Aims. The Oxford Shoulder Score (OSS) is a 12-item measure commonly used for the assessment of shoulder surgeries. This study explores whether computerized adaptive testing (CAT) provides a shortened, individually tailored questionnaire while maintaining test accuracy. Methods. A total of 16,238 preoperative OSS were available in the National Joint Registry (NJR) for England, Wales, Northern Ireland, the Isle of Man, and the States of Guernsey dataset (April 2012 to April 2022). Prior to CAT, the foundational item response theory (IRT) assumptions of unidimensionality, monotonicity, and local independence were established. CAT compared sequential item selection with stopping criteria set at standard error (SE) < 0.32 and SE < 0.45 (equivalent to reliability coefficients of 0.90 and 0.80) to full-length patient-reported outcome measure (PROM) precision. Results. Confirmatory factor analysis (CFA) for unidimensionality exhibited satisfactory fit with root mean square standardized residual (RSMSR) of 0.06 (cut-off ≤ 0.08) but not with comparative fit index (CFI) of 0.85 or Tucker-Lewis index (TLI) of 0.82 (cut-off > 0.90). Monotonicity, measured by H value, yielded 0.482, signifying good monotonic trends. Local independence was generally met, with Yen’s Q3 statistic > 0.2 for most items. The median item count for completing the CAT simulation with a SE of 0.32 was 3 (IQR 3 to 12), while for a SE of 0.45 it was 2 (IQR 2 to 6). This constituted only 25% and 16%, respectively, when compared to the 12-item full-length questionnaire. Conclusion. Calibrating IRT for the OSS has resulted in the development of an efficient and shortened CAT while maintaining accuracy and reliability. Through the reduction of redundant items and implementation of a standardized measurement scale, our study highlights a promising approach to alleviate time burden and potentially enhance compliance with these widely used outcome measures. Cite this article: Bone Joint Res 2024;13(8):392–400

Aims. Bacteriophages infect, replicate inside bacteria, and are released from the host through lysis. Here, we evaluate the effects of repetitive doses of the Staphylococcus aureus phage 191219 and gentamicin against haematogenous and early-stage biofilm implant-related infections in Galleria mellonella. Methods. For the haematogenous infection, G. mellonella larvae were implanted with a Kirschner wire (K-wire), infected with S. aureus, and subsequently phages and/or gentamicin were administered. For the early-stage biofilm implant infection, the K-wires were pre-incubated with S. aureus suspension before implantation. After 24 hours, the larvae received phages and/or gentamicin. In both models, the larvae also received daily doses of phages and/or gentamicin for up to five days. The effect was determined by survival analysis for five days and quantitative culture of bacteria after two days of repetitive doses. Results. In the haematogenous infection, a single combined dose of phages and gentamicin, and repetitive injections with gentamicin or in combination with phages, resulted in significantly improved survival rates. In the early-stage biofilm infection, only repetitive combined administration of phages and gentamicin led to a significantly increased survival. Additionally, a significant reduction in number of bacteria was observed in the larvae after receiving repetitive doses of phages and/or gentamicin in both infection models. Conclusion. Based on our results, a single dose of the combination of phages and gentamicin is sufficient to prevent a haematogenous S. aureus implant-related infection, whereas gentamicin needs to be administered daily for the same effect. To treat early-stage S. aureus implant-related infection, repetitive doses of the combination of phages and gentamicin are required. Cite this article: Bone Joint Res 2024;13(8):383–391

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. The metabolic variations between the cartilage of osteoarthritis (OA) and Kashin-Beck disease (KBD) remain largely unknown. Our study aimed to address this by conducting a comparative analysis of the metabolic profiles present in the cartilage of KBD and OA. Methods. Cartilage samples from patients with KBD (n = 10) and patients with OA (n = 10) were collected during total knee arthroplasty surgery. An untargeted metabolomics approach using liquid chromatography coupled with mass spectrometry (LC-MS) was conducted to investigate the metabolomics profiles of KBD and OA. LC-MS raw data files were converted into mzXML format and then processed by the XCMS, CAMERA, and metaX toolbox implemented with R software. The online Kyoto Encyclopedia of Genes and Genomes (KEGG) database was used to annotate the metabolites by matching the exact molecular mass data of samples with those from the database. Results. A total of 807 ion features were identified for KBD and OA, including 577 positive (240 for upregulated and 337 for downregulated) and 230 negative (107 for upregulated and 123 for downregulated) ions. After annotation, LC-MS identified significant expressions of ten upregulated and eight downregulated second-level metabolites, and 183 upregulated and 162 downregulated first-level metabolites between KBD and OA. We identified differentially expressed second-level metabolites that are highly associated with cartilage damage, including dimethyl sulfoxide, uric acid, and betaine. These metabolites exist in sulphur metabolism, purine metabolism, and glycine, serine, and threonine metabolism. Conclusion. This comprehensive comparative analysis of metabolism in OA and KBD cartilage provides new evidence of differences in the pathogenetic mechanisms underlying cartilage damage in these two conditions. Cite this article: Bone Joint Res 2024;13(7):362–371

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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.

