COPD (FEV1% predicted: 102.0% and 32.0%, respectively; p < 0.0001). We compared the autophagosome formation, the expression of autophagy markers, and the autophagic flux in healthy subjects and the patients with COPD, and we evaluated the effects of the 3-methyladenine (3-MA) autophagy inhibitor on the atrophy of COPD myotubes. Autophagy was also assessed in COPD myotubes treated with an antioxidant molecule, ascorbic acid. Autophagosome formation was increased in COPD myoblasts and myotubes (p = 0.011; p < 0.001), and the LC3 2/LC3 1 ratio (p = 0.002), SQSTM1 mRNA and protein expression (p = 0.023; p = 0.007), BNIP3 expression (p = 0.031), and autophagic flux (p = 0.002) were higher in COPD myoblasts. Inhibition of autophagy with 3-MA increased the COPD myotube diameter (p < 0.001) to a level similar to the diameter of healthy subject myotubes. Treatment of COPD myotubes with ascorbic acid decreased ROS concentration (p < 0.001), ROS-induced protein carbonylation (p = 0.019), the LC3 2/LC3 1 ratio (p = 0.037), the expression of SQSTM1 (p < 0.001) and BNIP3 (p < 0.001), and increased the COPD myotube diameter (p < 0.001). Thus, autophagy signaling is enhanced in cultured COPD muscle cells. Furthermore, the oxidative stress level contributes to the regulation of autophagy, which is involved in the atrophy of COPD myotubes in vitro

Effects of a human microenvironment on the differentiation of human myoblasts

International audienceMyogenic differentiation mechanisms are generally assessed using a murine cell line placed in low concentrations of an animal-derived serum. To more closely approximate in vivo pathophysiological conditions, recent studies have combined the use of human muscle cells with human serum. Nevertheless, the in vitro studies of the effects of a human microenvironment on the differentiation process of human myoblasts require the identification of the culture conditions that would provide an optimal and reproducible differentiation process of human muscle cells. We assessed the differentiation variability resulting from the use of human myoblasts and serums from healthy subjects by measuring the myotube diameter, fusion index and surface covered by myotubes. We showed the preserved cell-dependent variability of the differentiation response of myoblasts cultured in human serums compared to FBS. We found that using a pool of serums reduced the serum-dependent variability of the myogenic response compared to individual serums. We validated our methodology by showing the atrophying effect of pooled serums from COPD patients on healthy human myotubes. By replacing animal-derived tissues with human myoblasts and serums, and by validating the sensitivity of cultured human muscle cells to a pathological microenvironment, this human cell culture model offers a valuable tool for studying the role of the microenvironment in chronic disease

Fiber atrophy, oxidative stress, and oxidative fiber reduction are the attributes of different phenotypes in chronic obstructive pulmonary disease patients

International audienceFiber atrophy, oxidative stress, and oxidative fiber reduction are the attributes of different phenotypes in chronic obstructive pulmonary disease patients..—Peripheral muscle dysfunction, associated with reductions in fiber cross-sectional area (CSA) and in type I fibers, is a key outcome in chronic obstructive pulmonary disease (COPD). However, COPD peripheral muscle function and structure show great heterogeneity, overlapping those in sedentary healthy subjects (SHS). While discrepancies in the link between muscle structure and phenotype remain unexplained, we tested whether the fiber CSA and the type I fiber reductions were the attributes of different phenotypes of the disease, using unsupervised clustering method and post hoc validation. Principal component analysis performed on functional and histomorphological parameters in 64 COPD patients {forced expiratory volume in 1 s (FEV1) 42.0 [30.0 –58.5]% predicted} and 27 SHS (FEV 1 105.0 [95.0 –114.0]% predicted) revealed two COPD clusters with distinct peripheral muscle dysfunctions. These two clusters had different type I fiber proportion (26.0 14.0% vs. 39.8 12.6%; P 0.05), and fiber CSA (3,731 1,233 vs. 5,657 1,098 m 2 ; P 0.05). The " atrophic " cluster showed an increase in muscle protein carbonylation (131.5 [83.6 –200.3] vs. 83.0 [68.3–105.1]; P 0.05). Then, COPD patients underwent pulmonary rehabilitation. If the higher risk of exacerba-tions in the " atrophic " cluster did not reach statistical significance after adjustment for FEV1 (hazard ratio: 2.43; P 0.11, n 54), the improvement of VO 2sl after training was greater than in the nonatro-phic cluster (24 16% vs. 6 13%; P 0.01). Last, their age was similar (60.4 8.8 vs. 60.8 9.0 yr; P 0.87), suggesting a different time course of the disease. We identified and validated two phenotypes of COPD patients showing different muscle histomor-phology and level of oxidative stress. Thus our study demonstrates that the muscle heterogeneity is the translation of different phenotypes of the disease

