Transforming growth factor-beta2 (TGF-β2) is recognized as a versatile cytokine that plays a vital role in regulation of joint development, homeostasis, and diseases, but its role as a biological mechanism is understood far less than that of its counterpart, TGF-β1. Cartilage as a load-resisting structure in vertebrates however displays a fragile performance when any tissue disturbance occurs, due to its lack of blood vessels, nerves, and lymphatics. Recent reports have indicated that TGF-β2 is involved in the physiological processes of chondrocytes such as proliferation, differentiation, migration, and apoptosis, and the pathological progress of cartilage such as osteoarthritis (OA) and rheumatoid arthritis (RA). TGF-β2 also shows its potent capacity in the repair of cartilage defects by recruiting autologous mesenchymal stem cells and promoting secretion of other growth factor clusters. In addition, some pioneering studies have already considered it as a potential target in the treatment of OA and RA. This article aims to summarize the current progress of TGF-β2 in cartilage development and diseases, which might provide new cues for remodelling of cartilage defect and intervention of cartilage diseases

Aims. Lower limb reconstruction (LLR) has a profound impact on patients, affecting multiple areas of their lives. Many patient-reported outcome measures (PROMs) are employed to assess these impacts; however, there are concerns that they do not adequately capture all outcomes important to patients, and may lack content validity in this context. This review explored whether PROMs used with adults requiring, undergoing, or after undergoing LLR exhibited content validity and adequately captured outcomes considered relevant and important to patients. Methods. A total of 37 PROMs were identified. Systematic searches were performed to retrieve content validity studies in the adult LLR population, and hand-searches used to find PROM development studies. Content validity assessments for each measure were performed following Consensus-based Standards for the selection of health measurement Instruments (COSMIN) guidelines. A mapping exercise compared all PROMs to a conceptual framework previously developed by the study team (‘the PROLLIT framework’) to explore whether each PROM covered important and relevant concepts. Results. The systematic searches found 13 studies, while hand searches found 50 PROM development studies, and copies of all 37 measures. Although several studies discussed content validity, none were found which formally assessed this measurement property in the adult LLR population. Development of many PROMs was rated as inadequate, no PROM had sufficient content validity in the study population, and none covered all areas of the PROLLIT framework. The LIMB-Q was the most promising and comprehensive measure assessed, although further validation in a wider sample of LLR patients was recommended. Conclusion. Current PROMs used in adults requiring, undergoing, or after undergoing LLR lack content validity and do not assess all important and relevant outcomes. There is an urgent need for improved outcome measurement in this population. This can be achieved through development of a new PROM, or through validation of existing measures in representative samples. Cite this article: Bone Jt Open 2024;5(12):1049–1066

Aims. Machine-learning (ML) prediction models in orthopaedic trauma hold great promise in assisting clinicians in various tasks, such as personalized risk stratification. However, an overview of current applications and critical appraisal to peer-reviewed guidelines is lacking. The objectives of this study are to 1) provide an overview of current ML prediction models in orthopaedic trauma; 2) evaluate the completeness of reporting following the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) statement; and 3) assess the risk of bias following the Prediction model Risk Of Bias Assessment Tool (PROBAST) tool. Methods. A systematic search screening 3,252 studies identified 45 ML-based prediction models in orthopaedic trauma up to January 2023. The TRIPOD statement assessed transparent reporting and the PROBAST tool the risk of bias. Results. A total of 40 studies reported on training and internal validation; four studies performed both development and external validation, and one study performed only external validation. The most commonly reported outcomes were mortality (33%, 15/45) and length of hospital stay (9%, 4/45), and the majority of prediction models were developed in the hip fracture population (60%, 27/45). The overall median completeness for the TRIPOD statement was 62% (interquartile range 30 to 81%). The overall risk of bias in the PROBAST tool was low in 24% (11/45), high in 69% (31/45), and unclear in 7% (3/45) of the studies. High risk of bias was mainly due to analysis domain concerns including small datasets with low number of outcomes, complete-case analysis in case of missing data, and no reporting of performance measures. Conclusion. The results of this study showed that despite a myriad of potential clinically useful applications, a substantial part of ML studies in orthopaedic trauma lack transparent reporting, and are at high risk of bias. These problems must be resolved by following established guidelines to instil confidence in ML models among patients and clinicians. Otherwise, there will remain a sizeable gap between the development of ML prediction models and their clinical application in our day-to-day orthopaedic trauma practice. Cite this article: Bone Jt Open 2024;5(1):9–19

Aims. To systematically review the efficacy of split tendon transfer surgery on gait-related outcomes for children and adolescents with cerebral palsy (CP) and spastic equinovarus foot deformity. Methods. Five databases (CENTRAL, CINAHL, PubMed, Embase, Web of Science) were systematically screened for studies investigating split tibialis anterior or split tibialis posterior tendon transfer for spastic equinovarus foot deformity, with gait-related outcomes (published pre-September 2022). Study quality and evidence were assessed using the Methodological Index for Non-Randomized Studies, the Risk of Bias In Non-Randomized Studies of Interventions, and the Grading of Recommendations Assessment, Development and Evaluation. Results. Overall, 17 studies (566 feet) were included: 13 studies used clinical grading criteria to report a postoperative ‘success’ of 87% (75% to 100%), 14 reported on orthotic use with 88% reduced postoperative use, and one study reported on ankle kinematics improvements. Ten studies reported post-surgical complications at a rate of 11/390 feet (2.8%), but 84 feet (14.8%) had recurrent varus (68 feet, 12%) or occurrence of valgus (16 feet, 2.8%). Only one study included a patient-reported outcome measure (pain). Conclusion. Split tendon transfers are an effective treatment for children and youth with CP and spastic equinovarus foot deformities. Clinical data presented can be used for future study designs; a more standardized functional and patient-focused approach to evaluating outcomes of surgical intervention of gait may be warranted. Cite this article: Bone Jt Open 2023;4(5):283–298

