Search

Objective: This study aims to examine the comparative effects of 75 min of volume-matched once-weekly and thrice-weekly high-intensity interval training (HIIT) on body adiposity in adults with central obesity., Methods: This assessor-blinded, three-arm, randomized controlled trial will recruit 315 physically inactive adults with central obesity (aged ≥18 years, body mass index ≥23, waist circumference ≥90 cm for men and ≥80 cm for women). Participants will be randomly allocated to the once-weekly HIIT, thrice-weekly HIIT or usual care control group. Participants in the HIIT groups will receive weekly exercise training sessions for 16 weeks, prescribed either once or three times weekly. Each HIIT session will consist of a supervised program of four 4-min high-intensity intervals at 85%-95% peak heart rate (HR peak ) interspersed with 3-min active recovery intervals at 50%-70% HR peak . Participants in the once-weekly HIIT group will perform the 25-min HIIT bout three times with a break between each 25-min HIIT bout. The usual care control group will receive bi-weekly health education classes. The outcome assessments will be conducted at baseline, 16 weeks (post-intervention) and 32 weeks (follow-up). The primary outcome will be total body adiposity assessed by dual-energy X-ray absorptiometry (DXA). The secondary outcome measures will include markers of cardiovascular and metabolic health (body composition, cardiorespiratory fitness, blood pressure, and blood lipids), mental health, cognitive performance, health-related quality of life, sleep quality, habitual physical activity, diet, medication, adverse events and adherence to the intervention., Impact of the Project: The findings from this study are expected to consolidate the therapeutic efficacy of HIIT for the management of central obesity and inform the comparative compliance, feasibility and suitability of once-weekly and thrice-weekly HIIT as exercise strategies to manage obesity. In particular, the present study is expected to provide a novel perspective on the utility of low-frequency HIIT (i.e., once-weekly) as an effective and sustainable exercise strategy to tackle the obesity pandemic. The anticipated findings will hold substantial translational value by informing public health policies and enhancing exercise compliance in the physically inactive obese population., Trial Registration: ClinicalTrials.gov (NCT04887454)., Competing Interests: The authors declared no competing interests., (© 2024 The Society of Chinese Scholars on Exercise Physiology and Fitness. Published by Elsevier (Singapore) Pte Ltd.)

Background/purpose: Every year, unintentional injury claims thousands of children's lives and causes disabilities in many more. For very young children, these injuries often occur at home. The risks of domestic injury can be reduced through proper implementation of injury preventive measures. In this study, we investigated the motivational and belief processes underlying childhood domestic injury prevention in grandparent caregivers based on the integrated model of self-determination theory and theory of planned behaviour., Method: Grandparents (n=299, mean age=62.61 years, SD=5.91, men=20.07%) of 0-2-year-old infants and toddlers self-reported their perceived psychological need support, autonomous motivation, perceived behavioural control (PBC), subjective norms, attitude, intention and adherence with regard to domestic injury prevention for their children at two time points (T1: baseline, T2: 4-month follow-up)., Results/outcomes: Data were analysed with structural equation modelling, and the proposed model yielded an acceptable fit with the data: χ 2 =905.09 (df=531), Comparative Fit Index=0.94, Tucker-Lewis Index=0.93, root mean square error of approximation=0.05 and standardised root mean square residual=0.078. Our results supported our hypothesis, demonstrating significant and positive associations between the following key constructs: (1) psychological need support from family and autonomous motivation; (2) autonomous motivation and social-cognitive beliefs; (3) social-cognitive beliefs and intentions; and (4) intention and behavioural adherence. Subjective norms and PBC, but not attitudes, were also found to significantly mediate the indirect effects of psychological need support and autonomous motivation on intention and behavioural adherence., Conclusions: Overall, the integrated model seems to be a feasible framework for explaining grandparents' domestic injury prevention behaviour., Competing Interests: None declared., (Copyright © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. Published by BMJ.)

Objectives: Excessive inflammation contributes to the pathogenesis of tendinopathy. Fatty acid binding protein 4 (FABP4) is a pro-inflammatory adipokine mediating various metabolic and inflammatory diseases. This study aimed to examine the expression of FABP4 and its association with the expressions of inflammatory cytokines in tendinopathy. The effects of a single injection of FABP4 on tendon pathology and inflammation were examined. The effect of FABP4 on the expressions of inflammatory cytokines and the effect of IL-1β on the expression of FABP4 in tendon-derived stem/progenitor cells (TDSCs) were also investigated., Methods: 1) Clinical patellar tendinopathy samples, healthy hamstring tendon samples, and healthy patellar tendon samples, 2) rotator cuff tendinopathy samples and healthy hamstring tendon samples; and 3) Achilles tendons of mice after saline or collagenase injection (CI) were stained for FABP4, IL-1β, IL-6, TNF-α and IL-10 by immunohistochemistry (IHC). For the rotator cuff tendinopathy samples, co-localization of FABP4 with IL-1β and TNF-α was done by immunofluorescent staining (IF). Mouse Achilles tendons injected with FABP4 or saline were collected for histology and IHC as well as microCT imaging post-injection. TDSCs were isolated from human and mouse tendons. The mRNA expressions of inflammatory cytokines in human and mouse TDSCs after the addition of FABP4 was quantified by qRT-PCR. The expression of FABP4 in TDSCs isolated from rotator cuff tendinopathy samples and healthy hamstring tendon samples was examined by IF. Mouse Achilles TDSCs were treated with IL-1β. The mRNA and protein expressions of FABP4 were examined by qRT-PCR and IF, respectively., Results: There was significant upregulation of FABP4 in the patellar tendinopathy samples and rotator cuff tendinopathy samples compared to their corresponding controls. FABP4 was mainly expressed in the pathological areas including blood vessels, hypercellular and calcified regions. The expressions of IL-1β and TNF-α increased in human rotator cuff tendinopathy samples and co-localized with the expression of FABP4. Collagenase induced tendinopathic-like histopathological changes and ectopic calcification in the mouse Achilles tendinopathy model. The expressions of inflammatory cytokines (IL-1β, IL-6, TNF-α, IL-10) and FABP4 increased in hypercellular region, round cells chondrocyte-like cells and calcified regions in the mouse Achilles tendons post-collagenase injection. A single injection of FABP4 in mouse Achilles tendons induced histopathological changes resembling tendinopathy, with increased cell rounding, loss of collagen fiber alignment, and additionally presence of chondrocyte-like cells and calcification post-injection. The expressions of IL1-β, IL-6, TNF-α and IL-10 increased in mouse Achilles tendons post-FABP4 injection. FABP4 increased the expressions of IL10 , IL6 , and TNFa in human TDSCs as well as the expressions of Il1b , Il6 , and Il10 in mouse TDSCs. Human tendinopathy TDSCs expressed higher level of FABP4 compared to healthy hamstring TDSCs. Besides, IL-1β increased the expression of FABP4 in mouse TDSCs., Conclusion: In conclusion, an upregulation of FABP4 is involved in excessive inflammation and pathogenesis of tendinopathy. TDSCs is a potential source of FABP4 during tendon inflammation., Translation Potential of This Article: FABP4 can be a potential treatment target of tendinopathy., Competing Interests: We don't any potential conflicts of interest., (© 2024 The Authors.)

This study aimed to develop and validate a new measurement tool, the Rehabilitation Adherence Inventory (RAI), to measure patients' rehabilitation adherence. We recruited 236 patients with anterior cruciate ligament (ACL) ruptures from the United Kingdom (Mage = 33.58 ± 10.03, range = 18 to 59; female = 46.2%). Participants completed a survey, that measured their rehabilitation adherence, rehabilitation volume, psychological needs support, autonomous motivation, and intention at baseline, and at the 2nd and 4th month. Factorial, convergent, discriminant, concurrent, predictive, ecological validity and test-retest reliability of the RAI were tested via exploratory factor analysis (EFA), confirmatory factor analysis (CFA), and structural equation modelling (SEM). All the EFAs, CFAs, and SEMs yielded acceptable to excellent goodness-of-fit, χ2 = 10.51 to 224.12, df = 9 to 161, CFI > 0.95, TLI > 0.95, RMSEA <0.09 [90%C I < 0.06 to 0.12], SRMR <0.04. Results fully supported the RAI's factorial, convergent, discriminant, and ecological validity, and test-retest reliability. The concurrent and predictive validity of the RAI was only partially supported because the RAI scores at baseline was positively associated with rehabilitation frequency at all time points ( r  = 0.34 to 0.38, p  < 0.001), but its corresponding associations with rehabilitation duration were not statistically significant ( p  = 0.07 to 0.93). Overall, our findings suggest that this six-item RAI is a reliable and valid tool for evaluating patients' rehabilitation adherence., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Lee, Xu, Yung, Ong, Chan, Chung and Chan.)

