Background: Lateral elbow tendinopathy is a disabling tendon overuse injury. It remains unknown if a corticosteroid injection (CSI) or tendon needling (TN) combined with heavy slow resistance (HSR) training is superior to HSR alone in treating lateral elbow tendinopathy. Purpose/Hypothesis: The purpose was to investigate the effects of HSR combined with either (1) a CSI, (2) TN, or (3) placebo needling (PN) as treatment for lateral elbow tendinopathy. We hypothesized that 12 weeks of HSR in combination with a CSI or TN would have superior effects compared with PN at 12, 26, and 52 (primary endpoint) weeks’ follow-up on primary (Disabilities of the Arm, Shoulder and Hand [DASH] score) and secondary outcomes in patients with chronic unilateral lateral elbow tendinopathy. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A total of 60 patients with chronic unilateral lateral elbow tendinopathy were randomized to perform 12 weeks of home-based HSR with elastic band exercises combined with either (1) a CSI, (2) TN, or (3) PN, and at 12, 26, and 52 weeks, we assessed the primary outcome, the DASH score, and secondary outcomes: shortened version of the DASH (QuickDASH) score, pain (numerical rating scale [NRS] score), pain-free grip strength, and hypervascularization (power Doppler area). Results: A CSI, TN, and PN improved patient outcomes equally based on the DASH (Δ20 points), QuickDASH (Δ21 points), and NRS (Δ2.5 points) scores after 12 weeks. Further, after 12 weeks, a CSI also resulted in decreased hypervascularization (power Doppler area) compared with PN (Δ–2251 pixels, P = .0418). Except for the QuickDASH score (CSI increased score by Δ15 points compared with PN; P = .0427), there were no differences between the groups after 52 weeks. Conclusion: These results suggest that 12 weeks of HSR improved symptoms in both the short and the long term and that a CSI or TN did not amplify this effect. In addition, a CSI seemed to impair patient-reported outcomes compared with HSR alone at long-term follow-up. Registration: NCT02521298 ( ClinicalTrials.gov identifier).

Individuals with cerebral palsy (CP) develop skeletal muscle contractures that impair muscle function. In turn, contractures affect the ability to ambulate and often promote a sedentary lifestyle. The aim of the present study was to investigate the systemic inflammatory markers transforming growth factor beta-1 (TGFβ1), C-reactive protein (CRP), and interleukin-6 (IL-6) in children and adults with CP. Blood samples of n = 34 participants (24 individuals with CP (n = 14 children with CP age 10.36 ± 1.1 and n = 10 adults with CP age 38.80 ± 3.6) and 10 healthy adults age 36.63 ± 3.8) were analyzed for circulating levels of TGFβ1, CRP, and IL-6 using Sandwich Enzyme linked immunosorbent assay (ELISA) analyses (R&D systems). TGFβ1 and CRP levels were significantly higher in children with CP compared to both adults with CP (TGFβ1: P < 0.0005 and P < 0.0002, respectively) and healthy adults (CRP: P < 0.0001 and P < 0.0001, respectively), while no differences were observed between the adults with CP and healthy adults in TGFβ1 ( P = 0.29) and CRP ( P = 0.59), respectively. Furthermore, IL-6 levels showed no significant differences between the groups. The present findings indicate that the level of systemic inflammation is increased in children with CP. We speculate that persisting inflammation in children with CP might influence the development of muscle contractures, resulting in reduced muscle mass and marked muscle weakness in adults with CP.

