Differentiating mesenchymal stromal cells (MSCs) into articular chondrocytes (ACs) for application in clinical cartilage regeneration requires a profound understanding of signaling pathways regulating stem cell chondrogenesis and hypertrophic degeneration. Classifying endochondral signals into drivers of chondrogenic speed versus hypertrophy, we here focused on insulin/insulin-like growth factor 1 (IGF1)-induced phosphoinositide 3-kinase (PI3K)/AKT signaling. Aware of its proliferative function during early but not late MSC chondrogenesis, we aimed to unravel the late pro-chondrogenic versus pro-hypertrophic PI3K/AKT role. PI3K/AKT activity in human MSC and AC chondrogenic 3D cultures was assessed via Western blot detection of phosphorylated AKT. The effects of PI3K inhibition with LY294002 on chondrogenesis and hypertrophy were assessed via histology, qPCR, the quantification of proteoglycans, and alkaline phosphatase activity. Being repressed by ACs, PI3K/AKT activity transiently rose in differentiating MSCs independent of TGFβ or endogenous BMP/WNT activity and climaxed around day 21. PI3K/AKT inhibition from day 21 on equally reduced chondrocyte and hypertrophy markers. Proving important for TGFβ-induced SMAD2 phosphorylation and SOX9 accumulation, PI3K/AKT activity was here identified as a required stage-dependent driver of chondrogenic speed but not of hypertrophy. Thus, future attempts to improve MSC chondrogenesis will depend on the adequate stimulation and upregulation of PI3K/AKT activity to generate high-quality cartilage from human MSCs.

Chêneau-brace (C-Brace) is a potential tool for the treatment of adolescent idiopathic scoliosis (AIS) with a Cobb angle between 20° and 45° for the primary curve. The aim of the present study was (1) to estimate study cohorts with C-brace therapy success and therapy failure and (2) to analyze possible factors that influence the therapy outcome. Seventy-eight patients with AIS were assessed before the initiation of C-brace treatment. Each patient underwent radiography examinations before the brace, in-brace, and at the therapy end. Cobb angle was considered as increased when the value at the end of therapy was increased more than 5° (Δ > 5°), unchanged—when the value was unchanged within ± 5° and decreased- when the value was decreased more than 5° (Δ < −5°). The study cohort was stratified due to curve topography in the thoracic, thoracolumbar, and lumbar scoliosis groups. Global analysis revealed no statistically significant modification of the Cobb angle (Cobb angle pre-brace vs. Cobb angle post-brace: 30.8° ± 8.2 vs. 29.3° ± 15.2, p = 0.26). However, at the end of C-brace therapy, the primary Cobb angle was decreased by more than 5° in 27 patients (35%), unchanged (Δ within the range of ±5°) in 36 patients (46%), and increased more than 5° in 15 patients (19%). Sub-group analysis due to curve topography and skeletal maturity has shown higher rates of brace therapy failure in thoracic curves and in younger patients (Risser grade 0). Patients with higher Cobb angle correction with C-brace had lower rates of therapy failure. The C-brace can be useful for the prevention of scoliotic curve progression in patients with AIS. However, many factors influence the therapy effect.

Background: We conducted this systematic review to provide comprehensive evidence on the prevalence, clinical features and outcomes of young extraosseous Ewing sarcoma (EES) cases. Methods: PubMed, Scopus, Web of Science, and Google Scholar were searched for articles reporting the occurrence of EES among children and adolescents (<21 years). The primary outcome included the rate of occurrence of EES among children and adolescents, while the secondary outcomes included the descriptive analyses of the demographic characteristics, tumor characteristics, and clinical outcomes of the affected cases. The data are reported as the effect size (ES) and its corresponding 95% confidence interval (CI). Results: A total of 29 studies were included. Twenty-four reported instances of childhood disease among all the EES cases [ES = 30%; 95%CI: 29–31%], while five studies reported extraosseous cases among the pediatric EES cases [ES = 22%; 95%CI: 13–31%]. The thorax is the most common location of childhood EES [33%; 95%CI: 20–46%] followed by the extremities [31%; 95%CI: 22–40%]. Concurrent chemotherapy and radiotherapy [57%; 95%CI: 25–84%] was the most commonly implemented management protocol in the pediatric EES cases. The rate of no evidence of disease and 5-year overall survival was 69% for both outcomes. Mortality occurred in 29% of cases, while recurrence and secondary metastasis occurred in 35% and 16% of cases, respectively. Conclusions: Our findings provide insight into the clinical features and outcomes of EES among children and adolescents.