There is no mouse model of patellar tendinopathy. This study aimed to establish a mouse inflammatory and degenerative patellar tendon injury model, which will facilitate research on patellar tendinopathy using advanced molecular tools including transgenic models. Collagenase at different doses (low dose (LD), medium dose (MD), high dose (HD)) or saline was injected over the mouse patellar tendon. At weeks 1, 2, 4, and 8 post-injection, the tendons were harvested for histology and further examined by micro-computed tomography (microCT) imaging at week 8. The optimal dose group and the saline group were further evaluated by immunohistochemical staining, gait pattern, and biomechanical properties. The histopathological score increased dose-dependently post-collagenase injection. Ectopic mineralization was observed and increased with collagenase dose. The LD group was selected for further analysis. The expression of IL-10, TNF-α, and MMP-1 significantly increased post-injection. The changes of limb idleness index (ΔLII) compared to preinjury state were significantly higher, while the ultimate load, stiffness, ultimate stress, and maximum Young's modulus were significantly lower in the LD group compared to the saline group. A mouse inflammatory degenerative model of patellar tendon injury resembling tendinopathy was established as indicated by the dose-dependent increase in tendon histopathology, ectopic calcification, decrease in biomechanical properties, and pain-associated gait changes.

Repair of functionally graded biological interfaces requires joining dissimilar materials such as hard bone to soft tendon/ligament, with re-injuries/re-tears expected to be minimized by incorporating biomimicking, stress-reducing features within grafts. At bone-tendon interfaces (entheses), stress can be reduced via angled insertion, geometric flaring, mechanical gradation, and interdigitation of tissues. Here, we incorporated enthesis attributes into 3D in silico and physical models of a unique suture anchor-tendon hybrid graft (SATHG) and investigated their effects on stress reduction via finite element analyses (FEA) studies. Over 20 different simulations altering SATHG angulation, flaring, mechanical gradation, and interdigitation identified an optimal design, which included 90° angulation, 25° flaring, and a compliant (ascending then descending) mechanical gradient in SATHG's bone-to-tendon-like transitional region. This design reduced peak stress concentration factor (SCF) by 43.6 % relative to an ascending-only mechanical gradient typically used in hard-to-soft tissue engineering. To verify FEA results, SATHG models were fabricated using a photocrosslinkable bone-tendon-like polyurethane (QHM polymer) for ex vivo tensile assessment. Tensile testing showed that ultimate load (132.9 N), displacement-at-failure (1.78 mm), stiffness (135.4 N/mm), and total work-to-failure (422.1 × 10 -3 J) were highest in the optimized design. Furthermore, to assess envisioned usage, SATHG pull-out testing and 6-week in vivo implantation into large, 0.5-cm segmental supraspinatus tendon defects was performed. SATHG pull-out testing showed secure bone attachment while histological assessment such as hematoxylin and eosin (H&E) together with Safranin-O staining showed biocompatibility including enthesis regeneration. This work demonstrates that engineering biomaterials with FEA-optimized, enthesis-like attributes shows potential for enhancing hard-to-soft tissue repair. STATEMENT OF SIGNIFICANCE: Successful repair of hard-to-soft tissue injuries is challenging due to high stress concentrations within bone-tendon/ligament grafts that mechanically compromise repair strength. While stress-reducing gradient biomaterials have been reported, little-to-no attention has focused on other bone-tendon/ligament interface (enthesis) features. To this end, a unique bone-tendon graft (SATHG) was developed by combining two common orthopaedic devices along with biomimetic incorporation of four enthesis-like features to reduce stress and encourage widespread clinician adoption. Notably, utilizing designs based on natural stress dissipation principles such as anchor insertion angle, geometric flaring, and mechanical gradation reduced stress by 43.6 % in silico, which was confirmed ex vivo, while in vivo studies showed SATHG's ability to support native enthesis regeneration. Thus, SATHG shows promise for hard-to-soft tissue repairs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Tranexamic acid (TXA) has been increasingly used in arthroscopic surgery to prevent hemarthrosis. Despite its effectiveness, safety concerns have been raised regarding its potential cytotoxicity to articular cartilage and meniscus following intra-articular injection., Methods: To evaluate the impact of TXA on cartilage and meniscus, a rat model of knee instability was utilized wherein anterior cruciate ligament (ACL) transection surgery was followed by a single intra-articular injection of TXA at varying concentrations (0, 20, 50, 100, and 150 mg/mL) in saline solution. Cell viability assessment of the cartilage and meniscus (n = 6 per group) was conducted at 24 hours, and gross observation and histological analysis of the medial tibial plateau and medial meniscus were conducted at 2, 4, and 8 weeks (n = 6 per group and time point)., Results: The chondrocyte viability was significantly decreased in the 50, 100, and 150 mg/mL TXA groups compared with the specimens injected with saline solution only (saline group) (p = 0.001, p < 0.001, p < 0.001, respectively), as was meniscal cell viability (p = 0.042, p < 0.001, p < 0.001, respectively). At week 8, the saline and 20 and 50 mg/mL groups showed relatively normal appearances, whereas the 100 and 150 mg/mL groups exhibited increased and varying severity of cartilage and meniscal degeneration. In the 150 mg/mL group, the mean Osteoarthritis Research Society International score was significantly higher than that in the saline and 20 mg/mL groups (p = 0.010 and p = 0.007). Additionally, the mean meniscus score in the 150 mg/mL group was significantly higher than that in the saline, 20 mg/mL, and 50 mg/mL groups (p = 0.020, p = 0.021, p = 0.031, respectively)., Conclusions: Our findings indicate that concentrations of TXA at or above 100 mg/mL can lead to decreased cell viability in both cartilage and meniscus, resulting in significant cartilage degeneration in rats with ACL transection. Furthermore, the use of 150 mg/mL of TXA led to significant meniscal degeneration., Clinical Relevance: It is prudent to avoid using concentrations of TXA at or above 100 mg/mL for intra-articular injection, as such concentrations may result in adverse effects on the cartilage and meniscus., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article ( http://links.lww.com/JBJS/H786 )., (Copyright © 2023 The Authors. Published by The Journal of Bone and Joint Surgery, Incorporated. All rights reserved.)

While Chinese dance is a popular dance genre among Chinese teenagers and adults, little is known regarding the prevalence of dance-related injuries or factors associated with such injuries among Chinese dance practitioners. The current cross-sectional study aimed to determine the prevalence of dance-related injuries and their associated risk factors among young Chinese dance practitioners in Hong Kong. Online surveys were distributed to dancers through local dance associations, while paper-based surveys were distributed to young Chinese dance performers during the 54th School Dance Festival in Hong Kong. Self-reported hours of dancing, injuries in the last 12 months, injury sites, and related factors were collected. The injury rate, 12-month prevalence of dance-related injuries were determined. Risk factors for common dance injuries were analyzed using separate multivariate regression models. A total of 175 children (aged 10-14 years) and 118 young (aged 15-24 years) Chinese dance practitioners provided their dance injury information. Young dancers had a significantly higher injury rate (6.5 injuries vs 4.6 injuries/1000 dance hours) and 12-month prevalence (52.5% vs 19.4%) than their child counterparts. The most commonly injured sites were the knee (children:7.4%; young:15.3%), lower back (children: 4.6%; young: 9.5%), and ankles (children: 5.1%; young: 16.9%). Age was a significant independent risk factor for dance-related injuries to the upper back, lower back, and pelvis/buttock (odds ratios ranging from 1.2 to 1.3/additional years). Additionally, height was a significant independent risk factor for lower limb injury (odds ratios ranging from 1.0-1.1/additional centimeter). Collectively, young Chinese dance practitioners are more vulnerable to dance-related injuries than are child dancers. Older age increases the risk of trunk injuries, whereas taller dancers are more likely to sustain lower-limb injuries. Future research should determine the mechanisms underlying dance-related injuries among these dancers., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: This study uses a practical positional MRI protocol to evaluate tibiofemoral translation and rotation in normal and injured knees., Methods: Following ethics approval, positional knee MRI of both knees was performed at 35° flexion, extension, and hyperextension in 34 normal subjects (mean age 31.1 ± 10 years) and 51 knee injury patients (mean age 36.4 ± 11.5 years, ACL tear n = 23, non-ACL injury n = 28). At each position, tibiofemoral translation and rotation were measured., Results: Normal knees showed 8.1 ± 3.3° external tibial rotation (i.e., compatible with physiological screw home mechanism) in hyperextension. The unaffected knee of ACL tear patients showed increased tibial anterior translation laterally (p = 0.005) and decreased external rotation (p = 0.002) in hyperextension compared to normal knees. ACL-tear knees had increased tibial anterior translation laterally (p < 0.001) and decreased external rotation (p < 0.001) compared to normal knees. Applying normal thresholds, fifteen (65%) of 23 ACL knees had excessive tibial anterior translation laterally while 17 (74%) had limited external rotation. None (0%) of 28 non-ACL-injured knees had excessive tibial anterior translation laterally while 13 (46%) had limited external rotation. Multidirectional malalignment was much more common in ACL-tear knees., Conclusions: Positional MRI shows (a) physiological tibiofemoral movement in normal knees, (b) aberrant tibiofemoral alignment in the unaffected knee of ACL tear patients, and (c) a high frequency of abnormal tibiofemoral malalignment in injured knees which was more frequent, more pronounced, more multidirectional, and of a different pattern in ACL-tear knees than non-ACL-injured knees., Key Points: • Positional MRI shows physiological tibiofemoral translation and rotation in normal knees. • Positional MRI shows a different pattern of tibiofemoral alignment in the unaffected knee of ACL tear patients compared to normal control knees. • Positional MRI shows a high prevalence of abnormal tibiofemoral alignment in injured knees, which is more frequent and pronounced in ACL-tear knees than in ACL-intact injured knees., (© 2022. The Author(s), under exclusive licence to European Society of Radiology.)

