Background
As muscle capillarization is related to the oxidative capacity of the muscle and the size of muscle fibres, capillary rarefaction may contribute to sarcopenia and functional impairment in ...older adults. Therefore, it is important to assess how ageing affects muscle capillarization and the interrelationship between fibre capillary supply with the oxidative capacity and size of the fibres.
Methods
Muscle biopsies from healthy recreationally active young (22 years; 14 men and 5 women) and older (74 years; 22 men and 6 women) people were assessed for muscle capillarization and the distribution of capillaries with the method of capillary domains. Oxidative capacity of muscle fibres was assessed with quantitative histochemistry for succinate dehydrogenase (SDH) activity.
Results
There was no significant age‐related reduction in muscle fibre oxidative capacity. Despite 18% type II fibre atrophy (P = 0.019) and 23% fewer capillaries per fibre (P < 0.002) in the old people, there was no significant difference in capillary distribution between young and old people, irrespective of sex. The capillary supply to a fibre was primarily determined by fibre size and only to a small extent by oxidative capacity, irrespective of age and sex. Based on SDH, the maximal oxygen consumption supported by a capillary did not differ significantly between young and old people.
Conclusions
The similar quantitative and qualitative distribution of capillaries within muscle from healthy recreationally active older people and young adults indicates that the age‐related capillary rarefaction, which does occur, nevertheless maintains the coupling between skeletal muscle fibre size and capillarization during healthy ageing.
Keywords: cervical magnetic stimulation; contractility; diaphragm; phrenic nerves; skeletal muscle; ultrafast ultrasound imaging Article Note: Edited by: Scott Powers & Ken O'Halloran Linked ...articles: This is a reply to a Letter to the Editor by Beltrami. To read the Letter to the Editor, visit Poulard et al. To read the article, visit Jean-Luc Gennisson and Damien Bachansson contributed equally to this work. Byline: Thomas Poulard, Martin Dres, Marie-Cecile Nierat, Isabelle Rivals, Jean-Yves Hogrel, Thomas Similowski, Jean-Luc Gennisson, Damien Bachasson
Background
Handgrip strength (HGS) is used to identify individuals with low muscle strength (dynapenia). The influence of the number of attempts on maximal HGS is not yet known and may differ ...depending on age and health status. This study aimed to assess how many attempts of HGS are required to obtain maximal HGS.
Methods
Three cohorts (939 individuals) differing in age and health status were included. HGS was assessed three times and explored as continuous and dichotomous variable. Paired t‐test, intraclass correlation coefficients (ICC) and Bland–Altman analysis were used to test reproducibility of HGS. The number of individuals with misclassified dynapenia at attempts 1 and 2 with respect to attempt 3 were assessed.
Results
Results showed the same pattern in all three cohorts. Maximal HGS at attempts 1 and 2 was higher than at attempt 3 on population level (P < 0.001 for all three cohorts). ICC values between all attempts were above 0.8, indicating moderate to high reproducibility. Bland–Altman analysis showed that 41.0 to 58.9% of individuals had the highest HGS at attempt 2 and 12.4 to 37.2% at attempt 3. The percentage of individuals with a maximal HGS above the gender‐specific cut‐off value at attempt 3 compared with attempts 1 and 2 ranged from 0 to 50.0%, with a higher percentage of misclassification in middle‐aged and older populations.
Conclusions
Maximal HGS is dependent on the number of attempts, independent of age and health status. To assess maximal HGS, at least three attempts are needed if HGS is considered to be a continuous variable. If HGS is considered as a discrete variable to assess dynapenia, two attempts are sufficient to assess dynapenia in younger populations. Misclassification should be taken into account in middle‐aged and older populations.
Muscle strength is a critical clinical hallmark in both health and disease. The current study introduces a novel portable device prototype (MyoQuad) for assessing and monitoring maximal voluntary ...isometric knee extension torque (MVIT).
Fifty-six patients with inclusion body myositis were studied. Knee extension weakness is a key feature in this inflammatory muscle disease. Cross-validation with an isokinetic dynamometer (Biodex System 3 Pro) was performed. Between-day reproducibility and ability to monitor changes in muscle strength over time compared to the gold standard method as a reference, were also investigated.
The measurement was feasible even in the weakest patients. Agreement between methods was excellent (standard error of measurement (SEM) was 3.8 Nm and intra-class correlation coefficient (ICC) was 0.973). Least significant difference (LSD) was 4.9 and 5.3 Nm for the MyoQuad and the Biodex, respectively Measurements using the MyoQuad exhibited excellent between-day reproducibility (SEM was 2.4 Nm and ICC was 0.989 versus 2.6 Nm and 0.988 using the Biodex). Changes in MVIT at 6 and 12 months were similar between methods (timepoint × method interaction was not significant; all p > 0.19); strength changes classified according to LSD at 6 and 12 months were consistent between methods (>70% consistent classification)).