Aims. The aim of this study was to report the pooled prevalence of post-traumatic osteoarthritis (PTOA) and examine whether the risk of developing PTOA after anterior cruciate ligament (ACL) injury has decreased in recent decades. Methods. The PubMed and Web of Science databases were searched from 1 January 1980 to 11 May 2022. Patient series, observational studies, and clinical trials having reported the prevalence of radiologically confirmed PTOA after ACL injury, with at least a ten-year follow-up, were included. All studies were analyzed simultaneously, and separate analyses of the operative and nonoperative knees were performed. The prevalence of PTOA was calculated separately for each study, and pooled prevalence was reported with 95% confidence intervals (CIs) using either a fixed or random effects model. To examine the effect of the year of injury on the prevalence, a logit transformed meta-regression analysis was used with a maximum-likelihood estimator. Results from meta-regression analyses were reported with the unstandardized coefficient (β). Results. The pooled prevalence of PTOA was 37.9% (95% CI 32.1 to 44) for operatively treated ACL injuries with a median follow-up of 14.6 years (interquartile range (IQR) 10.6 to 16.7). For nonoperatively treated ACL injuries, the prevalence was 40.5% (95% CI 28.9 to 53.3), with a median of follow-up of 15 years (IQR 11.7 to 20.0). The association between the year of operation and the prevalence of PTOA was weak and imprecise and not related to the choice of treatment (operative β -0.038 (95% CI -0.076 to 0.000) and nonoperative β -0.011 (95% CI -0.101 to 0.079)). Conclusion. The initial injury, irrespective of management, has, by the balance of probability, resulted in PTOA within 20 years. In addition, the prevalence of PTOA has only slightly decreased during past decades. Therefore, further research is warranted to develop strategies to prevent the development of PTOA after ACL injuries. Cite this article: Bone Joint J 2023;105-B(11):1140–1148

Aims. The aims of this study were to identify and evaluate the current literature examining the prognostic factors which are associated with failure of total elbow arthroplasty (TEA). Methods. Electronic literature searches were conducted using MEDLINE, Embase, PubMed, and Cochrane. All studies reporting prognostic estimates for factors associated with the revision of a primary TEA were included. The risk of bias was assessed using the Quality In Prognosis Studies (QUIPS) tool, and the quality of evidence was assessed using the modified Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework. Due to low quality of the evidence and the heterogeneous nature of the studies, a narrative synthesis was used. Results. A total of 19 studies met the inclusion criteria, investigating 28 possible prognostic factors. Most QUIPS domains (84%) were rated as moderate to high risk of bias. The quality of the evidence was low or very low for all prognostic factors. In low-quality evidence, prognostic factors with consistent associations with failure of TEA in more than one study were: the sequelae of trauma leading to TEA, either independently or combined with acute trauma, and male sex. Several other studies investigating sex reported no association. The evidence for other factors was of very low quality and mostly involved exploratory studies. Conclusion. The current evidence investigating the prognostic factors associated with failure of TEA is of low or very low quality, and studies generally have a moderate to high risk of bias. Prognostic factors are subject to uncertainty, should be interpreted with caution, and are of little clinical value. Higher-quality evidence is required to determine robust prognostic factors for failure of TEA. Cite this article: Bone Joint Res 2024;13(5):201–213

Aims. This study evaluates the quality of patient-reported outcome measures (PROMs) reported in childhood fracture trials and recommends outcome measures to assess and report physical function, functional capacity, and quality of life using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) standards. Methods. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant systematic review of OVID Medline, Embase, and Cochrane CENTRAL was performed to identify all PROMs reported in trials. A search of OVID Medline, Embase, and PsycINFO was performed to identify all PROMs with validation studies in childhood fractures. Development studies were identified through hand-searching. Data extraction was undertaken by two reviewers. Study quality and risk of bias was evaluated by COSMIN guidelines and recorded on standardized checklists. Results. Searches yielded 13,672 studies, which were screened to identify 124 trials and two validation studies. Review of the 124 trials identified 16 reported PROMs, of which two had validation studies. The development papers were retrieved for all PROMs. The quality of the original development studies was adequate for Patient-Reported Outcomes Measurement Information System (PROMIS) Mobility and Upper Extremity and doubtful for the EuroQol Five Dimension Youth questionnaire (EQ-5D-Y). All other PROMs were found to have inadequate development studies. No content validity studies were identified. Reviewer-rated content validity was acceptable for six PROMs: Activity Scale for Kids (ASK), Childhood Health Assessment Questionnaire, PROMIS Upper Extremity, PROMIS Mobility, EQ-5D-Y, and Pediatric Quality of Life Inventory (PedsQL4.0). The Modified Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire was shown to have indeterminate reliability and convergence validity in one study and PROMIS Upper Extremity had insufficient convergence validity in one study. Conclusion. There is insufficient evidence to recommend strongly the use of any single PROM to assess and report physical function or quality of life following childhood fractures. There is a need to conduct validation studies for PROMs. In the absence of these studies, we cautiously recommend the use of the PROMIS or ASK-P for physical function and the PedsQL4.0 or EQ-5D-Y for quality of life. Cite this article: Bone Joint J 2020;102-B(12):1599–1607