Background: Doxycycline (Doxy) has been shown to facilitate tendon healing by reducing on-site matrix metalloproteinase (MMP) activity, but its effect on graft healing after anterior cruciate ligament reconstruction (ACLR) has not been investigated, and the therapeutic effect of Doxy in preventing ACLR-induced posttraumatic osteoarthritis (PTOA) is unclear., Hypothesis: Doxy promotes graft healing and alleviates the progression of PTOA after ACLR., Study Design: Controlled laboratory study., Methods: Sprague Dawley rats (n = 74; age, 12-13 weeks; male) that underwent ACLR were divided into untreated control and Doxy treatment (50 mg/kg/d orally until sacrifice) groups. At 2 and 6 weeks after surgery, graft healing was assessed by biomechanical testing, histology, immunohistochemical staining, and micro-computed tomography (μCT). The progression of PTOA was evaluated at 6 weeks by histology, the Mankin score, and immunofluorescence staining of the tibial plateau, and osteophyte formation was evaluated by μCT. Hindlimb weight distribution was evaluated at 6 weeks, and gait patterns were evaluated at 2 and 6 weeks. Intra-articular MMP activity was evaluated at 6 weeks in vivo using an MMP-activatable near-infrared fluorescent probe., Results: Graft healing was enhanced by Doxy treatment, and the ultimate failure load ( P = .002) and stiffness of the graft ( P = .007) were significantly higher in the Doxy group at week 2. Bone mineral density and bone volume/total volume for both the tibial and the femoral tunnels at week 6 in the Doxy group were significantly higher compared with in the control group ( P < .05). The overall graft healing scores were significantly higher in the Doxy group. Doxy treatment enhanced graft integration, intratunnel graft integrity, and collagen birefringence; more collagen types 1 and 10 and less MMP-13 were found at the graft-bone interface. At week 6, the Doxy group had a lower modified Mankin score ( P = .033) and showed fewer MMP 13-positive chondrocytes at the articular cartilage surface ( P = .002), indicating moderate joint cartilage damage. μCT revealed less osteophyte formation, and gait analysis revealed more symmetric weightbearing and gait patterns, after Doxy treatment at week 6 ( P < .05). In vivo imaging with the near-infrared fluorescent probe identified significantly lower intra-articular MMP activity in the Doxy group at week 6 ( P = .016)., Conclusion: The oral administration of Doxy was able to synchronously promote graft healing and attenuate PTOA in an ACLR rat model., Clinical Relevance: Our results indicated that Doxy, a widely used drug, is potentially beneficial to patients after ACLR.

Background: Stem cell sheets provide a scaffold-free option for the promotion of graft healing after anterior cruciate ligament reconstruction (ACLR). However, cell viability, stability, and potential uncontrolled actions create challenges for clinical translation. The decellularization of cell sheets may overcome these problems as studies have shown that the natural extracellular matrix of stem cells is bioactive and can promote tissue repair., Hypothesis: The decellularized tendon-derived stem cell (dTDSC) sheet can promote graft healing after ACLR., Study Design: Controlled laboratory study., Methods: An optimized decellularization protocol was developed to decellularize the TDSC sheets. A total of 64 Sprague-Dawley rats underwent ACLR with or without the dTDSC sheet wrapping the tendon graft (n = 32/group). At 2 and 6 weeks after surgery, graft healing was assessed by micro-computed tomography, histology, and biomechanical testing. The accumulation of iNOS + and CD206 + cells and the expression of metalloproteinase 1 (MMP-1), MMP-13, and tissue inhibitor of metalloprotease 1 (TIMP-1) were assessed by immunohistochemistry., Results: The decellularization was successful, with the removal of 98.4% nucleic acid while preserving the collagenous proteins and bioactive factors. The expression of bone morphogenetic protein 2 (BMP-2) and VEGF in the dTDSC sheet was comparable with the TDSC sheet ( P > .05). Micro-computed tomography showed significantly more tunnel bone formation in the dTDSC sheet group. The dTDSC sheet group demonstrated better graft osteointegration and higher integrity of graft midsubstance with significantly higher ultimate failure load (16.58 ± 7.24 vs 8.93 ± 2.45 N; P = .002) and stiffness (11.97 ± 5.21 vs 6.73 ± 2.20 N/mm; P = .027). Significantly fewer iNOS + cells but more CD206 + cells, as well as lower MMP-1 and MMP-13 but higher TIMP-1 expression, were detected at the tendon-bone interface and graft midsubstance in the dTDSC sheet group., Conclusion: An optimized decellularization protocol for producing bioactive dTDSC sheets was developed. Wrapping tendon graft with a dTDSC sheet promoted graft healing after ACLR, likely via enhancing bone formation and angiogenesis by BMP-2 and VEGF, modulating macrophage polarization and MMP/TIMP expression, and physically protecting the tendon graft., Clinical Relevance: dTDSC sheets alleviate the quality control and safety concerns of cell transplantation and can be used as a cell-free alternative for the promotion of graft healing in ACLR.

Background: Loosening is the leading cause of total knee arthroplasty (TKA) revision. This is a heavy burden toward the healthcare system owing to the difficulty in diagnosis and complications occurring from the delay management. Based on automatic analytical model building, machine learning, may potentially help to automatically recognize the risk of loosening based on radiographs alone. The aim of this study was to build an image-based machine-learning model for detecting TKA loosening., Methods: Image-based machine-learning model was developed based on ImageNet, Xception model and a TKA patient X-ray image dataset. Based on a dataset with TKA patient clinical parameters, another system was then created for developing the clinical-information-based machine learning model with random forest classifier. In addition, the Xception Model was pre-trained on the ImageNet database with python and TensorFlow deep learning library for the prediction of loosening. Class activation maps were also used to interpret the prediction decision made by model. Two senior orthopaedic specialists were invited to assess loosening from X-ray images for 3 attempts in setting up comparison benchmark., Result: In the image-based machine learning loosening model, the precision rate and recall rate were 0.92 and 0.96, respectively. While for the accuracy rate, 96.3% for visualization classification was observed. However, the addition of clinical-information-based model, with precision rate of 0.71 and recall rate of 0.20, did not further showed improvement on the accuracy. Moreover, as class activation maps showed corresponding signals over bone-implant interface that is loosened radiographically, this confirms that the current model utilized a similar image recognition pattern as that of inspection by clinical specialists., Conclusion: The image-based machine learning model developed demonstrated high accuracy and predictability of knee arthroplasty loosening. And the class activation heatmap matched well with the radiographic features used clinically to detect loosening, which highlighting its potential role in assisting clinicians in their daily practice. However, addition of clinical-information-based machine-learning model did not offer further improvement in detection. As far as we know, this is the first report of pure image-based machine learning model with high detection accuracy. Importantly, this is also the first model to show relevant class activation heatmap corresponding to loosening location., Translational Potential: The finding in this study indicated image-based machine learning model can detect knee arthroplasty loosening with high accuracy and predictability, which the class activation heatmap can potentially assist surgeons to identify the sites of loosening., Competing Interests: The authors have no conflicts of interest to disclose in relation to this article., (© 2022 The Chinese University of Hong Kong.)

