Aims. This study aimed, through bioinformatics analysis and in vitro experiment validation, to identify the key extracellular proteins of intervertebral disc degeneration (IDD). Methods. The gene expression profile of GSE23130 was downloaded from the Gene Expression Omnibus (GEO) database. Extracellular protein-differentially expressed genes (EP-DEGs) were screened by protein annotation databases, and we used Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) to analyze the functions and pathways of EP-DEGs. STRING and Cytoscape were used to construct protein-protein interaction (PPI) networks and identify hub EP-DEGs. NetworkAnalyst was used to analyze transcription factors (TFs) and microRNAs (miRNAs) that regulate hub EP-DEGs. A search of the Drug Signatures Database (DSigDB) for hub EP-DEGs revealed multiple drug molecules and drug-target interactions. Results. A total of 56 EP-DEGs were identified in the differential expression analysis. EP-DEGs were enriched in the extracellular structure organization, ageing, collagen-activated signalling pathway, PI3K-Akt signalling pathway, and AGE-RAGE signalling pathway. PPI network analysis showed that the top ten hub EP-DEGs are closely related to IDD. Correlation analysis also demonstrated a significant correlation between the ten hub EP-DEGs (p＜0.05), which were selected to construct TF–gene interaction and TF–miRNA coregulatory networks. In addition, ten candidate drugs were screened for the treatment of IDD. Conclusion. The findings clarify the roles of extracellular proteins in IDD and highlight their potential as promising novel therapeutic targets. Cite this article: Bone Joint Res 2023;12(9):522–535

Aims. Prior to the availability of vaccines, mortality for hip fracture patients with concomitant COVID-19 infection was three times higher than pre-pandemic rates. The primary aim of this study was to determine the 30-day mortality rate of hip fracture patients in the post-vaccine era. Methods. A multicentre observational study was carried out at 19 NHS Trusts in England. The study period for the data collection was 1 February 2021 until 28 February 2022, with mortality tracing until 28 March 2022. Data collection included demographic details, data points to calculate the Nottingham Hip Fracture Score, COVID-19 status, 30-day mortality, and vaccination status. Results. A total of 337 patients tested positive for COVID-19. The overall 30-day mortality in these patients was 7.7%: 5.5% in vaccinated patients and 21.7% in unvaccinated patients. There was no significant difference between post-vaccine mortality compared with pre-pandemic 2019 controls (7.7% vs 5.0%; p = 0.068). Independent risk factors for mortality included unvaccinated status, Abbreviated Mental Test Score ≤ 6, male sex, age > 80 years, and time to theatre > 36 hours, in decreasing order of effect size. Conclusion. The vaccination programme has reduced 30-day mortality rates in hip fracture patients with concomitant COVID-19 infection to a level similar to pre-pandemic. Mortality for unvaccinated patients remained high. Cite this article: Bone Joint J 2022;104-B(12):1362–1368

Aims. Ankle fracture fixation is commonly performed by junior trainees. Simulation training using cadavers may shorten the learning curve and result in a technically superior surgical performance. Methods. We undertook a preliminary, pragmatic, single-blinded, multicentre, randomized controlled trial of cadaveric simulation versus standard training. Primary outcome was fracture reduction on postoperative radiographs. Results. Overall, 139 ankle fractures were fixed by 28 postgraduate year three to five trainee surgeons (mean age 29.4 years; 71% males) during ten months' follow-up. Under the intention-to-treat principle, a technically superior fixation was performed by the cadaveric-trained group compared to the standard-trained group, as measured on the first postoperative radiograph against predefined acceptability thresholds. The cadaveric-trained group used a lower intraoperative dose of radiation than the standard-trained group (mean difference 0.011 Gym. 2. , 95% confidence interval 0.003 to 0.019; p = 0.009). There was no difference in procedure time. Conclusion. Trainees randomized to cadaveric training performed better ankle fracture fixations and irradiated patients less during surgery compared to standard-trained trainees. This effect, which was previously unknown, is likely to be a consequence of the intervention. Further study is required. Cite this article: Bone Jt Open 2023;4(8):594–601

