Aims. This study aimed, through bioinformatics analysis, to identify the potential diagnostic markers of osteoarthritis, and analyze the role of immune infiltration in synovial tissue. Methods. The gene expression profiles were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified by R software. Functional enrichment analyses were performed and protein-protein interaction networks (PPI) were constructed. Then the hub genes were screened. Biomarkers with high value for the diagnosis of early osteoarthritis (OA) were validated by GEO datasets. Finally, the CIBERSORT algorithm was used to evaluate the immune infiltration between early-stage OA and end-stage OA, and the correlation between the diagnostic marker and infiltrating immune cells was analyzed. Results. A total of 88 DEGs were identified. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that DEGs were significantly enriched in leucocyte migration and interleukin (IL)-17 signalling pathways. Disease ontology (DO) indicated that DEGs were mostly enriched in rheumatoid arthritis. Six hub genes including FosB proto-oncogene, AP-1 transcription factor subunit (FOSB); C-X-C motif chemokine ligand 2 (CXCL2); CXCL8; IL-6; Jun proto-oncogene, AP-1 transcription factor subunit (JUN); and Activating transcription factor 3 (ATF3) were identified and verified by GEO datasets. ATF3 (area under the curve = 0.975) turned out to be a potential biomarker for the diagnosis of early OA. Several infiltrating immune cells varied significantly between early-stage OA and end-stage OA, such as resting NK cells (p = 0.016), resting dendritic cells (p = 0.043), and plasma cells (p = 0.043). Additionally, ATF3 was significantly correlated with resting NK cells (p = 0.034), resting dendritic cells (p = 0.026), and regulatory T cells (Tregs, p = 0.018). Conclusion. ATF3 may be a potential diagnostic marker for early diagnosis and treatment of OA, and immune cell infiltration provides new perspectives for understanding the mechanism during OA progression. Cite this article: Bone Joint Res 2022;11(9):679–689

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The aim of this study was to evaluate the performance of metagenomic next-generation sequencing (mNGS) in detecting pathogens from synovial fluid of prosthetic joint infection (PJI) patients.

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Histology is an established tool in diagnosing periprosthetic joint infections (PJIs). Different thresholds, using various infection definitions and histopathological criteria, have been described. This study determined the performance of different thresholds of polymorphonuclear neutrophils (≥ 5 PMN/HPF, ≥ 10 PMN/HPF, ≥ 23 PMN/10 HPF) , when using the European Bone and Joint Infection Society (EBJIS), Infectious Diseases Society of America (IDSA), and the International Consensus Meeting (ICM) 2018 criteria for PJI.

Aims. This study aimed to explore the diagnostic value of synovial fluid neutrophil extracellular traps (SF-NETs) in periprosthetic joint infection (PJI) diagnosis, and compare it with that of microbial culture, serum ESR and CRP, synovial white blood cell (WBC) count, and polymorphonuclear neutrophil percentage (PMN%). Methods. In a single health centre, patients with suspected PJI were enrolled from January 2013 to December 2021. The inclusion criteria were: 1) patients who were suspected to have PJI; 2) patients with complete medical records; and 3) patients from whom sufficient synovial fluid was obtained for microbial culture and NET test. Patients who received revision surgeries due to aseptic failure (AF) were selected as controls. Synovial fluid was collected for microbial culture and SF-WBC, SF-PNM%, and SF-NET detection. The receiver operating characteristic curve (ROC) of synovial NET, WBC, PMN%, and area under the curve (AUC) were obtained; the diagnostic efficacies of these diagnostic indexes were calculated and compared. Results. The levels of SF-NETs in the PJI group were significantly higher than those of the AF group. The AUC of SF-NET was 0.971 (95% confidence interval (CI) 0.903 to 0.996), the sensitivity was 93.48% (95% CI 82.10% to 98.63%), the specificity was 96.43% (95% CI 81.65% to 99.91%), the accuracy was 94.60% (95% CI 86.73% to 98.50%), the positive predictive value was 97.73%, and the negative predictive value was 90%. Further analysis showed that SF-NET could improve the diagnosis of culture-negative PJI, patients with PJI who received antibiotic treatment preoperatively, and fungal PJI. Conclusion. SF-NET is a novel and ideal synovial fluid biomarker for PJI diagnosis, which could improve PJI diagnosis greatly. Cite this article: Bone Joint Res 2023;12(2):113–120