Background: Osteoarthritis (OA) affects the entire joint, initially with a low degree of inflammation. Synovitis is correlated with the severity of OA clinical symptoms and cartilage degradation. The synovial lymphatic system (SLS) plays a prominent role in clearing macromolecules within the joint, including the pro-inflammatory cytokines in arthritic status. Scattered evidence shows that impaired SLS drainage function leads to the accumulation of inflammatory factors in the joint and aggravates the progression of OA, and the role of SLS function in OA is less studied., Design: This review summarizes the current understanding of synovial lymphatic function in OA progression and potential regulatory pathways and aims to provide a framework of knowledge for the development of OA treatments targeting lymphatic structure and functions., Results: SLS locates in the subintima layer of the synovium and consists of lymphatic capillaries and lymphatic collecting vessels. Vascular endothelial growth factor C (VEGF-C) is the most critical regulating factor of lymphatic endothelial cells (LECs) and SLS. Nitric oxide production-induced impairment of lymphatic muscle cells (LMCs) and contractile function may attribute to drainage dysfunction. Preclinical evidence suggests that promoting lymphatic drainage may help restore intra-articular homeostasis to attenuate the progression of OA., Conclusion: SLS is actively involved in the homeostatic maintenance of the joint. Understanding the drainage function of the SLS at different stages of OA development is essential for further design of therapies targeting the function of these vessels., (Copyright © 2022 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Background: Foot and ankle injuries have been noted as the most common in dancers. However, the variability of injury epidemiology across different dance genres has not been clearly evaluated. Herein, this study aimed to evaluate the prevalence and incidence of foot and ankle problems in pre-professional ballet, contemporary, and Chinese dancers.
Methods: Participants (N = 54) were recruited from a local dance institution that offered a formal undergraduate dance program. Demographic characteristics and specifics of foot and ankle pain during dancing were collected through an online self-reporting survey from September 2018 to June 2019. Descriptive statistical analyses, including injury incidence and risk rates, were conducted.
Results: The overall response rate was 69.3%, with a total of 88 subjects eligible for analysis of which the results from 54 subjects were ultimately analyzed. The incidence of foot and ankle pain during the academic year of 2018 to 2019 was highest in contemporary dancers (0.38 per 1,000 dance hours) when compared to that of ballet (0.32 per 1,000 dance hours) and Chinese dancers (0.22 per 1,000 dance hours). Prevalence of foot and ankle pain within the same year was 84% in ballet dancers, 79% in Chinese dancers, and 70% in contemporary dancers. Ballet dancers were six times more likely to suffer from pain in the Achilles region than Chinese and contemporary dancers (p < 0.01). Chinese dancers were found to experience more forefoot and midfoot problems compared to ballet and contemporary dancers (p < 0.05).
Conclusion: This study illustrated that foot and ankle pain is highly prevalent among pre-profes- sional dancers. Ballet was associated with the highest prevalence of foot-ankle pain while contemporary dance was associated with the highest incidence. There were significant differences of foot and ankle pain among dance genres and anatomical subregions, which suggests a need for targeted genre-specific injury prevention programs in hopes of preventing potentially career-ending injuries in dancers.

Objective: This study aims to examine the effects of one-year, once-weekly high-intensity interval training (HIIT) on body adiposity and liver fat in adults with central obesity., Methods: One-hundred and twenty adults aged 18-60 years with central obesity (body mass index ≥25, waist circumference ≥90 cm for men and ≥80 cm for women). This is an assessor-blinded randomized controlled trial. Participants will be randomly assigned to the HIIT group or the usual care control group. Each HIIT session will consist of 4 × 4-min bouts at 85%-95% maximal heart rate, interspersed with 3-min bouts at 50%-70% maximal heart rate. The HIIT group will complete one session per week for 12 months, whereas the usual care control group will receive health education. The primary outcomes of this study are total body adiposity and intrahepatic triglyceride content. The secondary outcomes include abdominal visceral adipose tissue, subcutaneous adipose tissue, body mass index, waist circumference, hip circumference, cardiorespiratory fitness, lean body mass, bone mineral density, blood pressure, fasting blood glucose, insulin, triglycerides, glycated hemoglobin, cholesterol profile, liver function enzymes, medications, adherence to exercise, adverse events, quality of life, and mental health. Outcome measure will be conducted at baseline, 12 months (post-intervention), and 24 months (one-year follow-up)., Impact of the Project: This study will explore the benefits of long-term once-weekly HIIT with a follow-up period to assess its effectiveness, adherence, and sustainability. We expect this intervention will enhance the practical suitability of HIIT in inactive adults with central obesity, and provide insights on low-frequency HIIT as a novel exercise option for the management of patients with central obesity and liver fat., Trial Registration: ClinicalTrials.gov (NCT03912272) registered on 11 April 2019., Competing Interests: The authors declare no competing interests., (© 2022 The Society of Chinese Scholars on Exercise Physiology and Fitness. Published by Elsevier (Singapore) Pte Ltd.)

Some studies suggested that adolescent scoliotic dancers were more likely to sustain dance injuries than non-scoliotic dancers. This study aimed to investigate the association between scoliosis and dance injury among children and adolescent recreational dancers. Identical web-based and paper-based questionnaires were distributed to children and adolescent recreational dancers to collect demographic information, dance experiences, history and location of dance injuries, as well as the frequency of dance injury in the last 12 months. The prevalence rates of the top three dance injury sites (lower back, knee, and ankles) were estimated. Associations between the presence of scoliosis and various dance injuries in the last 12 months were evaluated by multivariate logistic regression. Data from 704 respondents (644 females, 13.3 ± 2.4 years) was analyzed. Ninety-one respondents (12.9%) reported scoliosis and 11 respondents (1.6%) were wearing scoliosis braces. The 12-month prevalence rates of lumbar, knee, and ankle injuries in scoliotic dancers (24.2%, 22.2%, and 28.5%, respectively) were significantly higher than those of non-scoliotic dancers (10.4%, 14.9%, and 14.8%, respectively). Scoliosis was an independent risk factor for lumbar spine injury (Odds ratio, OR = 2.7), knee injury (OR = 2.6), and multi-site dance-related injury (OR = 1.9). Given the observed strong associations between scoliosis and lumbar or knee dance injuries in the current study, future studies are warranted to investigate the underlying causes.

Background: Meniscus root tear is an uncommon but detrimental injury of the knee. Hoop stress is lost during meniscus root tear, which can lead to excessive tibiofemoral contact pressure and early development of osteoarthritis. Posterolateral meniscus root tears (PLRT) are more commonly associated with anterior cruciate ligament (ACL) tears. As the lateral compartment is less congruent than the medial compartment, it is more susceptible to a shearing force, which is increased in the ACL-deficient knee. In accordance with the compressive axial load, the increase in the tibial slope would generate a greater shearing force. The additional lateral compartment mobility caused by ACL tear should be reduced after ACL reconstruction (ACLR). However, there is a lack of evidence to conclude that ACLR can sufficiently limit the effect of large tibial slope (LTS) on the healing after PLRT repair. This study aimed to evaluate whether a steep LTS would be a risk factor for poorer clinical outcomes after PLRT repair concomitant with ACLR., Methods: In this retrospective study, a chart review was conducted to identify patients with concomitant unilateral primary ACLR and PLRT repair. Patients with a partial tear or healed tear were excluded. Postoperative MRI and clinical assessments were performed at a mean follow up of 35 months. MRI data was used to measure the LTS, medial tibial slope (MTS), coronal tibial slope (CTS), the lateral-to-medial slope difference (LTS-MTS) and meniscus healing and extrusion. Functional outcomes were evaluated by patient-reported outcomes (International Knee Documentation Committee [IKDC], Lysholm and Tegner scores) and KT-1000 arthrometer assessment. Interobserver reproducibility was assessed by two reviewers., Results: Twenty-five patients were identified for the analysis. Patients with larger LTS and larger LTS-MTS differences were shown to be correlated with poorer IKDC scores after surgery (R = -0.472, p = 0.017 and R = -0.429, p = 0.032, respectively). Herein, patients with LTS ≥ 6° or LTS-MTS ≥ 3° demonstrated poorer IKDC scores., Conclusion: A large LTS (≥ 6°) and a large difference of LTS-MTS (≥ 3°) were shown to be risk factors for poorer functional and radiological outcomes for PLRT repair in patients after ACLR. Clinically, closer monitoring and a more stringent rehabilitation plan for patients with LTS ≥ 6° or LTS-MTS ≥ 3° would be recommended., (© 2022. The Author(s).)

Anterior cruciate ligament (ACL) tear is common in sports and accidents, and accounts for over 50% of all knee injuries. ACL reconstruction (ACLR) is commonly indicated to restore the knee stability, prevent anterior-posterior translation, and reduce the risk of developing post-traumatic osteoarthritis. However, the outcome of biological graft healing is not satisfactory with graft failure after ACLR. Tendon graft-to-bone tunnel healing and graft mid-substance remodeling are two key challenges of biological graft healing after ACLR. Mounting evidence supports excessive inflammation due to ACL injury and ACLR, and tendon graft-to-bone tunnel motion negatively influences these two key processes. To tackle the problem of biological graft healing, we believe that an inductive approach should be adopted, starting from the endpoint that we expected after ACLR, even though the results may not be achievable at present, followed by developing clinically practical strategies to achieve this ultimate goal. We believe that mineralization of tunnel graft and ligamentization of graft mid-substance to restore the ultrastructure and anatomy of the original ACL are the ultimate targets of ACLR. Hence, strategies that are osteoinductive, angiogenic, or anti-inflammatory should drive graft healing toward the targets. This paper reviews pre-clinical and clinical literature supporting this claim and the role of inflammation in negatively influencing graft healing. The practical considerations when developing a biological therapy to promote ACLR for future clinical translation are also discussed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yao, Yung and Lui.)

Chronic tendinopathy is a debilitating tendon disorder with disappointing treatment outcomes. This review focuses on the potential roles of chronic low-grade inflammation in promoting tendinopathy in obesity. A systematic literature search was performed to identify all clinical studies supporting the actions of obesity-associated inflammatory mediators in the development of tendinopathy. The mechanisms of obesity-induced chronic inflammation in adipose tissue are firstly reviewed. Common inflammatory mediators potentially linking obesity and the development of tendinopathy, and their association with mechanical overuse, are discussed, along with pre-clinical evidences and a systematic literature search on clinical studies. The potential contribution of local adipose tissues in the promotion of inflammation, pain and tendon degeneration is then discussed. The future research directions are proposed., Translational Potential Statement: Better understanding of the roles of obesity-associated inflammatory mediators on tendons will clarify the pathophysiological drivers of tendinopathy in patients with obesity and identify possible treatment targets. Further studies on the mechanisms of obesity-induced chronic inflammation on tendon are a promising direction for the treatment of tendinopathy., Competing Interests: The authors have no conflicts of interest relevant to this article., (© 2021 The Authors.)