Background: The incidence of anterior cruciate ligament (ACL) injuries in children is increasing. However, no standardized core set of outcome measures exists for evaluating pediatric ACL injuries. Purpose: To perform a scoping review of the literature to identify patient-reported outcome measures (PROMs) and objective outcome measures used to evaluate pediatric patients after ACL injury and to classify these in accordance with the International Classification of Functioning, Disability, and Health (ICF) domains. Study Design: Systematic review; Level of evidence, 4. Methods: The literature was systematically searched with the PubMed, EMBASE, CINAHL, and PEDro databases. The inclusion criteria were Danish, Norwegian, Swedish, German, or English language; publication between 2010 and 2018; pediatric ACL injury (patients ≤15 years old); and outcome measures. The selected papers were screened for title, abstract, and full text in accordance with predefined inclusion and exclusion criteria. Results: A total of 68 papers (4286 patients; mean ± SD age, 12.2 ± 2.3 years) were included. Nineteen PROMs and 11 objective outcome measures were identified. The most frequently reported PROMs were the International Knee Documentation Committee (IKDC) Subjective Knee Form (51% of studies), Lysholm scoring scale (46% of studies) and Tegner activity rating scale (37% of studies). Additionally, return to sport was reported in 41% of studies. The most frequent objective measures were knee laxity (76% of studies), growth disturbances (69% of studies), range of motion (41% of studies), and muscle strength (21% of studies). With respect to the ICF domains, the IKDC covered all 3 ICF health domains, the Lysholm score covered the Body Structure and Function and the Activity Limitation domains, while the Tegner score covered the Participation Restriction domain. Objectively measured knee joint laxity, range of motion, and muscle strength covered 1 domain (Body Structure and Function). Conclusion: Pediatric patients with ACL injury were mainly evaluated subjectively with the IKDC and objectively by knee joint laxity. No consensus exists in the evaluation of children after ACL injury. The majority of applied outcome measures are developed for adults. To cover the ICF health domains, future research needs to consider reliable and valid outcome measures relevant for pediatric patients with ACL injury.

Tendinopathy is a condition of tendon overuse and is a very common cause of morbidity among recreational and competitive athletes. Chronic overload results in degenerative changes of the tendon, which becomes painful and swollen with impaired function. A reduction in the overloading activity is the mainstay of the treatment. A rehabilitating programme consisting of controlled loading of the affected tendon should follow this. Other modalities, which may facilitate treatment, are: injections with corticosteroid, platelet-rich plasma, and of high volume, as well as shock-wave therapy and surgery.

A clinically applicable and accurate method for measuring Achilles tendon length is needed to investigate the influence of elongation of the Achilles tendon after acute rupture. The purpose of this study was to develop and validate an ultrasonographic (US) length measurement of the Achilles tendon-aponeurosis complex.

One-legged dynamic knee-extension exercise (DKE) is a widely used model to study the local cardiovascular and metabolic responses to exercise of the quadriceps muscles. In this study, we explored the extent to which different muscles of the quadriceps are activated during exercise using positron emission tomography (PET) determined uptake of [(18)F]-fluoro-deoxy-glucose (GU) during DKE. Five healthy male subjects performed DKE at 25 W for 35 min and both the contracting and contralateral resting leg were scanned with PET from mid-thigh and distally. On average, exercise GU was the highest in the vastus intermedius (VI) and lowest in the vastus lateralis (VL; VI vs VL, p < 0.05), whereas the coefficient of variation was highest in VL (VL vs VI, p < 0.05). Coefficient of variation between the mean values of the four quadriceps femoris (QF) muscles in the exercising leg was 35 ± 9%. Compared to mean GU in QF (=100%), GU was on average 73% in VL, 84% in rectus femoris, 115% in vastus medialis, and 142% in VI. Variable activation of hamstring muscles and muscles of the lower leg was also observed. These results show that GU of different muscles of quadriceps muscle group as well as between individuals vary greatly during DKE, and suggests that muscle activity is not equal between quadriceps muscles in this exercise model. Furthermore, posterior thigh muscles and lower leg muscles are more active than hitherto thought even during this moderate exercise intensity.

Tendon is mainly composed of collagen and an aqueous matrix of proteoglycans that are regulated by enzymes called matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). Although it is known that resistance exercise (RE) and sex influence tendon metabolism and mechanical properties, it is uncertain what structural and regulatory components contribute to these responses. We measured the mRNA expression of tendon's main fibrillar collagens (type I and type III) and the main proteoglycans (decorin, biglycan, fibromodulin, and versican) and the regulatory enzymes MMP-2, MMP-9, MMP-3, and TIMP-1 at rest and after RE. Patellar tendon biopsy samples were taken from six individuals (3 men and 3 women) before and 4 h after a bout of RE and from a another six individuals (3 men and 3 women) before and 24 h after RE. Resting mRNA expression was used for sex comparisons (6 men and 6 women). Collagen type I, collagen type III, and MMP-2 were downregulated (P < 0.05) 4 h after RE but were unchanged (P > 0.05) 24 h after RE. All other genes remained unchanged (P > 0.05) after RE. Women had higher resting mRNA expression (P < 0.05) of collagen type III and a trend (P = 0.08) toward lower resting expression of MMP-3 than men. All other genes were not influenced (P > 0.05) by sex. Acute RE appears to stimulate a change in collagen type I, collagen type III, and MMP-2 gene regulation in the human patellar tendon. Sex influences the structural and regulatory mRNA expression of tendon.