Aims. Endoprosthetic reconstruction following distal femur tumour resection has been widely advocated. In this paper, we present the design of an uncemented endoprosthesis system featuring a short, curved stem, with the goal of enhancing long-term survivorship and functional outcomes. Methods. This study involved patients who underwent implantation of an uncemented distal femoral endoprosthesis with a short and curved stem between 2014 and 2019. Functional outcomes were assessed using the 1993 version of the Musculoskeletal Tumour Society (MSTS-93) score. Additionally, we quantified five types of complications and assessed osseointegration radiologically. The survivorship of the endoprosthesis was evaluated according to two endpoints. A total of 134 patients with a median age of 26 years (IQR 16 to 41) were included in our study. The median follow-up time was 61 months (IQR 56 to 76), and the median functional MSTS-93 was 83% (IQR 73 to 91) postoperatively. Results. Overall, 21 patients (16%) encountered complications, and the rate of aseptic loosening was 7% (9/134). The survival rate up to 8.5 years was 93% for aseptic loosening as the endpoint, and 88% for any reason as the endpoint, retrospectively. Conclusion. The use of an uncemented distal femoral endoprosthesis with a short, curved stem demonstrated a low incidence of aseptic loosening and achieved long-term survivorship of up to nine years. Meanwhile, aseptic loosening typically occurs in the early stage postoperatively. Cite this article: Bone Joint J 2024;106-B(9):1000–1007

Aims. To identify variables independently associated with same-day discharge (SDD) of patients following revision total knee arthroplasty (rTKA) and to develop machine learning algorithms to predict suitable candidates for outpatient rTKA. Methods. Data were obtained from the American College of Surgeons National Quality Improvement Programme (ACS-NSQIP) database from the years 2018 to 2020. Patients with elective, unilateral rTKA procedures and a total hospital length of stay between zero and four days were included. Demographic, preoperative, and intraoperative variables were analyzed. A multivariable logistic regression (MLR) model and various machine learning techniques were compared using area under the curve (AUC), calibration, and decision curve analysis. Important and significant variables were identified from the models. Results. Of the 5,600 patients included in this study, 342 (6.1%) underwent SDD. The random forest (RF) model performed the best overall, with an internally validated AUC of 0.810. The ten crucial factors favoring SDD in the RF model include operating time, anaesthesia type, age, BMI, American Society of Anesthesiologists grade, race, history of diabetes, rTKA type, sex, and smoking status. Eight of these variables were also found to be significant in the MLR model. Conclusion. The RF model displayed excellent accuracy and identified clinically important variables for determining candidates for SDD following rTKA. Machine learning techniques such as RF will allow clinicians to accurately risk-stratify their patients preoperatively, in order to optimize resources and improve patient outcomes. Cite this article: Bone Jt Open 2023;4(6):399–407

Aims. Micromotion of the polyethylene (PE) inlay may contribute to backside PE wear in addition to articulate wear of total knee arthroplasty (TKA). Using radiostereometric analysis (RSA) with tantalum beads in the PE inlay, we evaluated PE micromotion and its relationship to PE wear. Methods. A total of 23 patients with a mean age of 83 years (77 to 91), were available from a RSA study on cemented TKA with Maxim tibial components (Zimmer Biomet). PE inlay migration, PE wear, tibial component migration, and the anatomical knee axis were evaluated on weightbearing stereoradiographs. PE inlay wear was measured as the deepest penetration of the femoral component into the PE inlay. Results. At mean six years’ follow-up, the PE wear rate was 0.08 mm/year (95% confidence interval 0.06 to 0.09 mm/year). PE inlay external rotation was below the precision limit and did not influence PE wear. Varus knee alignment did not influence PE wear (p = 0.874), but increased tibial component total translation (p = 0.041). Conclusion. The PE inlay was well fixed and there was no relationship between PE stability and PE wear. The PE wear rate was low and similar in the medial and lateral compartments. Varus knee alignment did not influence PE wear. Cite this article: Bone Joint Res 2024;13(5):226–236