Background: When and where to apply the biological modulations is effective to promote healing in the anterior cruciate ligament (ACL) reconstruction remains unclear., Purpose: To perform a systematic review of preclinical animal studies on biological modulation in anterior cruciate ligament reconstruction (ACLR) concerning the time and site of delivery., Study Design: Systematic review of controlled laboratory studies., Methods: PubMed, Ovid, and Scopus were searched until December 2020 using a combination of keywords and their synonym to retrieve all animal studies about biological modulation in ACLR. Studies that assessed mechanical strength after ACLR and compared with negative control were included. The methodological quality of animal studies was evaluated., Results: 33 studies were included in this review and the majority reported mechanical strength improvement. 79 ​% of studies applied the biological modulations intra-operatively with different delivery systems used. For 21 ​% of post-operative delivery studies, intermittent delivery was tried. 21 of the included studies directly applied the biological modulations in the bone tunnels, 5 studies applied intra-articularly while 7 studies applied both in the bone tunnels and intra-articular part. Biological modulations applied intra-operatively and those applied in both parts showed better mechanical strength increase. A shift of the failure mode of pull-out from the bone tunnel in the early healing phase, to mid-substance rupture in the later phase was observed in most studies., Conclusion: The improvement of the mechanical strength depends on how the biological modulations (delivery phase, delivery site, delivery form) are applied. The intra-operative delivery showed an overall higher mechanical strength increase and bone tunnel only delivery or intra-articular and bone tunnel both delivery are preferred than intra-articular only delivery. In addition, intra-articular and bone tunnel both delivery can have better mechanical strength increase for a long follow-up time. Thus, intra-operative application with a carrier to control release rate in both parts should be recommended. Further studies are needed to achieve a better healing outcome and more attention should be given to the intra-articular remodeling of the graft along with the tendon bone healing to increase the final mechanical strength., The Translational Potential of This Article: Here, a systematic review of preclinical evidence of the time, site and the method the biological modulations being applied for ACLR to improve the graft healing would be performed. After reviewing the available studies, a choice of when and where to apply the biological modulations can achieve better mechanical strength after ACLR can be obtained. It provides evidence for both researchers and clinicians to decide when and where to apply the biological modulations can achieve their best effectiveness for ACLR before implementing. Promoting graft healing with targeted time and targeted site may reduce the risk of graft failure, safeguard return to sport., Competing Interests: The authors declared that they have no conflicts of interest to this work. We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (© 2021 The Authors.)

Background: This case study describes an atypical presentation of avascular necrosis (AVN) of the first metatarsal head, which is largely unfounded in the literature., Case Summary: A healthy 24-year-old female initially presented with pain at the first metatarsophalangeal joint (MTPJ) and was diagnosed with AVN by physical examination and magnetic resonance imaging. The patient demonstrated atypically poor progress in recovery, despite being in otherwise good health and being of young age, with no history of corticosteroid or alcohol use. The patient also did not have any history or clinical features of autoimmune disease or vasculitis, such as systemic lupus erythematosus. The patient was managed with conservative treatment for 18 mo, which allowed for gradual return of full range of motion of the first MTPJ and subsiding pain, permitting the patient to return to high-intensity sports training and full weight-bearing. Throughout her recovery, many differential diagnoses were ruled out through specific investigations leading to further reinforcement of the diagnosis of AVN of the 1 st metatarsal head., Conclusion: Atypical AVN may occur with no predisposing risk factors. Treatment is mainly conservative, with unclear guidelines in literature on management., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Ankle sprain is very common in sports. Research on its prevention is as important as on its treatment as recommended in the 2016 consensus statement of the International Ankle Consortium. Successful prevention depends on the understanding of its mechanism, which has been presented with quantities in some recent case reports. Inciting event was suggested to be an inverted ankle joint at foot strike, however, is still lacking evidence from comparison with non-injury trials. This study investigated the ankle joint orientation at foot strike in successful non-injury cases and compared them with a previously analysed ankle sprain injury case. Two injury-free cutting motions with similar movement approach to a previously analysed ankle sprain injury performed by the same athlete were collected from an online search and were trimmed from 0.05 s before until 0.30 s after the foot strike. The video sequences were then processed by video editing software and then analysed by a model-based image-matching motion analysis technique. Ankle joint orientation at foot strike and the profiles were presented in inversion, plantarflexion and rotation planes, for both the previously analysed injury case and the two non-injury cases. The ankle joint orientation at foot strike was 0-1 degree inverted and 10-21° dorsiflexed in the two non-injury cases, compared to 14° inverted and 16° plantarflexed in the previously analysed injury case. From the case comparison, it can be observed that an inverted ankle joint orientation at foot strike in an inciting event of ankle inversion sprain., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

This study developed a method that predicts laterally deviated plantar pressure during stance by lower limb anthropometrics and self-reported ability to stop an ankle which has started to roll over. Thirty-two males ran on a treadmill for 2 minutes at 11 km/h. Foot pressure data were collected by a pressure insole system for classifying the participants as medial or lateral strikers. Cumberland Ankle Instability Tool score, Tegner Activity Scale score, foot arch height, active and passive ankle and knee range of motion, bi-malleolar width, foot length, foot width and calf circumference were measured. Binary logistic regressions were performed to produce a model which estimated if an individual showed laterally deviated foot pressure during stance. The model utilized the score of Cumberland Ankle Instability Tool Question 8, active and passive knee joint external rotation, height, body mass and bimalleolar width (explained variance of 47.3%, p = 0.037), producing a sensitivity of 71.4% and a specificity of 54.5%. A validation trial on another 15 runners reported a 73.3% accuracy in prediction if they are medial or lateral strikes.

The association between the risk of fractures and suboptimal vitamin D (Vit-D) status remains controversial in children. This meta-analysis suggested that serum 25(OH)Vit-D levels were lower in pediatric cases with fractures. 25-hydroxyvitamin D (25(OH)Vit-D) levels less than 50 nmol/L were associated with increased fracture risk in children., Introduction: This study aimed to assess the association between serum 25(OH)Vit-D and the risk of fractures in children, and to explore the sources of heterogeneity and investigate their impact on results., Methods: Systematic review and meta-analysis were conducted for observational studies comparing serum 25(OH)Vit-D levels between fracture and non-fracture pediatric cases. The quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS)., Results: Analysis on 17 case-control and 6 cross-sectional studies (2929 fracture cases and 5000 controls) suggested that 25(OH)Vit-D was lower in fracture cases than in controls (pooled mean difference (MD) = - 3.51 nmol/L; 95% confidence interval (CI): - 5.60 to - 1.42) with a heterogeneity (I 2 ) of 73.9%. The sensitivity analysis which merged the case-control studies that had a NOS score ≥ 4 showed a pooled MD of - 4.35 nmol/L (95% CI: - 6.64 to - 2.06) with a heterogeneity (I 2 ) of 35.9%. Pooled odds ratio of fracture in subjects with 25(OH)Vit-D ≤ 50 nmol/L compared to subjects with 25(OH)Vit-D > 50 nmol/L was 1.29 (95% CI: 1.10 to 1.53; I 2 < 1%)., Conclusion: This study indicated that serum 25(OH)Vit-D levels were lower in pediatric patients with fractures. 25(OH)Vit-D ≤ 50 nmol/L was associated with increased fracture risk in children.

Objective: Osteoarthritis (OA) has long been regarded as a disease of cartilage degeneration, whereas mounting evidence implies that low-grade inflammation contributes to OA. Among inflammatory cells involved, macrophages play a crucial role and are mediated by the local microenvironment to exhibit different phenotypes and polarization states. Therefore, we conducted a systematic review to uncover the phenotypic alterations of macrophages during OA and summarized the potential therapeutic interventions via modulating macrophages., Methods: A systematic review of multiple databases (PubMed, Web of Science, ScienceDirect, Medline) was performed up to February 29, 2020. Included articles were discussed and evaluated by two independent reviewers. Relevant information was analyzed with a standardized and well-designed template., Results: A total of 28 studies were included. Results were subcategorized into two sections depending on sources from human tissue/cell-based studies (12 studies) and animal experiments (16 studies). The overall observation indicated that M1 macrophages elevated in both synovium and circulation during OA development, along with lower numbers of M2 macrophages. The detailed alterations of macrophages in both synovium and circulation were listed and analyzed. Furthermore, interventions against OA via regulating macrophages in animal models were highlighted., Conclusion: This study emphasized the importance of the phenotypic alterations of macrophages in OA development. The classical phenotypic subcategory of M1 and M2 macrophages was questionable due to controversial and conflicting results. Therefore, further efforts are needed to categorize macrophages in an exhaustive manner and to use advanced technologies to identify the individual roles of each subtype of macrophages in OA.