Aims. To explore the efficacy of extracorporeal shockwave therapy (ESWT) in the treatment of osteochondral defect (OCD), and its effects on the levels of transforming growth factor (TGF)-β, bone morphogenetic protein (BMP)-2, -3, -4, -5, and -7 in terms of cartilage and bone regeneration. Methods. The OCD lesion was created on the trochlear groove of left articular cartilage of femur per rat (40 rats in total). The experimental groups were Sham, OCD, and ESWT (0.25 mJ/mm. 2. , 800 impulses, 4 Hz). The animals were euthanized at 2, 4, 8, and 12 weeks post-treatment, and histopathological analysis, micro-CT scanning, and immunohistochemical staining were performed for the specimens. Results. In the histopathological analysis, the macro-morphological grading scale showed a significant increase, while the histological score and cartilage repair scale of ESWT exhibited a significant decrease compared to OCD at the 8- and 12-week timepoints. At the 12-week follow-up, ESWT exhibited a significant improvement in the volume of damaged bone compared to OCD. Furthermore, immunohistochemistry analysis revealed a significant decrease in type I collagen and a significant increase in type II collagen within the newly formed hyaline cartilage following ESWT, compared to OCD. Finally, SRY-box transcription factor 9 (SOX9), aggrecan, and TGF-β, BMP-2, -3, -4, -5, and -7 were significantly higher in ESWT than in OCD at 12 weeks. Conclusion. ESWT promoted the effect of TGF-β/BMPs, thereby modulating the production of extracellular matrix proteins and transcription factor involved in the regeneration of articular cartilage and subchondral bone in an OCD rat model. Cite this article: Bone Joint Res 2024;13(7):342–352

Aims. Although low-intensity pulsed ultrasound (LIPUS) combined with disinfectants has been shown to effectively eliminate portions of biofilm in vitro, its efficacy in vivo remains uncertain. Our objective was to assess the antibiofilm potential and safety of LIPUS combined with 0.35% povidone-iodine (PI) in a rat debridement, antibiotics, and implant retention (DAIR) model of periprosthetic joint infection (PJI). Methods. A total of 56 male Sprague-Dawley rats were established in acute PJI models by intra-articular injection of bacteria. The rats were divided into four groups: a Control group, a 0.35% PI group, a LIPUS and saline group, and a LIPUS and 0.35% PI group. All rats underwent DAIR, except for Control, which underwent a sham procedure. General status, serum biochemical markers, weightbearing analysis, radiographs, micro-CT analysis, scanning electron microscopy of the prostheses, microbiological analysis, macroscope, and histopathology evaluation were performed 14 days after DAIR. Results. The group with LIPUS and 0.35% PI exhibited decreased levels of serum biochemical markers, improved weightbearing scores, reduced reactive bone changes, absence of viable bacteria, and decreased inflammation compared to the Control group. Despite the greater antibiofilm activity observed in the PI group compared to the LIPUS and saline group, none of the monotherapies were successful in preventing reactive bone changes or eliminating the infection. Conclusion. In the rat model of PJI treated with DAIR, LIPUS combined with 0.35% PI demonstrated stronger antibiofilm potential than monotherapy, without impairing any local soft-tissue. Cite this article: Bone Joint Res 2024;13(7):332–341

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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.

Aims. Achilles tendon re-rupture (ATRR) poses a significant risk of postoperative complication, even after a successful initial surgical repair. This study aimed to identify risk factors associated with Achilles tendon re-rupture following operative fixation. Methods. This retrospective cohort study analyzed a total of 43,287 patients from national health claims data spanning 2008 to 2018, focusing on patients who underwent surgical treatment for primary Achilles tendon rupture. Short-term ATRR was defined as cases that required revision surgery occurring between six weeks and one year after the initial surgical repair, while omitting cases with simultaneous infection or skin necrosis. Variables such as age, sex, the presence of Achilles tendinopathy, and comorbidities were systematically collected for the analysis. We employed multivariate stepwise logistic regression to identify potential risk factors associated with short-term ATRR. Results. From 2009 to 2018, the short-term re-rupture rate for Achilles tendon surgeries was 2.14%. Risk factors included male sex, younger age, and the presence of Achilles tendinopathy. Conclusion. This large-scale, big-data study reaffirmed known risk factors for short-term Achilles tendon re-rupture, specifically identifying male sex and younger age. Moreover, this study discovered that a prior history of Achilles tendinopathy emerges as an independent risk factor for re-rupture, even following initial operative fixation. Cite this article: Bone Joint Res 2024;13(7):315–320

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To explore the clinical efficacy of using two different types of articulating spacers in two-stage revision for chronic knee periprosthetic joint infection (kPJI).