Aims. The aim of this study was to identify the origin and development of the threshold for surgical intervention, highlight the consequences of residual displacement, and justify the importance of accurate measurement. Methods. A systematic review of three databases was performed to establish the origin and adaptations of the threshold, with papers screened and relevant citations reviewed. This search identified papers investigating functional outcome, including presence of arthritis, following injury. Orthopaedic textbooks were reviewed to ensure no earlier mention of the threshold was present. Results. Knirk and Jupiter (1986) were the first to quantify a threshold, with all their patients developing arthritis with > 2 mm displacement. Some papers have discussed using 1 mm, although 2 mm is most widely reported. Current guidance from the British Society for Surgery of the Hand and a Delphi panel support 2 mm as an appropriate value. Although this paper is still widely cited, the authors published a re-examination of the data showing methodological flaws which is not as widely reported. They claim their conclusions are still relevant today; however, radiological arthritis does not correlate with the clinical presentation. Function following injury has been shown to be equivalent to an uninjured population, with arthritis progressing slowly or not at all. Joint space narrowing has also been shown to often be benign. Conclusion. Knirk and Jupiter originated the threshold value of 2 mm. The lack of correlation between the radiological and clinical presentations warrants further modern investigation. Measurement often varies between observers, calling a threshold concept into question and showing the need for further development in this area. The principle of treatment remains restoration of normal anatomical position. Cite this article: Bone Joint J 2021;103-B(9):1457–1461

Aims. The aim of this study was to review the current evidence surrounding curve type and morphology on curve progression risk in adolescent idiopathic scoliosis (AIS). Methods. A comprehensive search was conducted by two independent reviewers on PubMed, Embase, Medline, and Web of Science to obtain all published information on morphological predictors of AIS progression. Search items included ‘adolescent idiopathic scoliosis’, ‘progression’, and ‘imaging’. The inclusion and exclusion criteria were carefully defined. Risk of bias of studies was assessed with the Quality in Prognostic Studies tool, and level of evidence for each predictor was rated with the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. In all, 6,286 publications were identified with 3,598 being subjected to secondary scrutiny. Ultimately, 26 publications (25 datasets) were included in this review. Results. For unbraced patients, high and moderate evidence was found for Cobb angle and curve type as predictors, respectively. Initial Cobb angle > 25° and thoracic curves were predictive of curve progression. For braced patients, flexibility < 28% and limited in-brace correction were factors predictive of progression with high and moderate evidence, respectively. Thoracic curves, high apical vertebral rotation, large rib vertebra angle difference, small rib vertebra angle on the convex side, and low pelvic tilt had weak evidence as predictors of curve progression. Conclusion. For curve progression, strong and consistent evidence is found for Cobb angle, curve type, flexibility, and correction rate. Cobb angle > 25° and flexibility < 28% are found to be important thresholds to guide clinical prognostication. Despite the low evidence, apical vertebral rotation, rib morphology, and pelvic tilt may be promising factors. Cite this article: Bone Joint J 2022;104-B(4):424–432

Aims. This systematic review and meta-analysis was conducted to compare open reduction and internal fixation (ORIF) with primary arthrodesis (PA) in the treatment of Lisfranc injuries, regarding patient-reported outcome measures (PROMs), and risk of secondary surgery. The aim was to conclusively determine the best available treatment based on the most complete and recent evidence available. Methods. A systematic search was conducted in PubMed, Cochrane Controlled Register of Trials (CENTRAL), EMBASE, CINAHL, PEDro, and SPORTDiscus. Additionally, ongoing trial registers and reference lists of included articles were screened. Risk of bias (RoB) and level of evidence were assessed using the Cochrane risk of bias tools and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool. The random and fixed-effect models were used for the statistical analysis. Results. A total of 20 studies were selected for this review, of which 12 were comparative studies fit for meta-analysis, including three randomized controlled trials (RCTs). This resulted in a total analyzed population of 392 patients treated with ORIF and 249 patients treated with PA. The mean differences between the two groups in American Orthopedic Foot and Ankle Society (AOFAS), VAS, and SF-36 scores were -7.41 (95% confidence interval (CI) -13.31 to -1.51), 0.77 (95% CI -0.85 to 2.39), and -1.20 (95% CI -3.86 to 1.46), respectively. Conclusion. This is the first study to find a statistically significant difference in PROMs, as measured by the AOFAS score, in favour of PA for the treatment of Lisfranc injuries. However, this difference may not be clinically relevant, and therefore drawing a definitive conclusion requires confirmation by a large prospective high-quality RCT. Such a study should also assess cost-effectiveness, as cost considerations might be decisive in decision-making. Level of Evidence: I. Cite this article: Bone Jt Open 2021;2(10):842–849