Introduction: High tibial osteotomy (HTO) is a treatment of choice for active adult with knee osteoarthritis. With advancement in CT imaging with three-dimensional (3D) model reconstruction, virtual planning and 3D printing, patient-specific instrumentation (PSI) in form of cutting jigs is employed to improve surgical accuracy and outcome of HTO. The aim of this randomised controlled trial (RCT) is to explore the surgical outcomes of HTO for the treatment of medial compartment knee osteoarthritis with or without a 3D printed patient-specific jig., Methods and Analysis: A double-blind RCT will be conducted with patients and outcome assessors blinded to treatment allocation. This meant that neither the patients nor the outcome assessors would know the actual treatment allocated during the trial. Thirty-six patients with symptomatic medial compartment knee osteoarthritis fulfilling our inclusion criteria will be invited to participate the study. Participants will be randomly allocated to one of two groups (1:1 ratio): operation with 3D printed patient-specific jig or operation without jig. Measurements will be taken before surgery (baseline) and at postoperatively (6, 12 and 24 months). The primary outcome includes radiological accuracy of osteotomy. Secondary outcomes include a change in knee function from baseline to postoperatively as measured by three questionnaires: Knee Society Scores (Knee Scores and Functional Scores), Oxford Knee Scores and pain visual analogue scale (VAS) score., Ethics and Dissemination: Ethical approval has been obtained from the Joint Chinese University of Hong Kong - New Territories East Cluster Clinical Research Ethics Committee (CREC no. 2019.050), in accordance with the Declaration of Helsinki. The results will be presented at international scientific meetings and through publications in peer-reviewed journals., Trial Registration Number: NCT04000672; Pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

There is emerging awareness that subchondral bone remodeling plays an important role in the development of osteoarthritis (OA). This review presents recent investigations on the cellular and molecular mechanism of subchondral bone remodeling, and summarizes the current interventions and potential therapeutic targets related to OA subchondral bone remodeling. The first part of this review covers key cells and molecular mediators involved in subchondral bone remodeling (osteoclasts, osteoblasts, osteocytes, bone extracellular matrix, vascularization, nerve innervation, and related signaling pathways). The second part of this review describes candidate treatments for OA subchondral bone remodeling, including the use of bone-acting reagents and the application of regenerative therapies. Currently available clinical OA therapies and known responses in subchondral bone remodeling are summarized as a basis for the investigation of potential therapeutic mediators., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhu, Chan, Yung, Tuan and Jiang.)

To determine whether state-of-the-art multi-energy spectral photon-counting computed tomography (MARS) can detect knee arthroplasty implant failure not detected by standard pre-operative imaging techniques. A total knee arthroplasty (TKA) removed from a patient was reviewed. The extracted prosthesis [NexGen Legacy Posterior Stabilized (LPS) TKA] was analyzed as were pre-operative imaging examination and compared with a MARS-CT examination obtained of the extracted TKA prosthesis. Radiographs, fluoroscopy, ultrasound and MRI preoperatively did not reveal the cause of the implant failure. MARS CT images of the extracted prosthesis clearly showed the presence of posteromedial polyethylene and tibial tray wear which is compatible with the clinical appearance of the extracted TKA. MARS can identify polyethylene insert and metallic tibial tray wear as a cause of TKA failure, that could not be identified with on standard pre-operative imaging. Although clinical MARS CT system is still under development, this case does illustrate its potential clinical usefulness. This is the first study to document how MARS CT imaging can detect orthopedic implant failure not detected by standard current imaging techniques. This system has a potential clinical application in orthopedic patients.

The phenotypic change of macrophages (Mφs) plays a crucial role in the musculoskeletal homeostasis and repair process. Although mesenchymal stem cells (MSCs) have been shown as a novel approach in tissue regeneration, the therapeutic potential of MSCs mediated by the interaction between MSC-derived paracrine mediators and Mφs remains elusive. This review focused on the elucidation of paracrine crosstalk between MSCs and Mφs during musculoskeletal diseases and injury. The search method was based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and Cochrane Guidelines. The search strategies included MeSH terms and other related terms of MSC-derived mediators and Mφs. Ten studies formed the basis of this review. The current finding suggested that MSC administration promoted proliferation and activation of CD163 + or CD206 + M2 Mφs in parallel with reduction of proinflammatory cytokines and increase in anti-inflammatory cytokines. During such period, Mφs also induced MSCs into a motile and active phenotype via the influence of proinflammatory cytokines. Such crosstalk between Mφs and MSCs further strengthens the effect of paracrine mediators from MSCs to regulate Mφs phenotypic alteration. In conclusion, MSCs in musculoskeletal system, mediated by the interaction between MSC paracrine and Mφs, have therapeutic potential in musculoskeletal diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Xu, Lee, Wang, Huang, Shin, Wang, Wan, Zhu, Yung and Lee.)

Background: Foot pain experienced by long-distance runners could be relieved by functional insoles which aim at evenly distributing the plantar pressure., Research Question: We hypothesised that an individually moulded insole with medial arch support would reduce the impact and loading under the heel and metatarsal regions., Methods: Twelve male recreational runners ran on a treadmill at 10 km/h for 1 hour with flat insoles and medial arch supported insoles. A pressure insole system (Novel Pedar, Germany) was used to obtain the peak pressure, peak force, time normalised pressure-time integrals, and the percentage of the total force-time integrals under 10 regions., Results: Medial arch supported insoles reduced the peak force under the heel (medial: -15.3%, p = 0.001; lateral: -19.2%, p = 0.037) during the initial run, and reduced peak pressure under the heel (medial: -13.3%, p = 0.005; lateral: -9.9%, p = 0.006), and peak force under the medial heel (-17.8%, p = 0.006) after the run. The percentage of the total force-time integrals under the heel was reduced (medial: -23.8%, p = 0.004; lateral: -13.6%, p = 0.022) after the run. No significant difference was found under the metatarsal regions. There is shift of load from the metatarsal regions to the medial mid-foot as indicated by the change of the percentage of total force-time integrals., Significance: Medial arch supported insoles were effective in reducing the impact and loading under the heel region in prolonged running on a treadmill., Level of Evidence: Controlled laboratory study, Level V., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: Ankle sprain injury rate is reported to be higher towards the end of a football match. Muscle fatigue may contribute to the delayed muscle reaction and subsequent injury. This study investigated the ankle muscle reaction time during a simulated, prolonged football protocol., Methods: Seven amateur female football players participated in a 105-min simulated, prolonged football protocol. An ankle muscle reaction test was conducted with a pair of ankle sprain simulators at a scheduled interval every 15-min. The reaction times of peroneus longus, tibialis anterior, and lateral gastrocnemius were collected using an electromyography system sampling at 1000 Hz. Repeated measures one-way multivariate analysis of variance with post-hoc paired t-tests were conducted to evaluate if the reaction time at each time point significantly differed from baseline. Statistical significance was set at p < 0.05 level., Results: Reaction times started from 40.5-47.7 ms at baseline and increased to 48.6-55.7 ms at the end. Reaction times significantly increased in all muscles after the first 15 min except for the dominant lateral gastrocnemius. Increased reaction times were seen in the non-dominant limb after 60 min for tibialis anterior, after 75 min for peroneus longus, and after 90 min for the lateral gastrocnemius., Conclusions: Delayed reaction time of the ankle muscles were found after the first 15 min and in the final 45 min of a simulated prolonged football protocol. Strategies for injury prevention should also focus on tackling the delayed ankle muscle reaction time in the acute phase (the first 15 min), in addition to the latter minutes in the second half., Level of Evidence: Controlled laboratory study, Level V.

Treatment of tendon injuries is challenging. To develop means to augment tendon regeneration, we have previously prepared a soluble, low immunogenic (DNA-free), tendon extracellular matrix fraction (tECM) by urea extraction of juvenile bovine tendons, which is capable of enhancing transforming growth factor-β (TGF-β) mediated tenogenesis in human adipose-derived stem cells (hASCs). Here, we aimed to elucidate the mechanism of tECM-driven hASC tenogenic differentiation in vitro, focusing on the integrin and TGF-β/SMAD pathways. Our results showed that tECM promoted hASC proliferation and tenogenic differentiation in vitro based on tenogenesis-associated markers. tECM also induced higher expression of several integrin subunits and TGF-β receptors, and nuclear translocation of p-SMAD2 in hASCs. Pharmacological inhibition of integrin-ECM binding, focal adhesion kinase (FAK) signaling, or TGF-β signaling independently led to compromised pro-tenogenic effects of tECM and actin fiber polymerization. Additionally, integrin blockade inhibited tECM-driven TGFBR2 expression, while inhibiting TGF-β signaling decreased tECM-mediated expression of integrin α1, α2, and β1 in hASCs. Together, these findings suggest that the strong pro-tenogenic bioactivity of tECM is regulated via integrin/TGF-β signaling crosstalk. Understanding how integrins interact with signaling by TGF-β and/or other growth factors (GFs) within the tendon ECM microenvironment will provide a rational basis for an ECM-based approach for tendon repair., (© 2020 Federation of American Societies for Experimental Biology.)