Aims. This study aimed to determine the expression and clinical significance of a cartilage protein, cartilage oligomeric matrix protein (COMP), in knee osteoarthritis (OA) patients. Methods. A total of 270 knee OA patients and 93 healthy controls were recruited. COMP messenger RNA (mRNA) and protein levels in serum, synovial fluid, synovial tissue, and fibroblast-like synoviocytes (FLSs) of knee OA patients were determined using enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and immunohistochemistry. Results. COMP protein levels were significantly elevated in serum and synovial fluid of knee OA patients, especially those in the advanced stages of the disease. Serum COMP was significantly correlated with radiological severity as well as measures of body composition, physical performance, knee pain, and disability. Receiver operating characteristic curve analysis unveiled a diagnostic value of serum COMP as a biomarker of knee OA (41.64 ng/ml, area under the curve (AUC) = 1.00), with a sensitivity of 99.6% and a specificity of 100.0%. Further analysis uncovered that COMP mRNA expression was markedly upregulated in the inflamed synovium of knee OA, consistent with immunohistochemical staining revealing localization of COMP protein in the lining and sub-lining layers of knee OA inflamed synovium. Most notably, relative COMP mRNA expression in knee OA synovium was positively associated with its protein levels in serum and synovial fluid of knee OA patients. In human knee OA FLSs activated with tumour necrosis factor-alpha, COMP mRNA expression was considerably up-regulated in a time-dependent manner. Conclusion. All results indicate that COMP might serve as a supportive diagnostic marker for knee OA in conjunction with the standard diagnostic methods. Cite this article: Bone Joint Res 2024;13(6):261–271

Aims. Serum inflammatory parameters are widely used to aid in diagnosing a periprosthetic joint infection (PJI). Due to their limited performances in the literature, novel and more accurate biomarkers are needed. Serum albumin-to-globulin ratio (AGR) and serum CRP-to-albumin ratio (CAR) have previously been proposed as potential new parameters, but results were mixed. The aim of this study was to assess the diagnostic accuracy of AGR and CAR in diagnosing PJI and to compare them to the established and widely used marker CRP. Methods. From 2015 to 2022, a consecutive series of 275 cases of revision total hip (n = 129) and knee arthroplasty (n = 146) were included in this retrospective cohort study. Based on the 2021 European Bone and Joint Infection Society (EBJIS) definition, 144 arthroplasties were classified as septic. Using receiver operating characteristic curve (ROC) analysis, the ideal thresholds and diagnostic performances were calculated. The areas under the curve (AUCs) were compared using the z-test. Results. AGR, CAR, and CRP were associated with PJI (p < 0.001). Sensitivities were 62.5% (95% CI 54.3 to 70.0), 73.6% (95% CI 65.8 to 80.1), and 71.5% (95% CI 63.6 to 78.3), respectively. Specificities were calculated with 84.7% (95% CI 77.5 to 89.9), 86.3% (95% CI 79.2 to 91.2), and 87.8% (95% CI 80.9 to 92.4), respectively. The AUC of CRP (0.797 (95% CI 0.750 to 0.843)) was significantly higher than the AUC of AGR (0.736 (95% CI 0.686 to 0.786), p < 0.001), and similar to AUC of CAR (0.799 (95% CI 0.753 to 0.846), p = 0.832). Decreased sensitivities were observed in PJIs caused by low-virulence organisms (AGR: 60%, CAR: 78%) compared to high-virulence pathogens (AGR: 80%, p = 0.042; CAR: 88%, p = 0.158). Higher sensitivities were seen in acute haematogenous (AGR: 83%, CAR: 96%) compared to chronic PJIs (AGR: 54%, p = 0.001; CAR: 65%, p < 0.001). Conclusion. Serum AGR and CAR showed limited diagnostic accuracy (especially in low-grade and chronic infections) and did not outperform the established marker CRP in our study. Hence, neither parameter can be recommended as an additional tool for diagnosing PJI. Cite this article: Bone Joint Res 2024;13(8):372–382

