Objectives The aim of this study was to investigate the systemic and skeletal muscle levels of atrophy-associated myokines in patients with idiopathic inflammatory myopathies (IIM) and their association with clinical characteristics of myositis. Methods A total of 94 IIM patients and 162 healthy controls were recruited. Of those, 20 IIM patients and 28 healthy controls underwent a muscle biopsy. Circulating concentrations of myostatin, follistatin, activin A and TGF-β1 were assessed by ELISA. The expression of myokines and associated genes involved in the myostatin signalling pathway in muscle tissue was determined by real-time PCR. Results We report decreased levels of circulating myostatin (median 1817 vs 2659 pg/ml; P = 0.003) and increased follistatin (1319 vs 1055 pg/ml; P = 0.028) in IIM compared with healthy controls. Activin A levels were also higher in IIM (414 vs 309 pg/ml; P = 0.0005) compared with controls. Myostatin was negatively correlated to muscle disease activity assessed by physician on visual analogue scale (MDA) (r = −0.289, P = 0.015) and positively to manual muscle testing of eight muscles (r = 0.366, P = 0.002). On the other hand, follistatin correlated positively with MDA (r = 0.235, P = 0.047). Gene expression analysis showed higher follistatin (P = 0.003) and myostatin inhibitor follistatin-like 3 protein (FSTL3) (P = 0.008) and lower expression of activin receptor type 1B (ALK4) (P = 0.034), signal transducer SMAD3 (P = 0.023) and atrophy marker atrogin-1 (P = 0.0009) in IIM muscle tissue compared with controls. Conclusion This study shows lower myostatin and higher follistatin levels in circulation and attenuated expression of myostatin pathway signalling components in skeletal muscle of patients with myositis, a newly emerging pattern of the activin A–myostatin–follistatin system in muscle wasting diseases.

There is a need to create a standardized and validated protocol for evaluation of pathological changes in muscle MRI in IIM. The most appropriate number and distribution of muscle groups as well as evaluated pathological features need to be determined. Based on this literature search, the future scoring system should include assessment of muscle oedema, fatty infiltration, muscle atrophy and possibly the presence of fascial and subcutaneous inflammation. Whether the quantitative methods provide more reliable information regarding disease activity remains unclear.

Background The structural and functional changes of the skeletal muscles in idiopathic inflammatory myopathies (IIM) caused by inflammation and immune changes can be severely disabling. The objective of this study was to assess the effect of a 24-week program combining a supervised training of activities of daily living (ADL), resistance, and stability with home exercise for improving muscle function, compared to a daily home-based exercise representing the regular outpatient care. Methods Fifty-seven patients with IIM were consecutively and non-selectively enrolled in an intervention (IG, n = 30) or control (CG, n = 27) group. Both groups were provided a standard-of-care pharmacological treatment and follow-up. Only the IG underwent the supervised intervention twice a week for 1 h per session. At baseline, 12, 24, and 48 weeks, all patients were assessed by an assessor blinded to the intervention for primary outcomes: muscle strength (Manual Muscle Testing of eight muscle groups [MMT-8]) and endurance (Functional Index-2 [FI-2]), and secondary outcomes: stability and body composition. Secondary outcomes also included questionnaires evaluating disability (Health Assessment Questionnaire [HAQ]), quality of life (Short Form 36 [SF-36]), depression (Beck’s Depression Inventory-II [BDI-II]), and fatigue (Fatigue Impact Scale [FIS]), and analysis of the systemic and local inflammatory response and perceived exertion to assess the safety of the intervention. Results Twenty-seven patients in the IG and 23 in the CG completed the entire program and follow-up. At week 24, compared to deterioration in the CG, we found a significant improvement in the IG in muscle strength (mean % improvement compared to baseline by 26%), endurance (135%), disability (39%), depression (26%), stability (11%), and basal metabolism (2%) and a stabilization of fitness for physical exercise. The improvement was clinically meaningful (a 24-week change by >20%) in most outcomes in a substantial proportion of patients. Although the improvement was still present at 48 weeks, the effect was not sustained during follow-up. No significant increase in the systemic or local expression of inflammatory markers was found throughout the intervention. Conclusions This 24-week supervised intervention focused on ADL training proved to be safe and effective. It not only prevented the progressive deterioration, but also resulted in a significant improvement in muscle strength, endurance, stability, and disability, which was clinically meaningful in a substantial proportion of patients. Trial registration ISRCTN35925199 (retrospectively registered on 22 May 2020).