Aims. The use of high tibial osteotomy (HTO) to delay total knee arthroplasty (TKA) in young patients with osteoarthritis (OA) and constitutional deformity remains debated. The aim of this study was to compare the long-term outcomes of TKA after HTO compared to TKA without HTO, using the time from the index OA surgery as reference (HTO for the study group, TKA for the control group). Methods. This was a case-control study of consecutive patients receiving a posterior-stabilized TKA for OA between 1996 and 2010 with previous HTO. A total of 73 TKAs after HTO with minimum ten years’ follow-up were included. Cases were matched with a TKA without previous HTO for age at the time of the HTO. All revisions were recorded. Kaplan-Meier survivorship analysis was performed using revision of metal component as the endpoint. The Knee Society Score, range of motion, and patient satisfaction were assessed. Results. Mean follow-up was 13 years (SD 3) after TKA in both groups. The 20-year Kaplan-Meier survival estimate was 98.6% in TKA post-HTO group (HTO as timing reference) and 81.4% in control group (TKA as timing reference) (p = 0.030). There was no significant difference in clinical outcomes, radiological outcomes, and complications at the last follow-up. Conclusion. At the same delay from index surgery (HTO or TKA), a strategy of HTO followed by TKA had superior knee survivorship compared to early TKA at long term in young patients. Level of evidence: III. Cite this article: Bone Jt Open 2023;4(2):62–71

Aims. To determine the major risk factors for unplanned reoperations (UROs) following corrective surgery for adult spinal deformity (ASD) and their interactions, using machine learning-based prediction algorithms and game theory. Methods. Patients who underwent surgery for ASD, with a minimum of two-year follow-up, were retrospectively reviewed. In total, 210 patients were included and randomly allocated into training (70% of the sample size) and test (the remaining 30%) sets to develop the machine learning algorithm. Risk factors were included in the analysis, along with clinical characteristics and parameters acquired through diagnostic radiology. Results. Overall, 152 patients without and 58 with a history of surgical revision following surgery for ASD were observed; the mean age was 68.9 years (SD 8.7) and 66.9 years (SD 6.6), respectively. On implementing a random forest model, the classification of URO events resulted in a balanced accuracy of 86.8%. Among machine learning-extracted risk factors, URO, proximal junction failure (PJF), and postoperative distance from the posterosuperior corner of C7 and the vertical axis from the centroid of C2 (SVA) were significant upon Kaplan-Meier survival analysis. Conclusion. The major risk factors for URO following surgery for ASD, i.e. postoperative SVA and PJF, and their interactions were identified using a machine learning algorithm and game theory. Clinical benefits will depend on patient risk profiles. Cite this article: Bone Joint Res 2023;12(4):245–255

Aims. There is a lack of high-quality research investigating outcomes of Ponseti-treated idiopathic clubfeet and correlation with relapse. This study assessed clinical and quality of life (QoL) outcomes using a standardized core outcome set (COS), comparing children with and without relapse. Methods. A total of 11 international centres participated in this institutional review board-approved observational study. Data including demographics, information regarding presentation, treatment, and details of subsequent relapse and management were collected between 1 June 2022 and 30 June 2023 from consecutive clinic patients who had a minimum five-year follow-up. The clubfoot COS incorporating 31 parameters was used. A regression model assessed relationships between baseline variables and outcomes (clinical/QoL). Results. Overall, 293 patients (432 feet) with a median age of 89 months (interquartile range 72 to 113) were included. The relapse rate was 37%, with repeated relapse in 14%. Treatment considered a standard part of the Ponseti journey (recasting, repeat tenotomy, and tibialis anterior tendon transfer) was performed in 35% of cases, with soft-tissue release and osteotomies in 5% and 2% of cases, respectively. Predictors of relapse included duration of follow-up, higher initial Pirani score, and poor Evertor muscle activity. Relapse was associated with poorer outcomes. Conclusion. This is the first multicentre study using a standardized COS following clubfoot treatment. It distinguishes patients with and without relapse in terms of clinical outcomes and QoL, with poorer outcomes in the relapse group. This tool allows comparison of treatment methods and outcomes, facilitates information sharing, and sets family expectations. Predictors of relapse encourage us to create appropriate treatment pathways to reduce relapse and improve outcome. Cite this article: Bone Joint J 2024;106-B(7):735–743

