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Altered neuronal nitric oxide synthase function in Duchenne muscular dystrophy leads to impaired mitochondrial function which is thought to be one cause of muscle damage in this disease. The study tested if increased intramuscular nitric oxide concentration can improve mitochondrial energy metabolism in Duchenne muscular dystrophy using a novel therapeutic approach through the combination of L-arginine with metformin. Five ambulatory, genetically confirmed Duchenne muscular dystrophy patients aged between 7–10 years were treated with L-arginine (3 x 2.5 g/d) and metformin (2 x 250 mg/d) for 16 weeks. Treatment effects were assessed using mitochondrial protein expression analysis in muscular biopsies, indirect calorimetry, Dual-Energy X-Ray Absorptiometry, quantitative thigh muscle MRI, and clinical scores of muscle performance. There were no serious side effects and no patient dropped out. Muscle biopsy results showed pre-treatment a significantly reduced mitochondrial protein expression and increased oxidative stress in Duchenne muscular dystrophy patients compared to controls. Post-treatment a significant elevation of proteins of the mitochondrial electron transport chain was observed as well as a reduction in oxidative stress. Treatment also decreased resting energy expenditure rates and energy substrate use shifted from carbohydrates to fatty acids. These changes were associated with improved clinical scores. In conclusion pharmacological stimulation of the nitric oxide pathway leads to improved mitochondria function and clinically a slowing of disease progression in Duchenne muscular dystrophy. This study shall lead to further development of this novel therapeutic approach into a real alternative for Duchenne muscular dystrophy patients.Trial RegistrationClinicalTrials.gov NCT02516085

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Purpose The Knee Injury Osteoarthritis Outcome Score for children (KOOS-Child) is a self-administered, valid and reliable questionnaire for children and adolescents with knee disorders such as Osgood Schlatter disease, anterior knee pain, and patella dislocation. This study aimed to cross-culturally adapt the German version of the KOOS-Child questionnaire and test the reliability in two groups of children, one treated conservatively and the other surgically. Methods A forward–backward translation of the original questionnaire into the German language was conducted. Children and adolescents between 10 and 18 years of age with knee disorders were included. Two groups were compared: sample one consisted of 24 participants with knee pain [20.8% boys; mean age = 13.4 (1.8) years treated conservatively. These participants completed the KOOS-Child questionnaire twice within two weeks to assess test–retest reliability. The second sample included 23 subjects (21.7% boys; mean age = 15.3 (1.9) years] treated surgically due to a knee disorder. They completed the questionnaire before surgery and six months postoperatively. Test–retest reliability and internal consistency were assessed using Spearman’s rank correlation and Cronbach’s alpha. Results All subscales showed a good to excellent internal consistency at both measurement points in both groups (conservatively treated group: a = 0.88–0.95; surgery group a = 0.80–0.91), with the exception of the subscale knee problems (conservatively treated: a = 0.60 and 0.52; surgery: α = 0.77 and 0.66). Test–retest reliability was between r = 0.85 and 0.94. Conclusion The predominantly good to excellent internal consistency and the high test–retest reliability justifies the use of the German adaptation of the KOOS-Child questionnaire as a reliable multidimensional instrument for measuring health status and therapeutic effects in adolescents’ knee disorders.

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It remains controversial whether physical activity promotes bone health in childhood cancer survivors (CCS). We aimed to assess the effect of a one-year general exercise intervention on lower body bone parameters of CCS. CCS ≥16 years at enrollment, <16 years at diagnosis and ≥5 years in remission were identified from the national Childhood Cancer Registry. Participants randomized to the intervention group were asked to perform an additional ≥2.5 hours of intense physical activity/week, controls continued exercise as usual. Bone health was assessed as a secondary trial endpoint at baseline and after 12-months. We measured tibia bone mineral density (BMD) and morphology by peripheral quantitative computed tomography and lumbar spine, hip and femoral neck BMD by dual-energy x-ray absorptiometry. We performed intention-to-treat, per protocol, and an explorative subgroup analyses looking at low Abbreviations: BMD, bone mineral density (mg/cm 3 or g/cm 2 ); CCS, childhood cancer survivor(s); CPET, cardiopulmonary exercise test; DXA, dual-energy x-ray absorptiometry; ITT, intention-totreat analysis; PA, physical activity; pQCT, peripheral quantitative computed tomography; RCT, randomized controlled trial.

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