Patient-reported outcome measures (PROMs) are being used increasingly in total knee arthroplasty (TKA). We conducted a systematic review aimed at identifying psychometrically sound PROMs by appraising their measurement properties. Studies concerning the development and/or evaluation of the measurement properties of PROMs used in a TKA population were systematically retrieved via PubMed, Web of Science, Embase, and Scopus. Ratings for methodological quality and measurement properties were conducted according to updated COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) methodology. Of the 155 articles on 34 instruments included, nine PROMs met the minimum requirements for psychometric validation and can be recommended to use as measures of TKA outcome: Oxford Knee Score (OKS); OKS–Activity and Participation Questionnaire (OKS-APQ); 12-item short form Knee Injury and Osteoarthritis Outcome (KOOS-12); KOOS Physical function Short form (KOOS-PS); Western Ontario and McMaster Universities Arthritis Index-Total Knee Replacement function short form (WOMAC-TKR); Lower Extremity Functional Scale (LEFS); Forgotten Joint Score (FJS); Patient’s Knee Implant Performance (PKIP); and University of California Los Angeles (UCLA) activity score. The pain and function subscales in WOMAC, as well as the pain, function, and quality of life subscales in KOOS, were validated psychometrically as standalone subscales instead of as whole instruments. However, none of the included PROMs have been validated for all measurement properties. Thus, further studies are still warranted to evaluate those PROMs. Use of the other 25 scales and subscales should be tempered until further studies validate their measurement properties. Cite this article: Bone Joint Res 2021;10(3):203–217

Aims

Machine learning (ML), a branch of artificial intelligence that uses algorithms to learn from data and make predictions, offers a pathway towards more personalized and tailored surgical treatments. This approach is particularly relevant to prevalent joint diseases such as osteoarthritis (OA). In contrast to end-stage disease, where joint arthroplasty provides excellent results, early stages of OA currently lack effective therapies to halt or reverse progression. Accurate prediction of OA progression is crucial if timely interventions are to be developed, to enhance patient care and optimize the design of clinical trials.

Osteoarthritis (OA) is mainly caused by ageing, strain, trauma, and congenital joint abnormalities, resulting in articular cartilage degeneration. During the pathogenesis of OA, the changes in subchondral bone (SB) are not only secondary manifestations of OA, but also an active part of the disease, and are closely associated with the severity of OA. In different stages of OA, there were microstructural changes in SB. Osteocytes, osteoblasts, and osteoclasts in SB are important in the pathogenesis of OA. The signal transduction mechanism in SB is necessary to maintain the balance of a stable phenotype, extracellular matrix (ECM) synthesis, and bone remodelling between articular cartilage and SB. An imbalance in signal transduction can lead to reduced cartilage quality and SB thickening, which leads to the progression of OA. By understanding changes in SB in OA, researchers are exploring drugs that can regulate these changes, which will help to provide new ideas for the treatment of OA.

Cite this article: Bone Joint Res 2023;12(9):536–545.

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To analyze whether the addition of risk-based criteria to clinical examination-based selective ultrasound screening would increase the rates of early detected cases of developmental dysplasia of the hip (DDH) and decrease the rate of late detected cases.

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Open lower limb fracture is a life-changing injury affecting 11.5 per 100,000 adults each year, and causes significant morbidity and resource demand on trauma infrastructures. This study aims to identify what, and how, outcomes have been reported for people following open lower limb fracture over ten years.

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Day-case knee and hip replacement, in which patients are discharged on the day of surgery, has been gaining popularity during the last two decades, and particularly since the COVID-19 pandemic. This systematic review presents the evidence comparing day-case to inpatient-stay surgery.

Literature surrounding artificial intelligence (AI)-related applications for hip and knee arthroplasty has proliferated. However, meaningful advances that fundamentally transform the practice and delivery of joint arthroplasty are yet to be realized, despite the broad range of applications as we continue to search for meaningful and appropriate use of AI. AI literature in hip and knee arthroplasty between 2018 and 2021 regarding image-based analyses, value-based care, remote patient monitoring, and augmented reality was reviewed. Concerns surrounding meaningful use and appropriate methodological approaches of AI in joint arthroplasty research are summarized. Of the 233 AI-related orthopaedics articles published, 178 (76%) constituted original research, while the rest consisted of editorials or reviews. A total of 52% of original AI-related research concerns hip and knee arthroplasty (n = 92), and a narrative review is described. Three studies were externally validated. Pitfalls surrounding present-day research include conflating vernacular (“AI/machine learning”), repackaging limited registry data, prematurely releasing internally validated prediction models, appraising model architecture instead of inputted data, withholding code, and evaluating studies using antiquated regression-based guidelines. While AI has been applied to a variety of hip and knee arthroplasty applications with limited clinical impact, the future remains promising if the question is meaningful, the methodology is rigorous and transparent, the data are rich, and the model is externally validated. Simple checkpoints for meaningful AI adoption include ensuring applications focus on: administrative support over clinical evaluation and management; necessity of the advanced model; and the novelty of the question being answered.

Cite this article: Bone Joint J 2022;104-B(12):1292–1303.

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Spinopelvic characteristics influence the hip’s biomechanical behaviour. However, to date there is little knowledge defining what ‘normal’ spinopelvic characteristics are. This study aims to determine how static spinopelvic characteristics change with age and ethnicity among asymptomatic, healthy individuals.