Aims. To investigate the optimal thresholds and diagnostic efficacy of commonly used serological and synovial fluid detection indexes for diagnosing periprosthetic joint infection (PJI) in patients who have rheumatoid arthritis (RA). Methods. The data from 348 patients who had RA or osteoarthritis (OA) and had previously undergone a total knee (TKA) and/or a total hip arthroplasty (THA) (including RA-PJI: 60 cases, RA-non-PJI: 80 cases; OA-PJI: 104 cases, OA-non-PJI: 104 cases) were retrospectively analyzed. A receiver operating characteristic curve was used to determine the optimal thresholds of the CRP, ESR, synovial fluid white blood cell count (WBC), and polymorphonuclear neutrophil percentage (PMN%) for diagnosing RA-PJI and OA-PJI. The diagnostic efficacy was evaluated by comparing the area under the curve (AUC) of each index and applying the results of the combined index diagnostic test. Results. For PJI prediction, the results of serological and synovial fluid indexes were different between the RA-PJI and OA-PJI groups. The optimal cutoff value of CRP for diagnosing RA-PJI was 12.5 mg/l, ESR was 39 mm/hour, synovial fluid WBC was 3,654/μl, and PMN% was 65.9%; and those of OA-PJI were 8.2 mg/l, 31 mm/hour, 2,673/μl, and 62.0%, respectively. In the RA-PJI group, the specificity (94.4%), positive predictive value (97.1%), and AUC (0.916) of synovial fluid WBC were higher than those of the other indexes. The optimal cutoff values of synovial fluid WBC and PMN% for diagnosing RA-PJI after THA were significantly higher than those of TKA. The specificity and positive predictive value of the combined index were 100%. Conclusion. Serum inflammatory and synovial fluid indexes can be used for diagnosing RA-PJI, for which synovial fluid WBC is the best detection index. Combining multiple detection indexes can provide a reference basis for the early and accurate diagnosis of RA-PJI. Cite this article: Bone Joint Res 2023;12(9):559–570

Aims. We aimed to evaluate the utility of . 68. Ga-citrate positron emission tomography (PET)/CT in the differentiation of periprosthetic joint infection (PJI) and aseptic loosening (AL), and compare it with . 99m. Tc-methylene bisphosphonates (. 99m. Tc-MDP) bone scan. Methods. We studied 39 patients with suspected PJI or AL. These patients underwent . 68. Ga-citrate PET/CT, . 99m. Tc-MDP three-phase bone scan and single-photon emission CT (SPECT)/CT. PET/CT was performed at ten minutes and 60 minutes after injection, respectively. Images were evaluated by three nuclear medicine doctors based on: 1) visual analysis of the three methods based on tracer uptake model, and PET images attenuation-corrected with CT and those not attenuation-corrected with CT were analyzed, respectively; and 2) semi-quantitative analysis of PET/CT: maximum standardized uptake value (SUVmax) of lesions, SUVmax of the lesion/SUVmean of the normal bone, and SUVmax of the lesion/SUVmean of the normal muscle. The final diagnosis was based on the clinical and intraoperative findings, and histopathological and microbiological examinations. Results. Overall, 23 and 16 patients were diagnosed with PJI and AL, respectively. The sensitivity and specificity of three-phase bone scan and SPECT/CT were 100% and 62.5%, 82.6%, and 100%, respectively. Attenuation correction (AC) at 60 minutes and non-AC at 60 minutes of PET/CT had the same highest sensitivity and specificity (91.3% and 100%), and AC at 60 minutes combined with SPECT/CT could improve the diagnostic efficiency (sensitivity = 95.7%). Diagnostic efficacy of the SUVmax was low (area under the curve (AUC) of ten minutes and 60 minutes was 0.814 and 0.806, respectively), and SUVmax of the lesion/SUVmean of the normal bone at 60 minutes was the best semi-quantitative parameter (AUC = 0.969). Conclusion. 68. Ga-citrate showed the potential to differentiate PJI from AL, and visual analysis based on uptake pattern of tracer was reliable. The visual analysis method of AC at 60 minutes, combined with . 99m. Tc-MDP SPECT/CT, could improve the sensitivity from 91.3% to 95.7%. In addition, a major limitation of our study was that it had a limited sample size, and more detailed studies with a larger sample size are warranted. Cite this article: Bone Joint Res 2022;11(6):398–408