The measurement of MVIT using the MyoQuad offers a cost-effective, portable and immediate alternative for the routine measurement of maximal voluntary isometric strength of the quadriceps. The MyoQuad offers a comfort and stability that cannot be provided by standard hand-held dynamometers. These results support quantitative muscle strength assessment using fixed yet flexible dynamometry within clinical routine and multicenter trials.
Age-related sarcopenia is a major health issue. To improve elderly person quality of life, it is important to characterize age-associated structural changes within the skeletal muscle. NMR imaging ...offers quantitative tools to monitor these changes. We scanned 93 subjects: 33 young adults aged between 19 and 27years old and 60 older adults between 69 and 80years old. Their physical activity was assessed using a tri-axial accelerometer and they were classified either as active or sedentary. A standard multi-slice multi-echo (MSME) sequence was run and water T2 maps were extracted using a tri-exponential fit. Fat fraction was quantified using three-point Dixon technique. Each quadriceps muscle was characterized by: water T2 mean value, water T2 heterogeneity and the mean fat fraction.
Statistical analysis (ANOVA) showed that water T2 mean values and its heterogeneity indices as well as fat fraction were significantly higher in the elderly group (p<0.05). Only fat fraction was significantly lower in the active group compared to the sedentary one (p<0.05). Linear regression confirmed the significant impact of age on these NMR parameters whereas physical activity impact was not systematic.
NMR imaging provided a comprehensive assessment of the aging process impact on skeletal muscle composition. Water T2 increase might be related to changes in fiber typology while increased T2 heterogeneities might correlate with some degree of tissue disorganization, like the development of interstitial fibrosis. Fat fraction and water T2 heterogeneity increase was partly slowed down by physical activity. These changes were not gender dependent.
•Intramuscular mean fat ratio, is significantly higher in older healthy volunteers.•Water T2 mean value and water T2 heterogeneity increase with age.•Intramuscular mean fat ratio is lower in active older volunteer.•The process of muscle aging is not different between men and women.
Update on outcome assessment in myositis Rider, Lisa G; Aggarwal, Rohit; Machado, Pedro M ...
Nature reviews. Rheumatology,
05/2018, Letnik:
14, Številka:
5
Journal Article
Recenzirano
Odprti dostop
The adult and juvenile myositis syndromes, commonly referred to collectively as idiopathic inflammatory myopathies (IIMs), are systemic autoimmune diseases with the hallmarks of muscle weakness and ...inflammation. Validated, well-standardized measures to assess disease activity, known as core set measures, were developed by international networks of myositis researchers for use in clinical trials. Composite response criteria using weighted changes in the core set measures of disease activity were developed and validated for adult and juvenile patients with dermatomyositis and adult patients with polymyositis, with different thresholds for minimal, moderate and major improvement in adults and juveniles. Additional measures of muscle strength and function are being validated to improve content validity and sensitivity to change. A health-related quality of life measure, which incorporates patient input, is being developed for adult patients with IIM. Disease state criteria, including criteria for inactive disease and remission, are being used as secondary end points in clinical trials. MRI of muscle and immunological biomarkers are promising approaches to discriminate between disease activity and damage and might provide much-needed objective outcome measures. These advances in the assessment of outcomes for myositis treatment, along with collaborations between international networks, should facilitate further development of new therapies for patients with IIM.
Abstract
Background
Diaphragm dysfunction is highly prevalent in mechanically ventilated patients. Recent work showed that changes in diaphragm shear modulus (ΔSMdi) assessed using ultrasound shear ...wave elastography (SWE) are strongly related to changes in Pdi (ΔPdi) in healthy subjects. The aims of this study were to investigate the relationship between ΔSMdi and ΔPdi in mechanically ventilated patients, and whether ΔSMdi is responsive to change in respiratory load when varying the ventilator settings.
Methods
A prospective, monocentric study was conducted in a 15-bed ICU. Patients were included if they met the readiness-to-wean criteria. Pdi was continuously monitored using a double-balloon feeding catheter orally introduced. The zone of apposition of the right hemidiaphragm was imaged using a linear transducer (SL10-2, Aixplorer, Supersonic Imagine, France). Ultrasound recordings were performed under various pressure support settings and during a spontaneous breathing trial (SBT). A breath-by-breath analysis was performed, allowing the direct comparison between ΔPdi and ΔSMdi. Pearson’s correlation coefficients (
r
) were used to investigate within-individual relationships between variables, and repeated measure correlations (
R
) were used for determining overall relationships between variables. Linear mixed models were used to compare breathing indices across the conditions of ventilation.