Objectives. This review aims to summarize the outcomes used to describe effectiveness of treatments for paediatric wrist fractures within existing literature. Method. We searched the Cochrane Library, Scopus, and Ovid Medline for studies pertaining to paediatric wrist fractures. Three authors independently identified and reviewed eligible studies. This resulted in a list of outcome domains and outcomes measures used within clinical research. Outcomes were mapped onto domains defined by the COMET collaborative. Results. Our search terms identified 4,262 different papers. Screening of titles excluded 2,975, leaving 1,287 papers to be assessed for eligibility. Of this 1,287, 30 studies were included for full analysis. Overall, five outcome domains, 16 outcome measures, and 28 measurement instruments were identified as outcomes within these studies. 24 studies used at least one measurement pertaining to the physiological/clinical outcome domain. The technical, life impact, and adverse effect domains were recorded in 23, 20, and 11 of the studies respectively. Within each domain it was common for different measurement instruments to be used to assess each outcome measure. The most commonly reported outcome measures were range of movement, a broad array of “radiological measures” and pain intensity, which were used in 24, 23, and 12 of the 30 studies. Conclusion. This study highlights the heterogeneity in outcomes reported within clinical effectiveness studies of paediatric wrist fractures. We provided an overview of the types of outcomes reported in paediatric wrist fracture studies and identified a list of potentially relevant outcomes required for the development of a core outcome set

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Frozen shoulder is a common and debilitating condition characterized by pain and restricted movement at the glenohumeral joint. Various treatment methods have been explored to alleviate symptoms, with suprascapular nerve block (SSNB) emerging as a promising intervention. This meta-analysis aimed to assess the effectiveness of SSNB in treating frozen shoulder.

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Research on hip biomechanics has analyzed femoroacetabular contact pressures and forces in distinct hip conditions, with different procedures, and used diverse loading and testing conditions. The aim of this scoping review was to identify and summarize the available evidence in the literature for hip contact pressures and force in cadaver and in vivo studies, and how joint loading, labral status, and femoral and acetabular morphology can affect these biomechanical parameters.

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This meta-analysis and systematic review aimed to comprehensively investigate the effects of vitamin K supplementation on bone mineral density (BMD) at various sites and bone metabolism in middle-aged and older adults.

Bone is one of the most highly adaptive tissues in the body, possessing the capability to alter its morphology and function in response to stimuli in its surrounding environment. The ability of bone to sense and convert external mechanical stimuli into a biochemical response, which ultimately alters the phenotype and function of the cell, is described as mechanotransduction. This review aims to describe the fundamental physiology and biomechanisms that occur to induce osteogenic adaptation of a cell following application of a physical stimulus. Considerable developments have been made in recent years in our understanding of how cells orchestrate this complex interplay of processes, and have become the focus of research in osteogenesis. We will discuss current areas of preclinical and clinical research exploring the harnessing of mechanotransductive properties of cells and applying them therapeutically, both in the context of fracture healing and de novo bone formation in situations such as nonunion. Cite this article: Bone Joint Res 2019;9(1):1–14

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Biofilm-related infection is a major complication that occurs in orthopaedic surgery. Various treatments are available but efficacy to eradicate infections varies significantly. A systematic review was performed to evaluate therapeutic interventions combating biofilm-related infections on in vivo animal models.

Aims. Patients with metabolic syndrome (MetS) are known to be at increased risk of postoperative complications, but it is unclear whether MetS is also associated with complications after total hip arthroplasty (THA) or total knee arthroplasty (TKA). Here, we perform a systematic review and meta-analysis linking MetS to postoperative complications in THA and TKA. Methods. The PubMed, OVID, and ScienceDirect databases were comprehensively searched and studies were selected and analyzed according to the guidelines of the Meta-analysis of Observational Studies in Epidemiology (MOOSE). We assessed the methodological quality of each study using the Newcastle-Ottawa Scale (NOS), and we evaluated the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Data were extracted and meta-analyzed or qualitatively synthesized for several outcomes. Results. Ten cohort studies involving 1,352,685 patients were included. Qualitative analysis suggested that MetS was associated with a higher incidence of cardiovascular events, and meta-analysis showed that MetS increased the risk of all-cause complications (risk ratio (RR) 1.55, 95% confidence interval (CI) 1.28 to 1.89), surgical site infection (SSI; RR 2.99, 95% CI 1.30 to 6.90), urinary tract infection (UTI; RR 2.58, 95% CI 1.03 to 6.43), and 30-day readmission (RR 1.45, 95% CI 1.33 to 1.59). There was insufficient evidence for assessing an association between MetS and venous thromboembolism events, pulmonary or gastrointestinal complications, or mortality. Conclusion. Patients with MetS undergoing THA and TKA are at increased risk of all-cause complications, cardiovascular complications, SSI, UTI, and 30-day readmission. Surgeons should be aware of the increased risk of these complications in MetS, and presurgical protocols for these complications should give special consideration to MetS patients. Cite this article:Bone Joint Res. 2020;9(3):120–129