Aims. The aim of this investigation was to compare risk of infection in both cemented and uncemented hemiarthroplasty (HA) as well as in total hip arthroplasty (THA) following femoral neck fracture. Methods. Data collection was performed using the German Arthroplasty Registry (EPRD). In HA and THA following femoral neck fracture, fixation method was divided into cemented and uncemented prostheses and paired according to age, sex, BMI, and the Elixhauser Comorbidity Index using Mahalanobis distance matching. Results. Overall in 13,612 cases of intracapsular femoral neck fracture, 9,110 (66.9%) HAs and 4,502 (33.1%) THAs were analyzed. Infection rate in HA was significantly reduced in cases with use of antibiotic-loaded cement compared with uncemented fixated prosthesis (p = 0.013). In patients with THA no statistical difference between cemented and uncemented prosthesis was registered, however after one year 2.4% of infections were detected in uncemented and 2.1% in cemented THA. In the subpopulation of HA after one year, 1.9% of infections were registered in cemented and 2.8% in uncemented HA. BMI (p = 0.001) and Elixhauser Comorbidity Index (p < 0.003) were identified as risk factors of periprosthetic joint infection (PJI), while in THA cemented prosthesis also demonstrated an increased risk within the first 30 days (hazard ratio (HR) = 2.73; p = 0.010). Conclusion. The rate of infection after intracapsular femoral neck fracture was statistically significantly reduced in patients treated by antibiotic-loaded cemented HA. Particularly for patients with multiple risk factors for the development of a PJI, the usage of antibiotic-loaded bone cement seems to be a reasonable procedure for prevention of infection. Cite this article: Bone Joint Res 2023;12(5):331–338

Aims. The aim of this study was to identify factors associated with five-year cancer-related mortality in patients with limb and trunk soft-tissue sarcoma (STS) and develop and validate machine learning algorithms in order to predict five-year cancer-related mortality in these patients. Methods. Demographic, clinicopathological, and treatment variables of limb and trunk STS patients in the Surveillance, Epidemiology, and End Results Program (SEER) database from 2004 to 2017 were analyzed. Multivariable logistic regression was used to determine factors significantly associated with five-year cancer-related mortality. Various machine learning models were developed and compared using area under the curve (AUC), calibration, and decision curve analysis. The model that performed best on the SEER testing data was further assessed to determine the variables most important in its predictive capacity. This model was externally validated using our institutional dataset. Results. A total of 13,646 patients with STS from the SEER database were included, of whom 35.9% experienced five-year cancer-related mortality. The random forest model performed the best overall and identified tumour size as the most important variable when predicting mortality in patients with STS, followed by M stage, histological subtype, age, and surgical excision. Each variable was significant in logistic regression. External validation yielded an AUC of 0.752. Conclusion. This study identified clinically important variables associated with five-year cancer-related mortality in patients with limb and trunk STS, and developed a predictive model that demonstrated good accuracy and predictability. Orthopaedic oncologists may use these findings to further risk-stratify their patients and recommend an optimal course of treatment. Cite this article: Bone Joint J 2023;105-B(6):702–710

Aims. Patients with midcarpal instability are difficult to manage. It is a rare condition, and few studies have reported the outcomes of surgical treatment. No prospective or retrospective study has reported the results of arthroscopic palmar capsuloligamentous suturing. Our aim was to report the results of a prospective study of arthroscopic suture of this ligament complex in patients with midcarpal instability. Methods. This prospective single-centre study was undertaken between March 2012 and May 2022. The primary outcome was to evaluate the functional outcomes of arthroscopic palmar midcarpal suture. The study included 12 patients, eight male and four female, with a mean age of 27.5 years (19 to 42). They were reviewed at three months, six months, and one year postoperatively. Results. There was a significant improvement in flexion, extension, grip strength, abbreviated version of the Disabilities of the Arm, Shoulder and Hand questionnaire score, and pain, in all patients. After telephone contact with all patients in March 2023, at a mean follow-up of 3.85 years (2.2 to 6.25), no patient had a persistent or recurrent clunk. Conclusion. Arthroscopic suture of the midcarpal capsuloligamentous complex represents a minimally invasive, easy, and reproducible technique for the management of patients with midcarpal instbility, with a clear improvement in function outcomes and no complications. Cite this article: Bone Joint J 2024;106-B(3):262–267