Aims. The diagnosis of periprosthetic joint infection (PJI) has always been challenging. Recently, D-dimer has become a promising biomarker in diagnosing PJI. However, there is controversy regarding its diagnostic value. We aim to investigate the diagnostic value of D-dimer in comparison to ESR and CRP. Methods. PubMed, Embase, and the Cochrane Library were searched in February 2020 to identify articles reporting on the diagnostic value of D-dimer on PJI. Pooled analysis was conducted to investigate the diagnostic value of D-dimer, CRP, and ESR. Results. Six studies with 1,255 cases were included (374 PJI cases and 881 non-PJI cases). Overall D-dimer showed sensitivity of 0.80 (95% confidence interval (CI) 0.69 to 0.87) and specificity of 0.76 (95% CI 0.63 to 0.86). Sub-group analysis by excluding patients with thrombosis and hyper-coagulation disorders showed sensitivity of 0.82 (95% CI 0.70 to 0.90) and specificity of 0.80 (95% CI 0.70 to 0.88). Serum D-dimer showed sensitivity of 0.85 (95% CI 0.76 to 0.92), specificity of 0.83 (95% CI 0.74 to 0.90). Plasma D-dimer showed sensitivity of 0.67 (95% CI 0.60 to 0.73), specificity of 0.58 (95% CI 0.45 to 0.72). CRP showed sensitivity of 0.78 (95% CI 0.72 to 0.83), specificity of 0.81 (95% CI 0.72 to 0.87). ESR showed sensitivity of 0.68 (95% CI 0.63 to 0.73), specificity of 0.83 (95% CI 0.78 to 0.87). Conclusion. In patients without thrombosis or a hyper-coagulation disorder, D-dimer has a higher diagnostic value compared to CRP and ESR. In patients with the aforementioned conditions, D-dimer has higher sensitivity but lower specificity compared to ESR and CRP. We do not recommend the use of serum D-dimer in patients with thrombosis and hyper-coagulation disorders for diagnosing PJI. Serum D-dimer may perform better than plasma D-dimer. Further studies are needed to compare serum D-dimer and plasma D-dimer in arthroplasty patients. Cite this article: Bone Joint Res 2020;9(10):701–708

The use of artificial intelligence (AI) is rapidly growing across many domains, of which the medical field is no exception. AI is an umbrella term defining the practical application of algorithms to generate useful output, without the need of human cognition. Owing to the expanding volume of patient information collected, known as ‘big data’, AI is showing promise as a useful tool in healthcare research and across all aspects of patient care pathways. Practical applications in orthopaedic surgery include: diagnostics, such as fracture recognition and tumour detection; predictive models of clinical and patient-reported outcome measures, such as calculating mortality rates and length of hospital stay; and real-time rehabilitation monitoring and surgical training. However, clinicians should remain cognizant of AI’s limitations, as the development of robust reporting and validation frameworks is of paramount importance to prevent avoidable errors and biases. The aim of this review article is to provide a comprehensive understanding of AI and its subfields, as well as to delineate its existing clinical applications in trauma and orthopaedic surgery. Furthermore, this narrative review expands upon the limitations of AI and future direction. Cite this article: Bone Joint Res 2023;12(7):447–454

Aims. This study evaluated the definitions developed by the European Bone and Joint Infection Society (EBJIS) 2021, the International Consensus Meeting (ICM) 2018, and the Infectious Diseases Society of America (IDSA) 2013, for the diagnosis of periprosthetic joint infection (PJI). Methods. In this single-centre, retrospective analysis of prospectively collected data, patients with an indicated revision surgery after a total hip or knee arthroplasty were included between 2015 and 2020. A standardized diagnostic workup was performed, identifying the components of the EBJIS, ICM, and IDSA criteria in each patient. Results. Of 206 included patients, 101 (49%) were diagnosed with PJI with the EBJIS definition. IDSA and ICM diagnosed 99 (48%) and 86 (42%) as infected, respectively. A total of 84 cases (41%) had an infection based on all three criteria. In 15 cases (n = 15/206; 7%), PJI was present when applying only the IDSA and EBJIS criteria. No infection was detected by one definition alone. Inconclusive diagnoses occurred more frequently with the ICM criteria (n = 30/206; 15%) compared to EBJIS (likely infections: n = 16/206; 8%) (p = 0.029). A better preoperative performance of the EBJIS definition was seen compared with the ICM and IDSA definitions (p < 0.001). Conclusion. The novel EBJIS definition identified all PJIs diagnosed by any other criteria. Use of the EBJIS definition significantly reduced the number of uncertain diagnoses, allowing easier clinical decision-making. Cite this article: Bone Joint Res 2022;11(9):608–618