Background: This prospective cohort study was designed to evaluate the survivorship and functional outcomes associated with long-term results of medial open-wedge high tibial osteotomy (MOWHTO) for the treatment of medial compartment knee osteoarthritis in the Chinese population. Although MOWHTO is a well-established procedure in the management of medial osteoarthritis of the knee, the long-term outcome in the Chinese population has not been reported in current literature. We hypothesised that MOWHTO would result in long-term preservation of knee function in Chinese, similar to that reported in the Caucasian population., Methods: A cohort of 22 young adult patients (age < 55 years old) undergoing MOWHTO for the treatment of symptomatic medial compartment knee osteoarthritis between 2002 and 2008 was retrospectively surveyed with a minimum follow-up of 10 years. Kaplan-Meier survival analysis was performed, and the failure modes were investigated. The outcomes on survival (not requiring arthroplasty), clinical outcome (Knee Society Knee Score and Knee Society Function Score) and range of motion (numeric rating scale) at preoperative, 1-year postoperative follow-up and at last follow-up (>10 years) were evaluated. In addition, the mechanical tibiofemoral angle was also measured. The Wilcoxon signed-rank test was used for statistical evaluation of nonparametric data in these related samples., Result: A total of 31 knees in these 22 cases were included. The follow-up rate was 100% at 13.4 ± 1.9 years (11-17). Mean age at time of surgery was 45.8 ± 9.5 years (18-53). At 10-year follow-up, four knees converted to require total knee arthroplasty (survival: 87.1%). Preoperative varus alignment with mechanical tibiofemoral angle of -9.26 ± 2.83 was corrected to 2.58 ± 2.46 after surgery and remained 2.01 ± 3.52 at the latest follow-up. Knee Society Knee Score increased significantly from 53.7 ± 11.1 preoperatively to 93.8 ± 6.8 at 1-year follow-up and 91.8 ± 9.7 at latest follow-up. Similarly, the functional score also increased significantly from 67.4 ± 21.0 preoperatively to 86.3 ± 14.5 at 1-year follow-up and 82.1 ± 16.6 at latest follow-up ( p  < 0.01). Whereas, the range of motion significantly decreased from 122.7 ± 6.6 preoperatively to 116.1 ± 15.5 at the latest follow-up., Conclusion: Even in cases of severe medial osteoarthritis and varus malalignment, MOWHTO would be a good treatment option for management in active Chinese population less than 55 years. Although t he long-term survival and functional outcome after MOWHTO was proven to be satisfactory in our cohort during the 10-year follow-up, a larger cohort to illustrate the long-term functional outcome is still warranted., Translational Potential: The finding in this study indicated MOWHTO is a feasible treatment option for young adult patients with osteoarthritis to achieve long-term satisfactory results., Competing Interests: The authors have no conflicts of interest to disclose in relation to this article., (© 2020 The Author(s).)

Release of the tight lateral soft tissue is an important procedure during surgery for hallux valgus. The authors describe an arthroscopic assisted lateral soft tissue release technique that is minimally invasive and easy to perform, while also providing precise visualization of the released structures., (Copyright © 2019 the American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The relationship between the frequency of high-intensity interval training (HIIT) and the resultant adaptations is largely unclear., Purpose: This study compared the effects of different frequencies of HIIT with those of moderate-intensity continuous training (MICT) on body composition in overweight or obese adults., Methods: Fifty-six overweight or obese (body mass index = 26.4 ± 2.9) men between 18 and 30 yr old (age = 22.8 ± 3.1 yr) were randomly assigned to the following groups: no-intervention control (CON; n = 14), MICT performed thrice weekly (MICT×3/wk; n = 9), HIIT performed thrice weekly (HIIT×3/wk; n = 14), HIIT performed twice weekly (HIIT×2/wk; n = 10), and HIIT performed once weekly (HIIT×1/wk; n = 9). Each HIIT session consisted of 12 × 1-min bouts at 90% heart rate reserve, interspersed with 11 × 1-min bouts at 70% heart rate reserve. Aerobic capacity, body composition, resting heart rate, vascular function, insulin resistance, and biomarkers of metabolic syndrome risk factor were examined at baseline, after 4 wk, and after 8 wk of intervention., Results: Aerobic capacity and percent fat-free mass significantly increased in all exercise groups compared with those in the CON group (CON vs all exercise groups, P < 0.05), whereas body fat mass and systolic blood pressure significantly decreased after 8 wk of intervention in all exercise groups compared with those in the CON group (CON vs all exercise groups, P < 0.05). Body fat mass significantly decreased after 4 wk in all HIIT groups compared with those in the CON group (CON vs all HIIT groups, P < 0.05) but not in the MICT×3/wk group., Conclusion: These novel results demonstrated that performing HIIT once weekly, even with a lower weekly volume of exercise, improved cardiorespiratory fitness, body composition, and blood pressure in overweight/obese adults. Low-frequency HIIT might be a feasible and effective strategy for the prescription of an initial exercise program for inactive, overweight, or obese young men.

Background: Achilles tendinopathy is one of the most common overuse injuries in running, and forefoot pronation, seen in flatfeet participants, has been proposed to cause additional loading across the Achilles tendon. Foot orthoses are one of the common and effective conservative treatment prescribed for Achilles tendinopathy, it works by correcting the biomechanical malalignment and reducing tendon load. Previous studies have shown reduction of Achilles Tendon load (ATL) during running by using customized arch support orthosis (CASO) or an orthotic heel lift (HL). However, there are still little biomechanical evidence and comparative studies to guide orthotic prescriptions for Achilles tendinopathy management. Therefore, this study seeks to investigate the two currently employed orthotic treatment options for Achilles tendinopathy: CASO and HL for the reduction of ATL and Achilles tendon loading rate (ATLR) in recreational runners with flatfeet., Methods: Twelve participants were recruited and run along the runway in the laboratory for three conditions: (1) without orthoses, (2) with CASO (3) with HL. Kinematic and kinetic data were recorded by 3D motion capturing system and force platform. Ankle joint moments and ATL were computed and compared within the three conditions., Results: Participants who ran with CASO (p = 0.001, d = 0.43) or HL (p = 0.001, d = 0.48) associated with a significant reduction in ATL when compared to without orthotics while there was no significant difference between the two types of orthoses, the mean peak ATL of CASO was slightly lower than HL. Regarding the ATLR, both orthoses, CASO (p = 0.003, d = 0.93) and HL (p = 0.004, d = 0.78), exhibited significant lower value than the control but similarly, no significant difference was noted between them in which the use of CASO yielded a slightly lower loading rate than that of HL., Conclusions: Both CASO and HL were able to cause a significant reduction in peak ATL and ATLR comparing to without orthotics condition. There were subtle but no statistically significant differences in the biomechanical effects between the two types of orthoses. The findings help to quantify the effect of CASO and HL on load reduction of Achilles tendon and suggests that foot orthoses may serve to prevent the incidence of Achilles tendon pathologies., Trial Registration: NCT04003870 on clinicaltrials.gov 1 July 2019.

Context: Fatigue of the shoulder rotators may cause reduction of the subacromial space (SAS) and contribute to rotator cuff tendinopathy., Objectives: To compare the isokinetic peak torques and fatigue ratios of shoulder external rotators (ER) and internal rotators (IR) between elite softball athletes with and without rotator cuff tendinopathy and to investigate their associations with the SAS., Design: Cross-sectional study., Setting: University laboratory., Participants: Twenty-five elite softball players and 31 asymptomatic sedentary controls participated in this study., Main Outcome Measures: Isokinetic concentric IR and ER peak torque and fatigue ratio were measured at 60°/s and at 180°/s, respectively; and ultrasound measurement of the SAS was measured during 0° and 60° of shoulder abduction., Results: Athletes with rotator cuff tendinopathy demonstrated lower peak torque in shoulder concentric ER when compared with their healthy counterparts (37.8 [5.8%] vs 43.6 [8.5%]). No significant difference was found in the fatigue ratios of ER, IR, and ER/IR when compared between elite softball athletes with and without rotator cuff tendinopathy (all P > .24). In asymptomatic athletes, greater IR peak torque (r = .583, P = .03), lower ER/IR strength ratio (r = -.605, P = .02), and greater ER/IR fatigue ratio (r = .575, P = .03) were moderately associated with more reduction of the SAS during 0° and 60° of shoulder abduction., Conclusions: Decreased strength ratio and fatigue ratio of ER/IR were related to reduction of the SAS.