Aims. With up to 40% of patients having patellofemoral joint osteoarthritis (PFJ OA), the two arthroplasty options are to replace solely the patellofemoral joint via patellofemoral arthroplasty (PFA), or the entire knee via total knee arthroplasty (TKA). The aim of this study was to assess postoperative success of second-generation PFAs compared to TKAs for patients treated for PFJ OA using patient-reported outcome measures (PROMs) and domains deemed important by patients following a patient and public involvement meeting. Methods. MEDLINE, EMBASE via OVID, CINAHL, and EBSCO were searched from inception to January 2022. Any study addressing surgical treatment of primary patellofemoral joint OA using second generation PFA and TKA in patients aged above 18 years with follow-up data of 30 days were included. Studies relating to OA secondary to trauma were excluded. ROB-2 and ROBINS-I bias tools were used. Results. A total of nine studies were included, made up of four randomized controlled trials (domain 1) and five cohort studies (domain 2). PROMs and knee function specific scores developed for reporting TKA were unable to detect any difference between PFA and TKA. There was no significant difference in complications between PFA and TKA. PFAs were found to have a better postoperative range of motion. Conclusion. TKA and PFA are both viable options for patients with primary PFJ OA. Over time, we have seen an emphasis on patient satisfaction and better quality of life. Recommending sacrificing healthy medial and lateral compartments to treat patellofemoral joint arthritis should be given further thought. Cite this article: Bone Jt Open 2023;4(12):948–956

Aims. Shoulder arthroplasty is effective in the management of end-stage glenohumeral joint arthritis. However, it is major surgery and patients must balance multiple factors when considering the procedure. An understanding of patients’ decision-making processes may facilitate greater support of those considering shoulder arthroplasty and inform the outcomes of future research. Methods. Participants were recruited from waiting lists of three consultant upper limb surgeons across two NHS hospitals. Semi-structured interviews were conducted with 12 participants who were awaiting elective shoulder arthroplasty. Transcribed interviews were analyzed using a grounded theory approach. Systematic coding was performed; initial codes were categorized and further developed into summary narratives through a process of discussion and refinement. Data collection and analyses continued until thematic saturation was reached. Results. Two overall categories emerged: the motivations to consider surgery, and the information participants used to inform their decision-making. Motivations were, broadly, the relief of pain and the opportunity to get on with life and regain independence. When participants’ symptoms and restrictions prevented them enjoying life to a sufficient extent, this provided the motivation to proceed with surgery. Younger participants tended to focus on maintaining employment and recreational activities, and older patients were eager to make the most of their remaining lifetime. Participants gathered information from a range of sources and were keen to optimize their recovery where possible. An important factor for participants was whether they trusted their surgeon and were prepared to delegate responsibility for elements of their care. Conclusion. Relief of pain and the opportunity to get on with life were the primary reasons to undergo shoulder arthroplasty. Participants highlighted the importance of the patient-surgeon relationship and the need for accurate information in an accessible format which is relevant to people of different ages and functional demands. Cite this article: Bone Jt Open 2024;5(7):543–549

Aims. The use of a porous metal shell supported by two augments with the ‘footing’ technique is one solution to manage Paprosky IIIB acetabular defects in revision total hip arthroplasty. The aim of this study was to assess the medium-term implant survival and radiological and clinical outcomes of this technique. Methods. We undertook a retrospective, two-centre series of 39 hips in 39 patients (15 male, 24 female) treated with the ‘footing’ technique for Paprosky IIIB acetabular defects between 2007 and 2020. The median age at the time of surgery was 64.4 years (interquartile range (IQR) 54.4 to 71.0). The median follow-up was 3.9 years (IQR 3.1 to 7.0). Results. The cumulative medium-term survival of the acetabular construct was 89%. Two hips (5.1%) required further revision due to shell loosening, one hip (2.6%) due to shell dislocation, and one hip (2.6%) due to infection. The median Harris Hip Score improved significantly from 47 points (IQR 41.5 to 54.9) preoperatively to 80 points (IQR 73.5 to 88.6) at the latest follow-up (p < 0.001). Conclusion. The reconstruction of Paprosky IIIB acetabular defects with porous tantalum shells and two augments using the ‘footing’ technique showed excellent medium-term results. It is a viable option for treating these challenging defects. Cite this article: Bone Joint J 2024;106-B(5 Supple B):54–58