Aims. This study aimed to evaluate the BioFire Joint Infection (JI) Panel in cases of hip and knee periprosthetic joint infection (PJI) where conventional microbiology is unclear, and to assess its role as a complementary intraoperative diagnostic tool. Methods. Five groups representing common microbiological scenarios in hip and knee revision arthroplasty were selected from our arthroplasty registry, prospectively maintained PJI databases, and biobank: 1) unexpected-negative cultures (UNCs), 2) unexpected-positive cultures (UPCs), 3) single-positive intraoperative cultures (SPCs), and 4) clearly septic and 5) aseptic cases. In total, 268 archived synovial fluid samples from 195 patients who underwent acute/chronic revision total hip or knee arthroplasty were included. Cases were classified according to the International Consensus Meeting 2018 criteria. JI panel evaluation of synovial fluid was performed, and the results were compared with cultures. Results. The JI panel detected microorganisms in 7/48 (14.5%) and 15/67 (22.4%) cases related to UNCs and SPCs, respectively, but not in cases of UPCs. The correlation between JI panel detection and infection classification criteria for early/late acute and chronic PJI was 46.6%, 73%, and 40%, respectively. Overall, the JI panel identified 12.6% additional microorganisms and three new species. The JI panel pathogen identification showed a sensitivity and specificity of 41.4% (95% confidence interval (CI) 33.7 to 49.5) and 91.1% (95% CI 84.7 to 94.9), respectively. In total, 19/195 (9.7%) could have been managed differently and more accurately upon JI panel evaluation. Conclusion. Despite its microbial limitation, JI panel demonstrated clinical usefulness by complementing the traditional methods based on multiple cultures, particularly in PJI with unclear microbiological results. Cite this article: Bone Joint Res 2024;13(7):353–361

Aims. This study aimed to explore the biological and clinical importance of dysregulated key genes in osteoarthritis (OA) patients at the cartilage level to find potential biomarkers and targets for diagnosing and treating OA. Methods. Six sets of gene expression profiles were obtained from the Gene Expression Omnibus database. Differential expression analysis, weighted gene coexpression network analysis (WGCNA), and multiple machine-learning algorithms were used to screen crucial genes in osteoarthritic cartilage, and genome enrichment and functional annotation analyses were used to decipher the related categories of gene function. Single-sample gene set enrichment analysis was performed to analyze immune cell infiltration. Correlation analysis was used to explore the relationship among the hub genes and immune cells, as well as markers related to articular cartilage degradation and bone mineralization. Results. A total of 46 genes were obtained from the intersection of significantly upregulated genes in osteoarthritic cartilage and the key module genes screened by WGCNA. Functional annotation analysis revealed that these genes were closely related to pathological responses associated with OA, such as inflammation and immunity. Four key dysregulated genes (cartilage acidic protein 1 (CRTAC1), iodothyronine deiodinase 2 (DIO2), angiopoietin-related protein 2 (ANGPTL2), and MAGE family member D1 (MAGED1)) were identified after using machine-learning algorithms. These genes had high diagnostic value in both the training cohort and external validation cohort (receiver operating characteristic > 0.8). The upregulated expression of these hub genes in osteoarthritic cartilage signified higher levels of immune infiltration as well as the expression of metalloproteinases and mineralization markers, suggesting harmful biological alterations and indicating that these hub genes play an important role in the pathogenesis of OA. A competing endogenous RNA network was constructed to reveal the underlying post-transcriptional regulatory mechanisms. Conclusion. The current study explores and validates a dysregulated key gene set in osteoarthritic cartilage that is capable of accurately diagnosing OA and characterizing the biological alterations in osteoarthritic cartilage; this may become a promising indicator in clinical decision-making. This study indicates that dysregulated key genes play an important role in the development and progression of OA, and may be potential therapeutic targets. Cite this article: Bone Joint Res 2024;13(2):66–82