Regular exercise improves muscle functional capacity and clinical state of patients with idiopathic inflammatory myopathy (IIM). r In our study, we used an in vitro model of human primary muscle cell cultures, derived from IIM patients before and after a 6-month intensive supervised training intervention to assess the impact of disease and exercise on lipid metabolism dynamics. r We provide evidence that muscle cells from IIM patients display altered dynamics of lipid metabolism and impaired adaptive response to saturated fatty acid load compared to healthy controls. r A 6-month intensive supervised exercise training intervention in patients with IIM mitigated disease effects in their cultured muscle cells, improving or normalizing their capacity to handle lipids. r These findings highlight the putative role of intrinsic metabolic defects of skeletal muscle in the pathogenesis of IIM and the positive impact of exercise, maintained in vitro by yet unknown epigenetic mechanisms.

The modified DETECT algorithm detects all patients with PAH diagnosed according to ECS/ERS 2009 guidelines and RHC. Data of the 2-year follow-up indicate a possible positive predictive role for the modified DETECT calculator.

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BackgroundIdiopathic inflammatory myopathy are characterized by muscle weakness, caused by inflammation and immune changes in the affected muscles, which lead to a limitation in the execution of day-to-day activities (ADL). The aim of our study was to investigate the impact of specialized and intensive aDL training on muscle strength and endurance, depression and QoL of IIM patients.ObjectivesThe study included a total of 50 IIM patients who fulfilled the Bohan and Peter 1975 criteria and had skeletal muscle involvement. 27 patients were recruited into the intervention group (IG) and 23 patients into the control group (CG). Both groups received an educational material for home exercise, but only the IG underwent a 6-month intensive training with a subsequent 6-month follow-up period.MethodsPatients were assessed by a physician and a physiotherapist blinded to intervention at months 0, 3, 6, and 12. Patients also filled out patient reported outcomes questionnaires and provided blood for routine laboratory analysis and bio-banking. Data analysis was performed between groups and within the group.ResultsCompared to the observed statistically significant deterioration in the CG over the intervention period, we found a statistically significant improvement in the IG in objectively assessed strength and endurance of muscles as well as in subjectively assessed functional abilities and depression (Table). During the follow-up period, there was a significant deterioration or stagnation of the achieved positive results in the IG. Nevertheless, improved functional ability during the intervention period persisted in the IG in the follow-up period as well. Only numerical improvements in the IG during the intervention compared to the numerical deterioration in CG, that did not reach statistical significance, were observed in some subjectively assessed domains of QoL (SF-36) and fatigue (FIS – in physical dimension). Parameter (unit) Intervention group Mean ± SEM Control group Mean ± SEM Intra-group analysis (Friedman+Dunn ) Inter-group analysis (2WA) Interevention gr. Control group MMT8 m0: 54.7 ± 2.6m3: 60.7 ± 2.4m6: 69.1 ± 1.9m12: 64.0 ± 2.5m0: 63.6 ± 2.0m3: 57.9 ± 1.8m6: 54.2 ± 1.9m12: 56.5 ± 2.2m0-3: p<0.01m3-6: p<0.0001m0-6: p<0.0001m6-12: p<0.05m0-3: p<0.05m3-6: NS m0-6: p<0.0001m6-12:NSp<0.0001 FI-2 (%) m0: 30.0 ± 4.4m3: 46.9 ± 4.7m6: 70.6 ± 4.9m12: 58.4 ± 5.8m0: 38.3 ± 5.3m3: 29.6 ± 4.6m6: 26.1 ± 4.1m12: 25.7 ± 3.6m0-3: p<0.01m3-6: p<0.0001m0-6: p<0.0001m6-12: p<0.05m0-3: NS m3-6: NS m0-6: p<0.01m6-12: NSp<0.0001 HAQ m0: 0.9 ± 0.2m3: 0.7 ± 0.1m6: 0.6 ± 0.1m12: 0.8 ± 0.2m0: 1.3 ± 0.2m3: 1.4 ± 0.2m6: 1.4 ± 0.2m12: 1.5 ± 0.2m0-3: NS m3-6: NS m0-6: p<0.01m6-12: p<0.05m0-3: NS m3-6: NS m0-6: NS m6-12: NSp=0.0002 BDI-II m0: 11.9 ± 2.1m3: 10.7 ± 1.7m6: 8.9 ± 1.5m12: 10.5 ± 2.0m0: 13.0 ± 1.4m3: 14.3 ± 1.7m6: 15.7 ± 1.m12: 16.0 ± 2.0m0-3: NS m3-6: NS m0-6: p<0.05m6-12: NSm0-3: NS m3-6: NS m0-6: NS m6-12: NSp=0.0025ConclusionOur specialized and intensive aDL workout led to a significant improvement in the observed paramet...

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