Objectives. Emerging evidence indicates that tendon disease is an active process with inflammation that is critical to disease onset and progression. However, the key cytokines responsible for driving and sustaining inflammation have not been identified. Methods. We performed a systematic review of the literature using MEDLINE (U.S. National Library of Medicine, Bethesda, Maryland) in March 2017. Studies reporting the expression of interleukins (ILs), tumour necrosis factor alpha (TNF-α) and interferon gamma in diseased human tendon tissues, and animal models of tendon injury or exercise in comparison with healthy control tissues were included. Results. IL-1β, IL-6, IL-10, and TNF-α are the cytokines that have been most frequently investigated. In clinical samples of tendinopathy and tendon tears, the expression of TNF-α tended not to change but IL-6 increased in tears. Healthy human tendons showed increased IL-6 expression after exercise; however, IL-10 remained unchanged. Animal tendon injury models showed that IL-1β, IL-6, and TNF-α tend to increase from the early phase of tendon healing. In animal exercise studies, IL-1β expression showed a tendency to increase at the early stage after exercise, but IL-10 expression remained unchanged with exercise. Conclusions. This review highlights the roles of IL-1β, IL-6, IL-10, and TNF-α in the development of tendon disease, during tendon healing, and in response to exercise. However, there is evidence accumulating that suggests that other cytokines are also contributing to tendon inflammatory processes. Further work with hypothesis-free methods is warranted in order to identify the key cytokines, with subsequent mechanistic and interaction studies to elucidate their roles in tendon disease development. Cite this article: W. Morita, S. G. Dakin, S. J. B. Snelling, A. J. Carr. Cytokines in tendon disease: A Systematic Review. Bone Joint Res 2017;6:656–664. DOI: 10.1302/2046-3758.612.BJR-2017-0112.R1

Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides with limited coding potential, which have emerged as novel regulators in many biological and pathological processes, including growth, development, and oncogenesis. Accumulating evidence suggests that lncRNAs have a special role in the osteogenic differentiation of various types of cell, including stem cells from different sources such as embryo, bone marrow, adipose tissue and periodontal ligaments, and induced pluripotent stem cells. Involved in complex mechanisms, lncRNAs regulate osteogenic markers and key regulators and pathways in osteogenic differentiation. In this review, we provide insights into the functions and molecular mechanisms of lncRNAs in osteogenesis and highlight their emerging roles and clinical value in regenerative medicine and osteogenesis-related diseases. Cite this article: J. Zhang, X. Hao, M. Yin, T. Xu, F. Guo. Long non-coding RNA in osteogenesis: A new world to be explored. Bone Joint Res 2019;8:73–80. DOI: 10.1302/2046-3758.82.BJR-2018-0074.R1

Aims. We set out to determine if there is a difference in perioperative outcomes between early and delayed surgery in paediatric supracondylar humeral fractures in the absence of vascular compromise through a systematic review and meta-analysis. Materials and Methods. A literature search was performed, with search outputs screened for studies meeting the inclusion criteria. The groups of early surgery (ES) and delayed surgery (DS) were classified by study authors. The primary outcome measure was open reduction requirement. Meta-analysis was performed in the presence of sufficient study homogeneity. Individual study risk of bias was assessed using the Risk of Bias in Non-Randomised Studies – of Interventions (ROBINS-I) criteria, with the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) criteria used to evaluate outcomes independently. Results. A total of 12 studies met the inclusion criteria (1735 fractures). Pooled mean time to surgery from injury was and 10.7 hours for ES and 91.8 hours for DS. On meta-analysis there was no significant difference between ES versus DS for the outcome of open reduction requirement. There was also no significant difference for the outcomes: Iatrogenic nerve injury, pin site infection, and re-operation. The quality of evidence for all the individual outcomes was low or very low. Conclusions. There is no evidence that delaying supracondylar fracture surgery negatively influences outcomes in the absence of vascular compromise. There are, however, notable limitations to the existing available literature

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Evidence exists of a consistent decline in the value and time that medical schools place upon their undergraduate orthopaedic placements. This limited exposure to trauma and orthopaedics (T&O) during medical school will be the only experience in the speciality for the majority of doctors. This review aims to provide an overview of undergraduate orthopaedic training in the UK.

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Arthroplasty is being increasingly used for the management of distal humeral fractures (DHFs) in elderly patients. Arthroplasty options include total elbow arthroplasty (TEA) and hemiarthroplasty (HA); both have unique complications and there is not yet a consensus on which implant is superior. This systematic review asked: in patients aged over 65 years with unreconstructable DHFs, what differences are there in outcomes, as measured by patient-reported outcome measures (PROMs), range of motion (ROM), and complications, between distal humeral HA and TEA?

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Avulsion of the proximal hamstring tendon origin can result in significant functional impairment, with surgical re-attachment of the tendons becoming an increasingly recognized treatment. The aim of this study was to assess the outcomes of surgical management of proximal hamstring tendon avulsions, and to compare the results between acute and chronic repairs, as well as between partial and complete injuries.

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Sarcopenia is characterized by a generalized progressive loss of skeletal muscle mass, strength, and physical performance. This systematic review primarily evaluated the effects of sarcopenia on postoperative functional recovery and mortality in patients undergoing orthopaedic surgery, and secondarily assessed the methods used to diagnose and define sarcopenia in the orthopaedic literature.