Aims. In this study, we aimed to visualize the spatial distribution characteristics of femoral head necrosis using a novel measurement method. Methods. We retrospectively collected CT imaging data of 108 hips with non-traumatic osteonecrosis of the femoral head from 76 consecutive patients (mean age 34.3 years (SD 8.1), 56.58% male (n = 43)) in two clinical centres. The femoral head was divided into 288 standard units (based on the orientation of units within the femoral head, designated as N[Superior], S[Inferior], E[Anterior], and W[Posterior]) using a new measurement system called the longitude and latitude division system (LLDS). A computer-aided design (CAD) measurement tool was also developed to visualize the measurement of the spatial location of necrotic lesions in CT images. Two orthopaedic surgeons independently performed measurements, and the results were used to draw 2D and 3D heat maps of spatial distribution of necrotic lesions in the femoral head, and for statistical analysis. Results. The results showed that the LLDS has high inter-rater reliability. As illustrated by the heat map, the distribution of Japanese Investigation Committee (JIC) classification type C necrotic lesions exhibited clustering characteristics, with the lesions being concentrated in the northern and eastern regions, forming a hot zone (90% probability) centred on the N4-N6E2, N3-N6E units of outer ring blocks. Statistical results showed that the distribution difference between type C2 and type C1 was most significant in the E1 and E2 units and, combined with the heat map, indicated that the spatial distribution differences at N3-N6E1 and N1-N3E2 units are crucial in understanding type C1 and C2 necrotic lesions. Conclusion. The LLDS can be used to accurately measure the spatial location of necrotic lesions and display their distribution characteristics. Cite this article: Bone Joint Res 2024;13(6):294–305

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Adenosine, lidocaine, and Mg²⁺ (ALM) therapy exerts differential immuno-inflammatory responses in males and females early after anterior cruciate ligament (ACL) reconstruction (ACLR). Our aim was to investigate sex-specific effects of ALM therapy on joint tissue repair and recovery 28 days after surgery.

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Periprosthetic fracture and implant loosening are two of the major reasons for revision surgery of cementless implants. Optimal implant fixation with minimal bone damage is challenging in this procedure. This pilot study investigates whether vibratory implant insertion is gentler compared to consecutive single blows for acetabular component implantation in a surrogate polyurethane (PU) model.

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

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In this investigation, we administered oxidative stress to nucleus pulposus cells (NPCs), recognized DNA-damage-inducible transcript 4 (DDIT4) as a component in intervertebral disc degeneration (IVDD), and devised a hydrogel capable of conveying small interfering RNA (siRNA) to IVDD.

Aims. To assess the alterations in cell-specific DNA methylation associated with chondroitin sulphate response using peripheral blood collected from Kashin-Beck disease (KBD) patients before initiation of chondroitin sulphate treatment. Methods. Peripheral blood samples were collected from KBD patients at baseline of chondroitin sulphate treatment. Methylation profiles were generated using reduced representation bisulphite sequencing (RRBS) from peripheral blood. Differentially methylated regions (DMRs) were identified using MethylKit, while DMR-related genes were defined as those annotated to the gene body or 2.2-kilobase upstream regions of DMRs. Selected DMR-related genes were further validated by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) to assess expression levels. Tensor composition analysis was performed to identify cell-specific differential DNA methylation from bulk tissue. Results. This study revealed 21,060 hypermethylated and 44,472 hypomethylated DMRs, and 13,194 hypermethylated and 22,448 hypomethylated CpG islands for differential global methylation for chondroitin sulphate treatment response. A total of 12,666 DMR-related genes containing DMRs were identified in their promoter regions, such as CHL1 (false discovery rate (FDR) = 2.11 × 10. -11. ), RIC8A (FDR = 7.05 × 10. -4. ), and SOX12 (FDR = 1.43 × 10. -3. ). Additionally, RIC8A and CHL1 were hypermethylated in responders, while SOX12 was hypomethylated in responders, all showing decreased gene expression. The patterns of cell-specific differential global methylation associated with chondroitin sulphate response were observed. Specifically, we found that DMRs located in TESPA1 and ATP11A exhibited differential DNA methylation between responders and non-responders in granulocytes, monocytes, and B cells. Conclusion. Our study identified cell-specific changes in DNA methylation associated with chondroitin sulphate response in KBD patients. Cite this article: Bone Joint Res 2024;13(5):237–246

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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.

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The aim of this study was to determine the fracture haematoma (fxH) proteome after multiple trauma using label-free proteomics, comparing two different fracture treatment strategies.

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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).

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Manual impaction, with a mallet and introducer, remains the standard method of installing cementless acetabular cups during total hip arthroplasty (THA). This study aims to quantify the accuracy and precision of manual impaction strikes during the seating of an acetabular component. This understanding aims to help improve impaction surgical techniques and inform the development of future technologies.