Objective: The project aimed to implement neuromuscular training during a full soccer and handball league season and to experimentally analyze the neuromuscular adaptation mechanisms elicited by this training during a standardized sidecutting maneuver known to be associated with non-contact anterior cruciate ligament (ACL) injury. Design: The players were tested before and after 1 season without implementation of the prophylactic training and subsequently before and after a full season with the implementation of prophylactic training. Participants: A total of 12 female elite soccer players and 8 female elite team handball players aged 26 ± 3 years at the start of the study. Intervention: The subjects participated in a specific neuromuscular training program previously shown to reduce non-contact ACL injury. Methods: Neuromuscular activity at the knee joint, joint angles at the hip and knee, and ground reaction forces were recorded during a sidecutting maneuver. Neuromuscular activity in the prelanding phase was obtained 10 and 50 ms before foot strike on a force plate and at 10 and 50 ms after foot strike on a force plate. Results: Neuromuscular training markedly increased before activity and landing activity electromyography (EMG) of the semitendinosus (P < 0.05), while quadriceps EMG activity remained unchanged. Conclusions: Neuromuscular training increased EMG activity for the medial hamstring muscles, thereby decreasing the risk of dynamic valgus. This observed neuromuscular adaptation during sidecutting could potentially reduce the risk for non-contact ACL injury.

We aimed to investigate whether oral contraceptives (OC), resulting in enhanced circulating level of ethinyl‐estradiol, influences tendon collagen metabolism at rest and after exercise. Healthy young women, OC‐users (n=11) and control (n=12), were studied 24h following one‐legged kicking exercise (EX) for 60 min at 67 % of Wattmax. Microdialysis catheters were placed anterior to the patellar tendon of both legs, and interstitial fluid was collected and analyzed for the amino‐terminal propeptide of type I collagen (PINP), a marker of tendon collagen synthesis. An exercise‐induced increase in tendon synthesis was observed in control (PINP: Rest: 25.3 ± 11 (mean ± SD) ng ml−1 vs. EX: 48.3 ± 28 ng ml−1, P < 0.05), but not in OC‐users (EX: 27.4 ± 16 ng ml−1 vs. Rest: 31.5 ± 20 ng ml−1). Insulin‐like growth factor I (IGF‐I) both in serum and in the interstitial tendon tissue fluid was significantly lower in OC‐users compared to control, whereas IGFBPs were significantly higher, which in combination with lower IGF‐I. In conclusion, OC seems to have an inhibiting effect on tendon synthesis in response to exercise either directly or indirectly by a reduction of the bioavailability of IGF‐I.

Exercise has been shown to acutely elevate several metabolic processes in tendon tissue, many of which are regulated by the cyclooxygenase (COX) enzymes. We measured the expression levels of COX‐1 (variants 1 and 2), COX‐2, and the recently discovered intron 1‐retaining COX‐1 variants (COX‐1b1, ‐1b2, ‐1b3) at rest and following resistance exercise (RE). Patellar tendon biopsy samples were taken from six individuals (3M, 3F) before and 4h following a bout of RE (3 sets of 10 repetitions at ~70% of 1RM) and from a separate six individuals (3M, 3F) before and 24h following RE and analyzed using real‐time RT‐PCR. The COX‐1 variants were the most abundant COX mRNAs before exercise and remained unchanged (p>0.05) following exercise. COX‐2 was also expressed in tendon at rest and was unchanged (p>0.05) following exercise. The intron 1‐retaining COX‐1 variants were not detectable in tendon tissue before or after exercise. Compared to our previous work in quadriceps skeletal muscle, the patellar tendon expressed much higher levels of COX‐1 and COX‐2, although the overall COX mRNA expression patterns were similar in skeletal muscle and tendon (COX‐1v2 > COX‐1v1, P<0.05; COX‐1:COX‐2 ≅ 4:1). These results suggest both COX‐1 and COX‐2 are constitutively expressed at relatively high levels in human patellar tendon and are likely targets of COX inhibiting drugs at rest and following physical activity.NIH R01 AG020532 (TT)