Aims. The aim of this study was to determine how the short- and medium- to long-term outcome measures after total disc replacement (TDR) compare with those of anterior cervical discectomy and fusion (ACDF), using a systematic review and meta-analysis. Patients and Methods. Databases including Medline, Embase, and Scopus were searched. Inclusion criteria involved prospective randomized control trials (RCTs) reporting the surgical treatment of patients with symptomatic degenerative cervical disc disease. Two independent investigators extracted the data. The strength of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) criteria. The primary outcome measures were overall and neurological success, and these were included in the meta-analysis. Standardized patient-reported outcomes, including the incidence of further surgery and adjacent segment disease, were summarized and discussed. Results. A total of 22 papers published from 14 RCTs were included, representing 3160 patients with follow-up of up to ten years. Meta-analysis indicated that TDR is superior to ACDF at two years and between four and seven years. In the short-term, patients who underwent TDR had better patient-reported outcomes than those who underwent ACDF, but at two years this was typically not significant. Results between four and seven years showed significant differences in Neck Disability Index (NDI), 36-Item Short-Form Health Survey (SF-36) physical component scores, dysphagia, and satisfaction, all favouring TDR. Most trials found significantly less adjacent segment disease after TDR at both two years (short-term) and between four and seven years (medium- to long-term). Conclusion. TDR is as effective as ACDF and superior for some outcomes. Disc replacement reduces the risk of adjacent segment disease. Continued uncertainty remains about degeneration of the prosthesis. Long-term surveillance of patients who undergo TDR may allow its routine use. Cite this article: Bone Joint J 2018;100-B:991–1001

This systematic review examines the current literature regarding surgical techniques for restoring articular cartilage in the hip, from the older microfracture techniques involving perforation to the subchondral bone, to adaptations of this technique using nanofractures and scaffolds. This review discusses the autologous and allograft transfer systems and the autologous matrix-induced chondrogenesis (AMIC) technique, as well as a summary of the previously discussed techniques, which could become common practice for restoring articular cartilage, thus reducing the need for total hip arthroplasty. Using the British Medical Journal Grading of Recommendations, Assessment, Development and Evaluation (BMJ GRADE) system and Grade system. Comparison of the studies discussed shows that microfracture has the greatest quantity and quality of research, whereas the newer AMIC technique requires more research, but shows promise. Cite this article: W. E. Hotham, A. Malviya. A systematic review of surgical methods to restore articular cartilage in the hip. Bone Joint Res 2018;7:336–342. DOI: 10.1302/2046-3758.75.BJR-2017-0331

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The aim of this meta-analysis is to assess the association between exchange of modular parts in debridement, antibiotics, and implant retention (DAIR) procedure and outcomes for hip and knee periprosthetic joint infection (PJI).

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Metal allergy in knee arthroplasty patients is a controversial topic. We aimed to conduct a scoping review to clarify the management of metal allergy in primary and revision total knee arthroplasty (TKA).

Osteoarthritis (OA), one of the most common motor system disorders, is a degenerative disease involving progressive joint destruction caused by a variety of factors. At present, OA has become the fourth most common cause of disability in the world. However, the pathogenesis of OA is complex and has not yet been clarified. Long non-coding RNA (lncRNA) refers to a group of RNAs more than 200 nucleotides in length with limited protein-coding potential, which have a wide range of biological functions including regulating transcriptional patterns and protein activity, as well as binding to form endogenous small interference RNAs (siRNAs) and natural microRNA (miRNA) molecular sponges. In recent years, a large number of lncRNAs have been found to be differentially expressed in a variety of pathological processes of OA, including extracellular matrix (ECM) degradation, synovial inflammation, chondrocyte apoptosis, and angiogenesis. Obviously, lncRNAs play important roles in regulating gene expression, maintaining the phenotype of cartilage and synovial cells, and the stability of the intra-articular environment. This article reviews the results of the latest research into the role of lncRNAs in a variety of pathological processes of OA, in order to provide a new direction for the study of OA pathogenesis and a new target for prevention and treatment.

Cite this article: Bone Joint Res 2021;10(2):122–133.

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The aim of this meta-analysis was to assess the prognosis after early functional rehabilitation or traditional immobilization in patients who underwent operative or nonoperative treatment for rupture of the Achilles tendon.

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A systematic literature review focusing on how long before surgery concurrent viral or bacterial infections (respiratory and urinary infections) should be treated in hip fracture patients, and if there is evidence for delaying this surgery.

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The effect of the gut microbiota (GM) and its metabolite on bone health is termed the gut-bone axis. Multiple studies have elucidated the mechanisms but findings vary greatly. A systematic review was performed to analyze current animal models and explore the effect of GM on bone.

The ability to edit DNA at the nucleotide level using clustered regularly interspaced short palindromic repeats (CRISPR) systems is a relatively new investigative tool that is revolutionizing the analysis of many aspects of human health and disease, including orthopaedic disease. CRISPR, adapted for mammalian cell genome editing from a bacterial defence system, has been shown to be a flexible, programmable, scalable, and easy-to-use gene editing tool. Recent improvements increase the functionality of CRISPR through the engineering of specific elements of CRISPR systems, the discovery of new, naturally occurring CRISPR molecules, and modifications that take CRISPR beyond gene editing to the regulation of gene transcription and the manipulation of RNA. Here, the basics of CRISPR genome editing will be reviewed, including a description of how it has transformed some aspects of molecular musculoskeletal research, and will conclude by speculating what the future holds for the use of CRISPR-related treatments and therapies in clinical orthopaedic practice.

Cite this article: Bone Joint Res 2020;9(7):351–359.