Running-related injuries have been associated with excessive foot pronation and high vertical loading rates. Traditional plaster-molded (TPM) foot orthoses are commonly prescribed to minimize these atypical biomechanical patterns. Recently, 3D printed (3DP) orthoses have become popular, yet the functional difference between these two types of orthoses remains unknown. Therefore, this study compared running biomechanics and perceived comfort during treadmill running in three orthotic conditions: 3DP orthoses, TPM orthoses, and a no-orthoses control condition (CON). Thirteen female asymptomatic runners with excessive foot pronation were recruited. Rearfoot eversion angle and velocity (at initial contact and peak) during stance, vertical loading rates, and perceived comfort were compared. Results showed lower peak rearfoot eversion angles during running with TPM ( p =0.001, d =0.38) or 3DP orthoses ( p =0.002, d =0.24) than CON. No differences were observed in other biomechanical parameters among the three conditions ( p >0.05). Running with TPM ( p ≤0.001, d =1.74-1.82) and 3DP orthoses ( p <0.003, d =1.06-1.34) resulted in better perceived comfort in "medial-lateral control" and "heel cushioning" than CON. There were no statistical differences in all parameters between TPM and 3DP orthoses. The present findings indicate improved comfort during running with TPM or 3DP orthoses, which hinted 3DP orthoses could be a viable alternative to TPM orthoses for clinical practice.

Background: The anterior cruciate ligament (ACL) has poor regenerative capacity, and an injury leads to loss of function, limiting quality of life and increasing the incidence of osteoarthritis. Surgical interventions can stabilize the joint and improve functional recovery. The delivery of growth factors (GFs) enhances the healing process; however, this is complex in its regulation, is high in costs, has side effects, and can only be accomplished with supraphysiological concentrations and thus is currently not clinically feasible. However, the immobilization of a patient's endogenous GFs in biomaterials can overcome these problems., Purpose: To develop a method to capture endogenous bone morphogenetic protein-2 (BMP-2) and ultimately show enhanced ACL healing in vivo using this novel methodology., Study Design: Controlled laboratory study., Methods: BMP-2 binding peptides were synthetized, purified, and immobilized on polycaprolactone (PCL) films. The affinity between the peptide and human BMP-2 (hBMP-2) was confirmed with immunofluorescence and enzyme-linked immunosorbent assay. The C2C12 Luc reporter cell line was used to confirm the bioactivity of immobilized BMP-2. For in vivo experiments, the same functionalization technology was applied to the commercially available Polytape, and the functionalized tape was sutured together with the graft used for ACL reconstruction in rats. Each animal underwent reconstruction with either native Polytape (n = 3) or Polytape with BMP-2 binding peptides (n = 3). At 2 and 6 weeks after surgery, the graft was assessed by histology and micro-computed tomography., Results: The covalent immobilization of the peptide in PCL was successful, allowing the peptide to capture hBMP-2, which remained bioactive and led to the osteogenic differentiation of C2C12. In vivo experiments confirmed the potential of the Polytape functionalized with the BMP-2 binding peptide to capture endogenous BMP-2, leading to enhanced bone formation inside the femoral and tibial tunnels and ultimately improving the graft's quality., Conclusion: The incorporation of BMP-2 binding peptides into materials used for ACL reconstruction can capture endogenous hBMP-2, which enhances the healing process inside the bone tunnels., Clinical Relevance: These results demonstrate the potential of using synthetic peptides to endow biomaterials with novel biological functions, namely to capture and immobilize endogenous GFs.

Objectives: The purpose of this study was to investigate whether preseason isokinetic strength measures were predictive of future HSI among professional football players., Design: Prospective cohort study, Level of evidence 2., Methods: A total of 169 professional players participated in a preseason isokinetic strength screening, followed by a 10-month competitive season. Testing protocol included the concentric performance of both knee flexion and extension at 60degs -1 and 240degs -1 and the eccentric performance of the knee flexor at 30degs -1 . Strength deficits, bilateral differences, and hamstring to quadriceps strength ratios were computed. Univariate and multivariate logistic regressions were used to identify potential risk factors of HSI. Receiver operating characteristic (ROC) curves were used to investigate the sensitivity and specificity of the strength measures., Results: Forty-one acute HSIs were sustained, and 12% (n=5) reoccurred within the study period. In the multivariate analysis, we have shown an association between the injury risk and eccentric hamstring peak torque below 2.4Nmkg -1 (OR=5.59; 95% CI, 2.20-12.92); concentric H/Q ratio below 50.5% (OR=3.14; 95% CI, 1.37-2.22); players with previous injury of HSI (OR=3.57; 95% CI, 3.13-8.62). ROC analysis displayed an area under curve (AUC) of 0.77, indicating fair combined sensitivity and specificity of the overall predicting model., Conclusions: Professional football players with significant lower isokinetic hamstring strength, lower hamstring-to-quadriceps strength ratio, and a previous injury of HSI were linked to an increased risk of acute HSI., (Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.)

Purpose: To evaluate the test-retest reliability, sensitivity, and concurrent validity of a smartphone-based method for assessing eccentric hamstring strength among male professional football players., Methods: A total of 25 healthy male professional football players performed the Chinese University of Hong Kong (CUHK) Nordic break-point test, hamstring fatigue protocol, and isokinetic hamstring strength test. The CUHK Nordic break-point test is based on a Nordic hamstring exercise. The Nordic break-point angle was defined as the maximum point where the participant could no longer support the weight of his body against gravity. The criterion for the sensitivity test was the presprinting and postsprinting difference of the Nordic break-point angle with a hamstring fatigue protocol. The hamstring fatigue protocol consists of 12 repetitions of the 30-m sprint with 30-s recoveries between sprints. Hamstring peak torque of the isokinetic hamstring strength test was used as the criterion for validity., Results: A high test-retest reliability (intraclass correlation coefficient = .94; 95% confidence interval, .82-.98) was found in the Nordic break-point angle measurements. The Nordic break-point angle significantly correlated with isokinetic hamstring peak torques at eccentric action of 30°/s (r = .88, r 2  = .77, P < .001). The minimal detectable difference was 8.03°. The sensitivity of the measure was good enough that a significance difference (effect size = 0.70, P < .001) was found between presprinting and postsprinting values., Conclusion: The CUHK Nordic break-point test is a simple, portable, quick smartphone-based method to provide reliable and accurate eccentric hamstring strength measures among male professional football players.

Background/objective: Evaluating hamstring strength by isokinetic dynamometry is limited by various practical issues such as time and cost. A video-based Nordic hamstring exercise is introduced as an alternative option. The aims of this study are to evaluate 1.) the between-session reliability and 2.) concurrent validity of the testing method compared to a standardized isokinetic dynamometry., Methods: Thirty male elite footballers were recruited for the study. From the Nordic hamstring exercise, the video-analysis-determined Nordic break-point angles where the participant could no longer withstand the force of the fall (eccentric mode) and the number of seconds that the player could hold at 30° forward flexion angle (isometric mode) were measured. Intra-class correlation coefficients for between-session reliability, Pearson r correlations between the current method and isokinetic dynamometry were calculated., Results: The reliability of the eccentric mode was moderate (ICC (2,1)  = 0.82) while that of isometric mode was poor (ICC (2,1)  = 0.57). The Nordic break-point angle of the eccentric mode significantly correlated with the concentric and eccentric hamstring peak torque (r = 0.48 and 0.58, p < 0.001), while the isometric was not (r = 0.02 - 0.07, p > 0.05)., Conclusion: The eccentric mode of the video-based hamstring strength test was a moderately reliable and valid method to measure the eccentric hamstring strength in elite football players.

Anterior cruciate ligament (ACL) injury is common in knee joint accounting for 40% of sports injury. ACL injury leads to knee instability, therefore, understanding knee stability assessments would be useful for diagnosis of ACL injury, comparison between operation treatments and establishing return-to-sport standard. This article firstly introduces a management model for ACL injury and the contribution of knee stability assessment to the corresponding stages of the model. Secondly, standard clinical examination, intra-operative stability measurement and motion analysis for functional assessment are reviewed. Orthopaedic surgeons and scientists with related background are encouraged to understand knee biomechanics and stability assessment for ACL injury patients.

Background: Excessive pronation (or eversion) at ankle joint in heel-toe running correlated with lower extremity overuse injuries. Orthotics and inserts are often prescribed to limit the pronation range to tackle the problem. Previous studies revealed that the effect is product-specific. This study investigated the effect of medial arch-heel support in inserts on reducing ankle eversion in standing, walking and running., Methods: Thirteen pronators and 13 normal subjects participated in standing, walking and running trials in each of the following conditions: (1) barefoot, and shod condition with insert with (2) no, (3) low, (4) medium, and (5) high medial arch-heel support. Motions were captured and processed by an eight-camera motion capture system. Maximum ankle eversion was calculated by incorporating the raw coordinates of 15 anatomical positions to a self-compiled Matlab program with kinematics equations. Analysis of variance with repeated measures with post-hoc Tukey pairwise comparisons was performed on the data among the five walking conditions and the five running conditions separately., Results: Results showed that the inserts with medial arch-heel support were effective in dynamics trials but not static trials. In walking, they successfully reduced the maximum eversion by 2.1 degrees in normal subjects and by 2.5-3.0 degrees in pronators. In running, the insert with low medial arch support significantly reduced maximum eversion angle by 3.6 and 3.1 degrees in normal subjects and pronators respectively., Conclusion: Medial arch-heel support in inserts is effective in reducing ankle eversion in walking and running, but not in standing. In walking, there is a trend to bring the over-pronated feet of the pronators back to the normal eversion range. In running, it shows an effect to restore normal eversion range in 84% of the pronators.