Satellite cells increase in number with heavy resistance training, but the response to very light muscle loading is unknown. We recruited 12 young healthy male (mean age 25 ± SD 3 yrs) volunteers to train one leg with a heavy load (H) and the other leg with a light load (L), for 12 weeks. We hypothesized that, compared to L training, H training would induce a greater response of the satellite cell pool. Satellite cells were visualised by immunohistochemistry on muscle biopsies collected from the m. vastus lateralis of both legs before and after the training period. Compared to the pre training values, there was a significant increase in the number of NCAM+ cells (per myonuclear number) post training in both groups (H: from 4.16 ± 1.01 to 5.32 ± 1.22; L: from 4.01 ± 0.78 to 4.72 ± 1.72; mean ± SD, p < 0.05). The finding that 12 weeks of training skeletal muscle with very low loads can induce an increase in the number of satellite cells reveals a new aspect of myogenic precursor cell activation. This knowledge could be relevant in considering training regimens where heavy resistance training is not possible.Funded by Lundbeck Foundation and the Danish National Research Foundation.

The consumption of nonsteroidal anti-inflammatory drugs (NSAIDs) is widespread among athletes when faced with muscle soreness or injury, but the effects of NSAIDs on satellite cell activity in humans are unknown. To investigate this, 14 healthy male endurance athletes (mean peak oxygen consumption 62 ml x kg(-1) x min(-1)) volunteered for the study, which involved running 36 km. They were divided into two groups and received either 100 mg indomethacin per day or placebo. Muscle biopsies collected before the run and on days 1, 3, and 8 afterward were analyzed for satellite cells by immunohistochemistry with the aid of neural cell adhesion molecule (NCAM) and fetal antigen-1 (FA1) antibodies. Muscle biopsies were also collected from untrained individuals for comparison. Compared with preexercise levels, a 27% increase in the number of NCAM+ cells was observed on day 8 postexercise in the placebo group (P < 0.05), while levels remained similar at all time points in the NSAID group. No change was seen in the proportion of FA1+ cells, although lower levels were found in the muscle of endurance-trained athletes compared with untrained individuals (P < 0.05). These results suggest that ingestion of anti-inflammatory drugs attenuates the exercise-induced increase in satellite cell number, supporting the role of the cyclooxygenase pathway in satellite cell activity.

Cerebral palsy (CP) is a non-progressive motor disorder that affects posture and gait due to contracture development. The purpose of this study is to analyze a possible relation between muscle stiffness and gene expression levels in muscle tissue of children with CP. Next-generation sequencing (NGS) of gene transcripts was carried out in muscle biopsies from gastrocnemius muscle (n = 13 children with CP and n = 13 typical developed (TD) children). Passive stiffness of the ankle plantarflexors was measured. Structural changes of the basement membranes and the sarcomere length were measured. Twelve pre-defined gene target sub-categories of muscle function, structure and metabolism showed significant differences between muscle tissue of CP and TD children. Passive stiffness was significantly correlated to gene expression levels of HSPG2 (p = 0.02; R2 = 0.67), PRELP (p = 0.002; R2 = 0.84), RYR3 (p = 0.04; R2 = 0.66), C COL5A3 (p = 0.0007; R2 = 0.88), ASPH (p = 0.002; R2 = 0.82) and COL4A6 (p = 0.03; R2 = 0.97). Morphological differences in the basement membrane were observed between children with CP and TD children. The sarcomere length was significantly increased in children with CP when compared with TD (p = 0.04). These findings show that gene targets in the categories: calcium handling, basement membrane and collagens, were significantly correlated to passive muscle stiffness. A Reactome pathway analysis showed that pathways involved in DNA repair, ECM proteoglycans and ion homeostasis were amongst the most upregulated pathways in CP, while pathways involved in collagen fibril crosslinking, collagen fibril assembly and collagen turnover were amongst the most downregulated pathways when compared with TD children. These results underline that contracture formation and motor impairment in CP is an interplay between multiple factors.