Aims. This study aimed to develop and validate a fully automated system that quantifies proximal femoral bone mineral density (BMD) from CT images. Methods. The study analyzed 978 pairs of hip CT and dual-energy X-ray absorptiometry (DXA) measurements of the proximal femur (DXA-BMD) collected from three institutions. From the CT images, the femur and a calibration phantom were automatically segmented using previously trained deep-learning models. The Hounsfield units of each voxel were converted into density (mg/cm. 3. ). Then, a deep-learning model trained by manual landmark selection of 315 cases was developed to select the landmarks at the proximal femur to rotate the CT volume to the neutral position. Finally, the CT volume of the femur was projected onto the coronal plane, and the areal BMD of the proximal femur (CT-aBMD) was quantified. CT-aBMD correlated to DXA-BMD, and a receiver operating characteristic (ROC) analysis quantified the accuracy in diagnosing osteoporosis. Results. CT-aBMD was successfully measured in 976/978 hips (99.8%). A significant correlation was found between CT-aBMD and DXA-BMD (r = 0.941; p < 0.001). In the ROC analysis, the area under the curve to diagnose osteoporosis was 0.976. The diagnostic sensitivity and specificity were 88.9% and 96%, respectively, with the cutoff set at 0.625 g/cm. 2. . Conclusion. Accurate DXA-BMD measurements and diagnosis of osteoporosis were performed from CT images using the system developed herein. As the models are open-source, clinicians can use the proposed system to screen osteoporosis and determine the surgical strategy for hip surgery. Cite this article: Bone Joint Res 2023;12(9):590–597

Aims. This study aimed to evaluate calprotectin in synovial fluid for diagnosing chronic prosthetic joint infection (PJI) . Methods. A total of 63 patients who were suspected of PJI were enrolled. The synovial fluid calprotectin was tested by an enzyme-linked immunosorbent assay (ELISA). Laboratory test data, such as ESR, CRP, synovial fluid white blood cells (SF-WBCs), and synovial fluid polymorphonuclear cells (SF-PMNs), were documented. Chi-squared tests were used to compare the sensitivity and specificity of calprotectin and laboratory tests. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was calculated to determine diagnostic efficacy. Results. The median calprotectin level was 776 μg/ml (interquartile range (IQR) 536.5 to 1132) in the PJI group and 54.5 μg/ml (IQR, 38.75 to 78.25) in the aseptic failure (AF) group (p < 0.05). Using a threshold of 173 ug/ml, the sensitivity was 95.2%, with a 97.6% specificity, and the AUC was 0.993. The sensitivity of calprotectin of the antibiotic-treated PJI group was 100% versus 90.9% of the non-antibiotic-treated PJI group. Although 47.6% (ten cases) of the patients in the PJI group received antibiotics before aspiration, the diagnostic efficacy of calprotectin was not affected. The sensitivity and specificity of ESR, CRP, SF-WBCs, and SF-PMNs ranged from 76.2% to 90.5% and 64.3% to 85.7%, respectively. Conclusion. Calprotectin in synovial fluid has great diagnostic efficacy for PJI diagnosisand outperformed ESR, CRP, SF-WBCs, and SF-PMNs. Cite this article: Bone Joint Res 2020;9(8):450–456

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. 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. The lack of disease-modifying treatments for osteoarthritis (OA) is linked to a shortage of suitable biomarkers. This study combines multi-molecule synovial fluid analysis with machine learning to produce an accurate diagnostic biomarker model for end-stage knee OA (esOA). Methods. Synovial fluid (SF) from patients with esOA, non-OA knee injury, and inflammatory knee arthritis were analyzed for 35 potential markers using immunoassays. Partial least square discriminant analysis (PLS-DA) was used to derive a biomarker model for cohort classification. The ability of the biomarker model to diagnose esOA was validated by identical wide-spectrum SF analysis of a test cohort of ten patients with esOA. Results. PLS-DA produced a streamlined biomarker model with excellent sensitivity (95%), specificity (98.4%), and reliability (97.4%). The eight-biomarker model produced a fingerprint for esOA comprising type IIA procollagen N-terminal propeptide (PIIANP), tissue inhibitor of metalloproteinase (TIMP)-1, a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4), monocyte chemoattractant protein (MCP)-1, interferon-γ-inducible protein-10 (IP-10), and transforming growth factor (TGF)-β3. Receiver operating characteristic (ROC) analysis demonstrated excellent discriminatory accuracy: area under the curve (AUC) being 0.970 for esOA, 0.957 for knee injury, and 1 for inflammatory arthritis. All ten validation test patients were classified correctly as esOA (accuracy 100%; reliability 100%) by the biomarker model. Conclusion. SF analysis coupled with machine learning produced a partially validated biomarker model with cohort-specific fingerprints that accurately and reliably discriminated esOA from knee injury and inflammatory arthritis with almost 100% efficacy. The presented findings and approach represent a new biomarker concept and potential diagnostic tool to stage disease in therapy trials and monitor the efficacy of such interventions. Cite this article: Bone Joint Res 2020;9(9):623–632