Impact of a Mobile Telerehabilitation Solution on Metabolic Health Outcomes and Rehabilitation Adherence in Patients With Obesity: Randomized Controlled Trial

International audienceBackground Obesity is a major public health issue. Combining exercise training, nutrition, and therapeutic education in metabolic rehabilitation (MR) is recommended for obesity management. However, evidence from randomized controlled studies is lacking. In addition, MR is associated with poor patient adherence. Mobile health devices improve access to MR components. Objective The aim of this study is to compare the changes in body composition, anthropometric parameters, exercise capacity, and quality of life (QOL) within 12 weeks of patients in the telerehabilitation (TR) program to those of usual care patients with obesity. Methods This was a parallel-design randomized controlled study. In total, 50 patients with obesity (BMI>30 kg/m²) were included in a TR group (TRG) or a usual care group (UCG) for 12 weeks. Patients underwent biometric impedance analyses, metabolic exercise tests, actimetry, and QOL and satisfaction questionnaires. The primary outcome was the change in fat mass at 12 weeks from baseline. Secondary outcomes were changes in body weight, metabolic parameters, exercise capacity, QOL, patients’ adhesion, and satisfaction. Results A total of 49 patients completed the study. No significant group × time interaction was found for fat mass (TRG: mean 1.7 kg, SD 2.6 kg; UCG: mean 1.2 kg, SD 2.4 kg; P=.48). Compared with the UCG, TRG patients tended to significantly improve their waist to hip ratios (TRG: −0.01 kg, SD 0.04; UCG: +0.01 kg, SD 0.06; P=.07) and improved QOL physical impact (TRG: +21.8, SD 43.6; UCG: −1.2, SD 15.4; P=.005). Significant time effects were observed for body composition, 6-minute walk test distance, exercise metabolism, sedentary time, and QOL. Adherence (95%) and satisfaction in the TRG were good. Conclusions In adults with obesity, the TR program was not superior to usual care for improving body composition. However, TR was able to deliver full multidisciplinary rehabilitation to patients with obesity and improve some health outcomes. Given the patients’ adherence and satisfaction, pragmatic programs should consider mobile health devices to improve access to MR. Further studies are warranted to further establish the benefits that TR has over usual care. Trial Registration ClinicalTrials.gov NCT03396666; http://clinicaltrials.gov/ct2/show/NCT0339666

Skeletal Muscle Phenotype in Patients Undergoing Long-Term Hemodialysis Awaiting Kidney Transplantation

International audienceBackground and objectives Age and comorbidity-related sarcopenia represent a main cause of muscle dysfunction in patients on long-term hemodialysis. However, recent findings suggest muscle abnormalities that are not associated with sarcopenia. The aim of this study was to isolate functional and cellular muscle abnormalities independently of other major confounding factors, including malnutrition, age, comorbidity, or sedentary lifestyle, which are common in patients on maintenance hemodialysis. To overcome these confounding factors, alterations in skeletal muscle were analyzed in highly selected patients on long-term hemodialysis undergoing kidney transplantation. Design, setting, participants, & measurements In total, 22 patients on long-term hemodialysis scheduled for kidney transplantation with few comorbidities, but with a long-term uremic milieu exposure, and 22 age, sex, and physical activity level frequency-matched control participants were recruited. We compared biochemical, functional, and molecular characteristics of the skeletal muscle using maximal voluntary force and endurance of the quadriceps, 6-minute walking test, and muscle biopsy of vastus lateralis . For statistical analysis, mean comparison and multiple regression tests were used. Results In patients on long-term hemodialysis, muscle endurance was lower, whereas maximal voluntary force was not significantly different. We observed a transition from type I (oxidative) to type II (glycolytic) muscle fibers, and an alteration of mitochondrial structure (swelling) without changes in DNA content, genome replication (peroxisome proliferator activator receptor γ coactivator-1 α and mitochondrial transcription factor A), regulation of fusion (mitofusin and optic atrophy 1), or fission (dynamin-related protein 1). Notably, there were autophagosome structures containing glycogen along with mitochondrial debris, with a higher expression of light chain 3 (LC3) protein, indicating phagophore formation. This was associated with a greater conversion of LC3-I to LC3-II and the expression of Gabaralp1 and Bnip3l genes involved in mitophagy. Conclusions In this highly selected long-term hemodialysis population, a low oxidative phenotype could be defined by a poor endurance, a fiber-type switch, and an alteration of mitochondria structure, without evidence of sarcopenia. This phenotype could be related to uremia through the activation of autophagy/mitophagy. Clinical Trial registration numbers: NCT02794142 and NCT02040363