A balanced inflammatory response is important for successful fracture healing. The response of osteoporotic fracture healing is deranged and an altered inflammatory response can be one underlying cause. The objectives of this review were to compare the inflammatory responses between normal and osteoporotic fractures and to examine the potential effects on different healing outcomes. A systematic literature search was conducted with relevant keywords in PubMed, Embase, and Web of Science independently. Original preclinical studies and clinical studies involving the investigation of inflammatory response in fracture healing in ovariectomized (OVX) animals or osteoporotic/elderly patients with available full text and written in English were included. In total, 14 articles were selected. Various inflammatory factors were reported; of those tumour necrosis factor-α (TNF-α) and interleukin (IL)-6 are two commonly studied markers. Preclinical studies showed that OVX animals generally demonstrated higher systemic inflammatory response and poorer healing outcomes compared to normal controls (SHAM). However, it is inconclusive if the local inflammatory response is higher or lower in OVX animals. As for clinical studies, they mainly examine the temporal changes of the inflammatory stage or perform comparison between osteoporotic/fragility fracture patients and normal subjects without fracture. Our review of these studies emphasizes the lack of understanding that inflammation plays in the altered fracture healing response of osteoporotic/elderly patients. Taken together, it is clear that additional studies, preclinical and clinical, are required to dissect the regulatory role of inflammatory response in osteoporotic fracture healing.

Cite this article: Bone Joint Res 2020;9(7):368–385.

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Metabolic profiling is a top-down method of analysis looking at metabolites, which are the intermediate or end products of various cellular pathways. Our primary objective was to perform a systematic review of the published literature to identify metabolites in human synovial fluid (HSF), which have been categorized by metabolic profiling techniques. A secondary objective was to identify any metabolites that may represent potential biomarkers of orthopaedic disease processes.

Deep gluteal syndrome is an increasingly recognized disease entity, caused by compression of the sciatic or pudendal nerve due to non-discogenic pelvic lesions. It includes the piriformis syndrome, the gemelli-obturator internus syndrome, the ischiofemoral impingement syndrome, and the proximal hamstring syndrome. The concept of the deep gluteal syndrome extends our understanding of posterior hip pain due to nerve entrapment beyond the traditional model of the piriformis syndrome. Nevertheless, there has been terminological confusion and the deep gluteal syndrome has often been undiagnosed or mistaken for other conditions. Careful history-taking, a physical examination including provocation tests, an electrodiagnostic study, and imaging are necessary for an accurate diagnosis.

After excluding spinal lesions, MRI scans of the pelvis are helpful in diagnosing deep gluteal syndrome and identifying pathological conditions entrapping the nerves. It can be conservatively treated with multidisciplinary treatment including rest, the avoidance of provoking activities, medication, injections, and physiotherapy.

Endoscopic or open surgical decompression is recommended in patients with persistent or recurrent symptoms after conservative treatment or in those who may have masses compressing the sciatic nerve.

Many physicians remain unfamiliar with this syndrome and there is a lack of relevant literature. This comprehensive review aims to provide the latest information about the epidemiology, aetiology, pathology, clinical features, diagnosis, and treatment.

Cite this article: Bone Joint J 2020;102-B(5):556–567.

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Computer-based applications are increasingly being used by orthopaedic surgeons in their clinical practice. With the integration of technology in surgery, augmented reality (AR) may become an important tool for surgeons in the future. By superimposing a digital image on a user’s view of the physical world, this technology shows great promise in orthopaedics. The aim of this review is to investigate the current and potential uses of AR in orthopaedics.

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We performed a meta-analysis investigating the association between preoperative psychological distress and postoperative pain and function after total knee arthroplasty (TKA).

Despite its intrinsic ability to regenerate form and function after injury, bone tissue can be challenged by a multitude of pathological conditions. While innovative approaches have helped to unravel the cascades of bone healing, this knowledge has so far not improved the clinical outcomes of bone defect treatment. Recent findings have allowed us to gain in-depth knowledge about the physiological conditions and biological principles of bone regeneration. Now it is time to transfer the lessons learned from bone healing to the challenging scenarios in defects and employ innovative technologies to enable biomaterial-based strategies for bone defect healing. This review aims to provide an overview on endogenous cascades of bone material formation and how these are transferred to new perspectives in biomaterial-driven approaches in bone regeneration.

Cite this article: T. Winkler, F. A. Sass, G. N. Duda, K. Schmidt-Bleek. A review of biomaterials in bone defect healing, remaining shortcomings and future opportunities for bone tissue engineering: The unsolved challenge. Bone Joint Res 2018;7:232–243. DOI: 10.1302/2046-3758.73.BJR-2017-0270.R1.

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Dupuytren’s contracture is a benign, myoproliferative condition affecting the palmar fascia that results in progressive contractures of the fingers. Despite increased knowledge of the cellular and connective tissue changes involved, neither a cure nor an optimum form of treatment exists. The aim of this systematic review was to summarize the best available evidence on the management of this condition.

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The success of anterior cruciate ligament reconstruction (ACLR) depends on osseointegration at the graft-tunnel interface and intra-articular ligamentization. Our aim was to conduct a systematic review of clinical and preclinical studies that evaluated biological augmentation of graft healing in ACLR.

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Periprosthetic joint infection (PJI) is a serious complication of total hip arthroplasty (THA). Different bearing surface materials have different surface properties and it has been suggested that the choice of bearing surface may influence the risk of PJI after THA. The objective of this meta-analysis was to compare the rate of PJI between metal-on-polyethylene (MoP), ceramic-on-polyethylene (CoP), and ceramic-on-ceramic (CoC) bearings.