Results
Thirty patients were included and 930 respiratory cycles were analyzed. Twenty-five were considered for the analysis. A significant correlation was found between ΔPdi and ΔSMdi (
R
= 0.45, 95% CIs 0.35 0.54,
p
< 0.001). Individual correlation displays a significant correlation in 8 patients out of 25 (
r
= 0.55–0.86, all
p
< 0.05, versus
r
= − 0.43–0.52, all
p
> 0.06). Changing the condition of ventilation similarly affected ΔPdi and ΔSMdi. Patients in which ΔPdi–ΔSMdi correlation was non-significant had a faster respiratory rate as compared to that of patient with a significant ΔPdi–ΔSMdi relationship (median (Q1–Q3), 25 (18–33) vs. 21 (15–26) breaths.min
−1
, respectively).
Conclusions
We demonstrate that ultrasound SWE may be a promising surrogate to Pdi in mechanically ventilated patients. Respiratory rate appears to negatively impact SMdi measurement. Technological developments are needed to generalize this method in tachypneic patients.
Trial registration
NCT03832231
.
Objective
To characterize the natural history of spinal muscular atrophy (SMA) over 24 months using innovative measures such as wearable devices, and to provide evidence for the sensitivity of these ...measures to determine their suitability as endpoints in clinical trials.
Methods
Patients with Type 2 and 3 SMA (N = 81) with varied functional abilities (sitters, nonsitters, nonambulant, and ambulant) who were not receiving disease‐modifying treatment were assessed over 24 months: motor function (Motor Function Measure MFM), upper limb strength (MyoGrip, MyoPinch), upper limb activity (ActiMyo®), quantitative magnetic resonance imaging (fat fraction FFT2 mapping and contractile cross‐sectional area C‐CSA), pulmonary function (forced vital capacity FVC, peak cough flow, maximum expiratory pressure, maximum inspiratory pressure, and sniff nasal inspiratory pressure), and survival of motor neuron (SMN) protein levels.
Results
MFM32 scores declined significantly over 24 months, but not 12 months. Changes in upper limb activity could be detected over 6 months and continued to decrease significantly over 12 months, but not 24 months. Upper limb strength decreased significantly over 12 and 24 months. FVC declined significantly over 12 months, but not 24 months. FFT2 increased over 12 and 24 months, although not with statistical significance. A significant increase in C‐CSA was observed at 12 but not 24 months. Blood SMN protein levels were stable over 12 and 24 months.
Interpretation
These data demonstrate that the MFM32, MyoGrip, MyoPinch, and ActiMyo® enable the detection of a significant decline in patients with Type 2 and 3 SMA over 12 or 24 months.
Metformin, the classic anti-diabetic drug, improves motor symptoms in the DMSXL mouse model of myotonic dystrophy type 1. Bassez et al. now report a significant increase in patients' mobility ...following treatment with the maximal tolerated dose of metformin as compared to placebo in a double-blind randomized phase II clinical trial.
Abstract
Metformin, the well-known anti-diabetic drug, has been shown recently to improve the grip test performance of the DMSXL mouse model of myotonic dystrophy type 1. The drug may have positively affected muscle function via several molecular mechanisms, on RNA splicing, autophagia, insulin sensitivity or glycogen synthesis. Myotonic dystrophy remains essentially an unmet medical need. Since metformin benefits from a good toxicity profile, we investigated its potential for improving mobility in patients. Forty ambulatory adult patients were recruited consecutively at the neuromuscular reference centre of Henri-Mondor Hospital. Participants and investigators were all blinded to treatment until the end of the trial. Oral metformin or placebo was provided three times daily, with a dose-escalation period over 4 weeks up to 3 g/day, followed by 48 weeks at maximum dose. The primary outcome was the change in the distance walked during the 6-minute walk test, from baseline to the end of the study. Concomitant changes in muscle strength and effect on myotonia, gait variables, biological parameters and quality of life were explored. Patients randomized into two arms eventually revealed similar results in all physical measures and in the mean 6-minute walk test at baseline. For the 23/40 patients who fully completed the 1-year study, differences between the groups were statistically significant, with the treated group (n = 9) gaining a distance of 32.9 ± 32.7 m, while the placebo group (n = 14) gained 3.7 ± 32.4 m (P < 0.05). This improvement in mobility was associated with an increase in total mechanical power (P = 0.01), due to a concomitant increase in the cranial and antero-posterior directions suggesting an effect of the treatment on gait. Subanalysis revealed positive effects of metformin treatment on the 6-minute walk test at the first intermediate evaluation (after 16 weeks of treatment), quantitatively similar to those recorded at 1 year. In contrast, except for the expected limited weight loss associated to metformin treatment, there was no change in any of the other secondary endpoints, including myotonia and muscle strength. Patients in the treated group had a higher incidence of mild-to-moderate adverse effects, mostly gastrointestinal dysfunctions that required symptomatic treatment. Although results were statistically significant only for the per protocol population of patients and not in the intent-to-treat analysis, metformin at the maximal tolerated dose provided a promising effect on the mobility and gait abilities of myotonic patients. These encouraging results obtained in a small-scale monocentric phase II study call for replication in a well-powered multicentre phase III trial.
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