Aims. Unicompartmental knee arthroplasty (UKA) is the preferred treatment for anterior medial knee osteoarthritis (OA) owing to the rapid postoperative recovery. However, the risk factors for UKA failure remain controversial. Methods. The clinical data of Oxford mobile-bearing UKAs performed between 2011 and 2017 with a minimum follow-up of five years were retrospectively analyzed. Demographic, surgical, and follow-up data were collected. The Cox proportional hazards model was used to identify the risk factors that contribute to UKA failure. Kaplan-Meier survival was used to compare the effect of the prosthesis position on UKA survival. Results. A total of 407 patients who underwent UKA were included in the study. The mean age of patients was 61.8 years, and the mean follow-up period of the patients was 91.7 months. The mean Knee Society Score (KSS) preoperatively and at the last follow-up were 64.2 and 89.7, respectively (p = 0.001). Overall, 28 patients (6.9%) with UKA underwent revision due to prosthesis loosening (16 patients), dislocation (eight patients), and persistent pain (four patients). Cox proportional hazards model analysis identified malposition of the prostheses as a high-risk factor for UKA failure (p = 0.007). Kaplan-Meier analysis revealed that the five-year survival rate of the group with malposition was 85.1%, which was significantly lower than that of the group with normal position (96.2%; p < 0.001). Conclusion. UKA constitutes an effective method for treating anteromedial knee OA, with an excellent five-year survival rate. Aseptic loosening caused by prosthesis malposition was identified as the main cause of UKA failure. Surgeons should pay close attention to prevent the potential occurrence of this problem. Cite this article: Bone Jt Open 2023;4(12):914–922

Aims. The sensitivity and specificity of electrodiagnostic parameters in diagnosing carpal tunnel syndrome (CTS) have been reported differently, and this study aims to address this gap. Methods. This case-control study was conducted on 57 cases with CTS and 58 controls without complaints, such as pain or paresthesia on the median nerve. The main assessed electrodiagnostic parameters were terminal latency index (TLI), residual latency (RL), median ulnar F-wave latency difference (FdifMU), and median sensory latency-ulnar motor latency difference (MSUMLD). Results. The mean age in cases and controls were 50.7 years (SD 9.9) and 47.9 years (SD 12.1), respectively. The CTS severity was mild in 20 patients (34.4%), moderate in 19 patients (32.8%), and severe in 19 patients (32.8%). The sensitivity and specificity of the electrodiagnostic parameters in diagnosing CTS were as follows: TLI 75.4% and 87.8%; RL 85.9% and 82.5%; FdifMU 87.9% and 82.9%; and MSUMLD 94.8% and 60.0%, respectively. Conclusion. Our findings indicated that electrodiagnostic parameters are significantly associated with the clinical manifestation of CTS, and are associated with high diagnostic accuracy in CTS diagnosis. However, further studies are required to highlight the role of electrodiagnostic parameters and their combination in CTS detection. Cite this article: Bone Jt Open 2024;5(10):898–903

