Physical exercise as a targeted therapy in idiopathic inflammatory myopathies
Bibliographic record
Abstract
Idiopathic inflammatory myopathies are comprised of polymyositis (PM) and dermatomyositis (DM) with muscle impairment being the primary clinical feature. With the currently recommended treatment regimen, a majority of patients develop sustained impaired muscle performance and poor health for undetermined reasons. The overall aim was to test the hypothesis that sustained muscle impairment and poor health in patients with established PM/DM are consequences of low aerobic capacity and that the use of endurance exercise, as the targeted intervention, will contribute to beneficial systemic and muscle adaptations and to clinical improvement. A further aim was to evaluate the individual priorities (e.g., patient preferences) of patients with established PM/DM. \n \n \n \nThe effect of a 12-week endurance exercise intervention was evaluated in a multi- center, randomized control trial in patients with established PM/DM (Papers II-IV). Exercise performance, aerobic capacity (maximal oxygen uptake (VO2 max)), and lactate levels in skeletal muscle were compared between patients (n = 23) and healthy controls (HC) (n = 12). Patients (n = 21) were randomized into an endurance exercise program or a nonexercise control group. Clinical assessments were performed at 0 and 12 weeks and consisted of: VO2 max, health (SF-36), muscle performance and disease activity (International Myositis Assessment and Clinical Studies Group criteria). Disability assessments were repeated at 52 weeks in an open extension. Associations between changes in clinical outcome measures and muscle properties were studied in vastus lateralis muscles by measuring extracellular lactate levels with microdialysis and by analyzing muscle biopsies for: mitochondrial enzyme activities (citrate synthase and β-hydroxyacyl-CoA dehydrogenase); mRNA expression profile; target protein validation by western blot analysis and by immuno-histochemistry (capillary density and inflammatory markers). In Paper I, we describe the patient preference in patients with PM/DM (n = 28) using the MacMaster Toronto Arthritis Patient Preference Disability Questionnaire (MACTAR). \n \n \n \nExercise performance and VO2 max were lower in the patients than in the HCs, whereas their lactate levels at exhaustion were similar. 12 weeks of endurance exercise added to the recommended pharmacological treatment in patients with established PM/DM increased capillary density and mitochondrial capacity in skeletal muscle, which could have contributed to the markedly improved muscle performance through increased aerobic capacity. Lactate levels at exhaustion decreased. The improved health and decreased clinical disease activity could potentially be mediated through the demonstrated improved VO2 max from the endurance exercise. 12 weeks of endurance exercise only had a long-term beneficial effect on muscle strength. Changes in gene expression following the endurance exercise program indicate activation of the aerobic phenotype and muscle growth pathways, which overwrites the muscle atrophy process and simultaneously suppresses the inflammatory response. However, other mechanisms, such as muscle weakness, also seem to contribute to impaired muscle performance in patients. The MACTAR revealed disease consequences important to individual patients that were not assessed in the recommended PM/DM outcome measures. Altogether the results of this thesis indicate that endurance exercise is essential to improve aerobic capacity, muscle performance, and health in these patients.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.029 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; both teacher heads agree on what is shown here.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".