Objectives. Nasal carriers of Staphylococcus (S.) aureus (MRSA and MSSA) have an increased risk for healthcare-associated infections. There are currently limited national screening policies for the detection of S. aureus despite the World Health Organization’s recommendations. This study aimed to evaluate the diagnostic performance of molecular and culture techniques in S. aureus screening, determine the cause of any discrepancy between the diagnostic techniques, and model the potential effect of different diagnostic techniques on S. aureus detection in orthopaedic patients. Methods. Paired nasal swabs for polymerase chain reaction (PCR) assay and culture of S. aureus were collected from a study population of 273 orthopaedic outpatients due to undergo joint arthroplasty surgery. Results. The prevalence of MSSA nasal colonization was found to be between 22.4% to 35.6%. The current standard direct culturing methods for detecting S. aureus significantly underestimated the prevalence (p = 0.005), failing to identify its presence in approximately one-third of patients undergoing joint arthroplasty surgery. Conclusion. Modelling these results to national surveillance data, it was estimated that approximately 5000 to 8000 S. aureus surgical site infections could be prevented, and approximately $140 million to $950 million (approximately £110 million to £760 million) saved in treatment costs annually in the United States and United Kingdom combined, by using alternative diagnostic methods to direct culture in preoperative S. aureus screening and eradication programmes. Cite this article: S. T. J. Tsang, M. P. McHugh, D. Guerendiain, P. J. Gwynne, J. Boyd, A. H. R. W. Simpson, T. S. Walsh, I. F. Laurenson, K. E. Templeton. Underestimation of Staphylococcus aureus (MRSA and MSSA) carriage associated with standard culturing techniques: One third of carriers missed. Bone Joint Res 2018;7:79–84. DOI: 10.1302/2046-3758.71.BJR-2017-0175.R1

Objectives. The aim of this study was to review the current evidence and future application for the role of diagnostic and therapeutic ultrasound in fracture management. Methods. A review of relevant literature was undertaken, including articles indexed in PubMed with keywords “ultrasound” or “sonography” combined with “diagnosis”, “fracture healing”, “impaired fracture healing”, “nonunion”, “microbiology”, and “fracture-related infection”. Results. The use of ultrasound in musculoskeletal medicine has expanded rapidly over the last two decades, but the diagnostic use in fracture management is not routinely practised. Early studies have shown the potential of ultrasound as a valid alternative to radiographs to diagnose common paediatric fractures, to detect occult injuries in adults, and for rapid detection of long bone fractures in the resuscitation setting. Ultrasound has also been shown to be advantageous in the early identification of impaired fracture healing; with the advent of 3D image processing, there is potential for wider adoption. Detection of implant-related infection can be improved by ultrasound mediated sonication of microbiology samples. The use of therapeutic ultrasound to promote union in the management of acute fractures is currently a controversial topic. However, there is strong in vitro evidence that ultrasound can stimulate a biological effect with potential clinical benefit in established nonunions, which supports the need for further investigation. Conclusion. Modern ultrasound image processing has the potential to replace traditional imaging modalities in several areas of trauma practice, particularly in the early prediction of impaired fracture healing. Further understanding of the therapeutic application of ultrasound is required to understand and identify the use in promoting fracture healing. Cite this article: J. A. Nicholson, S. T. J. Tsang, T. J. MacGillivray, F. Perks, A. H. R. W. Simpson. What is the role of ultrasound in fracture management? Diagnosis and therapeutic potential for fractures, delayed unions, and fracture-related infection. Bone Joint Res 2019;8:304–312. DOI: 10.1302/2046-3758.87.BJR-2018-0215.R2