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BACKGROUND: We investigated the potential of magnetic resonance elastography (MRE) stiffness measurements in skeletal muscles as an outcome measure, by determining its test-retest reliability, as well as its sensitivity to change in a longitudinal follow-up study. METHODS: We assessed test-retest reliability of muscle MRE in 20 subjects with (n = 5) and without (n = 15) muscle diseases and compared this to Dixon proton density fat fraction (PDFF) and volume measurements. Next, we measured MRE muscle stiffness in 21 adults with Becker muscular dystrophy (BMD) and 21 age-matched healthy controls at baseline, and after 9 and 18 months. We compared two different methods of analysing MRE data in this study: 'Method A' used the stiffness maps generated by the Philips MRE software, and 'Method B' applied a custom-made procedure based on wavelength measurements on the MRE images. RESULTS: Intraclass correlation coefficients (ICC) of muscle stiffness ranged from good (0.83 for left vastus medialis, P < 0.001) to poor (0.19 for right rectus femoris, P = 0.212) for the examined thigh muscles with Method A, but we did not find a significant test-retest reliability with Method B (P > 0.050 for all). The ICC of muscle PDFF and volume measurements was excellent (>0.90; P < 0.001) for all muscles. At baseline, the average stiffness of all thigh muscles was significantly lower in adults with BMD than in controls for both Method A (-0.2 kPa, P = 0.025) and Method B (-0.6 kPa, P < 0.001). Regardless of which method was used, there was no significant difference in the evolution of muscle stiffness in patients and controls over 18 months. CONCLUSIONS: Test-retest reliability of muscle MRE using a simple 2D technique was suboptimal, and did not reliably measure muscle stiffness changes in adults with BMD as compared with controls over 18 months. While the results provide motivation for testing more advanced 3D MRE methods, we conclude that the simple 2D MRE implementation used in this study is not suitable as an outcome measure for characterizing thigh muscle in clinical trials.
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BACKGROUND AND OBJECTIVES: Limb-girdle muscular dystrophy autosomal recessive type 12 (LGMDR12) is a rare hereditary muscular dystrophy for which outcome measures are currently lacking. We evaluated quantitative MRI and clinical outcome measures to track disease progression to determine which tests could be useful in future clinical trials to evaluate potential therapies. METHODS: We prospectively measured the following outcome measures in all participants at baseline and after 1 and 2 years: 6-minute walk distance (6MWD), 10-meter walk test (10MWT), the Medical Research Council (MRC) sum scores, Biodex isometric dynamometry, serum creatine kinase, and 6-point Dixon MRI of the thighs. RESULTS: We included 24 genetically confirmed, adult patients with LGMDR12 and 24 age-matched and sex-matched healthy controls. Patients with intermediate-stage thigh muscle fat replacement at baseline (proton density fat fraction [PDFF] 20%-70%) already showed an increase in PDFF in 8 of the 14 evaluated thigh muscles after 1 year. The standardized response mean demonstrated a high responsiveness to change in PDFF for 6 individual muscles over 2 years in this group. However, in patients with early-stage (<20%) or end-stage (>70%) muscle fat replacement, PDFF did not increase significantly over 2 years of follow-up. Biodex isometric dynamometry showed a significant decrease in muscle strength in all patients in the right and left hamstrings (-6.2 Nm, p < 0.002 and -4.6 Nm, p < 0.009, respectively) and right quadriceps muscles (-9 Nm, p = 0.044) after 1 year of follow-up, whereas the 6MWD, 10MWT, and MRC sum scores were not able to detect a significant decrease in muscle function/strength even after 2 years. There was a moderately strong correlation between total thigh PDFF and clinical outcome measures at baseline. DISCUSSION: Thigh muscle PDFF imaging is a sensitive outcome measure to track progressive muscle fat replacement in selected patients with LGMDR12 even after 1 year of follow-up and correlates with clinical outcome measures. Biodex isometric dynamometry can reliably capture the loss of muscle strength over the course of 1 year in patients with LGMDR12 and should be included as an outcome measure in future clinical trials as well.