Aims. Knee osteoarthritis (OA) involves a variety of tissues in the joint. Gene expression profiles in different tissues are of great importance in order to understand OA. Methods. First, we obtained gene expression profiles of cartilage, synovium, subchondral bone, and meniscus from the Gene Expression Omnibus (GEO). Several datasets were standardized by merging and removing batch effects. Then, we used unsupervised clustering to divide OA into three subtypes. The gene ontology and pathway enrichment of three subtypes were analyzed. CIBERSORT was used to evaluate the infiltration of immune cells in different subtypes. Finally, OA-related genes were obtained from the Molecular Signatures Database for validation, and diagnostic markers were screened according to clinical characteristics. Quantitative reverse transcription polymerase chain reaction (qRT‐PCR) was used to verify the effectiveness of markers. Results. C1 subtype is mainly concentrated in the development of skeletal muscle organs, C2 lies in metabolic process and immune response, and C3 in pyroptosis and cell death process. Therefore, we divided OA into three subtypes: bone remodelling subtype (C1), immune metabolism subtype (C2), and cartilage degradation subtype (C3). The number of macrophage M0 and activated mast cells of C2 subtype was significantly higher than those of the other two subtypes. COL2A1 has significant differences in different subtypes. The expression of COL2A1 is related to age, and trafficking protein particle complex subunit 2 is related to the sex of OA patients. Conclusion. This study linked different tissues with gene expression profiles, revealing different molecular subtypes of patients with knee OA. The relationship between clinical characteristics and OA-related genes was also studied, which provides a new concept for the diagnosis and treatment of OA. Cite this article: Bone Joint Res 2023;12(12):702–711

Aims. The aim of this study was to perform the first population-based description of the epidemiological and health economic burden of fracture-related infection (FRI). Methods. This is a retrospective cohort study of operatively managed orthopaedic trauma patients from 1 January 2007 to 31 December 2016, performed in Queensland, Australia. Record linkage was used to develop a person-centric, population-based dataset incorporating routinely collected administrative, clinical, and health economic information. The FRI group consisted of patients with International Classification of Disease 10th Revision diagnosis codes for deep infection associated with an implanted device within two years following surgery, while all others were deemed not infected. Demographic and clinical variables, as well as healthcare utilization costs, were compared. Results. There were 111,402 patients operatively managed for orthopaedic trauma, with 2,775 of these (2.5%) complicated by FRI. The development of FRI had a statistically significant association with older age, male sex, residing in rural/remote areas, Aboriginal or Torres Strait Islander background, lower socioeconomic status, road traffic accident, work-related injuries, open fractures, anatomical region (lower limb, spine, pelvis), high injury severity, requiring soft-tissue coverage, and medical comorbidities (univariate analysis). Patients with FRI had an eight-times longer median inpatient length of stay (24 days vs 3 days), and a 2.8-times higher mean estimated inpatient hospitalization cost (AU$56,565 vs AU$19,773) compared with uninfected patients. The total estimated inpatient cost of the FRI cohort to the healthcare system was AU$156.9 million over the ten-year period. Conclusion. The results of this study advocate for improvements in trauma care and infection management, address social determinants of health, and highlight the upside potential to improve prevention and treatment strategies. Cite this article: Bone Joint J 2024;106-B(1):77–85

Aims. The antidiabetic agent metformin inhibits fibrosis in various organs. This study aims to elucidate the effects of hyperglycaemia and metformin on knee joint capsule fibrosis in mice. Methods. Eight-week-old wild-type (WT) and type 2 diabetic (db/db) mice were divided into four groups without or with metformin treatment (WT met(-/+), Db met(-/+)). Mice received daily intraperitoneal administration of metformin and were killed at 12 and 14 weeks of age. Fibrosis morphology and its related genes and proteins were evaluated. Fibroblasts were extracted from the capsules of 14-week-old mice, and the expression of fibrosis-related genes in response to glucose and metformin was evaluated in vitro. Results. The expression of all fibrosis-related genes was higher in Db met(-) than in WT met(-) and was suppressed by metformin. Increased levels of fibrosis-related genes, posterior capsule thickness, and collagen density were observed in the capsules of db/db mice compared with those in WT mice; these effects were suppressed by metformin. Glucose addition increased fibrosis-related gene expression in both groups of mice in vitro. When glucose was added, metformin inhibited the expression of fibrosis-related genes other than cellular communication network factor 2 (Ccn2) in WT mouse cells. Conclusion. Hyperglycaemia promotes fibrosis in the mouse knee joint capsule, which is inhibited by metformin. These findings can help inform the development of novel strategies for treating knee joint capsule fibrosis. Cite this article: Bone Joint Res 2024;13(7):321–331