Background: There is a lack of evidence regarding the impact of time loss, match exposure, and age at injury on career progression in elite football. Therefore, the aim of this study was to identify injury characteristics and their influence on career progression in a German youth academy. Methods: During the 2012/2013 season, a prospective cohort study reported 107 time-loss injuries among 130 young athletes from an elite German soccer academy. Individual career progression was analyzed using 10-year data. Results: Injuries and time loss were not associated with career progression (p > 0.05) in the overall cohort. In the U17 and U19 groups, 24% were able to reach the professional level, with injuries significantly decreasing this probability (p = 0.002). Injuries lasting more than 28 days had a negative impact on career progression compared to minor injuries (30% vs. 10%; p = 0.02). Conclusions: Not only the characteristics of injuries, but also their impact on career development, vary with age. In the U17 and U19 age groups, serious injuries resulting in more than 28 days of absence have a negative impact on career progression. It is important to be aware of these effects in order to focus on the prevention of long-term injuries to ensure the optimal development of young athletes.

Sports are relevant to younger populations in society. Adolescent idiopathic scoliosis (AIS) patients who undergo surgical correction of the spine are often intensively involved in sports. For that, returning to the sport is often an important concern for the patients and their families. To the best of our knowledge, there is still a lack of scientific data indicating established recommendations about the time of returning to sport activities after surgical spinal correction. The aim of this study was to investigate (1) when AIS patients return to athletic activities after a posterior fusion, and (2) if they change their activities postoperatively. Furthermore, another question was (3) if the length of the performed posterior fusion or (4) fusion to the lower lumbar spine could have an influence on the rates or time of returning to sport activities postoperatively. Data collection was performed using questionnaires assessing patients’ contentment and athletic activity. Athletic activities were categorized into three categories: (1) contact, (2) contact/non-contact and (3) non-contact sports. The intensity of exercised sports, the time of returning to the sport and changes in sport habits were documented. Radiographs were evaluated pre- and postoperatively to determine the Cobb angle and the length of the posterior fusion via the identification of the upper (UIV) and lower instrumented vertebra (LIV). Stratification analysis due to the fusion length was performed to answer a hypothetical question. This retrospective survery of 113 AIS patients treated with a posterior fusion revealed that, on average, returning to sport activities required 8 months of postoperative rest. The preoperative to postoperative rate of patients participating in sport activities increased from 88 (78%) to 94 (89%). Furthermore, postoperatively, a relevant shift of exercised activities from contact to non-contact sports was noted. Further subanalysis revealed that only 33 subjects were able to return to exactly the same athletic activities as before surgery (10 months postoperatively). The assessment of radiographs revealed that in this study group, the length of the performed posterior fusion and fusions to the lower lumbar spine had no influence on the time of return to athletic activities. The results of this study might shed some light on postoperative recommendations for sport activities after AIS treatment with a posterior fusion and may be beneficial for surgeons treating patients.

Background: Long-term clinical and radiographic outcome data after standard cemented long-stem reverse shoulder arthroplasty (RSA) remain underreported. The aim of this study is to report on medium- to long-term data of patients over 60 years of age. Methods: The same type of RSA (Aequalis Reverse II, Memphis, TN, USA) was implanted in 27 patients with a mean age of 73 years (range 61–84). Indications for RSA were cuff tear arthropathy (CTA) in 25 cases and osteoarthritis (OA) in two cases. Pre- and postoperative Constant Score was assessed and component loosening, polyethylene wear, scapular notching and revision rates were recorded at a mean clinical follow-up (FU) of 127.6 months (SD ± 33.7; range 83–185). Results: The mean-adjusted CS (aCS) improved from 30.0 (range 10–59) to 95.0 (range 33–141) points (p < 0.001). Glenoid loosening was found in two (9.1%) and stem loosening was found in three (13.6%) cases. Polyethylene wear was observed in four (18.2%) cases. Scapular notching appeared in 15 (68.2%) cases but was not associated with poor aCS (p = 0.423), high levels of pain (p = 0.798) or external rotation (p = 0.229). Revision surgery was necessary in three (11.1%) cases. Conclusions: RSA with a cemented standard long stem leads to improvement in forward elevation, abduction and pain after a mean FU of 10 years. However, external rotation does not improve with this prosthetic design. Moreover, scapular notching is observed in the majority of cases, and revision rates (11.1%) as well as humeral loosening rates (13.6%) remain a concern. Level of evidence: Level 4, retrospective cohort study.