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Imagen por Resonancia Magnética , Protones , Adulto , Creatina Quinasa , Humanos , Imagen por Resonancia Magnética/métodos , Músculo Esquelético/diagnóstico por imagen , Distrofia Muscular de Cinturas , Evaluación de Resultado en la Atención de Salud , Estudios ProspectivosRESUMEN
BACKGROUND & AIMS: Enteral nutrition with polymeric intact protein formula is the preferred medical nutrition strategy in critically ill patients when oral intake is insufficient. Enteral nutrition formulas are often rich in casein protein, which has coagulating properties. Coagulation in the stomach impedes gastric emptying and might result in high gastric residual volumes which are a clinical sign of gastrointestinal intolerance and a major reason to decrease or to discontinue enteral feeding. In this study the impact of protein composition of enteral formula on gastric content volume (GCV) during and after continuous feeding was tested in healthy volunteers in whom gastrointestinal conditions of critically ill patients were mimicked. METHODS: An enteral formula including 4 proteins (P4) with non-coagulating properties was compared to a casein-dominant formula (Cas) with coagulating properties. Esomeprazole and codeine were administered to mimic stress ulcer prophylaxis and induce gastroduodenal motor dysfunction, both being hallmarks of critically ill patients. GCV was measured with magnetic resonance imaging during and after continuous enteral feeding (100 mL/h for 4h) in a randomized single-center cross-over study. Results are provided as mean (SD). Significance level of p < 0.05 was applied. RESULTS: Twenty subjects completed the study (14 women, 6 men, 25.8 (4.6) years old, BMI: 22.5 (1.5) kg/m2). The GCV as change from baseline at T = 240 (primary endpoint) did not differ between study products (P4: 124.3 (83.4) vs. Cas: 137.1 (102.0) mL, 95% CI: -57.4, 27.0, p = 0.457). During feeding and after cessation of feeding, the area under the GCV-curve (AUC0-360 GCV) for P4 and Cas was 44631.1 (15546.1) and 52822.2 (19686.1) mL∗min, respectively (p = 0.061). During feeding the GCV was lower at T = 180 min (175.4 (64.8) vs. 205.2 (75.4) mL, p = 0.038) and after cessation of feeding at T = 300 min (81.3 (71.1) vs. 116.3 (84.3) mL, p = 0.004) and T = 330 min (39.9 (53.9) vs. 73.6 (81.1) mL, p = 0.031). With P4 it took less time to reach half of the GCV at T = 240 min compared to Cas (52.8 (27.6) vs. 65.4 (29.9) min, p = 0.020). CONCLUSIONS: In this study in which healthy volunteers received esomeprazole and codeine to mimic gastrointestinal conditions of critically ill patients, observations of secondary endpoints suggest faster gastric emptying with P4 compared to Cas, and less gastric accumulation, possibly due to the non-coagulating properties of the P4 protein blend. Considering the small effect and the possible clinical relevance of reduced intragastric accumulation of enteral nutrition, the potential impact of protein coagulation should be further investigated in relevant study populations. Registered under Netherlands Trial Register identifier no. NTR6423.
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Proteínas en la Dieta/administración & dosificación , Nutrición Enteral , Adulto , Aminoácidos/sangre , Analgésicos Opioides/farmacología , Antiulcerosos/farmacología , Área Bajo la Curva , Caseínas/química , Codeína/farmacología , Estudios Cruzados , Proteínas en la Dieta/análisis , Proteínas en la Dieta/farmacocinética , Esomeprazol/farmacología , Femenino , Semivida , Humanos , Masculino , Suero Lácteo/química , Adulto JovenRESUMEN
BACKGROUND: An isovolumetric intragastric balloon to continuously measure gastric phasic contractility was recently developed by us. We aimed to investigate the readout of this technique in relation to gastric content and gastric emptying. METHODS: In this crossover investigation, the VIPUNTM Gastric Monitoring System, which comprises a double lumen nasogastric feeding tube with integrated intragastric balloon, was used to assess phasic gastric contractility by interpretation of the pressure in an isovolumetric balloon in 10 healthy subjects. Balloon pressure was recorded in fasted state, during a 2-hour intragastric nutrient infusion (1 kcal/ml at 25, 75, or 250 ml/h) and 4 hours post-infusion, and quantified as Gastric Balloon Motility Index (GBMI), ranging from 0 (no contractility) to 1 (maximal contractility). Gastric accumulation was quantified with magnetic resonance imaging and gastric emptying with a13 C-breath test. Results are expressed as mean(SD). KEY RESULTS: GBMI was significantly lower during infusion at 250 ml/h compared to baseline (0.13(0.05) versus 0.46(0.12)) and compared to infusion at 25 (0.54(0.21)) and 75 ml/h (0.43(0.20)), all P < 0.005. Gastric content volume was larger after infusion at 250 versus 75 ml/h (P < 0.001). Half-emptying time and accumulation were both negatively correlated with postprandial contractility. Postprandial GBMI was significantly lower when GCV>0 ml compared to when the stomach was empty. CONCLUSIONS AND INFERENCES: Enteral nutrition dose-dependently decreased the contractility readout. This decrease was linked to gastric accumulation of enteral nutrition.